FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Dracheva, S Chin, B Haroutunian, V AF Dracheva, Stella Chin, Benjamin Haroutunian, Vahram TI Altered serotonin 2C receptor RNA splicing in suicide: association with editing SO NEUROREPORT LA English DT Article DE mRNA editing; serotonin 2C receptor; splice variant; suicide ID PRE-MESSENGER-RNA; SITE SELECTION; GENE; IDENTIFICATION; MUTATION; VARIANT; ROLES AB In an earlier study, we showed increases in serotonin 2C receptor (5-HT2CR) pre-mRNA editing in prefrontal cortex that were specific to suicide victims irrespective of associated psychiatric diagnoses. Here we demonstrate that the ratio between the two 5-HT2CR splice variants is increased in people who committed suicide, but does not vary among the diagnostic groups. This provides further evidence for suicide-specific neurobiology and suggests that, as it was previously shown in vitro, 5-HT2CR editing modulates its splicing in human brain. The association analysis indicates, however, that the efficiency of 5-HT2CR editing is an imperfect predictor of the splicing outcome, and that splice site selection is only partially controlled by the level of editing in vivo. C1 [Dracheva, Stella; Haroutunian, Vahram] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Dracheva, Stella; Chin, Benjamin; Haroutunian, Vahram] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. RP Dracheva, S (reprint author), Vet Adm Med Ctr, 4F-02,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Stella.Dracheva@mssm.edu NR 23 TC 24 Z9 26 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD FEB 12 PY 2008 VL 19 IS 3 BP 379 EP 382 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 264PR UT WOS:000253301400023 PM 18303585 ER PT J AU Kobayashi, T Lu, J Cobb, BS Rodda, SJ McMahon, AP Schipani, E Merkenschlager, M Kronenberg, HM AF Kobayashi, Tatsuya Lu, Jun Cobb, Bradley S. Rodda, Stephen J. McMahon, Andrew P. Schipani, Ernestina Merkenschlager, Matthias Kronenberg, Henry M. TI Dicer-dependent pathways regulate chondrocyte proliferation and differentiation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE microRNA; skeletal development ID MESSENGER-RNA DEGRADATION; HORMONE-RELATED PEPTIDE; EMBRYONIC STEM-CELLS; PARATHYROID-HORMONE; ENZYME DICER; HISTONE DEACETYLASE-4; TARGETED EXPRESSION; MICRORNA EXPRESSION; DOWN-REGULATION; MORPHOGENESIS AB Small noncoding RNAs, microRNAs (miRNAs), bind to messenger RNAs through base pairing to suppress gene expression. Despite accumulating evidence that miRNAs play critical roles in various biological processes across diverse organisms, their roles in mammalian skeletal development have not been demonstrated. Here, we show that Dicer, an essential component for biogenesis of miRNAs, is essential for normal skeletal development. Dicer-null growth plates show a progressive reduction in the proliferating pool of chondrocytes, leading to severe skeletal growth defects and premature death of mice. The reduction of proliferating chondrocytes in Dicer-null growth plates is caused by two distinct mechanisms: decreased chondrocyte proliferation and accelerated differentiation into postmitotic hypertrophic chondrocytes. These defects appear to be caused by mechanisms downstream or independent of the Ihh-PTHrP signaling pathway, a pivotal signaling system that regulates chondrocyte proliferation and differentiation. Microarray analysis of Dicer-null chondrocytes showed limited expression changes in miRNA-target genes, suggesting that, in the majority of cases, chondrocytic miRNAs do not directly regulate target RNA abundance. Our results demonstrate the critical role of the Dicer-dependent pathway in the regulation of chondrocyte proliferation and differentiation during skeletal development. C1 [Kobayashi, Tatsuya; Schipani, Ernestina; Kronenberg, Henry M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Kobayashi, Tatsuya; Schipani, Ernestina; Kronenberg, Henry M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Lu, Jun] Harvard Univ, Broad Inst, Cambridge, MA 02141 USA. [Lu, Jun] MIT, Broad Inst, Cambridge, MA 02141 USA. [Cobb, Bradley S.; Merkenschlager, Matthias] Univ London Imperial Coll Sci Technol & Med, MRC Clin Sci Ctr, Lymphocyte Dev Grp, London W12 0NN, England. [Rodda, Stephen J.; McMahon, Andrew P.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. RP Kobayashi, T (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. EM kobayash@helix.mgh.harvard.edu OI Merkenschlager, Matthias/0000-0003-2889-3288 FU Medical Research Council [MC_U120027516]; NIAMS NIH HHS [1R21AR054500, R21 AR054500]; NIDDK NIH HHS [DK56246, P01 DK056246] NR 54 TC 199 Z9 202 U1 0 U2 13 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 12 PY 2008 VL 105 IS 6 BP 1949 EP 1954 DI 10.1073/pnas.0707900105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 264CC UT WOS:000253261900033 PM 18238902 ER PT J AU Yun, CH Mengwasser, KE Toms, AV Woo, MS Greulich, H Wong, KK Meyerson, M Eck, MJ AF Yun, Cai-Hong Mengwasser, Kristen E. Toms, Angela V. Woo, Michele S. Greulich, Heidi Wong, Kwok-Kin Meyerson, Matthew Eck, Michael J. TI The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE lung cancer; tyrosine kinase; x-ray crystallography ID GROWTH-FACTOR-RECEPTOR; CELL LUNG-CANCER; CHRONIC MYELOID-LEUKEMIA; ACQUIRED-RESISTANCE; IRREVERSIBLE INHIBITORS; ALLOSTERIC MECHANISM; DOMAIN MUTATIONS; BCR-ABL; GEFITINIB; SENSITIVITY AB Lung cancers caused by activating mutations in the epidermal growth factor receptor (EGFR) are initially responsive to small molecule tyrosine kinase inhibitors (TKIs), but the efficacy of these agents is often limited because of the emergence of drug resistance conferred by a second mutation, T790M. Threonine 790 is the "gatekeeper" residue, an important determinant of inhibitor specificity in the ATP binding pocket. The T790M mutation has been thought to cause resistance by sterically blocking binding of TKIs such as gefitinib and erlotinib, but this explanation is difficult to reconcile with the fact that it remains sensitive to structurally similar irreversible inhibitors. Here, we show by using a direct binding assay that T790M mutants retain low-nanomolar affinity for gefitinib. Furthermore, we show that the T790M mutation activates WT EGFR and that introduction of the T790M mutation increases the ATP affinity of the oncogenic L858R mutant by more than an order of magnitude. The increased ATP affinity is the primary mechanism by which the T790M mutation confers drug resistance. Crystallographic analysis of the T790M mutant shows how it can adapt to accommodate tight binding of diverse inhibitors, including the irreversible inhibitor HKI-272, and also suggests a structural mechanism for catalytic activation. We conclude that the T790M mutation is a "generic" resistance mutation that will reduce the potency of any ATP-competitive kinase inhibitor and that irreversible inhibitors overcome this resistance simply through covalent binding, not as a result of an alternative binding mode. C1 [Yun, Cai-Hong; Toms, Angela V.; Eck, Michael J.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Yun, Cai-Hong; Mengwasser, Kristen E.; Toms, Angela V.; Eck, Michael J.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Woo, Michele S.; Greulich, Heidi; Wong, Kwok-Kin; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Wong, Kwok-Kin] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Greulich, Heidi; Meyerson, Matthew] Broad Inst Harvard, Boston, MA 02115 USA. [Greulich, Heidi; Meyerson, Matthew] MIT, Boston, MA 02115 USA. RP Eck, MJ (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, 25 Shattuck St, Boston, MA 02115 USA. EM eck@red.dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012; OI wong, kwok kin/0000-0001-6323-235X FU NCI NIH HHS [R01 CA080942, CA080942, CA116020, R01 CA116020] NR 40 TC 726 Z9 764 U1 8 U2 135 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 12 PY 2008 VL 105 IS 6 BP 2070 EP 2075 DI 10.1073/pnas.0709662105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 264CC UT WOS:000253261900054 PM 18227510 ER PT J AU Miller, SL Celone, K DePeau, K Diamond, E Dickerson, BC Rentz, D Pihlajamaki, M Sperling, RA AF Miller, Saul L. Celone, Kim DePeau, Kristina Diamond, Eli Dickerson, Bradford C. Rentz, Dorene Pihlajamaki, Maija Sperling, Reisa A. TI Age-related memory impairment associated with loss of parietal deactivation but preserved hippocampal activation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE aging; fMRI; hippocampus; default network; Alzheimer's disease ID MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; BRAIN ACTIVITY; DEFAULT-MODE; SUBSEQUENT MEMORY; ENCODING ACTIVITY; WORKING-MEMORY; RESTING STATE; NETWORKS; FMRI AB The neural underpinnings of age-related memory impairment remain to be fully elucidated. Using a subsequent memory face-name functional MRI (fMRI) paradigm, young and old adults showed a similar magnitude and extent of hippocampal activation during successful associative encoding. Young adults demonstrated greater deactivation (task-induced decrease in BOLD signal) in medial parietal regions during successful compared with failed encoding, whereas old adults as a group did not demonstrate a differential pattern of deactivation between trial types. The failure of deactivation was particularly evident in old adults who performed poorly on the memory task. These low-performing old adults demonstrated greater hippocampal and prefrontal activation to achieve successful encoding trials, possibly as a compensatory response. Findings suggest that successful encoding requires the coordination of neural activity in hippocampal, prefrontal, and parietal regions, and that age-related memory impairment may be primarily related to a loss of deactivation in medial parietal regions. C1 [Miller, Saul L.; Celone, Kim; DePeau, Kristina; Diamond, Eli; Dickerson, Bradford C.; Rentz, Dorene; Pihlajamaki, Maija; Sperling, Reisa A.] Brigham & Womens Hosp, Dept Neurol, Memory Disorders Unit, Boston, MA 02115 USA. [Miller, Saul L.; Celone, Kim] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02129 USA. [Dickerson, Bradford C.; Sperling, Reisa A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02129 USA. [Dickerson, Bradford C.; Sperling, Reisa A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Marinos Ctr Biomed Imaging, Boston, MA 02129 USA. RP Sperling, RA (reprint author), Brigham & Womens Hosp, Dept Neurol, Memory Disorders Unit, 221 Longwood Ave, Boston, MA 02115 USA. EM reisa@rics.bwh.harvard.edu FU NIA NIH HHS [P50-AG00513421, R01 AG027435, R01 AG027435-03, R01-AG027435] NR 46 TC 192 Z9 192 U1 1 U2 14 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 12 PY 2008 VL 105 IS 6 BP 2181 EP 2186 DI 10.1073/pnas.0706818105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 264CC UT WOS:000253261900073 PM 18238903 ER PT J AU Gralow, JR Zujewski, JA Winer, E AF Gralow, Julie R. Zujewski, Jo Anne Winer, Eric TI Preoperative therapy in invasive breast cancer: Reviewing the state of the science and exploring new research directions SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID SURGICAL ADJUVANT BREAST; CHEMOTHERAPY; WOMEN C1 [Gralow, Julie R.] Univ Washington, Dept Med Oncol, Seattle, WA 98195 USA. [Gralow, Julie R.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Zujewski, Jo Anne] NCI, Clin Invest Branch, Canc Therapy Evaluat Program, Div Canc Diag & Treatment, Bethesda, MD 20892 USA. [Winer, Eric] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. RP Gralow, JR (reprint author), Univ Washington, Dept Med Oncol, Seattle, WA 98195 USA. NR 9 TC 16 Z9 18 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 10 PY 2008 VL 26 IS 5 BP 696 EP 697 DI 10.1200/JCO.2007.15.9459 PG 2 WC Oncology SC Oncology GA 276XR UT WOS:000254177500002 PM 18258975 ER PT J AU Buchholz, TA Lehman, CD Harris, JR Pockaj, BA Khouri, N Hylton, NF Miller, MJ Whelan, T Pierce, LJ Esserman, LJ Newman, LA Smith, BL Bear, HD Mamounas, EP AF Buchholz, Thomas A. Lehman, Constance D. Harris, Jay R. Pockaj, Barbara A. Khouri, Nagi Hylton, Nola F. Miller, Michael J. Whelan, Timothy Pierce, Lori J. Esserman, Laura J. Newman, Lisa A. Smith, Barbara L. Bear, Harry D. Mamounas, Eleftherios P. TI Statement of the science concerning locoregional treatments after preoperative chemotherapy for breast cancer: A National Cancer Institute conference SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT National-Cancer-Institute Statement of Science Conference CY MAR 26-27, 2007 CL NCI, Bethesda, MD HO NCI ID SURGICAL ADJUVANT BREAST; POSTMASTECTOMY RADIATION IMPROVES; LOCAL-REGIONAL RECURRENCE; PATHOLOGICAL TUMOR SIZE; PROJECT PROTOCOL B-27; LYMPH-NODE BIOPSY; NEOADJUVANT CHEMOTHERAPY; MRI; RECONSTRUCTION; MASTECTOMY AB Purpose To review the state of the science with respect to diagnostic imaging and locoregional therapy for patients with breast cancer receiving preoperative chemotherapy. Methods Published data relevant to clinical staging, monitoring of tumor response, and locoregional therapy for patients with breast cancer treated with preoperative chemotherapy were reviewed. Results High-quality data from prospective randomized trials are limited. Available data suggest that locoregional therapy decisions should be based on both the pretreatment clinical extent of disease and the pathologic extent of the disease after chemotherapy. Accordingly, physical examination and imaging studies that accurately define the initial extent of disease are required before treatment. Sentinel lymph node biopsy can be performed either before or after preoperative chemotherapy for patients with clinical N0 disease. The success of breast conservation after preoperative chemotherapy depends on careful patient selection and achieving negative surgical margins. Adjuvant breast radiation is indicated for all patients treated with breast conservation. For patients treated with mastectomy, chest-wall and regional nodal radiation should be considered for those who present with clinical stage III disease or have histologically positive lymph nodes after preoperative chemotherapy. Additional prospective studies are needed to determine the value of postmastectomy radiation for patients with stage II breast cancer who have negative lymph nodes after chemotherapy. Conclusion The increased use of preoperative chemotherapy has raised new questions concerning the optimal methods to stage and monitor disease response to treatment and how to optimize locoregional treatment. The available evidence suggests that a multidisciplinary approach improves outcomes. C1 Univ Texas Houston, MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. Univ Washington, Dept Radiol, Seattle, WA 98195 USA. Seattle Canc Care Alliance, Seattle, WA USA. Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. MA Gen Hosp, Dept Surg, Boston, MA USA. Mayo Clin Arizona, Dept Surg, Scottsdale, AZ USA. Johns Hopkins Univ, Dept Radiol & Oncol, Baltimore, MD USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. Ohio State Univ, Dept Surg, Columbus Aultman Hlth Fen, Rootstown, OH USA. Northeastern Ohio Univ Coll Med & Pharm, Dept Surg, Rootstown, OH 44272 USA. McMaster Univ, Dept Oncol, Hamilton, ON, Canada. Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Surg, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Med Coll Virginia, Massey Canc Ctr, Richmond, VA 23298 USA. RP Buchholz, TA (reprint author), Univ Texas Houston, MD Anderson Canc Ctr, Dept Radiat Oncol, 1515 Holcombe Blvd,Unit 1202, Houston, TX 77030 USA. EM tbuchhol@mdanderson.org RI Whelan, Timothy/D-3185-2017 NR 44 TC 113 Z9 119 U1 1 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 10 PY 2008 VL 26 IS 5 BP 791 EP 797 DI 10.1200/JCO.2007.15.0326 PG 7 WC Oncology SC Oncology GA 276XR UT WOS:000254177500015 PM 18258988 ER PT J AU Lin, NU Winer, EP AF Lin, Nancy U. Winer, Eric P. TI Advances in adjuvant endocrine therapy for postmenopausal women SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID EARLY BREAST-CANCER; QUALITY-OF-LIFE; PLACEBO-CONTROLLED TRIAL; BONE-MINERAL DENSITY; FIRST-LINE THERAPY; BOWEL PROJECT P-1; RANDOMIZED-TRIAL; ESTROGEN-RECEPTOR; AROMATASE INHIBITOR; TAMOXIFEN THERAPY AB Hormone receptor-positive cancers are the most common tumor subtype among postmenopausal women with breast cancer. Despite substantial improvements in disease-free survival and overall survival with tamoxifen and chemotherapy, recurrences still occur, and may ultimately lead to death from breast cancer. Importantly, disease recurrence includes both early and late events, with over half of all recurrences detected more than 5 years from initial breast cancer diagnosis. In recent years, a number of large, randomized trials have evaluated the role of the aromatase inhibitors (AIs) in postmenopausal women with hormone receptor-positive breast cancer. These studies have tested one of three approaches: (1) an upfront AI, (2) a sequential approach after 2-3 years of tamoxifen, and (3) extended endocrine therapy beyond 5 years. Results of these studies have challenged the previous standard of a 5-year course of tamoxifen alone. While the AIs have become a standard component of treatment for most postmenopausal women, many questions remain as to how best tailor endocrine treatment to individual patients. In addition, despite the gains achieved with the AIs, many recurrences are not prevented, and novel strategies are urgently needed, particularly for those women at high risk of recurrence. In this article, we review the efficacy and toxicity data from the available trials of endocrine therapy in the postmenopausal setting. We outline controversies in choosing the optimal endocrine approach, and we discuss selected ongoing studies. Finally, we highlight future research directions, such as the need to understand host and tumor heterogeneity. C1 [Lin, Nancy U.; Winer, Eric P.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Winer, EP (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Mayer 232, Boston, MA 02115 USA. EM ewiner@partners.org FU NCI NIH HHS [CA89393] NR 95 TC 66 Z9 67 U1 1 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 10 PY 2008 VL 26 IS 5 BP 798 EP 805 DI 10.1200/JCO.2007.15.0946 PG 8 WC Oncology SC Oncology GA 276XR UT WOS:000254177500016 PM 18258989 ER PT J AU Wolff, AC Berry, D Carey, LA Colleoni, M Dowsett, M Ellis, M Garber, JE Mankoff, D Paik, S Pusztai, L Smith, ML Zujewski, J AF Wolff, Antonio C. Berry, Donald Carey, Lisa A. Colleoni, Marco Dowsett, Mitchell Ellis, Matthew Garber, Judy E. Mankoff, David Paik, Soonmyung Pusztai, Lajos Smith, Mary Lou Zujewski, JoAnne TI Research issues affecting preoperative systemic therapy for operable breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; PATHOLOGICAL COMPLETE RESPONSE; FACTOR RECEPTOR EXPRESSION; SURGICAL ADJUVANT BREAST; RECURRENCE-FREE SURVIVAL; PROJECT PROTOCOL B-27; BASAL-LIKE SUBTYPE; NEOADJUVANT CHEMOTHERAPY; GENE-EXPRESSION; CLINICAL-TRIAL AB Preoperative systemic therapy (PST) in operable breast cancer allows a small increase in breast conservation rates and has significant potential as a research platform. PST offers the ability to discern treatment effect in vivo, and may allow smaller trials targeting specific breast cancer subtypes and making more efficient use of resources. Early observations of a specific outcome of interest in individual patient subgroups may improve the design of larger definitive randomized adjuvant trials using survival as a main outcome. PST offers the potential for therapeutic adjustments midcourse, which assumes the existence of validated intermediate end points and effective alternative therapies. This article reviews critical research issues affecting the design of PST trials, including the appropriate selection of trial end points and markers for long-term outcome, baseline marker expression as a predictor of response, and statistical considerations using novel trial designs. Key issues regarding optimal tumor subtype selection for individual trials, novel approaches using nontherapeutic window trial designs, and ethical and advocacy considerations are also discussed. PST requires an experienced and cohesive multidisciplinary team for it to fulfill its potential in both research and clinical care. C1 Johns Hopkins Sydney Kimmel Canc Ctr, Baltimore, MD 21231 USA. NCI, Bethesda, MD 20892 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX USA. Univ N Carolina, Chapel Hill, NC USA. European Inst Oncol, Milan, Italy. Royal Marsden Hosp, London SW3 6JJ, England. Washington Univ, Sch Med, St Louis, MO USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. Natl Surg Adjuvant Breast & Bowel Project, Div Pathol, Pittsburgh, PA USA. Res Advocacy Network, Chicago, IL USA. RP Wolff, AC (reprint author), Johns Hopkins Sydney Kimmel Canc Ctr, 1650 Orleans St,Room 189, Baltimore, MD 21231 USA. EM awolff@jhmi.edu RI Mankoff, David/F-9576-2010; OI Wolff, Antonio/0000-0003-3734-1063 NR 83 TC 44 Z9 46 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 10 PY 2008 VL 26 IS 5 BP 806 EP 813 DI 10.1200/JCO.2007.15.2983 PG 8 WC Oncology SC Oncology GA 276XR UT WOS:000254177500017 PM 18258990 ER PT J AU Gralow, JR Burstein, HJ Wood, W Hortobagyi, GN Gianni, L Von Minckwitz, G Buzdar, AU Smith, IE Symmans, WF Singh, B Winer, EP AF Gralow, Julie R. Burstein, Harold J. Wood, William Hortobagyi, Gabriel N. Gianni, Luca Von Minckwitz, Gunter Buzdar, Aman U. Smith, Ian E. Symmans, William F. Singh, Baljit Winer, Eric P. TI Preoperative therapy in invasive breast cancer: Pathologic assessment and systemic therapy issues in operable disease SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID DOXORUBICIN PLUS CYCLOPHOSPHAMIDE; SURGICAL ADJUVANT BREAST; RANDOMIZED-TRIAL; NEOADJUVANT CHEMOTHERAPY; ENDOCRINE THERAPY; PROGNOSTIC-SIGNIFICANCE; RADIATION-THERAPY; FOLLOW-UP; TAMOXIFEN; WOMEN AB Purpose To review the state of the science with respect to preoperative systemic therapy and pathologic assessment in operable breast cancer. Methods This article reviews data presented at the National Cancer Institute State of the Science Conference on Preoperative Therapy in Invasive Breast Cancer as well as supporting published data. Results Preoperative chemotherapy in operable breast cancer has been shown to improve breast conservation rates as a result of tumor response to therapy. When patients are given preoperative systemic therapy, regimens should be the same as those established as safe and active in the adjuvant setting. At present, there are no data to suggest that systemic treatment should be tailored based on initial tumor response, or based on the extent of residual disease. In operable breast cancer, there seems to be no survival advantage from initiation of systemic therapy before surgery. A variety of clinical, imaging, and pathologic measurements are available to gauge tumor response to treatment. There is a clear correlation between tumor response in the breast and lymph nodes and both disease-free and overall survival. Pathologic complete response and other pathologic measures may be useful as surrogate end points in evaluating and understanding new therapies. Conclusion In operable breast cancer, preoperative systemic therapy is effective and can improve breast conservation rates. Unless the tumor is large or the patient is in a clinical trial, postoperative adjuvant systemic therapy is the standard of care. To achieve optimal outcomes, preoperative systemic therapy must be administered as part of a coordinated, multimodality treatment program. The preoperative setting provides a unique opportunity to study the impact of systemic therapies on breast cancer biology. C1 Univ Washington, Dept Med Oncol, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Emory Univ, Sch Med, Dept Surg, Atlanta, GA 30322 USA. Univ Texas Houston, MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA. Univ Texas Houston, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. Ist Nazl Tumori, Div Med Oncol, I-20133 Milan, Italy. Neu Isenburg Univ, Womens Hosp, German Breast Grp, Frankfurt, Germany. Royal Marsden Hosp, London SW3 6JJ, England. NYU, Med Ctr, Dept Pathol, New York, NY 10016 USA. RP Gralow, JR (reprint author), Seattle Canc Care Alliance, Dept Med, 825 Eastlake Ave,EMS G3-200, Seattle, WA 98109 USA. EM pink@u.washington.edu NR 45 TC 161 Z9 169 U1 0 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 10 PY 2008 VL 26 IS 5 BP 814 EP 819 DI 10.1200/JCO.2007.15.3510 PG 6 WC Oncology SC Oncology GA 276XR UT WOS:000254177500018 PM 18258991 ER PT J AU Hurley, BP Sin, A McCormick, BA AF Hurley, B. P. Sin, A. McCormick, B. A. TI Adhesion molecules involved in hepoxilin A(3)-mediated neutrophil transepithelial migration SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE adhesion molecules; hepoxilin A(3); neutrophils; Pseudomonas aeruginosa; Salmonella typhimurium ID INTESTINAL EPITHELIAL-CELLS; TRANSMIGRATION; EXPRESSION; A(3); LEUKOTRIENES; MECHANISMS; BARRIER; EVENTS AB A common feature underlying active states of inflammation is the migration of neutrophils (PMNs) from the circulation and across a number of tissue barriers in response to chemoattractant stimuli. Although our group has recently established a discreet role for the PMN chemoattractant, hepoxilin A(3) (HXA(3)) in the process of PMN recruitment, very little is known regarding the interaction of HXA(3) with PMNs. To characterize further the event of HXA(3)-induced PMN transepithelial migration, we sought to determine the adhesion molecules required for migration across different epithelial surfaces (T84 intestinal and A549 airway cells) relative to two well-studied PMN chemoattractants, formyl-methionyl-leucyl-phenylalanine (fMLP) and leukotriene B-4 (LTB4). Our findings reveal that the adhesion interaction profile of PMN transepithelial migration in response to HXA(3) differs from the adhesion interaction profile exhibited by the structurally related eicosanoid LTB4. Furthermore, unique to PMN transepithelial migration induced by gradients of HXA(3) was the critical dependency of all four major surface adhesion molecules examined (i.e. CD18, CD47, CD44 and CD55). Our results suggest that the particular chemoattractant gradient imposed, as well as the type of epithelial cell monolayer, each plays a role in determining the adhesion molecules involved in transepithelial migration. Given the complexities of these interactions, our findings are important to consider with respect to adhesion molecules that may be targeted for potential drug development. C1 [Hurley, B. P.; Sin, A.; McCormick, B. A.] Massachusetts Gen Hosp, Dept Pediat Gastroenterol & Nutr, Mucosal Immunol Lab, Charlestown, MA 02129 USA. [Hurley, B. P.; McCormick, B. A.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP McCormick, BA (reprint author), Massachusetts Gen Hosp, Dept Pediat Gastroenterol & Nutr, Mucosal Immunol Lab, 114 16th St 114-3503, Charlestown, MA 02129 USA. EM mccormic@helix.mgh.harvard.edu FU NIDDK NIH HHS [P01 DK033506, DK 33506, DK 56754, P30 DK040561, P30 DK040561-12, R01 DK056754] NR 27 TC 12 Z9 12 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD FEB 8 PY 2008 VL 151 IS 2 BP 297 EP 305 DI 10.1111/j.1365-2249.2007.03551.x PG 9 WC Immunology SC Immunology GA 249CU UT WOS:000252205300011 PM 18005361 ER PT J AU Anelli, V Gault, CR Cheng, AB Obeid, LM AF Anelli, Viviana Gault, Christopher R. Cheng, Amy B. Obeid, Lina M. TI Sphingosine kinase 1 is up-regulated during hypoxia in U87MG glioma cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; PROTEIN-COUPLED RECEPTORS; FACTOR-INDUCED ACTIVATION; INDUCIBLE FACTOR-ALPHA; HUMAN BREAST-CANCER; SPHINGOSINE-1-PHOSPHATE RECEPTOR; FUNCTIONAL-CHARACTERIZATION; EXTRACELLULAR RELEASE; MOLECULAR-CLONING; KINASE EXPRESSION AB Sphingosine 1-phosphate (S1P), a sphingolipid metabolite that plays an important role in the regulation of cell survival, growth, migration, and angiogenesis, acts both inside the cells and as an extracellular mediator through binding to five G protein-coupled receptors (S1P(1-5)). Sphingosine kinase 1 (SK1), the enzyme responsible for S1P production, is overexpressed in many solid tumors, including gliomas. One common feature of these tumors is the presence of "hypoxic regions," characterized by cells expressing high levels of hypoxia-inducible factors HIF-1 alpha and HIF-2 alpha, two transcription regulators that modulate the levels of proteins with crucial roles in tumor progression. So far, nothing is known about the role and the regulation of SK1 during tumor-induced hypoxia or about SK1 regulation and HIFs. Here we investigated the role of HIF-1 alpha and HIF-2 alpha in the regulation of SK1 during hypoxic stress in glioma-derived U87MG cells. We report that hypoxia increases SK1 mRNA levels, protein expression, and enzyme activity, followed by intracellular S1P production and S1P release. Interestingly, knockdown of HIF-2 alpha by small interfering RNA abolished the induction of SK1 and the production of extracellular S1P after CoCl2 treatment, whereas HIF-1 alpha small interfering RNA resulted in an increase of HIF-2 alpha and of SK1 protein levels. Moreover, using chromatin immunoprecipitation analysis, we demonstrate that HIF-2 alpha binds the SK1 promoter. Functionally, we demonstrate that conditioned medium from hypoxia-treated tumor cells results in neoangiogenesis in human umbilical vein endothelial cells in a S1P receptor-dependent manner. These studies provide evidence of a link between S1P production as a potent angiogenic agent and the hypoxic phenotype observed in many tumors. C1 [Obeid, Lina M.] Ralph H Johnson Affairs Med Ctr, Charleston, SC 29401 USA. [Gault, Christopher R.; Obeid, Lina M.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Anelli, Viviana; Cheng, Amy B.; Obeid, Lina M.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Anelli, Viviana] Univ Milan, Dept Med Chem Biochem & Biotechnol, I-20090 Milan, Italy. RP Obeid, LM (reprint author), Med Univ S Carolina, Dept Med, Div Gen Internal Med Geriatr, POB 250779, Charleston, SC 29403 USA. EM obeid@musc.edu FU NCI NIH HHS [P01 CA097132]; NIGMS NIH HHS [R01 GM062887] NR 62 TC 75 Z9 76 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 8 PY 2008 VL 283 IS 6 BP 3365 EP 3375 DI 10.1074/jbc.M708241200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 261MJ UT WOS:000253083000041 PM 18055454 ER PT J AU Song, YQ Cho, H Hopper, T Pomerantz, AE Sun, PZ AF Song, Yi-Qiao Cho, H. Hopper, Tim Pomerantz, Andrew E. Sun, Phillip Zhe TI Magnetic resonance in porous media: Recent progress SO JOURNAL OF CHEMICAL PHYSICS LA English DT Review ID SELF-DIFFUSION MEASUREMENTS; BACKGROUND GRADIENT SUPPRESSION; LAPLACE INVERSION SPECTRUM; SPIN-LATTICE-RELAXATION; SIDED NMR SENSOR; FIELD GRADIENT; SUSCEPTIBILITY DIFFERENCES; HETEROGENEOUS SYSTEMS; ACHILLES-TENDON; RESERVOIR CORES AB Recent years have seen significant progress in the NMR study of porous media from natural and industrial sources and of cultural significance such as paintings. This paper provides a brief outline of the recent technical development of NMR in this area. These advances are relevant for broad NMR applications in material characterization. (c) 2008 American Institute of Physics. C1 [Song, Yi-Qiao; Cho, H.; Hopper, Tim; Pomerantz, Andrew E.] Schlumberger Doll Res Ctr, Cambridge, MA 02139 USA. [Cho, H.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Song, Yi-Qiao; Sun, Phillip Zhe] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Song, Yi-Qiao; Sun, Phillip Zhe] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Song, YQ (reprint author), Schlumberger Doll Res Ctr, 1 Hampshire St, Cambridge, MA 02139 USA. EM ysong@slb.com RI Cho, HyungJoon/F-1423-2010 NR 118 TC 32 Z9 32 U1 2 U2 36 PU AMER INST PHYSICS PI MELVILLE PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA SN 0021-9606 EI 1089-7690 J9 J CHEM PHYS JI J. Chem. Phys. PD FEB 7 PY 2008 VL 128 IS 5 AR 052212 DI 10.1063/1.2833581 PG 12 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 262CD UT WOS:000253125700014 PM 18266417 ER PT J AU Meyer-Luehmann, M Spires-Jones, TL Prada, C Garcia-Alloza, M de Calignon, A Rozkalne, A Koenigsknecht-Talboo, J Holtzman, DM Bacskai, BJ Hyman, BT AF Meyer-Luehmann, Melanie Spires-Jones, Tara L. Prada, Claudia Garcia-Alloza, Monica de Calignon, Alix Rozkalne, Anete Koenigsknecht-Talboo, Jessica Holtzman, David M. Bacskai, Brian J. Hyman, Bradley T. TI Rapid appearance and local toxicity of amyloid-beta plaques in a mouse model of Alzheimer's disease SO NATURE LA English DT Article ID TRANSGENIC MICE; MULTIPHOTON MICROSCOPY; PRECURSOR PROTEIN; IN-VIVO; MICROGLIA; ABNORMALITIES; NEUROTOXICITY; DISRUPTION; DEFICITS; MEMORY AB Senile plaques accumulate over the course of decades in the brains of patients with Alzheimer's disease. A fundamental tenet of the amyloid hypothesis of Alzheimer's disease is that the deposition of amyloid-beta precedes and induces the neuronal abnormalities that underlie dementia(1). This idea has been challenged, however, by the suggestion that alterations in axonal trafficking and morphological abnormalities precede and lead to senile plaques(2). The role of microglia in accelerating or retarding these processes has been uncertain. To investigate the temporal relation between plaque formation and the changes in local neuritic architecture, we used longitudinal in vivo multiphoton microscopy to sequentially image young APPswe/ PS1d9xYFP ( B6C3-YFP) transgenic mice(3). Here we show that plaques form extraordinarily quickly, over 24 h. Within 1-2 days of a new plaque's appearance, microglia are activated and recruited to the site. Progressive neuritic changes ensue, leading to increasingly dysmorphic neurites over the next days to weeks. These data establish plaques as a critical mediator of neuritic pathology. C1 [Meyer-Luehmann, Melanie; Spires-Jones, Tara L.; Prada, Claudia; Garcia-Alloza, Monica; de Calignon, Alix; Rozkalne, Anete; Bacskai, Brian J.; Hyman, Bradley T.] Harvard Univ, Massgen Inst Neurodegenerat Dis, Massachusetts Gen Hosp, Alzheimers Dis Res Lab,Dept Neurol,Sch Med, Charlestown, MA 02129 USA. [Koenigsknecht-Talboo, Jessica; Holtzman, David M.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. RP Hyman, BT (reprint author), Harvard Univ, Massgen Inst Neurodegenerat Dis, Massachusetts Gen Hosp, Alzheimers Dis Res Lab,Dept Neurol,Sch Med, Charlestown, MA 02129 USA. EM bhyman@partners.org OI Meyer-Luehmann, Melanie/0000-0003-3661-2220 FU NIA NIH HHS [P50 AG005134, R01 AG008487, R01 AG008487-20]; NIDDK NIH HHS [P30 DK056341, P30 DK056341-07, P30 DK056341-08] NR 27 TC 518 Z9 526 U1 11 U2 68 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD FEB 7 PY 2008 VL 451 IS 7179 BP 720 EP U5 DI 10.1038/nature06616 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 259HD UT WOS:000252929500042 PM 18256671 ER PT J AU Lorenz, F Nalichowski, A Rosca, F Killoran, J Wenz, F Zygmanski, P AF Lorenz, Friedlieb Nalichowski, Adrian Rosca, Florin Killoran, Joseph Wenz, Frederik Zygmanski, Piotr TI An independent dose calculation algorithm for MLC-based radiotherapy including the spatial dependence of MLC transmission SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID RADIATION-THERAPY COMMITTEE; TREATMENT PLANNING SYSTEM; INTENSITY-MODULATED RADIOTHERAPY; MULTILEAF COLLIMATOR; QUALITY-ASSURANCE; DYNAMIC IMRT; VERIFICATION; SCATTER; FIELDS; DEPTH AB An analytical dose calculation algorithm was developed and commissioned to calculate dose delivered with both static and dynamic multileaf collimator (MLC) in a homogenous phantom. The algorithm is general; however, it was designed specifically to accurately model dose for large and complex IMRT fields. For such fields the delivered dose may have a considerable contribution from MLC transmission, which is dependent upon spatial considerations. Specifically, the algorithm models different MLC effects, such as interleaf transmission, the tongue-and-groove effect, rounded leaf ends, MLC scatter, beam hardening and divergence of the beam, which results in a gradual MLC transmission fall-off with increasing off-axis distance. The calculated dose distributions were compared to measured dose using different methods (film, ionization chamber array, single ionization chamber), and the differences among the treatment planning system, the measurements and the developed algorithm were analysed for static MLC and dynamic IMRT fields. It was found that the calculated dose from the developed algorithm agrees very well with the measurements (mostly within 1.5%) and that a constant value for MLC transmission is insufficient to accurately predict dose for large targets and complex IMRT plans with many monitor units. C1 [Lorenz, Friedlieb; Wenz, Frederik] Univ Heidelberg, Mannheim Med Ctr, Dept Radiat Oncol, D-6800 Mannheim, Germany. [Nalichowski, Adrian; Rosca, Florin; Killoran, Joseph; Zygmanski, Piotr] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. RP Lorenz, F (reprint author), Univ Heidelberg, Mannheim Med Ctr, Dept Radiat Oncol, D-6800 Mannheim, Germany. NR 21 TC 11 Z9 11 U1 0 U2 2 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD FEB 7 PY 2008 VL 53 IS 3 BP 557 EP 573 DI 10.1088/0031-9155/53/3/004 PG 17 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 257IP UT WOS:000252792700004 PM 18199902 ER PT J AU Jarlskog, CZ Lee, C Bolch, WE Xu, XG Paganetti, H AF Jarlskog, Christina Zacharatou Lee, Choonik Bolch, Wesley E. Xu, X. George Paganetti, Harald TI Assessment of organ-specific neutron equivalent doses in proton therapy using computational whole-body age-dependent voxel phantoms SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID RELATIVE BIOLOGICAL EFFECTIVENESS; MODULATED RADIATION-THERAPY; BIOL-PHYS 2006/65/1-7; INDUCED 2ND CANCERS; PEDIATRIC-PATIENTS; SECONDARY NEUTRON; UF SERIES; RADIOTHERAPY; SIMULATION; BEAMS AB Proton beams used for radiotherapy will produce neutrons when interacting with matter. The purpose of this study was to quantify the equivalent dose to tissue due to secondary neutrons in pediatric and adult patients treated by proton therapy for brain lesions. Assessment of the equivalent dose to organs away from the target requires whole-body geometrical information. Furthermore, because the patient geometry depends on age at exposure, age-dependent representations are also needed. We implemented age-dependent phantoms into our proton Monte Carlo dose calculation environment. We considered eight typical radiation fields, two of which had been previously used to treat pediatric patients. The other six fields were additionally considered to allow a systematic study of equivalent doses as a function of field parameters. For all phantoms and all fields, we simulated organ-specific equivalent neutron doses and analyzed for each organ (1) the equivalent dose due to neutrons as a function of distance to the target; (2) the equivalent dose due to neutrons as a function of patient age; (3) the equivalent dose due to neutrons as a function of field parameters; and (4) the ratio of contributions to secondary dose from the treatment head versus the contribution from the patient's body tissues. This work reports organ-specific equivalent neutron doses for up to 48 organs in a patient. We demonstrate quantitatively how organ equivalent doses for adult and pediatric patients vary as a function of patient's age, organ and field parameters. Neutron doses increase with increasing range and modulation width but decrease with field size (as defined by the aperture). We analyzed the ratio of neutron dose contributions from the patient and from the treatment head, and found that neutron-equivalent doses fall off rapidly as a function of distance from the target, in agreement with experimental data. It appears that for the fields used in this study, the neutron dose lateral to the field is smaller than the reported scattered photon doses in a typical intensity-modulated photon treatment. Most importantly, our study shows that neutron doses to specific organs depend considerably on the patient's age and body stature. The younger the patient, the higher the dose deposited due to neutrons. Given the fact that the risk also increases with decreasing patient age, this factor needs to be taken into account when treating pediatric patients of very young ages and/or of small body size. The neutron dose from a course of proton therapy treatment (assuming 70 Gy in 30 fractions) could potentially (depending on patient's age, organ, treatment site and area of CT scan) be equivalent to up to similar to 30 CT scans. C1 [Jarlskog, Christina Zacharatou] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Jarlskog, Christina Zacharatou] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Lee, Choonik; Bolch, Wesley E.] Univ Florida, Dept Nucl & Radiol Engn, Gainesville, FL 32611 USA. [Xu, X. George] Rensselaer Polytech Inst, Troy, NY 12180 USA. RP Jarlskog, CZ (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 53 TC 42 Z9 42 U1 1 U2 6 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD FEB 7 PY 2008 VL 53 IS 3 BP 693 EP 717 DI 10.1088/0031-9155/53/3/012 PG 25 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 257IP UT WOS:000252792700012 ER PT J AU Fan, BJ Pasquale, L Grosskreutz, CL Rhee, D Chen, T DeAngelis, MM Kim, I Del Bono, E Miller, JW Li, T Haines, JL Wiggs, JL AF Fan, Bao Jian Pasquale, Louis Grosskreutz, Cynthia L. Rhee, Douglas Chen, Teresa DeAngelis, Margaret M. Kim, Ivana Del Bono, Elizabeth Miller, Joan W. Li, Tiansen Haines, Jonathan L. Wiggs, Janey L. TI DNA sequence variants in the LOXL1 gene are associated with pseudoexfoliation glaucoma in a U.S. clinic-based population with broad ethnic diversity SO BMC MEDICAL GENETICS LA English DT Article ID OPEN-ANGLE GLAUCOMA; GENOME-WIDE SCAN; INTRAOCULAR-PRESSURE; EXFOLIATION-SYNDROME; UNITED-STATES; LOCUS; MAPS; IDENTIFICATION; LOCALIZATION; OPTINEURIN AB Background: Pseudoexfoliation syndrome is a major risk factor for glaucoma in many populations throughout the world. Using a U. S. clinic-based case control sample with broad ethnic diversity, we show that three common SNPs in LOXL1 previously associated with pseudoexfoliation in Nordic populations are significantly associated with pseudoexfoliation syndrome and pseudoexfoliation glaucoma. Methods: Three LOXL1 SNPs were genotyped in a patient sample (206 pseudoexfoliation, 331 primary open angle glaucoma, and 88 controls) from the Glaucoma Consultation Service at the Massachusetts Eye and Ear Infirmary. The SNPs were evaluation for association with pseudeoexfoliation syndrome, pseudoexfoliation glaucoma, and primary open angle glaucoma. Results: The strongest association was found for the G allele of marker rs3825942 (G153D) with a frequency of 99% in pseudoexfoliation patients (with and without glaucoma) compared with 79% in controls (p = 1.6 x 10(-15); OR = 20.93, 95% CI: 8.06, 54.39). The homozygous GG genotype is also associated with pseudoexfoliation when compared to controls (p = 1.2 x 10(-12); OR = 23.57, 95% CI: 7.95, 69.85). None of the SNPs were significantly associated with primary open angle glaucoma. Conclusion: The pseudoexfoliation syndrome is a common cause of glaucoma. These results indicate that the G153D LOXL1 variant is significantly associated with an increased risk of pseudoexfoliation and pseudoexfoliation glaucoma in an ethnically diverse patient population from the Northeastern United States. Given the high prevalence of pseudooexfoliation in this geographic region, these results also indicate that the G153D LOXL1 variant is a significant risk factor for adult-onset glaucoma in this clinic based population. C1 [Fan, Bao Jian; Pasquale, Louis; Grosskreutz, Cynthia L.; Rhee, Douglas; Chen, Teresa; DeAngelis, Margaret M.; Kim, Ivana; Del Bono, Elizabeth; Miller, Joan W.; Li, Tiansen; Wiggs, Janey L.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. [Haines, Jonathan L.] Vanderbilt Univ, Sch Med, Ctr Human Genet Res, Nashville, TN 37212 USA. RP Wiggs, JL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. EM BaoJian_Fan@meei.harvard.edu; Louis_Pasquale@meei.harvard.edu; cynthia_grosskreutz@meei.harvard.edu; douglas_rhee@meei.harvard.edu; chen@meei.harvard.edu; margaret_deangelis@meei.harvard.edu; ivana_kim@meei.harvard.edu; elizabeth_delbono@meei.harvard.edu; joan_miller@meei.harvard.edu; tiansen_li@meei.harvard.edu; jonathan@chgr.mc.vanderbilt.edu; janey_wiggs@meei.harvard.edu RI Haines, Jonathan/C-3374-2012; DeAngelis, e/J-7863-2015; OI Fan, Baojian/0000-0002-6851-2737 FU NEI NIH HHS [EY015882, P30 EY014104, P30EY014104] NR 38 TC 69 Z9 74 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PD FEB 6 PY 2008 VL 9 AR 5 DI 10.1186/1471-2350-9-5 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 279QE UT WOS:000254368900001 PM 18254956 ER PT J AU Krum, SA Miranda-Carboni, GA Hauschka, PV Carroll, JS Lane, TF Freedman, LP Brown, M AF Krum, Susan A. Miranda-Carboni, Gustavo A. Hauschka, Peter V. Carroll, Jason S. Lane, Timothy F. Freedman, Leonard P. Brown, Myles TI Estrogen protects bone by inducing Fas ligand in osteoblasts to regulate osteoclast survival SO EMBO JOURNAL LA English DT Article DE bone; estrogen; Fas ligand; osteoblast; osteoclast ID ISOFORM-SPECIFIC REGULATION; RECEPTOR-ALPHA; ER-BETA; LYMPHOPROLIFERATIVE DISEASE; GENE-EXPRESSION; IMMUNE-SYSTEM; BREAST-CANCER; IN-VITRO; MICE; OSTEOPOROSIS AB Estrogen deficiency in menopause is a major cause of osteoporosis in women. Estrogen acts to maintain the appropriate ratio between bone-forming osteoblasts and bone-resorbing osteoclasts in part through the induction of osteoclast apoptosis. Recent studies have suggested a role for Fas ligand (FasL) in estrogen-induced osteoclast apoptosis by an autocrine mechanism involving osteoclasts alone. In contrast, we describe a paracrine mechanism in which estrogen affects osteoclast survival through the upregulation of FasL in osteoblasts (and not osteoclasts) leading to the apoptosis of pre-osteoclasts. We have characterized a cell-type-specific hormone-inducible enhancer located 86 kb downstream of the FasL gene as the target of estrogen receptor-alpha induction of FasL expression in osteoblasts. In addition, tamoxifen and raloxifene, two selective estrogen receptor modulators that have protective effects in bone, induce apoptosis in pre-osteoclasts by the same osteoblast-dependent mechanism. These results demonstrate that estrogen protects bone by inducing a paracrine signal originating in osteoblasts leading to the death of pre-osteoclasts and offer an important new target for the prevention and treatment of osteoporosis. C1 [Krum, Susan A.; Carroll, Jason S.; Brown, Myles] Dana Farber Canc Inst, Div Mol & Cellular Oncol, Dept Med Oncol, Boston, MA 02115 USA. [Miranda-Carboni, Gustavo A.; Lane, Timothy F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept ObGyn, Los Angeles, CA 90095 USA. [Miranda-Carboni, Gustavo A.; Lane, Timothy F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biol Chem, Los Angeles, CA 90095 USA. [Hauschka, Peter V.] Childrens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. [Freedman, Leonard P.] Wyeth Res, Dept Womens Hlth & Musculoskeletal Biol, Collegeville, PA USA. RP Brown, M (reprint author), Dana Farber Canc Inst, Div Mol & Cellular Oncol, Dept Med Oncol, 44 Binney St,D730, Boston, MA 02115 USA. EM myles_brown@dfci.harvard.edu RI Myles, Brown/B-6906-2008; krum, susan/D-7282-2013; OI Krum, Susan/0000-0002-6414-6397; Brown, Myles/0000-0002-8213-1658 NR 37 TC 130 Z9 148 U1 3 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD FEB 6 PY 2008 VL 27 IS 3 BP 535 EP 545 DI 10.1038/sj.emboj.7601984 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 266CM UT WOS:000253408900006 PM 18219273 ER PT J AU Ho, PM Peterson, ED Wang, L Magid, DJ Fihn, SD Larsen, GC Jesse, RA Rumsfeld, JS AF Ho, P. Michael Peterson, Eric D. Wang, Li Magid, David J. Fihn, Stephan D. Larsen, Greg C. Jesse, Robert A. Rumsfeld, John S. TI Incidence of death and acute myocardial infarction associated with stopping clopidogrel after acute coronary syndrome SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ORAL ANTIPLATELET THERAPY; PLATELET ACTIVATION; CONTROLLED TRIAL; ASPIRIN THERAPY; ISCHEMIC-STROKE; UNSTABLE ANGINA; ARTERY-DISEASE; DRUG-THERAPY; WITHDRAWAL; HEPARIN AB Context It is unknown whether patients are at increased short- term risk for adverse events following clopidogrel cessation. Objective To assess the rates of adverse events after stopping treatment with clopidogrel in a national sample of patients with acute coronary syndrome ( ACS). Design, Setting, and Patients Retrospective cohort study of 3137 patients with ACS discharged from 127 Veterans Affairs hospitals between October 1, 2003, and March 31, 2005, with posthospital treatment with clopidogrel. Main Outcome Measure Rate of all- cause mortality or acute myocardial infarction ( AMI) after stopping treatment with clopidogrel. Results Mean ( SD) follow- up after stopping treatment with clopidogrel was 196 ( 152) days for medically treated patients with ACS without stents ( n= 1568) and 203 ( 148) days for patients with ACS treated with percutaneous coronary intervention ( PCI) ( n= 1569). Among medically treated patients, mean ( SD) duration of clopidogrel treatment was 302 ( 151) days and death or AMI occurred in 17.1%( n= 268) of patients, with 60.8%( n= 163) of events occurring during 0 to 90 days, 21.3% ( n= 57) during 91 to 180 days, and 9.7% ( n= 26) during 181 to 270 days after stopping treatment with clopidogrel. In multivariable analysis including adjustment for duration of clopidogrel treatment, the first 90- day interval after stopping treatment with clopidogrel was associated with a significantly higher risk of adverse events ( incidence rate ratio [ IRR], 1.98; 95% confidence interval [ CI], 1.46- 2.69 vs the interval of 91- 180 days). Similarly, among PCI- treated patients with ACS, mean( SD) duration of clopidogrel treatment was 278 ( 169) days and death or AMI occurred in 7.9% ( n= 124) of patients, with 58.9% ( n= 73) of events occurring during 0 to 90 days, 23.4% ( n= 29) during 91 to 180 days, and 6.5% ( n= 8) during 181 to 270 days after stopping clopidogrel treatment. In multivariable analysis including adjustment for duration of clopidogrel treatment, the first 90- day interval after stopping clopidogrel treatment was associated with a significantly higher risk of adverse events ( IRR, 1.82; 95% CI, 1.17- 2.83). Conclusions We observed a clustering of adverse events in the initial 90 days after stopping clopidogrel among both medically treated and PCI- treated patients with ACS, supporting the possibility of a clopidogrel rebound effect. Additional studies are needed to confirm the clustering of events after stopping clopidogrel, including associations with cardiovascular mortality and reasons for stopping clopidogrel, as well as to determine the mechanism of this phenomenon, and to identify strategies to reduce early events after clopidogrel cessation. C1 [Ho, P. Michael; Rumsfeld, John S.] Denver VA Med Ctr, Denver, CO 80220 USA. [Ho, P. Michael; Magid, David J.; Rumsfeld, John S.] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. [Peterson, Eric D.] Duke Clin Res Inst, Durham, NC USA. [Wang, Li; Fihn, Stephan D.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Ho, P. Michael; Magid, David J.; Rumsfeld, John S.] Kaiser Permanente Colorado, Inst Hlth Res, Aurora, CO USA. [Larsen, Greg C.] VA Med Ctr, Portland, OR USA. [Jesse, Robert A.] Richmond VA Med Ctr, Richmond, VA USA. [Jesse, Robert A.] Virginia Commonwealth Univ Hlth Syst, Richmond, VA USA. RP Rumsfeld, JS (reprint author), Denver VA Med Ctr, 111B,1055 Clermont St, Denver, CO 80220 USA. EM John.Rumsfeld@va.gov NR 33 TC 219 Z9 231 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 6 PY 2008 VL 299 IS 5 BP 532 EP 539 DI 10.1001/jama.299.5.532 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 258RB UT WOS:000252886100018 PM 18252883 ER PT J AU Brumback, AC Staley, KJ AF Brumback, Audrey C. Staley, Kevin J. TI Thermodynamic regulation of NKCC1-mediated Cl- cotransport underlies plasticity of GABA(A) signaling in neonatal neurons SO JOURNAL OF NEUROSCIENCE LA English DT Article DE seizure; sodium pump; development; long-term potentiation; dendrite; action potential; gramicidin-perforated patch ID CATION-CHLORIDE COTRANSPORTERS; INTRACELLULAR CHLORIDE; POSTTETANIC HYPERPOLARIZATION; DEVELOPMENTAL REGULATION; EXCITATORY ACTIONS; NEUROPATHIC PAIN; ANION GRADIENT; DENTATE GYRUS; NA+/K+-ATPASE; SODIUM-PUMP AB In the adult brain, chloride (Cl-) influx through GABA(A) receptors is an important mechanism of synaptic inhibition. However, under a variety of circumstances, including acquired epilepsy, neuropathic pain, after trains of action potentials or trauma, and during normal early brain development, GABAA receptor activation excites neurons by gating Cl- efflux because the intracellular Cl- concentration (Cl-i) is elevated. These findings require an inducible, active mechanism of chloride accumulation. We used gramicidin-perforated patch recordings to characterize Cl- transport via NKCC1, the principal neuronal Cl- accumulator, in neonatal CA1 pyramidal neurons. NKCC1 activity was required to maintain elevated Cli such that GABAA receptor activation was depolarizing. Kinetic analysis of NKCC1 revealed reversible transmembrane Cl- transport characterized by a large maximum velocity (v(max)) and high affinity (K-m), so that NKCC1 transport was limited only by the net electrochemical driving force for Na+, K+, and Cl+. At the steady-state Cl-i, NKCC1 was at thermodynamic equilibrium, and there was no evidence of net Cl- transport. Trains of action potentials that have been previously shown to induce persistent changes in neuronal E-Cl (reversal potential for Cl-) did not alter vmax or Km of NKCC1. Rather, action potentials shifted the thermodynamic set point, the steady-state Cl-i at which there was no net NKCC1-mediated Cl- transport. The persistent increase in Cl-i required intact alpha 2/alpha 3 Na+ -K+ -ATPase activity, indicating that trains of action potentials reset the thermodynamic equilibrium for NKCC1 transport by lowering Na-i. Activity-induced changes in Na+- K+ -ATPase activity comprise a novel mechanism for persistent alterations in synaptic signaling mediated by GABA. C1 [Staley, Kevin J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Staley, Kevin J.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Brumback, Audrey C.] Univ Colorado, Hlth Sci Ctr, Neurosci Program, Denver, CO 80262 USA. [Brumback, Audrey C.] Univ Colorado, Hlth Sci Ctr, Med Sci Training Program, Denver, CO 80262 USA. RP Staley, KJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM kstaley@partners.org OI Brumback, Audrey/0000-0002-4904-4368 NR 61 TC 63 Z9 63 U1 1 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD FEB 6 PY 2008 VL 28 IS 6 BP 1301 EP 1312 DI 10.1523/JNEUROSCI.3378-07.2008 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 259IF UT WOS:000252932300004 PM 18256250 ER PT J AU Viale, G Regan, MM Mastropasqua, MG Maffini, F Maiorano, E Colleoni, M Price, KN Golouh, R Perin, T Brown, RW Kovacs, A Pillay, K Ohlschlegel, C Gusterson, BA Castiglione-Gertsch, M Gelber, RD Goldhirsch, A Coates, AS AF Viale, Giuseppe Regan, Meredith M. Mastropasqua, Mauro G. Maffini, Fausto Maiorano, Eugenio Colleoni, Marco Price, Karen N. Golouh, Rastko Perin, Tiziana Brown, R. W. Kovacs, Aniko Pillay, Komala Oehlschlegel, Christian Gusterson, Barry A. Castiglione-Gertsch, Monica Gelber, Richard D. Goldhirsch, Aron Coates, Alan S. CA Int Breast Canc Study Grp TI Predictive value of tumor Ki-67 expression in two randomized trials of adjuvant chemoendocrine therapy for node-negative breast cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID UNITED-STATES FOOD; PRIMARY CHEMOTHERAPY; PROLIFERATIVE ACTIVITY; CELL-PROLIFERATION; PROGNOSTIC MARKER; MITOTIC INDEX; CARCINOMA; APOPTOSIS; ANTIBODY; RECEPTOR AB Several small studies have reported that having a high percentage of breast tumor cells that express the proliferation antigen Ki-67 (ie, a high Ki-67 labeling index) predicts better response to neoadjuvant chemotherapy. However, the predictive value of a high Ki-67 labeling index for response to adjuvant chemotherapy is unclear. To investigate whether Ki-67 labeling index predicts response to adjuvant chemoendocrine therapy, we assessed Ki-67 expression in tumor tissue from 1924 (70%) of 2732 patients who were enrolled in two randomized International Breast Cancer Study Group trials of adjuvant chemoendocrine therapy vs endocrine therapy alone for node-negative breast cancer. A high Ki-67 labeling index was associated with other factors that predict poor prognosis. Among the 1521 patients with endocrine-responsive tumors, a high Ki-67 labeling index was associated with worse disease-free survival but the Ki-67 labeling index did not predict the relative efficacy of chemoendocrine therapy compared with endocrine therapy alone. Thus, Ki-67 labeling index was an independent prognostic factor but was not predictive of better response to adjuvant chemotherapy in these studies. C1 [Castiglione-Gertsch, Monica] Int Breast Canc Study Grp Coordinating Ctr, CH-3008 Bern, Switzerland. [Viale, Giuseppe; Mastropasqua, Mauro G.; Maffini, Fausto] Univ Milan, European Inst Oncol, Div Pathol, Milan, Italy. [Viale, Giuseppe; Mastropasqua, Mauro G.; Maffini, Fausto] Univ Milan, European Inst Oncol, Div Lab Med, Milan, Italy. [Colleoni, Marco; Goldhirsch, Aron] Univ Milan, European Inst Oncol, Div Med Oncol, Milan, Italy. [Regan, Meredith M.; Price, Karen N.; Gelber, Richard D.] Harvard Univ, Sch Publ Hlth, Frontier Sci & Technol Res Fdn, Dana Farber Canc Inst,IBCSG Stat Ctr, Boston, MA 02115 USA. [Maiorano, Eugenio] Univ Bari, Dept Pathol Anat, Bari, Italy. [Perin, Tiziana] Ctr Riferimento Oncol, Div Pathol, I-33081 Aviano, Italy. [Golouh, Rastko] Inst Oncol, Ljubljana, Slovenia. [Kovacs, Aniko] Goteborg Sahlgrenska Univ Hosp, Dept Pathol, Gothenburg, Sweden. [Pillay, Komala] Univ Cape Town, Div Anat Pathol, Dept Clin Lab Sci, Natl Hlth Lab Serv, ZA-7925 Cape Town, South Africa. [Pillay, Komala] Groote Schuur Hosp, ZA-7925 Cape Town, South Africa. [Oehlschlegel, Christian] Swiss Grp Clin Can Res SAKK, Bern, Switzerland. [Oehlschlegel, Christian] Kantonsspital, St Gallen, Switzerland. [Gusterson, Barry A.] Univ Glasgow, Western Infirm, Div Canc Sci & Mol Pathol, Glasgow G12 8QQ, Lanark, Scotland. [Goldhirsch, Aron] Oncol Inst So Switzerland, Bellinzona, Switzerland. [Coates, Alan S.] Univ Sydney, Sydney, NSW 2006, Australia. [Coates, Alan S.] IBCSG, Bern, Switzerland. RP Viale, G (reprint author), Int Breast Canc Study Grp Coordinating Ctr, Effingerstr 40, CH-3008 Bern, Switzerland. EM giuseppe.viale@ieo.it RI gusterson, barry/D-3752-2009; Maiorano, Eugenio/F-1382-2015 FU NCI NIH HHS [CA75362] NR 29 TC 133 Z9 144 U1 0 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD FEB 6 PY 2008 VL 100 IS 3 BP 207 EP 212 DI 10.1093/jnci/djm289 PG 6 WC Oncology SC Oncology GA 271NZ UT WOS:000253796400012 PM 18230798 ER PT J AU Chen, YI Ren, JQ Wang, FN Xu, HB Mandeville, JB Kim, Y Rosen, BR Jenkins, BG Hui, KKS Kwong, KK AF Chen, Y. Iris Ren, Jiaqian Wang, Fu-Nien Xu, Haibo Mandeville, Joseph B. Kim, Young Rosen, Bruce R. Jenkins, Bruce G. Hui, Kathleen K. S. Kwong, Kenneth K. TI Inhibition of stimulated dopamine release and hemodynamic response in the brain through electrical stimulation of rat forepaw SO NEUROSCIENCE LETTERS LA English DT Article DE amphetamine; fMRI; rCBV; microdialysis; glutamate; GABA ID TRANSCRANIAL MAGNETIC STIMULATION; AMPA GLUTAMATE RECEPTORS; PARKINSONS-DISEASE; PREFRONTAL CORTEX; NUCLEUS-ACCUMBENS; BASAL GANGLIA; TRANSMISSION; STRIATUM; ACUPUNCTURE; NEOSTRIATUM AB The subcortical response to peripheral somatosensory stimulation is not well studied. Prior literature suggests that somatosensory stimulation can affect dopaminergic tone. We studied the effects of electrical stimulation near the median nerve on the response to an amphetamine-induced increase in synaptic dopamine. We applied the electrical stimulation close to the median nerve 20 min after administration of 3 mg/kg amphetamine. We used fMRI and microdialysis to measure markers of dopamine (DA) release, together with the release of associated neurotransmitters of striatal glutamate (Glu) and gamma-aminobutyric acid (GABA). Changes in cerebral blood volume (CBV), a marker used in fMRI, indicate that electrical stimulation significantly attenuated increased DA release (due to AMPH) in the striatum, thalamus, medial prefrontal and cingulate cortices. Microdialysis showed that electrical stimulation increased Glu and GABA release and attenuated the AMPH-enhanced DA release. The striatal DA dynamics correlated with the CBV response. These results demonstrate that electrical stimulation near the median nerve activates Glu/GABA release, which subsequently attenuate excess striatal DA release. These data provide evidence for physiologic modulation caused by electroacupuncture at points near the median nerve. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Chen, Y. Iris; Ren, Jiaqian; Wang, Fu-Nien; Xu, Haibo; Mandeville, Joseph B.; Kim, Young; Rosen, Bruce R.; Jenkins, Bruce G.; Hui, Kathleen K. S.; Kwong, Kenneth K.] Harvard Univ, Martinos Ctr Biomed Imaging, Dept Radiol, Massachusetts Gen Hosp,Med Sch, Charlestown, MA 02129 USA. [Wang, Fu-Nien] Natl Tsing Hua Univ, Dept Nucl Sci, Hsinchu, Taiwan. [Xu, Haibo] Union Hosp, Wuhan, Peoples R China. RP Chen, YI (reprint author), Harvard Univ, Martinos Ctr Biomed Imaging, Dept Radiol, Massachusetts Gen Hosp,Med Sch, Room 2301,Bldg 149,13th St, Charlestown, MA 02129 USA. EM iris@nmr.mgh.harvard.edu FU NCCIH NIH HHS [P01 AT002048, P01 AT002048-050004] NR 37 TC 14 Z9 15 U1 1 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD FEB 6 PY 2008 VL 431 IS 3 BP 231 EP 235 DI 10.1016/j.neulet.2007.11.063 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 263PK UT WOS:000253228800009 PM 18178315 ER PT J AU Braithwaite, RS Roberts, MS Chang, CCH Goetz, MB Gibert, CL Rodrigue-Barradas, MC Shechter, S Schaefer, A Nucifora, K Koppenhaver, R Justice, AC AF Braithwaite, R. Scott Roberts, Mark S. Chang, Chung Chou H. Goetz, Matthew Bidwell Gibert, Cynthia L. Rodrigue-Barradas, Maria C. Shechter, Steven Schaefer, Andrew Nucifora, Kimberly Koppenhaver, Robert Justice, Amy C. TI Influence of alternative thresholds for initiating HIV treatment on quality-adjusted life expectancy: A decision model SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; CD4 CELL COUNT; VIROLOGICAL FAILURE; COST-EFFECTIVENESS; INFECTION; OUTCOMES; COHORT; RESISTANCE; ADULTS AB Background: The optimal threshold for initiating HIV treatment is unclear. Objective: To compare different thresholds for initiating HIV treatment. Design: A validated computer simulation was used to weigh important harms from earlier initiation of antiretroviral therapy (toxicity, side effects, and resistance accumulation) against important benefits (decreased HIV-related mortality). Data Sources: Veterans Aging Cohort Study (5742 HIV-infected patients and 11 484 matched uninfected controls) and published reports. Target Population: Individuals with newly diagnosed chronic HIV infection and varying viral loads (10 000, 30 000, 100 000, and 300 000 copies/mL) and ages (30, 40, and 50 years). Time Horizon: Unlimited. Perspective: Societal. Intervention: Alternative thresholds for initiating antiretroviral therapy (CD4 counts of 200, 350, and 500 cells/mm(3)). Outcome Measures: Life-years and quality-adjusted life-years (QALYs). Results of Base-Case Analysis: Although the simulation was biased against earlier treatment initiation because it used an upper-bound assumption for therapy-related toxicity, earlier treatment increased life expectancy and QALYs at age 30 years regardless of viral load (life expectancies with CD4 initiation thresholds of 500, 350, and 200 cells/mm(3) were 18.2 years, 17.6 years, and 17.2 years, respectively, for a viral load of 10 000 copies/mL and 17.3 years, 15.9 years, and 14.5 years, respectively, for a viral load of 300000 copies/mL), and increased life expectancies at age 40 years if viral loads were greater than 30000 copies/mL (life expectancies were 12.5 years, 12.0 years, and 11.4 years, respectively, for a viral load of 300000 copies/mL). Results of Sensitivity Analysis: Findings favoring early treatment were generally robust. Limitations: Results favoring later treatment may not be valid. The findings may not be generalizable to women. Conclusion: This simulation suggests that earlier initiation of combination antiretroviral therapy is often favored compared with current recommendations. C1 [Braithwaite, R. Scott] Yale Univ, West Haven, CT 06516 USA. Vet Affairs Connecticut Healthcare Syst, West Haven, CT USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. George Washington Univ, Washington, DC USA. Vet Affairs Med Ctr, Washington, DC 20422 USA. Baylor Coll Med, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. RP Braithwaite, RS (reprint author), Yale Univ, 950 Campbell Ave, West Haven, CT 06516 USA. EM Ronald.Braithwaite@va.gov OI Goetz, Matthew/0000-0003-4542-992X FU NCATS NIH HHS [UL1 TR000005]; NIAAA NIH HHS [K23 AA14483-01, U10 AA013566-07, U10 AA013566, 2U10 AA13566, K23 AA014483] NR 30 TC 38 Z9 38 U1 1 U2 5 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD FEB 5 PY 2008 VL 148 IS 3 BP 178 EP 185 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 258DX UT WOS:000252849700002 PM 18252681 ER PT J AU MacLean, C Newberry, S Maglione, M McMahon, M Ranganath, V Suttorp, M Mojica, W Timmer, M Alexander, A McNamara, M Desai, SB Zhou, A Chen, S Carter, J Tringale, C Valentine, D Johnsen, B Grossman, J AF MacLean, Catherine Newberry, Sydne Maglione, Margaret McMahon, Maureen Ranganath, Veena Suttorp, Marika Mojica, Walter Timmer, Martha Alexander, Alicia McNamara, Melissa Desai, Sheetal B. Zhou, Annie Chen, Susan Carter, Jason Tringale, Carlo Valentine, Di Johnsen, Breanne Grossman, Jennifer TI Systematic review: Comparative effectiveness of treatments to prevent fractures in men and women with low bone density or osteoporosis SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; CORTICOSTEROID-INDUCED OSTEOPOROSIS; CYCLICAL ETIDRONATE THERAPY; EARLY POSTMENOPAUSAL WOMEN; GLUCOCORTICOID-INDUCED OSTEOPOROSIS; HORMONE REPLACEMENT THERAPY; VITAMIN-D SUPPLEMENTATION; PRIMARY BILIARY-CIRRHOSIS; ESTROGEN PLUS PROGESTIN AB Background: Although several agents are available to treat osteoporosis, the relative efficacy and toxicity of these agents when used to prevent fractures has not been well described. Purpose: To compare the benefits in fracture reduction and the harms from adverse events of various therapies for osteoporosis. Data Sources: MEDLINE (1966 to November 2007) and other selected databases were searched for English-language studies. Study Selection: For the efficacy analysis, investigators selected studies that reported the rate of or risk for fractures. For the adverse event analysis, they selected studies that reported the relationship between an agent and cardiovascular, thromboembolic, or upper gastrointestinal events; malignant conditions; and osteonecrosis. Data Extraction: Using a standardized protocol, investigators abstracted data on fractures and adverse events, agents and comparators, study design, and variables of methodological quality. Data Synthesis: Good evidence suggests that alendronate, etidronate, ibandronate, risedronate, zoledronic acid, estrogen, parathyroid hormone (1-34), and raloxifene prevent vertebral fractures more than placebo; the evidence for calcitonin was fair. Good evidence suggests that alendronate, risedronate, and estrogen prevent hip fractures more than placebo; the evidence for zoledronic acid was fair. The effects of vitamin D varied with dose, analogue, and study population for both vertebral and hip fractures. Raloxifene, estrogen, and estrogen-progestin increased the risk for thromboembolic events, and etidronate increased the risk for esophageal ulcerations and gastrointestinal perforations, ulcerations, and bleeding. Limitation: Few studies have directly compared different agents or classes of agents used to treat osteoporosis. Conclusion: Although good evidence suggests that many agents are effective in preventing osteoporotic fractures, the data are insufficient to determine the relative efficacy or safety of these agents. C1 [Maglione, Margaret] RAND Corp, MPP, So California Evidence Based Practice Ctr, Santa Monica, CA 90401 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Univ Calif Los Angeles, Greater Los Angeles Vet Adm Healthcare Syst, Los Angeles, CA USA. RP Maglione, M (reprint author), RAND Corp, MPP, So California Evidence Based Practice Ctr, 1776 Main St, Santa Monica, CA 90401 USA. EM maglione@rand.org FU PHS HHS [290-02-003] NR 162 TC 279 Z9 295 U1 6 U2 26 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD FEB 5 PY 2008 VL 148 IS 3 BP 197 EP 213 PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA 258DX UT WOS:000252849700004 PM 18087050 ER PT J AU Rosito, GA Massaro, JM Hoffmann, U Ruberg, FL Mahabadi, AA Vasan, RS O'Donnell, CJ Fox, CS AF Rosito, Guido A. Massaro, Joseph M. Hoffmann, Udo Ruberg, Frederick L. Mahabadi, Amir A. Vasan, Ramachandran S. O'Donnell, Christopher J. Fox, Caroline S. TI Pericardial fat, visceral abdominal fat, cardiovascular disease risk factors, and vascular calcification in a community-based sample - The framingham heart study SO CIRCULATION LA English DT Article DE pericardium; epidemiology; risk factors; obesity ID EPICARDIAL ADIPOSE-TISSUE; CORONARY-ARTERY-DISEASE; INSULIN-RESISTANCE; COMPUTED-TOMOGRAPHY; JAPANESE-AMERICANS; MEN; ASSOCIATION; HYPERTENSION; WOMEN; ECHOCARDIOGRAPHY AB Background - Pericardial fat may be an important mediator of metabolic risk. Correlations with cardiovascular disease risk factors and vascular calcification in a community-based sample are lacking. We sought to examine associations between pericardial fat, metabolic risk factors, and vascular calcification. Methods and Results - Participants free of cardiovascular disease from the Framingham Heart Study (n = 1155, mean age 63 years, 54.8% women) who were part of a multidetector computed tomography study underwent quantification of intrathoracic fat, pericardial fat, visceral abdominal fat (VAT), coronary artery calcification, and aortic artery calcification. Intrathoracic and pericardial fat volumes were examined in relation to body mass index, waist circumference, VAT, metabolic risk factors, coronary artery calcification, and abdominal aortic calcification. Intrathoracic and pericardial fat were directly correlated with body mass index (r = 0.41 to 0.51, P = 0.001), waist circumference (r = 0.43 to 0.53, P < 0.001), and VAT (r = 0.62 to 0.76, P < 0.001). Both intrathoracic and pericardial fat were associated with higher triglycerides (P < 0.0001), lower high-density lipoprotein (P < 0.0001), hypertension (P < 0.0001 to 0.01), impaired fasting glucose (P < 0.0001 to 0.001), diabetes mellitus (P = 0.0005 to 0.009), and metabolic syndrome (P < 0.0001) after multivariable adjustment. Associations generally persisted after additional adjustment for body mass index and waist circumference but not after adjustment for VAT (all P > 0.05). Pericardial fat, but not intrathoracic fat, was associated with coronary artery calcification after multivariable and VAT adjustment (odds ratio 1.21, 95% confidence interval 1.005 to 1.46, P = 0.04), whereas intrathoracic fat, but not pericardial fat, was associated with abdominal aortic calcification (odds ratio 1.32, 95% confidence interval 1.03 to 1.67, P = 0.03). Conclusions - Pericardial fat is correlated with multiple measures of adiposity and cardiovascular disease risk factors, but VAT is a stronger correlate of most metabolic risk factors. However, intrathoracic and pericardial fat are associated with vascular calcification, which suggests that these fat depots may exert local toxic effects on the vasculature. C1 [O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI Framingham Heart Study, Framingham, MA 01702 USA. [Rosito, Guido A.; Hoffmann, Udo; Mahabadi, Amir A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac MR CT PET Program, Boston, MA USA. [O'Donnell, Christopher J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA USA. [Rosito, Guido A.] Fed Fdn Sch Med Sci Porto Alegre, Rio Grande Do Sul, Brazil. [Massaro, Joseph M.] Boston Univ, Dept Math, Boston, MA USA. [Ruberg, Frederick L.; Vasan, Ramachandran S.] Boston Med Ctr, Dept Cardiol, Boston, MA USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol Metab & Diabet, Dept Med, Boston, MA 02115 USA. RP Fox, CS (reprint author), NHLBI Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov OI Ruberg, Frederick/0000-0002-6424-4413; Massaro, Joseph/0000-0002-2682-4812; Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [N01-HC-25195] NR 38 TC 442 Z9 462 U1 4 U2 22 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 5 PY 2008 VL 117 IS 5 BP 605 EP 613 DI 10.1161/CIRCULATIONAHA.107.743062 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 258UF UT WOS:000252894300004 PM 18212276 ER PT J AU Gibson, CM Pride, YB Buros, JL Lord, E Shui, A Murphy, SA Pinto, DS Zimetbaum, PJ Sabatine, MS Cannon, CP Josephson, ME AF Gibson, C. Michael Pride, Yuri B. Buros, Jacqueline L. Lord, Erin Shui, Amy Murphy, Sabina A. Pinto, Duane S. Zimetbaum, Peter J. Sabatine, Marc S. Cannon, Christopher P. Josephson, Mark E. CA TIMI Study Grp TI Association of impaired thrombolysis in myocardial infarction myocardial perfusion grade with ventricular tachycardia and ventricular fibrillation following fibrinolytic therapy for ST-Segment elevation myocardial infarction SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERY-DISEASE; SUDDEN CARDIAC DEATH; MICROVASCULAR OBSTRUCTION; UNSTABLE ANGINA; ISCHEMIA; REPERFUSION; OCCLUSION; IMPACT; RISK AB Objectives The goal of this analysis was to evaluate the association of impaired Thrombolysis In Myocardial Infarction myocardial perfusion grade (TMPG) with sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). Background Impaired TMPG after successful restoration of epicardial flow among patients treated with fibrinolytic therapy for ST-segment elevation myocardial infarction (STEMI) has been associated with adverse clinical outcomes, but its relationship to VT/VF has not been evaluated. Methods In the CLARITY-TIMI 28 (Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis In Myocardial Infarction 28) study, 3,491 patients underwent angiography a median of 3.5 days after fibrinolytic administration for STEMI; TMPG was assessed, and its association with VT/VF was evaluated. Results We observed VT/VF in 4.8% of patients. Impaired myocardial perfusion (TMPG 0/1/2) was associated with an increased incidence of VT/VF (7.1% vs. 2.6% with TMPG 3; log-rank p < 0.001). Among patients with restoration of normal epicardial flow (Thrombolysis In Myocardial Infarction flow grade 3), the incidence of VT/VF was increased among patients with impaired TMPG (4.7% vs. 2.7%; p = 0.02). Among patients with left ventricular ejection fraction >= 30%, impaired TMPG remained associated with an increased incidence of VT/VF (4.7% vs. 2.5%; p = 0.03). We found that VT/VF was associated with increased mortality (25.2% vs. 3.5%; p < 0.0001). Furthermore, among patients with VT/VF, impaired TMPG was associated with increased mortality (17.1% vs. 2.3%; p = 0.02). All but I death among patients who had VT/VF were among patients with impaired myocardial perfusion. Conclusions Despite restoration of normal epicardial flow or a left ventricular ejection fraction >= 30%, impaired myocardial perfusfon on angiography 3.5 days after fibrinolytic administration for STEMI is associated with an increased incidence of VT/VF. C1 [Gibson, C. Michael; Buros, Jacqueline L.; Lord, Erin; Shui, Amy; Murphy, Sabina A.] Beth Israel Deaconess Med Ctr, TIMI Study Grp, Boston, MA 02215 USA. [Sabatine, Marc S.; Cannon, Christopher P.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Pride, Yuri B.; Pinto, Duane S.; Zimetbaum, Peter J.; Josephson, Mark E.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Cardiol, Boston, MA 02215 USA. [Pride, Yuri B.; Pinto, Duane S.; Zimetbaum, Peter J.; Josephson, Mark E.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02215 USA. RP Gibson, CM (reprint author), TIMI Data Coordinating Ctr, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM mgibson@perfuse.org OI Buros, Jacqueline/0000-0001-9588-4889 NR 25 TC 14 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 5 PY 2008 VL 51 IS 5 SI 519 BP 546 EP 551 DI 10.1016/j.jacc.2007.08.061 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 258ZJ UT WOS:000252908600005 PM 18237683 ER PT J AU Reger, MA Watson, GS Green, PS Wilkinson, CW Baker, LD Cholerton, B Fishel, MA Plymate, SR Breitner, JCS DeGroodt, W Mehta, P Craft, S AF Reger, M. A. Watson, G. S. Green, P. S. Wilkinson, C. W. Baker, L. D. Cholerton, B. Fishel, M. A. Plymate, S. R. Breitner, J. C. S. DeGroodt, W. Mehta, P. Craft, S. TI Intranasal insulin improves cognition and modulates beta-amyloid in early AD SO NEUROLOGY LA English DT Article ID APOLIPOPROTEIN-E GENOTYPE; ALZHEIMERS-DISEASE; DEGRADING ENZYME; OLDER-ADULTS; DEMENTIA; MEMORY; PERFORMANCE; MECHANISMS; MUTATIONS; A-BETA-42 AB Background: Reduced brain insulin signaling and low CSF-to-plasma insulin ratios have been observed in patients with Alzheimer disease (AD). Furthermore, intracerebroventricular or IV insulin administration improve memory, alter evoked potentials, and modulate neurotransmitters, possibly by augmenting low brain levels. After intranasal administration, insulin-like peptides follow extracellular pathways to the brain within 15 minutes. Objective: We tested the hypothesis that daily intranasal insulin treatment would facilitate cognition in patients with early AD or its prodrome, amnestic mild cognitive impairment (MCI). The proportion of verbal information retained after a delay period was the planned primary outcome measure. Secondary outcome measures included attention, caregiver rating of functional status, and plasma levels of insulin, glucose, beta-amyloid, and cortisol. Methods: Twenty-five participants were randomly assigned to receive either placebo (n = 12) or 20 IU BID intranasal insulin treatment (n = 13) using an electronic atomizer, and 24 participants completed the study. Participants, caregivers, and all clinical evaluators were blinded to treatment assignment. Cognitive measures and blood were obtained at baseline and after 21 days of treatment. Results: Fasting plasma glucose and insulin were unchanged with treatment. The insulin-treated group retained more verbal information after a delay compared with the placebo-assigned group (p = 0.0374). Insulin-treated subjects also showed improved attention (p = 0.0108) and functional status (p = 0.0410). Insulin treatment raised fasting plasma concentrations of the short form of the beta-amyloid peptide (A beta 40; p = 0.0471) without affecting the longer isoform (A beta 42), resulting in an increased A beta 40/42 ratio (p = 0.0207). Conclusions: The results of this pilot study support further investigation of the benefits of intranasal insulin for patients with Alzheimer disease, and suggest that intranasal peptide administration may be a novel approach to the treatment of neurodegenerative disorders. C1 [Reger, M. A.; Watson, G. S.; Wilkinson, C. W.; Baker, L. D.; Cholerton, B.; Breitner, J. C. S.; Craft, S.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Green, P. S.; Plymate, S. R.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Fishel, M. A.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98195 USA. [Watson, G. S.; Wilkinson, C. W.; Baker, L. D.; Cholerton, B.; Fishel, M. A.; Plymate, S. R.; Breitner, J. C. S.; DeGroodt, W.] Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. [Green, P. S.] Vet Affairs Puget Sound Hlth Care Syst, Res & Dev, Seattle, WA USA. [DeGroodt, W.] Kurve Technol Inc, Bothell, WA USA. [Mehta, P.] Dept Immunol, Staten Isl, NY USA. [Reger, M. A.; Watson, G. S.; Green, P. S.; Wilkinson, C. W.; Baker, L. D.; Cholerton, B.; Fishel, M. A.; Plymate, S. R.; Breitner, J. C. S.; DeGroodt, W.; Mehta, P.; Craft, S.] Inst Basic Res Dev Disabilit, Staten Isl, NY USA. RP Craft, S (reprint author), VAPSHCS, GRECC S-182,1660 S Columbian Way, Seattle, WA 98108 USA. EM scraft@u.washington.edu FU NIA NIH HHS [R01 AG027415] NR 28 TC 357 Z9 369 U1 8 U2 31 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 5 PY 2008 VL 70 IS 6 BP 440 EP 448 DI 10.1212/01.WNL.0000265401.62434.36 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 258TS UT WOS:000252893000006 PM 17942819 ER PT J AU Uda, M Galanello, R Sanna, S Lettre, G Sankaran, VG Chen, WM Usala, G Busonero, F Maschio, A Albai, G Piras, MG Sestu, N Lai, S Dei, M Mulas, A Crisponi, L Naitza, S Asunis, I Deiana, M Nagaraja, R Perseu, L Satta, S Cipollina, MD Sollaino, C Moi, P Hirschhorn, JN Orkin, SH Abecasis, GR Schlessinger, D Cao, A AF Uda, Manuela Galanello, Renzo Sanna, Serena Lettre, Guillaume Sankaran, Vijay G. Chen, Weimin Usala, Gianluca Busonero, Fabio Maschio, Andrea Albai, Giuseppe Piras, Maria Grazia Sestu, Natascia Lai, Sandra Dei, Mariano Mulas, Antonella Crisponi, Laura Naitza, Silvia Asunis, Isadora Deiana, Manila Nagaraja, Ramaiah Perseu, Lucia Satta, Stefania Cipollina, Maria Dolores Sollaino, Carla Moi, Paolo Hirschhorn, Joel N. Orkin, Stuart H. Abecasis, Goncalo R. Schlessinger, David Cao, Antonio TI Genome-wide association study shows BCL11A associated with persistent fetal hemoglobin and Amelioration of the phenotype of beta-thalassemia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE globin gene regulation; polymorphism; sickle cell anemia ID SICKLE-CELL-DISEASE; LINKAGE ANALYSIS; RISK-FACTORS; HEREDITARY PERSISTENCE; F-CELLS; GENE; CHROMOSOME; PEDIGREES; VARIANCE; TRAITS AB beta-Thalassemia and sickle cell disease both display a great deal of phenotypic heterogeneity, despite being generally thought of as simple Mendelian diseases. The reasons for this are not well understood, although the level of fetal hemoglobin (HbF) is one well characterized ameliorating factor in both of these conditions. To better understand the genetic basis of this heterogeneity, we carried out genome-wide scans with 362,129 common SNPs on 4,305 Sardinians to look for genetic linkage and association with HbF levels, as well as other red blood cell-related traits. Among major variants affecting HbF levels, SNP rs11886868 in the BCL11A gene was strongly associated with this trait (P < 10(-35)). The C allele frequency was significantly higher in Sardinian individuals with elevated HbF levels, detected by screening for beta-thalassemia, and patients with attenuated forms of beta-thalassemia vs. those with thalassemia major. We also show that the same BCL11A variant is strongly associated with HbF levels in a large cohort of sickle cell patients. These results indicate that BCL11A variants, by modulating HbF levels, act as an important ameliorating factor of the beta-thalassemia phenotype, and it is likely they could help ameliorate other hemoglobin disorders. We expect our findings will help to characterize the molecular mechanisms of fetal globin regulation and could eventually contribute to the development of new therapeutic approaches for beta-thalassemia and sickle cell anemia. C1 [Lettre, Guillaume; Sankaran, Vijay G.; Hirschhorn, Joel N.; Orkin, Stuart H.] Childrens Hosp, Boston, MA 02115 USA. [Uda, Manuela; Sanna, Serena; Usala, Gianluca; Busonero, Fabio; Maschio, Andrea; Albai, Giuseppe; Piras, Maria Grazia; Sestu, Natascia; Lai, Sandra; Dei, Mariano; Mulas, Antonella; Crisponi, Laura; Naitza, Silvia; Asunis, Isadora; Deiana, Manila; Perseu, Lucia; Cao, Antonio] Cittadella Univ Monserrato, Consiglio Natl Ric, Ist Neurogenet & Neurofarmacol, I-09042 Cagliari, Italy. [Galanello, Renzo; Satta, Stefania; Cipollina, Maria Dolores; Sollaino, Carla; Moi, Paolo] Univ Cagliar, Dipartimento Sci Biomed & Biotechnol, Osped Microcitem, Pediat Clin, I-09121 Cagliari, Italy. [Lettre, Guillaume; Hirschhorn, Joel N.] Broad Inst Harvard, Cambridge, MA 02142 USA. [Lettre, Guillaume; Hirschhorn, Joel N.] MIT, Cambridge, MA 02142 USA. [Sankaran, Vijay G.; Orkin, Stuart H.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Chen, Weimin; Abecasis, Goncalo R.] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Nagaraja, Ramaiah; Schlessinger, David] NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Orkin, SH (reprint author), Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. EM stuart_orkin@dfci.harvard.edu; acao@mcweb.unica.it RI Chen, Wei-Min/A-8469-2009; Abecasis, Goncalo/B-7840-2010; Naitza, Silvia/D-5620-2017; OI sanna, serena/0000-0002-3768-1749; MOI, Paolo/0000-0001-7879-8057; Mulas, Antonella/0000-0002-6856-1483; Abecasis, Goncalo/0000-0003-1509-1825 FU Intramural NIH HHS; NIA NIH HHS [N01-AG-1-2109]; PHS HHS [263-MA-410953] NR 40 TC 252 Z9 259 U1 2 U2 17 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 5 PY 2008 VL 105 IS 5 BP 1620 EP 1625 DI 10.1073/pnas.0711566105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 261KQ UT WOS:000253077900043 PM 18245381 ER PT J AU Rober, M Quirynen, M Haffajee, AD Schepers, E Teughels, W AF Rober, M. Quirynen, M. Haffajee, A. D. Schepers, E. Teughels, W. TI Intra-oral microbial profiles of beagle dogs assessed by checkerboard DNA-DNA hybridization using human probes SO VETERINARY MICROBIOLOGY LA English DT Article DE supra- and subgingival plaque; soft tissue microbiota; dog; periodontitis; oral microbiology; ecology ID DENTAL PLAQUE FLORA; CANINE PERIODONTITIS; PORPHYROMONAS; BACTERIA; ECOLOGY; DISEASE; HEALTH; STREPTOCOCCI; ACTINOMYCES; GINGIVITIS AB Some investigators suggest a similarity between the oral microbiota of dogs and humans. The in vivo assessment of ecologic relationships among bacterial species and between bacterial species and their habitat is difficult to carry out. Consequently, this aspect is often neglected in animal oral microbiological studies. This study aimed to examine the proportions of 40 bacterial species in samples from five intra-oral habitats in beagle dogs using checkerboard DNA-DNA hybridization. Microbial samples were taken from subgingival and supra-gingival plaque, the tongue, tonsils and cheek mucosa in seven beagle dogs. Samples were individually evaluated for their content of 40 bacterial species and the percentage of total DNA probe count was determined for each species, at each habitat. All tested species could be detected in all sampled habitats but each habitat had a distinct community structure. The microbiotas colonizing the hard surfaces in the oral cavity were quite different from the microbiotas colonizing the soft tissues. Bacterial species that are in humans considered to be periodontopathogens are present in high proportions. This study underlines the importance of the habitat and the host on the local microbial profile. (c) 2007 Elsevier B.V. All rights reserved. C1 [Rober, M.; Quirynen, M.; Teughels, W.] Catholic Univ Louvain, Dept Periodontol, Res Grp Microbial Adhes, B-3000 Louvain, Belgium. [Haffajee, A. D.] Forsyth Inst, Dept Periodont, Boston, MA USA. [Schepers, E.] Catholic Univ Louvain, Dept Prosthet Dent, BioMat Res Ctr, B-3000 Louvain, Belgium. RP Teughels, W (reprint author), Catholic Univ Louvain, Dept Periodontol, Res Grp Microbial Adhes, Kapucijnenvoer 33, B-3000 Louvain, Belgium. EM Wim.Teughels@med.kuleuven.be RI Teughels, Wim/F-4337-2014; OI Teughels, Wim/0000-0001-7675-5643 FU NIDCR NIH HHS [DE 015360] NR 31 TC 7 Z9 7 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1135 J9 VET MICROBIOL JI Vet. Microbiol. PD FEB 5 PY 2008 VL 127 IS 1-2 BP 79 EP 88 DI 10.1016/j.vetmic.2007.08.007 PG 10 WC Microbiology; Veterinary Sciences SC Microbiology; Veterinary Sciences GA 254HR UT WOS:000252578200009 PM 17897795 ER PT J AU Januzzi, JL Richards, AM AF Januzzi, James L., Jr. Richards, A. Mark CA Int NT proBNP Consensus Panel TI An international consensus statement regarding amino-terminal pro-B-type natriuretic peptide testing: The international NT-proBNP consensus panel - Introduction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Editorial Material ID HEART-FAILURE C1 [Januzzi, James L., Jr.] Harvard Univ, Div Cardiol, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Richards, A. Mark] Christchurch Hosp, Christchurch, New Zealand. [Richards, A. Mark] Univ Otago, Dept Med, Christchurch Sch Med & Hlth Sci, Dunedin, New Zealand. RP Januzzi, JL (reprint author), Harvard Univ, Div Cardiol, Sch Med, Massachusetts Gen Hosp, 55 Fruit St,Yawkey 5984, Boston, MA 02114 USA. EM JJanuzzi@partners.org NR 6 TC 0 Z9 0 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD FEB 4 PY 2008 VL 101 IS 3A SU S BP 1A EP 2A DI 10.1016/j.amjcard.2007.11.011 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 260AF UT WOS:000252981400001 ER PT J AU Martinez-Rumayor, A Richards, M Burnett, JC Januzzi, JL AF Martinez-Rumayor, Abelardo Richards, Mark Burnett, John C. Januzzi, James L., Jr. TI Biology of the natriuretic peptides SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc ID SNAKE-VENOM LIGAND; HEART-FAILURE; NEUTRAL ENDOPEPTIDASE; CARDIAC MYOCYTES; GENE-EXPRESSION; BNP EXPRESSION; RESPONSE GENE; PORCINE BRAIN; RECEPTOR-A; ATRIAL AB The biology of the natriuretic peptide (NP) system is complex, yet highly phylogenetically preserved. It regulates salt and water handling, promotes vasodilatation, and exerts favorable effects on the heart in the context of processes such as heart failure. Prior assumptions about the production of B-type NP (BNP) and its amino-terminal precursor fragment (NT-proBNP) have recently been refuted. It is now recognized that rather than a 1:1 secretion of these 2 NPs, a mixture of cleaved and uncleaved NPs is released by the cardiomyocyte. It is also recognized that BNP is rapidly modified into a mixture of various fragments. Commercial assays for the detection of BNP and NT-proBNP measure a mixture of cleaved and uncleaved NPs as well as varying amounts of degraded BNP. BNP and NT-proBNP are cleared differentially: BNP is actively removed from the bloodstream and also has passive clearance mechanisms,. including renal clearance; NT-proBNP is cleared more passively by organs with high rates of blood flow, including the kidney. (c) 2008 Elsevier Inc. All rights reserved. C1 [Martinez-Rumayor, Abelardo; Januzzi, James L., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. [Richards, Mark] Univ Otago, Dept Med, Christchurch Sch Med & Hlth Sci, Dunedin, New Zealand. [Richards, Mark] Christchurch Hosp, Christchurch, New Zealand. [Burnett, John C.] Mayo Clin, Rochester, MN USA. RP Januzzi, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, 55 Fruit St,Yawkey 5984, Boston, MA 02114 USA. EM JJanuzzi@partners.org NR 72 TC 18 Z9 19 U1 0 U2 3 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD FEB 4 PY 2008 VL 101 IS 3A SU S BP 3A EP 8A DI 10.1016/j.amjcard.2007.11.012 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 260AF UT WOS:000252981400002 ER PT J AU Januzzi, JL Chen-Tournoux, AA Moe, G AF Januzzi, James L., Jr. Chen-Tournoux, Annabel A. Moe, Gordon TI Amino-terminal pro-B-type natriuretic peptide testing for the diagnosis or exclusion of heart failure in patients with acute symptoms SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc ID EMERGENCY-DEPARTMENT PRIDE; ACUTE PULMONARY-EMBOLISM; PLASMA NT-PROBNP; ATRIAL-FIBRILLATION; DYSPNEIC PATIENTS; PROGNOSTIC VALUE; ECHOCARDIOGRAPHIC FINDINGS; VENTRICULAR DYSFUNCTION; MITRAL REGURGITATION; PLEURAL EFFUSIONS AB When used for the evaluation of patients with acute symptoms in the emergency department setting, amino-terminal pro-B-type natriuretic peptide (NT-proBNP) testing is highly sensitive and specific for the diagnosis or exclusion of acute destabilized heart failure (HF), with results comparable to those reported for B-type natriuretic peptide (BNP) testing. When used for the diagnostic evaluation of the patient with possible HF, NT-proBNP testing returns information that may be superior to clinical judgment. However, the optimal application of NT-proBNP is in concert with history and physical examination, adjunctive testing, and with the knowledge of the differential diagnosis of an elevated NT-proBNP level. Studies indicate a dual use for NT-proBNP, both to exclude acute HF (where NT-proBNP concentrations < 300 ng/L have a 98% negative predictive value), as well as to identify the diagnosis.-To identify acute HF in patients with dyspnea, an age-independent NT-proBNP cut point of 900 ng/L has a similar value as that reported for a BNP. value of 100 ng/L. However, age stratification of NT-proBNP using cut points of 450, 900, and 1,800 ng/L (for age groups of < 50, 50 - 75, and > 75 years) reduces false-negative findings in younger patients, reduces false-positive findings in older patients, and improves the overall positive predictive value of the marker without a change in overall sensitivity or specificity. Clinically validated, cost-effective algorithms for the use of NT-proBNP testing exist. Therefore, the logical use of NT-proBNP for the evaluation of the patient with suspected acute HF is useful, cost-effective, and may reduce adverse outcomes compared with standard clinical evaluation without natriuretic peptide testing. (c) 2008 Elsevier Inc. All rights reserved. C1 [Januzzi, James L., Jr.; Chen-Tournoux, Annabel A.] Harvard Univ, Div Cardiol, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Moe, Gordon] Univ Toronto, St Michaels Hosp, Div Cardiol, Toronto, ON M5B 1W8, Canada. RP Januzzi, JL (reprint author), Harvard Univ, Div Cardiol, Sch Med, Massachusetts Gen Hosp, 55 Fruit St,Yawkey 5984, Boston, MA 02114 USA. EM JJanuzzi@partners.org NR 59 TC 10 Z9 10 U1 0 U2 4 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD FEB 4 PY 2008 VL 101 IS 3A SU S BP 29A EP 38A DI 10.1016/j.amjcard.2007.11.017 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 260AF UT WOS:000252981400007 ER PT J AU van Kimmenade, RRJ Pinto, YM Januzzi, JL AF van Kimmenade, Roland R. J. Pinto, Yigal M. Januzzi, James L., Jr. TI Importance and interpretation of intermediate (gray zone) amino-terminal pro-B-type natriuretic peptide concentrations SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc ID EMERGENCY-DEPARTMENT PRIDE; ACUTE HEART-FAILURE; BODY-MASS INDEX; EJECTION FRACTION; RENAL-FUNCTION; NT-PROBNP; DYSPNEA; DIAGNOSIS; PROGNOSIS AB Amino-terminal pro-B-type natriuretic peptide (NT-proBNP) values between the cut point of 300 ng/L for "ruling out" acute heart failure (HF) and the consensus-recommended age-adjusted cut points for "ruling in" acute HF are referred to as intermediate or gray zone values, which may be seen in approximately 20% of patients with dyspnea in the emergency department. Knowledge of the differential diagnosis of the causes of a gray zone NT-proBNP finding is useful to ascertain the correct diagnosis. Possible causes include cardiac ischemia, atrial fibrillation, and infectious/inflammatory pulmonary diseases. Importantly, a gray zone NT-proBNP result is not associated with a benign prognosis. Regardless of the cause, it should not be ignored because it is a "negative" result. Patients with a gray zone NT-proBNP value are at higher risk for hazard compared with those with a negative NT-proBNP result. (c) 2008 Elsevier Inc. All rights reserved. C1 [van Kimmenade, Roland R. J.; Januzzi, James L., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. [van Kimmenade, Roland R. J.; Pinto, Yigal M.] Acad Hosp Maastricht, Dept Cardiol, Maastricht, Netherlands. RP Januzzi, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, 55 Fruit St,Yawkey 5984, Boston, MA 02114 USA. EM JJanuzzi@partners.org RI Kimmenade, R.R.J./L-4432-2015 NR 15 TC 2 Z9 2 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD FEB 4 PY 2008 VL 101 IS 3A SU S BP 39A EP 42A DI 10.1016/j.amjcard.2007.11.018 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 260AF UT WOS:000252981400008 ER PT J AU Baggish, AL van Kimmenade, RRJ Januzzi, JL AF Baggish, Aaron L. van Kimmenade, Roland R. J. Januzzi, James L., Jr. TI The differential diagnosis of an elevated amino-terminal pro-B-type natriuretic peptide level SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc ID ACUTE HEART-FAILURE; CHRONIC AORTIC REGURGITATION; HODGKINS-LYMPHOMA PATIENTS; PREDICT EXERCISE CAPACITY; STEM-CELL TRANSPLANTATION; ACUTE PULMONARY-EMBOLISM; CRITICALLY-ILL PATIENTS; ACUTE ISCHEMIC-STROKE; HYPERTROPHIC CARDIOMYOPATHY; ATRIAL-FIBRILLATION AB Although amino-terminal pro-B-type natriuretic peptides (NT-proBNP) are useful for the diagnosis or exclusion of heart failure (HF), this marker may identify a wide range of disease processes other than HF. Indeed, elevation of NT-proBNP may occur in a number of heart diseases (including heart muscle disease, valve disease, rhythm abnormalities, pulmonary hypertension, and cytotoxic injury to the heart) and in disease processes other than primary cardiac illnesses, including gram-negative sepsis. Importantly, although NT-proBNP may increase in settings other than HF, the presence and severity of such NT-proBNP release is often significantly associated with risk for adverse outcome. Accordingly, elevation of NT-proBNP in the context of non-HF situations should not be regarded as a "false-positive" finding, and elevated NT-proBNP values should not be discarded without consideration of the serious adverse outcomes associated with the elevation. Future studies will be necessary to further understand the utility of NT-proBNP testing in states other than cardiovascular disease. (c) 2008 Elsevier Inc. All rights reserved. C1 [Baggish, Aaron L.; van Kimmenade, Roland R. J.; Januzzi, James L., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. [van Kimmenade, Roland R. J.] Acad Hosp Maastricht, Dept Cardiol, Maastricht, Netherlands. RP Januzzi, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, 55 Fruit St,Yawkey 5984, Boston, MA 02114 USA. EM JJanuzzi@partners.org RI Kimmenade, R.R.J./L-4432-2015 NR 64 TC 5 Z9 5 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD FEB 4 PY 2008 VL 101 IS 3A SU S BP 43A EP 48A DI 10.1016/j.amjcard.2007.11.019 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 260AF UT WOS:000252981400009 ER PT J AU Baggish, AL van Kimmenade, RRJ Januzzi, JL AF Baggish, Aaron L. van Kimmenade, Roland R. J. Januzzi, James L., Jr. TI Amino-terminal pro-B-type natriuretic peptide testing and prognosis in patients with acute dyspnea, including those with acute heart failure SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc ID EMERGENCY-DEPARTMENT PRIDE; ACUTE PULMONARY-EMBOLISM; IN-HOSPITAL MORTALITY; RISK STRATIFICATION; RENAL-FUNCTION; PREDICTION; UTILITY; ANEMIA AB In patients presenting with acute dyspnea of any cause, elevation of amino-terminal pro-B-type natriuretic peptides (NT-proBNP) is powerfully prognostic for adverse outcomes, including death. Among those with acute destabilized heart failure (HF), an NT-proBNP cut point of approximately 5,000 ng/L is powerfully predictive of death by 76 days after presentation. For 1-year risk stratification, an NT-proBNP value of approximately 1,000 ng/L at presentation is optimal. Among those patients with elevated NT-proBNP levels, a posttreatment NT-proBNP value may be of even greater value than the presenting value. Although NT-proBNP is powerfully prognostic in patients with acute dyspnea with and without HF, the addition of clinical variables strengthens the ability to discriminate risk. In addition, multimarker approaches, including NT-proBNP, for the assessment of acute dyspnea or acute HF appear promising. Indeed, when combined with conventional markers, such as measures of renal dysfunction, anemia, myocardial injury, or inflammation, the predictive value of NT-proBNP is considerably strengthened. Given the strong value of NT-proBNP for risk assessment of the patient with acute dyspnea, a baseline measurement for. all patients with dyspnea is recommended, with pretreatment and posttreatment measurement of NT-proBNP recommended for patients with an elevated value, especially those with HF. (c) 2008 Elsevier Inc. All. rights reserved. C1 [Baggish, Aaron L.; Januzzi, James L., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. [van Kimmenade, Roland R. J.] Acad Hosp Maastricht, Dept Cardiol, Maastricht, Netherlands. RP Januzzi, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, 55 Fruit St,Yawkey 5984, Boston, MA 02114 USA. EM JJanuzzi@partners.org RI Kimmenade, R.R.J./L-4432-2015 NR 21 TC 3 Z9 3 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD FEB 4 PY 2008 VL 101 IS 3A SU S BP 49A EP 55A DI 10.1016/j.amjcard.2007.11.020 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 260AF UT WOS:000252981400010 ER PT J AU Bettencourt, P Januzzi, JL AF Bettencourt, Paulo Januzzi, James L., Jr. TI Amino-terminal pro-B-type natriuretic peptide testing for inpatient monitoring and treatment guidance of acute destabilized heart failure SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc ID CONVERTING ENZYME-INHIBITOR; EMERGENCY-DEPARTMENT PRIDE; NT-PROBNP; ATRIAL-FIBRILLATION; FILLING PRESSURES; DIAGNOSIS; THERAPY; DYSPNEA; COMBINATION; OUTPATIENTS AB Although typically elevated at presentation in the context of destabilized heart failure (HF), amino-terminal pro-B-type natriuretic peptide (NT-proBNP) values typically decrease rapidly among patients who have a favorable response to therapy. Given this, it is natural to examine the relation between NT-proBNP and therapeutic interventions for acute HF. Both presentation and posttreatment NT-proBNP concentrations have some value for prognostication of recurrent HF hospitalization or death. However, the percent change in NT-proBNP after treatment for acute HF may be a more powerful method for risk stratification. Although prospective studies on the effect of NT-proBNP measurement in guiding therapy in acute destabilized HF are lacking, observational data suggest that a 30% decrease in NT-proBNP values during hospitalization is a reasonable goal. If a baseline measure of NT-proBNP is not available, an NT-proBNP level < 4,000 ng/L after acute treatment is an alternative goal. Because the criteria for determining restabilization from destabilized HF prominently include clinical and routine laboratory testing rather than NP measures, the frequency of NT-proBNP measurement should not be excessive in patients with acute HF, with measures at baseline/presentation and after perceived recompensation to evaluate for the desired decrease in NT-proBNP concentrations. A remeasurement of NT-proBNP may also be useful for evaluation of new or worsened symptoms. In those patients without a decrease in NT-proBNP despite. perceived recompensation from HF, a review of adequacy of treatment, goals of therapy, and consideration of prognosis is recommended. (c) 2008 Elsevier Inc. All rights reserved. C1 [Januzzi, James L., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. [Bettencourt, Paulo] Hosp S Joao Alameda Hernani Monteiro, Med Interna Serv, Oporto, Portugal. RP Januzzi, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, 55 Fruit St,Yawkey 5984, Boston, MA 02114 USA. EM JJanuzzi@partners.org OI Bettencourt, Paulo/0000-0003-1638-3993 NR 26 TC 3 Z9 4 U1 0 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD FEB 4 PY 2008 VL 101 IS 3A SU S BP 67A EP 71A DI 10.1016/j.amjcard.2007.11.026 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 260AF UT WOS:000252981400013 ER PT J AU Bayes-Genis, A DeFilippi, C Januzzi, JL AF Bayes-Genis, Antoni DeFilippi, Christopher Januzzi, James L., Jr. TI Understanding amino-terminal pro-B-type natriuretic peptide in obesity SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc ID CHRONIC HEART-FAILURE; BODY-MASS INDEX; EMERGENCY-DEPARTMENT; FOLLOW-UP; MORTALITY; DYSPNEA; RISK; EXPRESSION; PROGNOSIS; DIAGNOSIS AB Concentrations of both B-type natriuretic peptide (BNP) and its amino-terminal cleavage fragment (NT-proBNP) are relatively lower among patients with a higher body mass index (BMI). Based on data at hand, this is probably related to reduced synthesis or secretion of the peptides, rather than increased clearance (which may play only a minor role in this context). Despite this fact, age-adjusted NT-proBNP cut points to "rule in" heart failure (HF) and age-independent cut points to "rule out" HF in patients with acute dyspnea are equally useful for obese and lean patients, and no adjustment of NT-proBNP thresholds for BMI is recommended. Furthermore, the consensus-recommended NT-proBNP cut point of 1,000 ng/L for prognostication in acute dyspnea is equally useful across all BMI categories, without the need for further adjustment for weight. Thus, despite the BMI-related NP handicap observed in overweight and obese patients, NT-proBNP remains powerfully useful for diagnostic and prognostic evaluation across the entire range of BMI values. (c) 2008 Elsevier Inc. All rights reserved. C1 [Januzzi, James L., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. [DeFilippi, Christopher] Univ Maryland, Div Cardiol, Baltimore, MD 21201 USA. [Bayes-Genis, Antoni] Hosp Santa Creu & Sant Pau, Serv Cardiol, Barcelona, Spain. RP Januzzi, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, 55 Fruit St,Yawkey 5984, Boston, MA 02114 USA. EM JJanuzzi@partners.org RI Bayes-Genis, Antoni/C-4002-2015 OI Bayes-Genis, Antoni/0000-0002-3044-197X NR 23 TC 7 Z9 7 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD FEB 4 PY 2008 VL 101 IS 3A SU S BP 89A EP 94A DI 10.1016/j.amjcard.2007.11.030 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 260AF UT WOS:000252981400017 ER PT J AU Lesic, B Rahme, LG AF Lesic, Biliana Rahme, Laurence G. TI Use of the lambda Red recombinase system to rapidly generate mutants in Pseudomonas aeruginosa SO BMC MOLECULAR BIOLOGY LA English DT Article ID BACTERIOPHAGE-LAMBDA; CHROMOSOMAL GENES; ESCHERICHIA-COLI; EXCISION; YERSINIA; ENCODES; LIBRARY; PROTEIN; SIGNAL AB Background: The Red recombinase system of bacteriophage lambda has been used to inactivate chromosomal genes in various bacteria and fungi. The procedure consists of electroporating a polymerase chain reaction (PCR) fragment that was obtained with a 1- or3-step PCR protocol and that carries an antibiotic cassette flanked by a region homologous to the target locus into a strain that expresses the lambda Red recombination system. Results: This system has been modified for use in Pseudomonas aeruginosa. Chromosomal DNA deletions of single genes were generated using 3-step PCR products containing flanking regions 400-600 nucleotides (nt) in length that are homologous to the target sequence. A 1- step PCR product with a homologous extension flanking region of only 100 nt was in some cases sufficient to obtain the desired mutant. We further showed that the P. aeruginosa strain PA14 non-redundant transposon library can be used in conjunction with the lambda Red technique to rapidly generate large chromosomal deletions or transfer mutated genes into various PA14 isogenic mutants to create multi-locus knockout mutants. Conclusion: The lambda Red-based technique can be used efficiently to generate mutants in P. aeruginosa. The main advantage of this procedure is its rapidity as mutants can be easily obtained in less than a week if the 3-step PCR procedure is used, or in less than three days if the mutation needs to be transferred from one strain to another. C1 [Lesic, Biliana; Rahme, Laurence G.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02114 USA. [Lesic, Biliana; Rahme, Laurence G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lesic, Biliana; Rahme, Laurence G.] Shriners Res Inst, Boston, MA 02114 USA. [Lesic, Biliana; Rahme, Laurence G.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Rahme, LG (reprint author), Harvard Univ, Sch Med, Dept Surg, Boston, MA 02114 USA. EM lesic@molbio.mgh.harvard.edu; rahme@molbio.mgh.harvard.edu FU NIAID NIH HHS [R01 AI063433-05, R01 AI063433, R01AI063433, R33 AI105902] NR 21 TC 69 Z9 69 U1 0 U2 23 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2199 J9 BMC MOL BIOL JI BMC Mol. Biol. PD FEB 4 PY 2008 VL 9 AR 20 DI 10.1186/1471-2199-9-20 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 284NA UT WOS:000254711900001 PM 18248677 ER PT J AU Yelin, D Bouma, BE Tearney, GJ AF Yelin, D. Bouma, B. E. Tearney, G. J. TI Volumetric sub-surface imaging using spectrally encoded endoscopy SO OPTICS EXPRESS LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; PHASE-SHIFTING ALGORITHM; IN-VIVO; MINIATURE ENDOSCOPY; MICROSCOPY AB Endoscopic imaging below tissue surfaces and through turbid media may provide improved diagnostic capabilities and visibility in surgical settings. Spectrally encoded endoscopy (SEE) is a recently developed method that utilizes a single optical fiber, miniature optics and a diffractive grating for high-speed imaging through small diameter, flexible endoscopic probes. SEE has also been shown to provide three-dimensional topological imaging capabilities. In this paper, we have configured SEE to additionally image beneath tissue surfaces, by increasing the system's sensitivity and acquiring the complex spectral density for each spectrally resolved point on the sample. In order to demonstrate the capability of SEE to obtain subsurface information, we have utilized the system to image a resolution target through intralipid solution, and conduct volumetric imaging of a mouse embryo and excised human middle-ear ossicles. Our results demonstrate that real-time subsurface imaging is possible with this miniature endoscopy technique. C1 [Yelin, D.] Technion Israel Inst Technol, Dept Biomed Engn, IL-32000 Haifa, Israel. [Bouma, B. E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Tearney, G. J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed,Pathol Dept, Boston, MA 02114 USA. RP Yelin, D (reprint author), Technion Israel Inst Technol, Dept Biomed Engn, IL-32000 Haifa, Israel. EM yelin@bm.technion.ac.il FU NIBIB NIH HHS [1R21EB007718-01] NR 18 TC 12 Z9 14 U1 0 U2 4 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD FEB 4 PY 2008 VL 16 IS 3 BP 1748 EP 1757 DI 10.1364/OE.16.001748 PG 10 WC Optics SC Optics GA 259IH UT WOS:000252932500041 PM 18542254 ER PT J AU Kuter, DJ Bussel, JB Lyons, RM Pullarkat, V Gernsheimer, TB Senecal, FM Aledort, LM George, JN Kessler, CM Sanz, MA Liebman, HA Slovick, FT de Wolf, JTM Bourgeois, E Guthrie, TH Newland, A Wasser, JS Hamburg, SI Grande, C Lefrere, F Lichtin, AE Tarantino, MD Terebelo, HR Viallard, JF Cuevas, FJ Go, RS Henry, DH Redner, RL Rice, L Schipperus, MR Guo, DM Nichol, JL AF Kuter, David J. Bussel, James B. Lyons, Roger M. Pullarkat, Vinod Gernsheimer, Terry B. Senecal, Francis M. Aledort, Louis M. George, James N. Kessler, Craig M. Sanz, Miguel A. Liebman, Howard A. Slovick, Frank T. de Wolf, J. Th M. Bourgeois, Emmanuelle Guthrie, Troy H., Jr. Newland, Adrian Wasser, Jeffrey S. Hamburg, Solomon I. Grande, Carlos Lefrere, Francois Lichtin, Alan Eli Tarantino, Michael D. Terebelo, Howard R. Viallard, Jean-Francois Cuevas, Francis J. Go, Ronald S. Henry, David H. Redner, Robert L. Rice, Lawrence Schipperus, Martin R. Guo, D. Matthew Nichol, Janet L. TI Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial SO LANCET LA English DT Article ID ADULT PATIENTS; THROMBOPOIETIN LEVELS; PLATELET DESTRUCTION; CHRONIC ITP; IN-VITRO; AMG-531; MEGAKARYOCYTES; AUTOANTIBODIES; SPLENECTOMY; TGF-BETA-1 AB Background Chronic immune thrombocytopenic purpura (ITP) is characterised by accelerated platelet destruction and decreased platelet production. Short-term administration of the thrombopoiesis-stimulating protein, romiplostim, has been shown to increase platelet counts in most patients with chronic ITP. We assessed the long-term administration of romiplostim in splenectomised and non-splenectomised patients with ITP. Methods In two parallel trials, 63 splenectomised and 62 non-splenectomised patients with ITP and a mean of three platelet counts 30x10(9)/L or less were randomly assigned 2:1 to subcutaneous injections of romiplostim (n=42 in splenectomised study and n=41 in non-splenectomised study) or placebo (n=21 in both studies) every week for 24 weeks. Doses of study drug were adjusted to maintain platelet counts of 50x10(9)/L to 200x10(9)/L. The primary objectives were to assess the efficacy of romiplostim as measured by a durable platelet response (platelet count >= 50x10(9)/L during 6 or more of the last 8 weeks of treatment) and treatment safety. Analysis was per protocol. These studies are registered with ClinicalTrials.gov, numbers NCT00102323 and NCT00102336. Findings A durable platelet response was achieved by 16 of 42 splenectomised patients given romplostim versus none of 21 given placebo (difference in proportion of patients responding 38% [95% CI 23.4-52.8], p=0.0013), and by 25 of 41 non-splenectomised patients given romplostim versus one of 21 given placebo (56% [38.7-73.71, p<0.0001). The overall platelet response rate (either durable or transient platelet response) was noted in 88% (36/41) of non-splenectomised and 79% (33/42) of splenectomised patients given romiplostim compared with 14% (three of 21) of non-splenectomised and no splenectomised patients given placebo (p<0.0001). Patients given romiplostim achieved platelet counts of 50x10(9)/L or more on a mean of 13.8 (SE 0.9) weeks (mean 12.3 [1.2] weeks in splenectomised group vs 15.2 [1.2] weeks in non-splenectomised group) compared with 0 . 8 (0.4) weeks for those given placebo (0. 2 [0 . 1] weeks vs 1 . 3 [0.81 weeks). 87% (20/23) of patients given romiplostim (12/12 splenectomised and eight of 11 non-splenectomised patients) reduced or discontinued concurrent therapy compared with 38% (six of 16) of those given placebo (one of six splenectomised and five of ten non-splenectomised patients). Adverse events were much the same in patients given romiplostim and placebo. No antibodies against romiplostim or thrombopoietin were detected. Interpretation Romiplostim was well tolerated, and increased and maintained platelet counts in splenectomised and non-splenectomised patients with ITP. Many patients were able to reduce or discontinue other ITP medications. Stimulation of platelet production by romiplostim may provide a new therapeutic option for patients with ITP. C1 [Kuter, David J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bussel, James B.] New York Presbyterian Hosp, Div Pediat, New York, NY USA. [Lyons, Roger M.] Hematol Oncol Assoc S Texas, San Antonio, TX USA. [Pullarkat, Vinod] City Hope Natl Med Ctr, Div Hematol, Duarte, CA 91010 USA. [Gernsheimer, Terry B.] Puget Sound Blood Ctr, Seattle, WA 98104 USA. [Senecal, Francis M.] NW Med Specialties, Tacoma, WA USA. [Aledort, Louis M.] Mt Sinai Hosp, New York, NY 10029 USA. [George, James N.] Univ Oklahoma, Hlth Sci Ctr, Hematol Oncol Sect, Oklahoma City, OK USA. [Kessler, Craig M.] Georgetown Univ, Med Ctr, Washington, DC 20007 USA. [Sanz, Miguel A.] Hosp La Fe, E-46009 Valencia, Spain. [Liebman, Howard A.] Univ So Calif, Keck Sch Med, Div Hematol, Los Angeles, CA USA. [Slovick, Frank T.] Heartland Hematol Oncol Assoc Inc, Kansas City, MO USA. [de Wolf, J. Th M.] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands. [Bourgeois, Emmanuelle] CHU Lille, Serv Malad Sang, F-59037 Lille, France. [Guthrie, Troy H., Jr.] Baptist Canc Inst, Jacksonville, FL USA. [Newland, Adrian] Royal London Hosp, Dept Haematol, London E1 1BB, England. [Wasser, Jeffrey S.] DeQuattro Community Canc Ctr, Manchester, CT USA. [Hamburg, Solomon I.] Tower Canc Res Fdn, Beverly Hills, CA USA. [Grande, Carlos] Hosp 12 Octubre, E-28041 Madrid, Spain. [Lefrere, Francois] Hop Necker Enfants Malad, Serv Hematol Adulte, Paris, France. [Lichtin, Alan Eli] Cleveland Clin Fdn, Dept Hematol Oncol, Cleveland, OH 44195 USA. [Tarantino, Michael D.] Comprehens Bleeding Disorders Ctr, Peoria, IL USA. [Terebelo, Howard R.] Newland Med Assoc, Southfield, MI USA. [Viallard, Jean-Francois] Hop Haut Leveque, Pessac, France. [Cuevas, Francis J.] Marshall Univ, Huntington, WV USA. [Go, Ronald S.] Gundersen Lutheran Hlth Syst, La Crosse, WI USA. [Henry, David H.] Penn Oncol Hematol Assoc Inc, Philadelphia, PA USA. [Redner, Robert L.] Univ Pittsburgh, Dept Med, Hillman Canc Ctr, Pittsburgh, PA USA. [Rice, Lawrence] Baylor Coll Med, Houston, TX 77030 USA. [Schipperus, Martin R.] Ziekenhuis Leyenburg, The Hague, Netherlands. [Guo, D. Matthew; Nichol, Janet L.] Amgen Inc, Thousand Oaks, CA 91320 USA. RP Kuter, DJ (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM kuter.david@MGH.harvard.edu FU NCATS NIH HHS [UL1 TR000005] NR 39 TC 358 Z9 378 U1 0 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD FEB 2 PY 2008 VL 371 IS 9610 BP 395 EP 403 DI 10.1016/S0140-6736(08)60203-2 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 260ED UT WOS:000252992700029 PM 18242413 ER PT J AU Mansbach, JM McAdam, AJ Clark, S Hain, PD Flood, RG Acholonu, U Camargo, CA AF Mansbach, Jonathan M. McAdam, Alexander J. Clark, Sunday Hain, Paul D. Flood, Robert G. Acholonu, Uchechi Camargo, Carlos A., Jr. TI Prospective multicenter study of the viral etiology of bronchiolitis in the emergency department SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE bronchiolitis; respiratory syncytial virus; rhinovirus; asthma ID RESPIRATORY SYNCYTIAL VIRUS; YOUNG-CHILDREN; INHALED CORTICOSTEROIDS; UNITED-STATES; HUMAN METAPNEUMOVIRUS; RHINOVIRUS INFECTION; HUMAN CORONAVIRUS; TRACT DISEASE; HIGH-RISK; ASTHMA AB Objectives: To determine the viral etiology of bronchiolitis and clinical characteristics of children age < 2 years presenting to the emergency department (ED) with bronchiolitis. Methods: The authors conducted a 14-center prospective cohort study during 2005-2006 of ED patients age < 2 years with bronchiolitis. The study was conducted in 10 states as part of the Emergency Medicine Network. Researchers collected nasopharyngeal aspirates and conducted structured interviews, medical record reviews, and 2-week follow-up telephone calls. Samples were tested using reverse transcription polymerase chain reaction for respiratory syncytial virus (RSV), rhinovirus (RV), human metapneumovirus (hMPV), and influenza viruses (Flu). Results: Testing of 277 samples revealed 176 (64%) positive for RSV, 44 (16%) for RV, 26 (9%) for hMPV, 17 (6%) for Flu A, and none for Flu B. When children were categorized as RSV only, RV only, RV and RSV, and all others (hMPV, Flu, no identified virus), children with RV only were more likely to be African American (19, 62, 14, and 40%, respectively; p < 0.001) and have a history of wheezing (23, 52, 21, and 15%, respectively; p = 0.01). In multivariate models, children with RV were more likely to receive corticosteroids (odds ratio [OR] 3.5; 95% confidence interval [CI] = 1.5 to 8.15). The duration of illness may be shorter for children with RV (Days 8, 3, 6, and 8; p = 0.07). Conclusions: In this multicenter study, RSV was the most frequent cause of bronchiolitis (64%). RV was present in 16%, and these children have a distinct profile in terms of demographics, medical history, and ED treatment. C1 [Mansbach, Jonathan M.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Med, Boston, MA 02115 USA. [McAdam, Alexander J.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Lab Med, Boston, MA USA. [Hain, Paul D.] Vanderbilt Childrens Hosp, Dept Pediat, Nashville, TN USA. [Flood, Robert G.] Temple Univ, Sch Med, Dept Pediat, Philadelphia, PA 19122 USA. [Clark, Sunday; Acholonu, Uchechi; Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Mansbach, JM (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Med, Boston, MA 02115 USA. EM jonathan.mansbach@childrens.harvard.edu NR 45 TC 55 Z9 59 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD FEB PY 2008 VL 15 IS 2 BP 111 EP 118 DI 10.1111/j.1553-2712.2007.00034.x PG 8 WC Emergency Medicine SC Emergency Medicine GA 260WO UT WOS:000253041300001 PM 18275439 ER PT J AU Ehrenkranz, PD Ahn, CJ Metlay, JP Camargo, CA Holmes, WC Rothman, R AF Ehrenkranz, Peter D. Ahn, Christina J. Metlay, Joshua P. Camargo, Carlos A. Holmes, William C. Rothman, Richard TI Availability of rapid human immunodeficiency virus testing in academic emergency departments SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE human immunodeficiency virus; emergency medicine; preventive medicine; diagnostic test; routine; cross-sectional studies; questionnaires ID HIV-INFECTED PERSONS; HEALTH-CARE SETTINGS; RECOMMENDATIONS; SITES AB Objectives: The Centers for Disease Control and Prevention (CDC) recommends routine human immunodeficiency virus (HIV) screening of emergency department (ED) patients aged 13 to 64 years. The study objectives were to determine the accessibility of rapid HIV testing in academic EDs, to identify factors that influence an ED's adoption of testing, and to describe current HIV testing practices. Methods: Online surveys were sent to EDs affiliated with emergency medicine (EM) residency programs (n = 128), excluding federal hospitals and facilities in U.S. territories. Eighty percent (n = 102) responded. Most e-mail recipients (n = 121) were Emergency Medicine Network (EMNet) investigators; remaining contacts were obtained from residency-related Web sites. Results: Most academic EDs (n = 58; 57%; 95% confidence interval (CI) = 47% to 66%) offer rapid HIV testing. Among this group, 26 (45%) allow providers to order tests without restrictions. Of the other 32 EDs, 100% have policies allowing for rapid HIV testing following occupational exposures, but less than 10% have guidelines for testing in other clinical situations. Forty-seven percent expect to routinely offer HIV testing in the next 2 to 3 years. Only 59% of the EDs that offered rapid tests in any situation could link an HIV-positive patient to subspecialty care. The facility characteristic most important to availability of rapid HIV testing was the presence of on-site HIV counselors. Conclusions: Most academic EDs now offer rapid HIV testing (57%), but few use it in situations other than occupational exposure. Less than half of academic EDs expect to implement CDC guidelines regarding routine screening within the next few years. The authors identified facility characteristics (e.g., counseling, ability to refer) that may influence adoption of rapid HIV testing. C1 [Ehrenkranz, Peter D.; Metlay, Joshua P.] Univ Penn, Robert Wood Johnson Clin Scholars Program, Philadelphia, PA 19104 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Ehrenkranz, Peter D.; Metlay, Joshua P.] Univ Penn, Ctr Educ & Res Therapeut, Philadelphia, PA 19104 USA. [Ehrenkranz, Peter D.; Metlay, Joshua P.; Holmes, William C.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Metlay, Joshua P.; Holmes, William C.] VA Med Ctr, Philadelphia, PA USA. [Ahn, Christina J.; Camargo, Carlos A.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Rothman, Richard] Johns Hopkins Med Ctr, Dept Emergency Med, Baltimore, MD USA. RP Metlay, JP (reprint author), Univ Penn, Robert Wood Johnson Clin Scholars Program, Philadelphia, PA 19104 USA. EM jmetlay@mail.med.upenn.edu OI Rothman, Richard/0000-0002-1017-9505 NR 27 TC 42 Z9 42 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD FEB PY 2008 VL 15 IS 2 BP 144 EP 150 DI 10.1111/j.1553-2712.2008.00028.x PG 7 WC Emergency Medicine SC Emergency Medicine GA 260WO UT WOS:000253041300005 PM 18275444 ER PT J AU Kimberly, HH Shah, S Marill, K Noble, V AF Kimberly, Heidi Harbison Shah, Sachita Marill, Keith Noble, Vicki TI Correlation of optic nerve sheath diameter with direct measurement of intracranial pressure SO ACADEMIC EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-of-Academic-Emergency-Medicine CY MAY 16-19, 2007 CL Chicago, IL SP Soc Acad Emergency Med DE ultrasound; intracranial pressure; optic nerve sheath diameter ID ULTRASOUND AB Background: Measurements of the optic nerve sheath diameter (ONSD) using bedside ultrasound (US) have been shown to correlate with clinical and radiologic signs and symptoms of increased intracranial pressure (ICP). Objectives: Previous literature has identified 5 mm as the ONSD measurement above which patients exhibit either clinical or radiologic signs of elevated ICP. The goals of this study were to evaluate the association between ONSD and ICP and to validate the commonly used ONSD threshold of 5 mm using direct measurements of ICP as measured by ventriculostomy. Methods: A prospective blinded observational study was performed using a convenience sample of adult patients in both the emergency department (ED) and the neurologic intensive care unit (ICU) who had invasive intracranial monitors placed as part of their clinical care. Ocular USs were performed with a 10-5 MHz linear probe. Emergency physicians (EPs) with previous ocular US experience performed ONSD measurements while blinded to the contemporaneous ICP reading obtained directly from invasive monitoring. The association between ONSD and ICP was assessed with the Spearman rank correlation coefficient, and a receiver operator characteristic (ROC) curve was created to determine the optimal ONSD cutoff to detect ICP > 20 cm H2O. Results: Thirty-eight ocular USs were performed on 15 individual patients. Spearman rank correlation coefficient of ONSD and ICP was 0.59 (p < 0.0005) demonstrating a significant positive correlation. An ROC curve was created to assess the ability of ONSD to distinguish an abnormal ICP greater than 20 cm H2O. The area under the ROC curve was 0.93 (95% confidence interval [CI] = 0.84 to 0.99). Based on inspection of the ROC curve, ONSD > 5 mm performed well to detect ICP > 20 cm H2O with a sensitivity of 88% (95% CI = 47% to 99%) and specificity of 93% (95% CI = 78% to 99%). Conclusions: Using an ROC curve the authors systematically confirmed the commonly used threshold of ONSD > 5 mm to detect ICP > 20 cm H2O. This study directly correlates ventriculostomy measurements of ICP with US ONSD measurements and provides further support for the use of ONSD measurements as a noninvasive test for elevated ICP. C1 [Kimberly, Heidi Harbison; Shah, Sachita; Marill, Keith; Noble, Vicki] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Kimberly, HH (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. EM hkimberly@partners.org NR 10 TC 137 Z9 143 U1 4 U2 11 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD FEB PY 2008 VL 15 IS 2 BP 201 EP 204 DI 10.1111/j.1553-2712.2007.00031.x PG 4 WC Emergency Medicine SC Emergency Medicine GA 260WO UT WOS:000253041300014 PM 18275454 ER PT J AU Mimiaga, MJ Fair, AD Mayer, KH Koenen, K Gortmaker, S Tetu, AM Hobson, J Safren, SA AF Mimiaga, Matthew J. Fair, Andrew D. Mayer, Kenneth H. Koenen, Karestan Gortmaker, Steven Tetu, Ashley M. Hobson, Jeremy Safren, Steven A. TI Experiences and sexual behaviors of HIV-infected MSM who acquired HIV in the context of crystal methamphetamine use SO AIDS EDUCATION AND PREVENTION LA English DT Article ID RISK BEHAVIORS; BISEXUAL MEN; DRUG-USE; GAY; MOTIVATIONS AB The prevalence of crystal methamphetamine "meth" use among men who have sex with men (MSM) has been shown to be 20 times that of the general population, and it has been linked to increased sexual risk taking in MSM and others. Although previously seen as a "West Coast" phenomenon, clinical and other reports indicate that it is problematic among MSM regardless of geographic location. To assist in future intervention development, we interviewed 20 HIV-infected MSM who believe they seroconverted in the context of using crystal meth. Topics included factors related to continued and previous meth use, HIV risk behavior prior to and after HIV infection, and the consequences of sustained use. Generally, participants openly discussed the highly destructive effects of using crystal meth. Almost every (95%) participant spoke of chronic depression and anxiety following cycles of discontinued use, and participants often claimed an inability to enjoy activities that used to be pleasurable. Almost all (90%) respondents also reported that their social relationships were compromised by their crystal addictions. Many had lost friends, and in some cases, non-drug-using friends distanced themselves because of the addiction. A striking number of participants felt strongly that MSM sexual partner-meeting Web sites represented a major starting point for crystal-influenced sexual "hookups," and that they should likewise be a starting point for interventions. Corroborating previous research in this arena, this study exhibits support for a link between crystal meth use and high-risk sexual behavior among East Coast MSM. The study also draws attention to the need for associated mental health, functional and quality-of life impairments that seem to accompany continued use in individuals with HIV. C1 [Mimiaga, Matthew J.; Safren, Steven A.] Res & Evaluat Dept, Fenway Inst, Fenway Community Hlth, Boston, MA 02199 USA. [Mimiaga, Matthew J.; Safren, Steven A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. [Fair, Andrew D.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Fair, Andrew D.; Tetu, Ashley M.] Fenway Inst, Boston, MA USA. [Mayer, Kenneth H.] Fenway Inst, Providence, RI USA. [Mayer, Kenneth H.] Brown Univ, Sch Med, Providence, RI 02912 USA. [Koenen, Karestan; Gortmaker, Steven] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. [Tetu, Ashley M.] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Hobson, Jeremy] Fenway Inst, Boston, MA USA. RP Mimiaga, MJ (reprint author), Res & Evaluat Dept, Fenway Inst, Fenway Community Hlth, Prudential Tower,4th Floor,800 Boylston St, Boston, MA 02199 USA. EM mmimiaga@partners.org NR 22 TC 25 Z9 25 U1 0 U2 5 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0899-9546 J9 AIDS EDUC PREV JI Aids Educ. Prev. PD FEB PY 2008 VL 20 IS 1 BP 30 EP 41 DI 10.1521/aeap.2008.20.1.30 PG 12 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA 268CG UT WOS:000253554900003 PM 18312065 ER PT J AU Ramduth, D Thobakgale, CF Mkhwanazi, NP De Pierres, C Reddy, S van der Stok, M Mncube, Z Mphatswe, W Blanckenberg, N Cengimbo, A Prendergast, A Tudor-Williams, G Dong, K Jeena, P Coovadia, HM Day, CL Kiepiela, P Goulder, PJR Walker, BD AF Ramduth, Danni Thobakgale, Christina F. Mkhwanazi, Nompumelelo P. De Pierres, Chantal Reddy, Sharon van der Stok, Mary Mncube, Zenele Mphatswe, Wendy Blanckenberg, Natasha Cengimbo, Ayanda Prendergast, Andrew Tudor-Williams, Gareth Dong, Krista Jeena, Prakash Coovadia, Hoosen M. Day, Cheryl L. Kiepiela, Photini Goulder, Philip J. R. Walker, Bruce D. TI Detection of HIV type 1 gag-specific CD4(+) T cell responses in acutely infected infants SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID IMMUNE-RESPONSES; VIRAL LOAD; CD8-T-CELL MEMORY; CD4-T-CELL HELP; 1ST YEAR; CHILDREN; CD8(+); SUPPRESSION; REPLICATION; LYMPHOCYTE AB Multiple HIV-1-specific cytokine and proliferative responses by CD4(+) T cells have not been studied in acutely infected infants. Using an intracellular cytokine staining assay, 34 untreated clade C HIV-1-infected infants (2-102 days old) were assessed for IFN-gamma, 28/34 for IL-2, and 26/34 for TNF-alpha responses to all HIV-1 proteins. Responses were detected in 29%, 36%, and 15% of infants, respectively. Twelve of the original 34 infants were then studied longitudinally for 14 months to determine the effect of viral load on IFN-gamma Gag-specific responses: seven infants were treated for 1 year, stopped treatment, and resumed when CD4% was <20 and five infants were treated only when the CD4% was <20. Following treatment cessation, there was an immediate increase in viral load followed by an increase in the magnitude of CD4(+) Gag-specific responses. Despite this, the majority of infants (54%) had to restart treatment by 24 months of age, indicating that the immune responses were antigen driven but not associated with protection. Among untreated infants HIV-specific CD4(+) responses were detected sporadically indicating a dysfunctional immune response in the face of constant exposure to high levels of viremia. C1 [Prendergast, Andrew; Tudor-Williams, Gareth; Goulder, Philip J. R.] Univ Oxford, Nuffield Dept Med, Dept Pediat, Oxford OX1 3SY, England. [Ramduth, Danni; Thobakgale, Christina F.; Mkhwanazi, Nompumelelo P.; De Pierres, Chantal; Reddy, Sharon; van der Stok, Mary; Mncube, Zenele; Mphatswe, Wendy; Blanckenberg, Natasha; Cengimbo, Ayanda; Jeena, Prakash; Coovadia, Hoosen M.; Day, Cheryl L.; Kiepiela, Photini; Goulder, Philip J. R.; Walker, Bruce D.] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Doris Duke Med Res Inst, HIV Pathogenesis Programme, ZA-4013 Congella, South Africa. [Dong, Krista; Day, Cheryl L.; Goulder, Philip J. R.; Walker, Bruce D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Goulder, PJR (reprint author), Univ Oxford, Nuffield Dept Med, Dept Pediat, Peter Medawar Bldg Pathogen Res,S Parks Rd, Oxford OX1 3SY, England. EM philip.goulder@ndm.ox.ac.uk RI Day, Cheryl/J-9844-2012 FU Howard Hughes Medical Institute; Medical Research Council [G0500384]; Wellcome Trust NR 36 TC 5 Z9 5 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD FEB PY 2008 VL 24 IS 2 BP 265 EP 270 DI 10.1089/aid.2007.0096 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 268PI UT WOS:000253591300018 PM 18284325 ER PT J AU McLean, DS Ravid, S Blazing, M Gersh, B Shui, A Cannon, CP AF McLean, Dalton S. Ravid, Shmuel Blazing, Michael Gersh, Bernard Shui, Amy Cannon, Christopher P. TI Effect of statin dose on incidence of atrial fibrillation: Data from the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) and Aggrastat to Zocor (A to Z) trials SO AMERICAN HEART JOURNAL LA English DT Article ID C-REACTIVE PROTEIN; ACUTE CORONARY SYNDROMES; ELECTRICAL CARDIOVERSION; CARDIAC-SURGERY; INFLAMMATION; RECURRENCE; REDUCTION; RISK; PERICARDITIS; ARRHYTHMIAS AB Background Inflammation has been suggested as a factor in the initiation and maintenance of atrial fibrillation (AF). Several observational studies have suggested that statins, presumably through their anti-inflammatory properties, decrease the risk of AF. Methods We analyzed 2 large, randomized trials, PROVE IT-TIMI 22 and phase Z of the A to Z trial, which compared lower- versus higher-intensity statin therapy to evaluate whether higher-intensity statin therapy lowered the risk of AF onset during the 2 years of follow-up. We hypothesized that higher-intensity statin therapy would decrease the risk of AF when compared to lower-intensity statin therapy. From each trial, patients experiencing the onset of AF during follow-up were identified from the adverse event reports. Results Neither study showed a decreased AF risk with higher-dose statin. In PROVE IT-TIMI 22, 2.9% versus 3.3% in the high- versus standard-dose statin therapy, respectively, experienced the onset of AF over 2 years (OR 0.86, 95% Cl 0.61-1.23, P =.41). In A to Z, rates were 1.6% versus 0.99%, respectively (OR 1.58, 95% Cl 0.92-2.70, P =.096). In both trials, C-reactive protein levels (plasma or serum) tended to be higher among patients experiencing the onset of AF. Conclusion Our randomized comparison among 8659 patients found that higher-dose statin therapy did not reduce the short term incidence of AF among patients after acute coronary syndromes when compared with standard dose statin treatment. C1 [McLean, Dalton S.; Shui, Amy; Cannon, Christopher P.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [McLean, Dalton S.; Shui, Amy; Cannon, Christopher P.] Harvard Univ, Sch Med, Boston, MA USA. [Ravid, Shmuel] Harvard Univ, Sch Med, Brigham & Womens Hosp, Lown Cardiovasc Ctr, Brookline, MA USA. [Blazing, Michael] Duke Clin Res Inst, Durham, NC USA. [Blazing, Michael] Mayo Clin, Coll Med, Rochester, MN USA. RP Cannon, CP (reprint author), TIMI Study Grp, Div Cardiovasc, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM cpcannon@partners.org NR 24 TC 24 Z9 25 U1 1 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD FEB PY 2008 VL 155 IS 2 BP 298 EP 302 DI 10.7016/j.ahj.2007.10.024 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 257QE UT WOS:000252812800018 PM 18215600 ER PT J AU Ting, HH Roe, MT Gersh, BJ Spertus, JA Rumsfeld, JS Ou, FS Kao, J Long, KH Holmes, DR Peterson, ED AF Ting, Henry H. Roe, Matthew T. Gersh, Bernard J. Spertus, John A. Rumsfeld, John S. Ou, Fang-Shu Kao, John Long, Kirsten Hall Holmes, David R., Jr. Peterson, Eric D. CA NCDR TI Factors associated with off-label use of drug-muting stents in patients with ST-elevation myocardial infarction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID SIROLIMUS-ELUTING STENTS; BARE-METAL STENTS; ACUTE CORONARY SYNDROMES; UNCOATED STENTS; THROMBOSIS; OUTCOMES; PREDICTORS; REGISTRY; TRIALS; HEALTH AB Drug-eluting stents (DESs) are used in > 80% of percutaneous coronary intervention (PCI) procedures; however, up to 2/3 are used for off-label indications. Factors associated with DES use in patients with ST-elevation myocardial infarction (STEMI) are not known in contemporary clinical practice. We analyzed temporal trends, geographic patterns, and sociodemographic factors associated with off-label use of DESs in patients undergoing primary PCI for STEMI from July 2004 to March 2006 in the National Cardiovascular Data Registry (NCDR). The main outcome of this study was receipt of any DES, and the candidate independent variables were sociodemographic, hospital, clinical, and procedural variables. We also analyzed temporal trends and geographic patterns for use of DESs. A total of 30,235 patients with STEMI underwent primary PCI with use of DESs (84%) or bare metal stents (16%). Adoption of DESs was rapid but varied widely as a function of geographic location. After adjusting for clinical and procedural variables, older age was associated with lower use (odds ratio [OR] 0.94, 95% confidence interval [CI] 0.91 to 0.98), whereas white race (OR 1.14, 95% CI 1.03 to 1.27), commercial insurance (OR 1.22, 95% CI 1.11 to 1.34), and the west census region (OR 137, 95% CI 1.04 to 1.81) were associated with higher use of DESs. In conclusion, adoption of DESs was rapid in patients with STEMI, but geographic location and sociodemographic and hospital factors were associated with the use DESs. (c) 2008 Elsevier Inc. All rights reserved. C1 [Ting, Henry H.; Gersh, Bernard J.; Holmes, David R., Jr.] Mayo Clin, Div Cardiovasc Dis, Rochester, MN 55905 USA. [Long, Kirsten Hall] Mayo Clin, Hlth Care Policy & Res, Rochester, MN USA. [Roe, Matthew T.; Ou, Fang-Shu; Peterson, Eric D.] Duke Clin Res Inst, Durham, NC USA. [Spertus, John A.] St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. [Spertus, John A.] Univ Missouri, Kansas City, MO 64110 USA. [Rumsfeld, John S.] Univ Colorado, Denver, CO 80202 USA. [Rumsfeld, John S.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Kao, John] Univ Illinois, Div Cardiol, Chicago, IL USA. RP Ting, HH (reprint author), Mayo Clin, Div Cardiovasc Dis, Rochester, MN 55905 USA. EM ting.henry@mayo.edu NR 30 TC 8 Z9 8 U1 1 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD FEB 1 PY 2008 VL 101 IS 3 BP 286 EP 292 DI 10.1016/j.amjcard.2007.09.084 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 259EY UT WOS:000252923100002 PM 18237586 ER PT J AU Pinto, DS Kirtane, AJ Pride, YB Murphy, SA Sabatine, MS Cannon, CP Gibson, CM AF Pinto, Duane S. Kirtane, Ajay J. Pride, Yuri B. Murphy, Sabina A. Sabatine, Marc S. Cannon, Christopher P. Gibson, C. Michael CA CLARITY-TIMI 28 Investigators TI Association of blood glucose with angiographic and clinical outcomes among patients with ST-segment elevation myocardial infarction (from the CLARITY-TIMI-28 study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE CORONARY SYNDROMES; TYPE-2 DIABETES-MELLITUS; LONG-TERM MORTALITY; REPERFUSION THERAPY; PLATELET ACTIVATION; METABOLIC-CONTROL; ADVERSE OUTCOMES; INSULIN THERAPY; HYPERGLYCEMIA; TRIAL AB Overt hyperglycemia has been associated with adverse clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). The association of hypoglycernia and mild hyperglycemia with angiographic outcomes and the effect of clopidogrel on these outcomes have not been extensively evaluated. Patients with STEMI enrolled in the CLARITY-TIMI 28 trial (n = 3,491) were divided into 6 groups based on admission blood glucose level (< 81, 81 to 99, 100 to 125, 126 to 149, 150 to 199, and > 199 mg/dl). Angiographic and clinical outcomes were analyzed. Thirty-day mortality was increased (p < 0.001) in patients with hypoglycemia (glucose < 81 mg/dl, 6.3%) and severe hyperglycemia (glucose > 199 mg/dl, 10.4%) compared with the euglycemic group (glucose 81 to 99 mg/dl, 2.6%). Occlusion of the infarct-related artery (IRA; Thrombolysis In Myocardial Infarction flow grade 0/1) at scheduled angiography was more common with increased glucose (9.3% for glucose 81 to 99 mg/dl, 15.6% for glucose > 199 mg/di, p = 0.004). Multivariable analysis demonstrated that hyperglycemia was associated with a twofold increase in the composite of an occluded IRA, death, or recurrent MI before angiography (glucose > 199 mg/dl, odds ratio 1.93, 95% confidence interval 1.17 to 3.18, p = 0.01; glucose 150 to 199 mg/dl, odds ratio 2.04, 95% confidence interval 1.30 to 3.22, p = 0.002). There was no significant interaction between clopidogrel administration and the association of glucose and IRA patency (p interaction = NS). In conclusion, in patients with STEMI, hypoglycernia and severe hyperglycemia are associated with increased 30-day mortality. IRA patency after fibrinolytic administration is related to admission glucose independent of clopidogrel administration. (c) 2008 Elsevier Inc. All rights reserved. C1 [Pinto, Duane S.; Kirtane, Ajay J.; Pride, Yuri B.; Murphy, Sabina A.; Gibson, C. Michael] Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiovasc, Boston, MA 02215 USA. [Pinto, Duane S.; Kirtane, Ajay J.; Pride, Yuri B.; Murphy, Sabina A.; Gibson, C. Michael] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Sabatine, Marc S.; Cannon, Christopher P.] Harvard Univ, Brigham & Womens Hosp, Dept Med, TIMI Study Grp, Boston, MA 02115 USA. RP Gibson, CM (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiovasc, Boston, MA 02215 USA. EM mgibson@perfuse.org NR 30 TC 34 Z9 38 U1 1 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD FEB 1 PY 2008 VL 101 IS 3 BP 303 EP 307 DI 10.1016/j.amjcard.2007.08.034 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 259EY UT WOS:000252923100005 PM 18237589 ER PT J AU Levitzky, YS Cupples, LA Murabito, JM Kannel, WB Kiel, DP Wilson, PWF Wolf, PA O'Donnell, CJ AF Levitzky, Yammi S. Cupples, L. Adrienne Murabito, Joanne M. Kannel, William B. Kiel, Douglas P. Wilson, Peter W. F. Wolf, Philip A. O'Donnell, Christopher J. TI Prediction of intermittent claudication, ischemic stroke, and other cardiovascular disease by detection of abdominal aortic calcific deposits by plain lumbar radiographs SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY-HEART-DISEASE; SURVIVAL ANALYSIS; NATURAL-HISTORY; RISK-FACTORS; FRAMINGHAM; ATHEROSCLEROSIS; ROTTERDAM; MORTALITY; DISCRIMINATION; CLASSIFICATION AB There has been little attention to vascular calcium testing for generalized assessment of cardiovascular disease (CVD) outcomes, such as intermittent claudication (IC) and ischemic stroke (IS). We hypothesize that aortic calcium is an important predictor of CVD outcomes. Lumbar x-rays were obtained in 848 men and 1,301 women (mean ages 59.7 and 60.1 years, respectively) from the original cohort of the Framingham Heart Study. Abdominal aortic calcium (AAC) deposits were graded using a previously validated scale. Participants were categorized according to a 10-year Framingham coronary heart disease (CHD) risk score. Multivariable Cox proportional hazards analyses were performed to relate AAC to CVD outcomes. There were 199 IC events, 201 IS events, 702 CHD events, and 1,121 CVD events' during 32 years of follow-up. Multivariable adjusted hazard ratios for the third versus first AAC tertile in the combined cohort were 1.68 (95 % confidence interval [CI] 1.12 to 2.50) for IC, 1.73 (95% CI 1.12 to 2.65) for IS, 1.59 (95% CI 1.26 to 2.00) for CHD, and 1.64 (95% CI 1.37 to 1.97) for CVD. Hazard ratios for IC and IS were similar in magnitude to those for CHD and CVD. A high AAC score was associated with significantly higher incidence of events in subjects at intermediate Framingham CHD risk for all end points. Risk prediction based on cardiovascular risk factors improved for most outcomes when AAC was added. In conclusion, there was a graded, increasing, and independent association of AAC with incident IC and IS, similar in magnitude to risks predicted for CHD and CVD. AAC appears to be useful for risk stratification in patients at intermediate CHD risk. (c) 2008 Elsevier Inc. All rights reserved. C1 [Levitzky, Yammi S.; Murabito, Joanne M.; Kannel, William B.; Wolf, Philip A.; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Wolf, Philip A.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. [Wolf, Philip A.] Boston Univ, Sch Med, Dept Prevent Med, Boston, MA 02215 USA. [Wolf, Philip A.] Boston Univ, Sch Med, Dept Epidemiol, Boston, MA 02215 USA. [Murabito, Joanne M.] Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02215 USA. [Kiel, Douglas P.] Harvard Univ, Sch Med, Inst Aging Res Hebrew SeniorLife, Massachusetts Gen Hosp, Boston, MA 02115 USA. [O'Donnell, Christopher J.] Harvard Univ, Sch Med, Div Cardiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Wilson, Peter W. F.] Emory Univ, Sch Med, Div Cardiol, Atlanta, GA 30322 USA. RP O'Donnell, CJ (reprint author), NHLBI, Framingham Heart Study, Framingham, MA USA. EM odonnellc@nhlbi.nih.gov OI Cupples, L. Adrienne/0000-0003-0273-7965; Murabito, Joanne/0000-0002-0192-7516; Kiel, Douglas/0000-0001-8474-0310 FU NHLBI NIH HHS [N01-HC-38038]; NIA NIH HHS [R01 AR/AG 41398]; NINDS NIH HHS [2R01 NS017950] NR 28 TC 27 Z9 27 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD FEB 1 PY 2008 VL 101 IS 3 BP 326 EP 331 DI 10.1016/j.amjcard.2007.08.032 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 259EY UT WOS:000252923100010 PM 18237594 ER PT J AU Harris, K Nguyen, P Van Cott, EM AF Harris, Kenneth Nguyen, Phan Van Cott, Elizabeth M. TI Platelet PIA2 polymorphism and the risk for thrombosis in heparin-induced thrombocytopenia SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE heparin-induced thrombocytopenia; HIT; HPA1; Pl(A2) ID CORONARY-ARTERY-DISEASE; MYOCARDIAL-INFARCTION; GLYCOPROTEIN IIIA; RECEPTOR; COMPLICATIONS; ASSOCIATION; FIBRINOGEN AB Platelet glycoprotein (GP) IIb/IIIa has an important role in platelet aggregation. A polymorphism of platelet GPIIIa (pl(A2), also called HPA1b) has been associated with a higher risk of thrombosis, but its implication in heparin-induced thrombocytopenia (HIT) is unclear To investigate the hypothesis that the pl(A2) polymorphism influences the prothrombotic effects of HIT, we conducted a prospective study of 66 consecutive patients with a laboratory diagnosis of HIT The end point of the study was the diagnosis of a thrombus within 30 days of the positive HIT test result. The Diagnostica Stago (Asnieres, France) enzyme-linked immunosorbent assay was used to detect HIT antibodies, and a polymerase chain reaction assay was used to detect the pl(A2) polymorphism. Of the 66 patients, thrombotic complications developed in 2 7 (41%). Patients with the pl(A2) allele demonstrated a significantly higher thrombosis risk than did patients without (69% vs 32%; P =.0088; odds ratio, 4.68; 95% confidence interval, 1.39-15.72). The risk was stronger for arterial thrombosis and for patients 60 years or older There was a significant association between the Pl(A2) polymorphism of GPIIIa and the risk of thrombosis inpatients with HIT antibodies. C1 [Harris, Kenneth; Nguyen, Phan; Van Cott, Elizabeth M.] Massachusetts Gen Hosp, Coagulat Lab, Dept Pathol, Boston, MA 02114 USA. RP Van Cott, EM (reprint author), Massachusetts Gen Hosp, Coagulat Lab, Dept Pathol, Jackson 235,55 Fruit St, Boston, MA 02114 USA. NR 23 TC 11 Z9 13 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD FEB PY 2008 VL 129 IS 2 BP 282 EP 286 DI 10.1309/BMW4M8NQBVOTKFRX PG 5 WC Pathology SC Pathology GA 255TG UT WOS:000252679700013 PM 18208809 ER PT J AU Shea, MK Booth, SL Massaro, JM Jacques, PF D'Agostino, RB Dawson-Hughes, B Ordovas, JM O'Donnell, CJ Kathiresan, S Keaney, JF Vasan, RS Benjamin, EJ AF Shea, M. Kyla Booth, Sarah L. Massaro, Joseph M. Jacques, Paul F. D'Agostino, Ralph B., Sr. Dawson-Hughes, Bess Ordovas, Jose M. O'Donnell, Christopher J. Kathiresan, Sekar Keaney, John F., Jr. Vasan, Ramachandran S. Benjamin, Emelia J. TI Vitamin K and vitamin D status: Associations with inflammatory markers in the framingham offspring study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE inflammation; vitamin D; vitamin K ID BONE-MINERAL DENSITY; CARDIOVASCULAR-DISEASE; POSTMENOPAUSAL WOMEN; PHYLLOQUINONE INTAKE; BIOCHEMICAL MEASURES; CYTOKINE PRODUCTION; D SUPPLEMENTATION; INHIBITORY FACTOR; OXIDATIVE STRESS; SERUM-LEVELS AB In vitro data suggest protective roles for vitamins K and D in inflammation. To examine associations between vitamins K and D and inflammation in vivo, the authors used multiple linear regression analyses, adjusted for age, sex, body mass index, triglyceride concentrations, use of aspirin, use of lipid-lowering medication, season, menopausal status, and hormone replacement therapy. Participants were from the Framingham Offspring Study (1997-2001; n = 1,381; mean age = 59 years; 52% women). Vitamin K status, measured by plasma phylloquinone concentration and phylloquinone intake, was inversely associated with circulating inflammatory markers as a group and with several individual inflammatory biomarkers (p < 0.01). Percentage of undercarboxylated osteocalcin, a functional measure of vitamin K status, was not associated with overall inflammation but was associated with C-reactive protein (p < 0.01). Although plasma 25-hydroxyvitamin D was inversely associated with urinary isoprostane concentration, an indicator of oxidative stress (p < 0.01), overall associations between vitamin D status and inflammation were inconsistent. The observation that high vitamin K status was associated with lower concentrations of inflammatory markers suggests that a possible protective role for vitamin K in inflammation merits further investigation. C1 [Shea, M. Kyla; Booth, Sarah L.; Jacques, Paul F.; Dawson-Hughes, Bess; Ordovas, Jose M.] Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Massaro, Joseph M.; D'Agostino, Ralph B., Sr.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Cardiol & Prevent Med Sect, Boston, MA 02215 USA. [Keaney, John F., Jr.; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Med Ctr, Whitaker Cardiovasc Inst, Boston, MA 02215 USA. [O'Donnell, Christopher J.; Kathiresan, Sekar] Harvard Univ, Massachusetts Gen Hosp, Dept Med, Boston, MA 02115 USA. [Massaro, Joseph M.; D'Agostino, Ralph B., Sr.; O'Donnell, Christopher J.; Vasan, Ramachandran S.; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA USA. RP Booth, SL (reprint author), Tufts Univ, USDA, Human Nutr Res Ctr Aging, 711 Washington St, Boston, MA 02111 USA. EM sarah.booth@tufts.edu OI Massaro, Joseph/0000-0002-2682-4812; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336; Ordovas, Jose/0000-0002-7581-5680 FU NCRR NIH HHS [M01 RR001066, M01-RR-01066]; NHLBI NIH HHS [HL076784, 2K24HL04334, HC-25195, HL064753, HL58090, K24 HL004334, N01 HC025195, N01-HC-38038, N01HC25195, R01 HL058090, R01 HL058090-02, R01 HL058090-07, R01 HL064753, R01 HL064753-04, R01 HL076784, R01 HL076784-01, R01 HL076784-05, T32HL69772-0141]; NIA NIH HHS [AG028321, AG14759, R01 AG014759, R01 AG014759-04, R01 AG028321, R01 AG028321-03] NR 49 TC 126 Z9 130 U1 0 U2 11 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD FEB 1 PY 2008 VL 167 IS 3 BP 313 EP 320 DI 10.1093/aje/kwm306 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 258XH UT WOS:000252903200009 PM 18006902 ER PT J AU Abraham, NS Hartman, C Castillo, D Richardson, P Smalley, W AF Abraham, Neena S. Hartman, Christine Castillo, Diana Richardson, Peter Smalley, Walter TI Effectiveness of national provider prescription of PPI gastroprotection among elderly NSAID users SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT 71st Annual Meeting of the American-College-of-Gastroenterology CY OCT 20-25, 2006 CL Las Vegas, NV SP Amer Coll Gastroenterol ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; PEPTIC-ULCER DISEASE; PROTON-PUMP INHIBITORS; GASTROINTESTINAL COMPLICATIONS; HELICOBACTER-PYLORI; PHARMACY RECORDS; RISK PATIENTS; ASPIRIN USE; PREVENTION; ADHERENCE AB OBJECTIVES: Our aim was to quantify the effect of provider adherence on the risk of NSAID-related upper gastrointestinal events (UGIE). METHODS: We identified from national pharmacy records veterans >= 65 yr prescribed an NSAID, a coxib, or salicylate (> 325 mg/day) at any Veterans Affairs (VA) facility (January 1, 2000 to December 31, 2002). Prescription fill data were linked in longitudinal fashion to VA inpatient, outpatient, and death files and merged with demographic, inpatient, outpatient, and provider data from Medicare. Each person-day of follow-up was assessed for exposure to NSAID alone, NSAID+proton pump inhibitor (PPI), coxib, or coxib+PPI. UGIE was defined using our published, validated algorithm. Unadjusted incidence density ratios were calculated for the 365 days following exposure. We assessed risk of UGIE using Cox proportional hazards models, while adjusting for demographics, UGIE risk factors, comorbidity, prescription channeling (i.e., propensity score), geographic location, and multiple time-dependent pharmacological covariates, including aspirin, steroids, anticoagulants, antiplatelets, statins, and selective serotonin reuptake inhibitors. RESULTS: In our cohort of 481,980 (97.8% male, 85.3% white, mean age 73.9, standard deviation 5.6), a safer strategy was prescribed for 19.8%, and 2,753 UGIE occurred in 220,662 person-years of follow-up. When adjusted for prescription channeling, confounders, and effect modification-associated PPI, risk of UGIE was 1.8 (95% confidence interval [CI] 1.6-2.0) on NSAID alone, :1.8 (95% CI 1.5-2.0) on coxib alone, 1.1 (95% CI 0.7-4.6) on NSAID+PPI, and 1.1 (0.6-5.2) on coxib+PPI. When the analysis was adjusted for cumulative percent time spent on a PPI, risk of UGIE decreased from HR 3.0 (95% CI 2.6-3.7) when a PPI was prescribed 0-20% of the time to 1.1 (95% CI 1.0-1.3) when a PPI was prescribed 80-100% of the time. CONCLUSIONS: Provider adherence to safer NSAID prescribing strategies is associated with fewer UGIE among the elderly. An adherent strategy lowers, but does not eliminate, risk of an NSAID-related UGIE. C1 [Abraham, Neena S.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Abraham, Neena S.] Baylor Coll Med, Houston, TX 77030 USA. [Abraham, Neena S.; Hartman, Christine; Castillo, Diana; Richardson, Peter] Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. [Smalley, Walter] Vanderbilt Univ, Nashville, TN USA. [Smalley, Walter] VA TVHS GRECC, Nashville, TN USA. RP Abraham, NS (reprint author), Michael E DeBakey Vet Affairs Med Ctr, 2002 Holcombe Blvd,152, Houston, TX 77030 USA. NR 40 TC 38 Z9 38 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD FEB PY 2008 VL 103 IS 2 BP 323 EP 332 DI 10.1111/j.1572-0241.2007.01595.x PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 260ZU UT WOS:000253049700011 PM 18289200 ER PT J AU Zhang, BH Mitchell, SL Bambauer, KZ Jones, R Prigerson, HG AF Zhang, Baohui Mitchell, Susan L. Bambauer, Kara Z. Jones, Rich Prigerson, Holly G. TI Depressive symptom trajectories and associated risks among bereaved Alzheimer disease caregivers SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE bereavement; caregiver; depression; trajectory; Alzheimer disease ID DEVELOPMENTAL TRAJECTORIES; SYNDROMAL SYMPTOMS; SOCIAL SUPPORT; DEMENTIA; CHECKLIST; DEATH; CARE AB Objectives: A recent study concluded that depressive symptoms among caregivers decline on average from before to after the Alzheimer disease (AD) patient's death. The present study sought to determine if subgroups of bereaved AD caregivers follow distinctive depressive symptom trajectories and the characteristics associated with membership in depressive symptom subgroups. Design: Latent class mixture models sought to identify clusters of homogeneous participants in the Resources for Enhancing Alzheimer's Caregiver Health study - a multisite, randomized caregiver intervention trial. Participants: One hundred eighty-two community-based bereaved caregivers were included in the study. Measurements: The Center for Epidemiologic Studies Depression Scale assessed depressive symptoms among the AD caregivers at baseline and three follow-up visits. Results: Three postloss depressive symptom trajectories emerged: persistently syndromal depression (N = 30, 16.5%); syndromal-becoming-threshold level depression (N = 62, 34.0%); and persistently absent depression (N = 90, 49.5%). Lower income, higher preloss depression levels, greater caregiver behavioral burden, less family support, and adverse health behaviors (e. g., smoking, skipped meals, and lack of exercise) after loss were risk factors for syndromal and syndromal-becoming-threshold level depression after loss. Conclusions: Early intervention to reduce caregiving behavioral burden and enhance family support and promote healthier behaviors of bereaved AD caregivers may decrease the risk of syndromal or syndromal-becoming-threshold level depression after loss. C1 [Zhang, Baohui; Prigerson, Holly G.] Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 02115 USA. [Mitchell, Susan L.; Jones, Rich] Hebrew Senior Life Inst Aging Res, Boston, MA USA. [Bambauer, Kara Z.] Treatment Res & Evaluat Ctr, Vet Adm Hlth Serv Res & Dev, Ann Arbor, MI USA. [Bambauer, Kara Z.] Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI 48109 USA. [Prigerson, Holly G.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Prigerson, Holly G.] Harvard Univ, Sch Med, Ctr Palliat Care Res, Boston, MA 02115 USA. RP Zhang, BH (reprint author), Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, 44 Binney St,SW G530C, Boston, MA 02115 USA. EM baohui_zhang@dfci.harvard.edu OI Jones, Richard/0000-0002-1049-218X FU NCI NIH HHS [CA106370, R01 CA106370]; NIA NIH HHS [P50 AG05134, R01 AG024091]; NIMH NIH HHS [MH63892, MH56529] NR 31 TC 26 Z9 28 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD FEB PY 2008 VL 16 IS 2 BP 145 EP 155 DI 10.1097/JGP.0b013e318157caec PG 11 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 257MW UT WOS:000252804200007 PM 18192497 ER PT J AU Rodig, SJ Payne, EG Degar, BA Rollins, B Feldman, AL Jaffe, ES Androkites, A Silverman, LB Longtine, JA Kutok, JL Fleming, MD Aster, JC AF Rodig, Scott J. Payne, Ethan G. Degar, Barbara A. Rollins, Barrett Feldman, Andrew L. Jaffe, Elaine S. Androkites, Arlene Silverman, Lewis B. Longtine, Janina A. Kutok, Jeffery L. Fleming, Mark D. Aster, Jon C. TI Aggressive Langerhans cell histiocytosis following T-ALL: Clonally related neoplasms with persistent expression of constitutively active NOTCH1 SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; C-MYC; PRECURSOR; DIFFERENTIATION; PATHWAY; LINEAGE AB Langerhans cell histiocytosis (LCH) and related entities are neoplasms of unknown pathogenesis. Here, we describe studies assessing the role of NOTCH1 mutations in LCH, which were based on a case of fatal Langerhans cell tumor after T-cell acute lymphoblastic leukemia (T-ALL). Although the two types of neoplasm in this patient were temporally and pathologically distinct, molecular analyses showed that they harbored the same T-cell receptor gene rearrangements and two activating NOTCH1 mutations involving exons 27 and 34. The exon 27 mutation altered a conserved cysteine residue in the N-terminal portion of the NOTCH1 heterodimerization domain, while the mutation in exon 34 introduced a premature stop codon that results in the deletion of C-terminal negative regulatory PEST domain. Analysis of cDNA prepared from the aggressive Langerhans cell tumor showed that the NOTCH1 mutations were aligned in cis, a configuration that caused synergistic increases in NOTCH1 signal strength in reporter gene assays. Immunohistochemistry confirmed that the Langerhans cell tumor also expressed NOTCH1 protein. Although these data suggested that NOTCH1 mutations might contribute to the pathogenesis of typical sporadic LCH and related neoplasms occurring in the absence of T-ALL, an analysis of 24 cases of LCH and Rosai-Dorfman Disease occurring in patients without an antecedent history of T-ALL revealed no mutations. Thus, activating NOTCH1 mutations appear to be unique to aggressive Langerhans cell tumors occurring after T-ALL. Persistent expression of NOTCH1 in such tumors suggests that Notch pathway inhibitors could have a role in the treatment of these unusual neoplasms. C1 [Fleming, Mark D.] Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. [Rodig, Scott J.; Payne, Ethan G.; Longtine, Janina A.; Kutok, Jeffery L.; Aster, Jon C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Degar, Barbara A.; Androkites, Arlene; Silverman, Lewis B.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Degar, Barbara A.; Rollins, Barrett] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Feldman, Andrew L.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MI USA. [Jaffe, Elaine S.] Natl Canc Inst, Pathol Lab, Bethesda, MD USA. RP Fleming, MD (reprint author), Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. EM mark.fleming@childrens.harvard.edu; jaster@rics.bwh.harvard.edu RI Feldman, Andrew/D-5028-2012 FU NCI NIH HHS [CA082308, P01 CA119070, P01 CA119070-02]; NIAID NIH HHS [AI050225] NR 21 TC 26 Z9 26 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD FEB PY 2008 VL 83 IS 2 BP 116 EP 121 DI 10.1002/ajh.21044 PG 6 WC Hematology SC Hematology GA 253JG UT WOS:000252513900007 PM 17874453 ER PT J AU Halperin, RO Gaziano, JM Sesso, HD AF Halperin, Ruben O. Gaziano, J. Michael Sesso, Howard D. TI Smoking and the risk of incident hypertension in middle-aged and older men SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article ID NORMOTENSIVE JAPANESE MEN; HIGH BLOOD-PRESSURE; CIGARETTE-SMOKING; CARDIOVASCULAR-DISEASE; HABITUAL SMOKERS; WEIGHT; CESSATION; WOMEN; ASSOCIATION; HEALTH AB BACKGROUND Cigarette smoking is a known risk factor for cardiovascular disease (CVD), but its relationship to the development of hypertension is unclear. Previous epidemiological studies have shown inconsistent results, having demonstrated inverse and positive associations between cigarette smoking and the development of hypertension. METHODS We analyzed 13,529 male participants from the Physicians' Health Study free of baseline hypertension and CVD who provided information about smoking status. Smoking status was categorized as never, past, or current <20 cigarettes/day, or current >= 20 cigarettes/day. Incident hypertension was defined as either the initiation of antihypertensive treatment, self-reported systolic blood pressure (BP) >= 40 mm Hg, or diastolic BP >= 90 mm Hg. RESULTS Over a median follow-up of 14.5 years, 4,904 men developed hypertension. We modeled the risk of developing hypertension by baseline smoking status adjusting for known risk factors for hypertension or CVD. In a fully adjusted Cox proportional hazards model, we found that compared with never smokers, past smokers and current smokers had corresponding relative risks (RRs) of 1.08 and 1.15 of developing hypertension. The risk for smokers did not appear to differ based on number of cigarettes smoked daily. Further, the RR of hypertension was higher for men with normal vs. prehypertensive levels of systolic (SBP) or diastolic BP (DBP). CONCLUSIONS This prospective cohort data suggests that cigarette smoking may be a modest but important risk factor for the development of hypertension. C1 [Halperin, Ruben O.] Providence Portland Med Ctr, Dept Med Educ, Portland, OR 97213 USA. [Halperin, Ruben O.; Gaziano, J. Michael; Sesso, Howard D.] VA Boston Healthcare Syst, Massachusetts Vet Epidemiiol Res & Informat Ctr, Boston, MA USA. [Gaziano, J. Michael; Sesso, Howard D.] Brigham & Womens Hosp, Div Prevent Med, Dept Med, Boston, MA 02115 USA. [Gaziano, J. Michael; Sesso, Howard D.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Gaziano, J. Michael; Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. RP Halperin, RO (reprint author), Providence Portland Med Ctr, Dept Med Educ, Portland, OR 97213 USA. EM ruben.halperin@providence.org FU NCI NIH HHS [CA40360, CA97193, R01 CA097193, CA34944] NR 32 TC 39 Z9 44 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD FEB PY 2008 VL 21 IS 2 BP 148 EP 152 DI 10.1038/ajh.2007.36 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 254XR UT WOS:000252621800011 PM 18174885 ER PT J AU McLennan, S Gillett, G Celi, LA AF McLennan, Stuart Gillett, Grant Celi, Leo Anthony TI Healer, heal thyself: Health care workers and the influenza vaccination SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Editorial Material ID LONG-TERM-CARE; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; IMMUNIZATION RATES; WORKING ADULTS; MORTALITY; TRANSMISSION; INDIVIDUALS; ACCEPTANCE; ATTITUDES C1 [McLennan, Stuart; Gillett, Grant] Univ Otago, Dunedin Sch Med, Ctr Bioeth, Dunedin, New Zealand. [Celi, Leo Anthony] Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA. RP McLennan, S (reprint author), Univ Otago, Dunedin Sch Med, Ctr Bioeth, POB 913, Dunedin, New Zealand. EM stumclennan@hotmail.com RI McLennan, Stuart/C-1048-2015 OI McLennan, Stuart/0000-0002-2019-6253 NR 40 TC 16 Z9 17 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-6553 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD FEB PY 2008 VL 36 IS 1 BP 1 EP 4 DI 10.1016/j.ajic.2007.07.010 PG 4 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 259NY UT WOS:000252947200001 PM 18241729 ER PT J AU Weiner, RB Weiner, SD Yurchak, PM AF Weiner, Rory B. Weiner, Shepard D. Yurchak, Peter M. TI Removing the mask SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID ST-SEGMENT ELEVATION; BUNDLE-BRANCH BLOCK; BRUGADA-SYNDROME; SUDDEN-DEATH; COCAINE; OVERDOSE; PROGRESS; PATTERN C1 [Weiner, Rory B.; Yurchak, Peter M.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Weiner, Rory B.; Yurchak, Peter M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Weiner, Shepard D.] Columbia Univ, Med Ctr, Dept Med, Div Cardiol, New York, NY USA. [Weiner, Shepard D.] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. RP Weiner, RB (reprint author), Massachusetts Gen Hosp, Dept Med, Div Cardiol, GRB 8,55 Fruit St, Boston, MA 02114 USA. EM rweiner@partners.org NR 18 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD FEB PY 2008 VL 121 IS 2 BP 113 EP 116 DI 10.1016/j.amjmed.2007.09.010 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 259RM UT WOS:000252956400008 PM 18261498 ER PT J AU Han, JK Feliciano, Z Bersohn, M AF Han, Janet Konkamol Feliciano, Zenaida Bersohn, Malcolm TI Hidden in plain sight SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID PACEMAKER LEAD C1 [Han, Janet Konkamol; Feliciano, Zenaida; Bersohn, Malcolm] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Dept Cardiol, Los Angeles, CA 90073 USA. RP Han, JK (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Dept Cardiol, 11301 Wilshire Blvd 111E, Los Angeles, CA 90073 USA. EM midge_jkh@yahoo.com NR 6 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD FEB PY 2008 VL 121 IS 2 BP 117 EP 118 DI 10.1016/j.amjmed.2007.08.030 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 259RM UT WOS:000252956400009 PM 18261499 ER PT J AU Soares, CN Joffe, H Viguera, AC Petrillo, L Rydzewski, M Yehezkel, R Somley, B Cohen, LS AF Soares, Claudio N. Joffe, Hadine Viguera, Adele C. Petrillo, Laura Rydzewski, Maya Yehezkel, Revital Somley, Brittny Cohen, Lee S. TI Paroxetine versus placebo for women in midlife after hormone therapy discontinuation SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE depression; hormone therapy; hot flashes; hot flushes; menopause; paroxetine; perimenopause; sleep; vasomotor symptoms; women ID RANDOMIZED CONTROLLED-TRIAL; POSTMENOPAUSAL WOMEN; REPLACEMENT THERAPY; VASOMOTOR SYMPTOMS; DOUBLE-BLIND; DEPRESSION; PERIMENOPAUSAL; ESTRADIOL; IMPACT AB OBJECTIVE: Concerns about hormone therapy have led many menopausal women to discontinue hormone treatment. This study examines the efficacy of paroxetine controlled-release versus placebo for the treatment of women with vasomotor symptoms after discontinuing hormone therapy. METHODS: Sixty-four perimenopausal and postmenopausal women without depression or anxiety but reporting vasomotor symptoms after hormone discontinuation entered a 1-week, single-blind, placebo lead-in phase, followed by a 6-week, flexible-dose, double-blind phase with paroxetine controlled-release (12.5-25 mg/d) or placebo. The primary outcome measure was a change in vasomotor symptoms. Other measures included changes in depressive symptoms and overall functioning. RESULTS: Fifty subjects (paroxetine controlled-release, n = 27; placebo, n = 23) completed the study. At study entry, subjects had an average of 17 hot flushes per week, had used hormones for more than 5 years (median = 66 months, interquartile range = 18-120 months), and had discontinued treatment for less than 1 year (median = 5 months, interquartile range = 2-10 months) before study enrollment. Paroxetine controlled-release was more efficacious than placebo for the alleviation of vasomotor symptoms (mean reduction of 6.1 vs 2.8 hot flashes per week, respectively; P =.03). Depressive symptoms also improved with paroxetine (mean reduction of 3.6 points vs 0.4 points in Montgomery-Asberg Depression Rating Scale total scores; P =.01). CONCLUSION: Treatment with paroxetine controlled-release may constitute an efficacious alternative for symptomatic perimenopausal and postmenopausal women after menopausal hormone discontinuation. (c) 2008 Elsevier Inc. All rights reserved. C1 [Soares, Claudio N.; Joffe, Hadine; Viguera, Adele C.; Petrillo, Laura; Rydzewski, Maya; Yehezkel, Revital; Somley, Brittny; Cohen, Lee S.] Massachusetts Gen Hosp, Perinatal & Reprod Psychiat Program, Boston, MA 02114 USA. [Soares, Claudio N.] McMaster Univ, Womens Hlth Concerns Clin, Dept Psychiat & Behav Neurosci, Hamilton, ON, Canada. RP Soares, CN (reprint author), Massachusetts Gen Hosp, Perinatal & Reprod Psychiat Program, Boston, MA 02114 USA. EM csoares@mcmaster.ca NR 13 TC 22 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD FEB PY 2008 VL 121 IS 2 BP 159 EP U12 DI 10.1016/j.amjmed.2007.10.007 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 259RM UT WOS:000252956400029 PM 18261506 ER PT J AU Valaikiene, J Schuierer, G Ziennus, B Dietrich, J Bogdahn, U Schlachetzki, F AF Valaikiene, J. Schuierer, G. Ziennus, B. Dietrich, J. Bogdahn, U. Schlachetzki, F. TI Transcranial color-coded duplex sonography for detection of distal internal carotid artery stenosis SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID INTRACRANIAL VASCULAR-DISEASE; CEREBROVASCULAR-DISEASE; MUSICAL MURMURS; MR-ANGIOGRAPHY; ANGIOPLASTY; SIPHON; ATHEROSCLEROSIS; ENDARTERECTOMY; STROKE; LIMITATIONS AB BACKGROUND AND PURPOSE: Gradation of high-grade intracranial internal carotid artery (ICA) stenosis poses a challenge to noninvasive neurovascular imaging, which seems critical for angioplasty in the ICA segments C1 and C5. We investigated cutoff values of intracranial ICA stenosis for transcranial color-coded sonography (TCCS) and compared this method with the "gold standard," digital subtraction angiography (DSA). MATERIALS AND METHODS: Forty patients (mean age, 58.9 +/- 13.8 years) with intracranial ICA lesions were prospectively examined by using TCCS and DSA. Two standard TCCS coronal imaging planes were used to evaluate the intracranial ICA. In addition, a control group of 128 volunteers without cerebrovascular disease (mean age, 48.8 +/- 15.9 years) was investigated to establish standard velocity values. RESULTS: DSA confirmed 96 stenoses and 8 occlusions of the intracranial ICA in the study population. in 9% and 7% of cases, stenosis confined to the C1 or C5 segment was > 50% and 70%, respectively. Receiver-operating curves demonstrated cutoff values for > 70% stenosis in C1 when the peak systolic velocity (PSV) was > 200 cm/s (specificity, 100%; sensitivity, 71 %) or the C1/submandibular ICA index was > 3 (specificity, 93%; sensitivity, 86%). CONCLUSIONS: TCCS is a reliable adjunctive method to detect and quantify significant stenosis of the intracranial ICA. The assessment of the C1/ICA index and peak systolic velocities maximizes the diagnostic accuracy of C1 stenosis to > 70% when extracranial ICA stenosis coexists. Further studies need to be performed to compare the diagnostic accuracies of MR angiography and TCCS with that of DSA. C1 [Valaikiene, J.] Vilnius Univ Hosp, Santariskiu Klin, Dept Neurol, Vilnius, Lithuania. [Schuierer, G.] Bezirksklin Regensburg, Inst Neuroradiol, Regensburg, Germany. [Ziennus, B.; Bogdahn, U.; Schlachetzki, F.] Univ Regensburg, Dept Neurol, Regensburg, Germany. [Dietrich, J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. RP Schlachetzki, F (reprint author), Univ Regensburg, Dept Neurol, Univstr 84, D-93053 Regensburg, Germany. EM felix.schlachetzki@klinik.uni-regensburg.de NR 47 TC 8 Z9 10 U1 0 U2 4 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD FEB PY 2008 VL 29 IS 2 BP 347 EP 353 DI 10.3174/ajnr.A0789 PG 7 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 265FT UT WOS:000253345200033 PM 18024581 ER PT J AU Huyck, KL Panhuysen, CIM Cuenco, KT Zhang, JM Goldhammer, H Jones, ES Somasundaram, P Lynch, AM Harlow, BL Lee, H Stewart, EA Morton, CC AF Huyck, Karen L. Panhuysen, Carolien I. M. Cuenco, Karen T. Zhang, Jingmei Goldhammer, Hilary Jones, Emlyn S. Somasundaram, Priya Lynch, Allison M. Harlow, Bernard L. Lee, Hang Stewart, Elizabeth A. Morton, Cynthia C. TI The impact of race as a risk factor for symptom severity and age at diagnosis of uterine leiomyomata among affected sisters SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE family study; fibroids; racial differences; symptom severity; uterine leiomyomata ID FUMARATE HYDRATASE; FIBROIDS; MUTATIONS; ETIOLOGY; CANCER AB OBJECTIVE: The objective of the study was to identify risk factors for uterine leiomyomata (UL) in a racially diverse population of women with a family history of UL, and to evaluate their contribution to disease severity and age at diagnosis. STUDY DESIGN: We collected and analyzed epidemiologic data from 285 sister pairs diagnosed with UL. Risk factors for UL-related outcomes were compared among black (n = 73) and white (n = 212) sister pairs using univariate and multivariate regression models. RESULTS: Black women reported an average age at diagnosis of 5.3 years younger (SE, 1.1; P < .001) and were more likely to report severe disease (odds ratio, 5.22; 95% confidence interval, 1.99-13.7, P <.001) than white women of similar socioeconomic status. CONCLUSION: Self-reported race is a significant factor in the severity of UL among women with a family history of UL. Differences in disease presentation between races likely reflect underlying genetic heterogeneity. The affected sister-pair study design can address both epidemiological and genetic hypotheses about UL. C1 [Goldhammer, Hilary; Jones, Emlyn S.; Somasundaram, Priya; Lynch, Allison M.; Harlow, Bernard L.; Stewart, Elizabeth A.; Morton, Cynthia C.] Brigham & Womens Hosp, Dept Obstet, Boston, MA 02115 USA. [Goldhammer, Hilary; Jones, Emlyn S.; Somasundaram, Priya; Lynch, Allison M.; Harlow, Bernard L.; Stewart, Elizabeth A.; Morton, Cynthia C.] Brigham & Womens Hosp, Dept Gynecol, Boston, MA 02115 USA. [Goldhammer, Hilary; Jones, Emlyn S.; Somasundaram, Priya; Lynch, Allison M.; Harlow, Bernard L.; Stewart, Elizabeth A.; Morton, Cynthia C.] Brigham & Womens Hosp, Dept Reprod Biol, Boston, MA 02115 USA. [Morton, Cynthia C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Harlow, Bernard L.] Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA. [Lee, Hang] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. [Lee, Hang] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Lee, Hang] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Huyck, Karen L.] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA. [Panhuysen, Carolien I. M.; Cuenco, Karen T.; Zhang, Jingmei] Boston Univ, Sch Med, Dept Med, Genet Program, Boston, MA 02118 USA. RP Morton, CC (reprint author), Brigham & Womens Hosp, Dept Obstet, 77 Ave Louis Pasteur,HNRB Room 160, Boston, MA 02115 USA. EM cmorton@partners.org FU NCI NIH HHS [P30 CA006516, P30 CA06516]; NICHD NIH HHS [HD046226, R01 HD046226, R01 HD046226-01, R01 HD046226-02, R01 HD046226-03, R01 HD046226-04, R01 HD046226-05] NR 25 TC 8 Z9 9 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD FEB PY 2008 VL 198 IS 2 AR 168.e1 DI 10.1016/j.ajog.2007.05.038 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 268NU UT WOS:000253587300006 PM 18226615 ER PT J AU Pastor-Soler, NM Hallows, KR Smolak, C Gong, F Brown, D Breton, S AF Pastor-Soler, Nuria M. Hallows, Kenneth R. Smolak, Christy Gong, Fan Brown, Dennis Breton, Sylvie TI Alkaline pH- and cAMP-induced V-ATPase membrane accumulation is mediated by protein kinase A in epididymal clear cells SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE vas deferens; Epac; protein kinase inhibitor ID MALE REPRODUCTIVE-TRACT; VACUOLAR H+-ATPASE; MEDULLARY COLLECTING DUCT; PROTON SECRETION; CYCLIC-AMP; AQUAPORIN-2 TRAFFICKING; VAS-DEFERENS; F-ACTIN; EPAC; ACIDIFICATION AB In the epididymis, low luminal bicarbonate and acidic pH maintain sperm quiescent during maturation and storage. The vacuolar H+-ATPase (V-ATPase) in epididymal clear cells plays a major role in luminal acidification. We have shown previously that cAMP, luminal alkaline pH, and activation of the bicarbonate-regulated soluble adenylyl cyclase (sAC) induce V-ATPase apical accumulation in these cells, thereby stimulating proton secretion into the epididymal lumen. Here we examined whether protein kinase A (PKA) is involved in this response. Confocal immunofluorescence labeling on rat epididymis perfused in vivo showed that at luminal acidic pH (6.5), V-ATPase was distributed between short apical microvilli and subapical endosomes. The specific PKA activator N-6-monobutyryl-3'-5'-cyclic monophosphate (6-MB-cAMP, 1 mM) induced elongation of apical microvilli and accumulation of V-ATPase in these structures. The PKA inhibitor myristoylated-PKI (mPKI, 10 mu M) inhibited the apical accumulation of V-ATPase induced by 6-MB-cAMP. Perfusion at pH 6.5 with 8-(4-chlorophenylthio)-2-O-methyl-cAMP (8CPT-2-O-Me-cAMP; 10 mu M), an activator of the exchange protein activated by cAMP (Epac), did not induce V-ATPase apical accumulation. When applied at a higher concentration (100 mu M), 8CPT-2-O-Me-cAMP induced V-ATPase apical accumulation, but this effect was completely inhibited by mPKI, suggesting crossover effects on the PKA pathway with this compound at high concentrations. Importantly, the physiologically relevant alkaline pH-induced apical V-ATPase accumulation was completely inhibited by pretreatment with mPKI. We conclude that direct stimulation of PKA activity by cAMP is necessary and sufficient for the alkaline pH-induced accumulation of V-ATPase in clear cell apical microvilli. C1 [Pastor-Soler, Nuria M.; Hallows, Kenneth R.; Smolak, Christy; Gong, Fan] Univ Pittsburgh, Sch Med, Div Renal Electrolyte, Dept Med, Pittsburgh, PA 15263 USA. [Hallows, Kenneth R.] Univ Pittsburgh, Sch Med, Dept Cell Biol & Physiol, Pittsburgh, PA 15263 USA. [Pastor-Soler, Nuria M.] Univ Pittsburgh, Sch Med, Ctr Res Reprod Physiol, Dept Cell Biol & Physiol, Pittsburgh, PA 15263 USA. [Brown, Dennis; Breton, Sylvie] Harvard Univ, Sch Med, Program Membrane Biol, Boston, MA 02115 USA. [Brown, Dennis; Breton, Sylvie] Harvard Univ, Sch Med, Dept Med, Nephrol Div,Ctr Syst Biol,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Pastor-Soler, NM (reprint author), Univ Pittsburgh, Sch Med, Div Renal Electrolyte, Dept Med, A915 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15263 USA. EM pastorn@dom.pitt.edu RI gong, fan/F-2376-2010; Li, Hui/J-9884-2013; gong, fan/K-6004-2013 FU NICHD NIH HHS [R01 HD040793, K08 HD-045524, K08 HD045524, R01 HD-40793]; NIDDK NIH HHS [P01 DK-38452, P01 DK038452, R01 DK-075048, R01 DK-42956, R01 DK042956, R01 DK075048, R01 DK075048-01A1] NR 47 TC 61 Z9 61 U1 0 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD FEB PY 2008 VL 294 IS 2 BP C488 EP C494 DI 10.1152/ajpcell.00537.2007 PG 7 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 263DD UT WOS:000253196900013 PM 18160485 ER PT J AU Deschamps, AM Zavadzkas, J Murphy, RL Koval, CN McLean, JE Jeffords, L Saunders, SM Sheats, NJ Stroud, RE Spinale, FG AF Deschamps, Anne M. Zavadzkas, Juozas Murphy, Rebecca L. Koval, Christine N. McLean, Julie E. Jeffords, Laura Saunders, Stuart M. Sheats, Nina J. Stroud, Robert E. Spinale, Francis G. TI Interruption of endothelin signaling modifies membrane type 1 matrix metalloproteinase activity during ischemia and reperfusion SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE myocardial interstitium; microdialysis; protein kinase C; phosphorylation; ischemia-reperfusion ID PROTEIN-KINASE-C; ACUTE MYOCARDIAL-INFARCTION; CARDIOPLEGIC ARREST; TISSUE INHIBITOR; HEART-FAILURE; CELL-SURFACE; ACTIVATION; EXPRESSION; MT1-MMP; MYOCYTE AB The matrix metalloproteinases ( MMPs), in particular, membrane type 1 MMP (MT1-MMP), are increased in the context of myocardial ischemia and reperfusion (I/R) and likely contribute to myocardial dysfunction. One potential upstream induction mechanism for MT1-MMP is endothelin (ET) release and subsequent protein kinase C (PKC) activation. Modulation of ET and PKC signaling with respect to MT1-MMP activity with I/R has yet to be explored. Accordingly, this study examined in vivo MT1-MMP activation during I/R following modification of ET signaling and PKC activation. With the use of a novel fluorogenic microdialysis system, myocardial interstitial MT1-MMP activity was measured in pigs ( 30 kg; n = 9) during I/R (90 min I/120 min R). Local ETA receptor antagonism (BQ-123, 1 mu M) and PKC inhibition (chelerythrine, 1 mu M) were performed in parallel microdialysis probes. MT1-MMP activity was increased during I/R by 122 +/- 10% ( P < 0.05) and was unchanged from baseline with ET antagonism and/or PKC inhibition. Selective PKC isoform induction occurred such that PKC-beta II increased by 198 +/- 31% ( P < 0.05). MT1-MMP phosphothreonine, a putative PKC phosphorylation site, was increased by 121 +/- 8% ( P < 0.05) in the I/R region. These studies demonstrate for the first time that increased interstitial MT1-MMP activity during I/ R is a result of the ET/ PKC pathway and may be due to enhanced phosphorylation of MT1-MMP. These findings identify multiple potential targets for modulating a local proteolytic pathway operative during I/R. C1 [Deschamps, Anne M.; Zavadzkas, Juozas; Murphy, Rebecca L.; Koval, Christine N.; McLean, Julie E.; Jeffords, Laura; Saunders, Stuart M.; Sheats, Nina J.; Stroud, Robert E.; Spinale, Francis G.] Med Univ S Carolina, Div Cardiothorac Surg, Charleston, SC 29403 USA. [Spinale, Francis G.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Spinale, FG (reprint author), Med Univ S Carolina, 114 Doughty St,Rm 625,Strom Thurmond Res Bldg, Charleston, SC 29403 USA. EM wilburnm@musc.edu OI Deschamps, Anne/0000-0001-7415-1408 FU NHLBI NIH HHS [HL-57952, HL-07260, HL-45024, HL-59165, HL-97012, P01 HL048788, P01-HL-48788, R01 HL057952, R01 HL057952-09, R01 HL059165, R03 HL097012, T32 HL007260] NR 48 TC 12 Z9 12 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD FEB PY 2008 VL 294 IS 2 BP H875 EP H883 DI 10.1152/ajpheart.00918.2007 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 261IN UT WOS:000253072400039 PM 18065523 ER PT J AU Petersen, B Bloch, KD Ichinose, F Shin, HS Shigematsu, M Bagchi, A Zapol, WM Hellman, J AF Petersen, Bodil Bloch, Kenneth D. Ichinose, Fumito Shin, Hae-Sook Shigematsu, Misako Bagchi, Aranya Zapol, Warren M. Hellman, Judith TI Activation of Toll-like receptor 2 impairs hypoxic pulmonary vasoconstriction in mice SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE hypoxic pulmonary vasoconstriction impairment; lung inflammation; sepsis ID PEPTIDOGLYCAN-ASSOCIATED LIPOPROTEIN; VASCULAR SMOOTH-MUSCLE; MEMBRANE PROTEIN-A; ALVEOLAR EPITHELIAL-CELLS; GRAM-NEGATIVE SEPSIS; ACETYL-L-CYSTEINE; MUREIN LIPOPROTEIN; SEPTIC SHOCK; BLOOD-STREAM; N-ACETYLCYSTEINE AB Toll-like receptors (TLRs) mediate inflammation in sepsis, but their role in sepsis-induced respiratory failure is unknown. Hypoxic pulmonary vasoconstriction (HPV) is a unique vasoconstrictor response that diverts blood flow away from poorly ventilated lung regions. HPV is impaired in sepsis and after challenge with the TLR4 agonist lipopolysaccharide (LPS). Unlike TLR4 agonists, which are present only in Gram-negative bacteria, TLR2 agonists are ubiquitously expressed in all of the major classes of microorganisms that cause sepsis, including both Gram-positive and Gram-negative bacteria and fungi. We tested the hypothesis that (S)-[ 2,3-bis(palmitoyloxy)-(2RS)-propyl]-N-palmi-toyl-(R)-Cys-(S)-Ser(S)-Lys(4)-OH, trihydrochloride (Pam3Cys), a TLR2 agonist, impairs HPV and compared selected pulmonary and systemic effects of Pam3Cys vs. LPS. HPV was assessed 22 h after challenge with saline, Pam3Cys, or LPS by measuring the increase in the pulmonary vascular resistance of the left lung before and during left lung alveolar hypoxia produced by left mainstem bronchus occlusion (LMBO). Additional endpoints included arterial blood gases during LMBO, hemodynamic parameters, weight loss, temperature, physical appearance, and several markers of lung inflammation. Compared with saline, challenge with Pam3Cys caused profound impairment of HPV, reduced systemic arterial oxygenation during LMBO, weight loss, leukopenia, and lung inflammation. In addition to these effects, LPS-challenged mice had lower rectal temperatures, metabolic acidosis, and were more ill appearing than Pam3Cys-challenged mice. These data indicate that TLR2 activation impairs HPV and induces deleterious systemic effects in mice and suggest that TLR2 pathways may be important in sepsis-induced respiratory failure. C1 [Petersen, Bodil; Bloch, Kenneth D.; Ichinose, Fumito; Shin, Hae-Sook; Shigematsu, Misako; Bagchi, Aranya; Zapol, Warren M.; Hellman, Judith] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Bloch, Kenneth D.; Hellman, Judith] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. RP Hellman, J (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM jhellman@partners.org FU NHLBI NIH HHS [HL 42397, HL 71987, HL 74352]; NIAID NIH HHS [AI 058106] NR 44 TC 11 Z9 12 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 EI 1522-1504 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD FEB PY 2008 VL 294 IS 2 BP L300 EP L308 DI 10.1152/ajplung.00243.2007 PG 9 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 261GP UT WOS:000253067400019 PM 18055842 ER PT J AU Mehta, NK Chang, VW AF Mehta, Neil K. Chang, Virginia W. TI Weight status and restaurant availability - A multilevel analysis SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID FACTOR SURVEILLANCE SYSTEM; FAST-FOOD RESTAURANTS; BODY-MASS INDEX; US ADULTS; PHYSICAL-ACTIVITY; OBESITY; HEALTH; NEIGHBORHOOD; PREVALENCE; ENVIRONMENT AB Background: Empiric studies find that contextual factors affect individual weight status over and above individual socioeconomic characteristics. Given increasing levels of obesity, researchers are examining how the food environment contributes to unhealthy weight status. An important change to this environment is the increasing availability of away-from-home eating establishments such as restaurants. Methods: This study analyzed the relationship between the restaurant environment and weight status across counties in the United States. Individual data from the 2002-2006 Behavioral Risk Factor Surveillance System (N=714,054) were linked with restaurant data from the 2002 U.S. Economic Census. Fast-food and full-service restaurant density, along with restaurant mix (the ratio of fast-food to full-service restaurants), were assessed. Results: Fast-food restaurant density and a higher ratio of fast-food to full-service restaurants were associated with higher individual-level weight status (BMI and the risk of being obese). In contrast, a higher density of full-service restaurants was associated with lower weight status. Conclusions: Area-level restaurant mix emerged as an important correlate of weight status, with components of the restaurant environment exhibiting differential associations. Hence, it is the availability of fast-food relative to other away from-home choices that appears salient for unhealthy weight outcomes. Areas with a high density of full-service restaurants were indicative of a more healthful eating environment, suggesting a need for research into the comparative healthfulness of foods served at different types of restaurants. Future prospective studies are required to delineate causal pathways. C1 [Mehta, Neil K.; Chang, Virginia W.] Univ Penn, Ctr Populat Studies, Grad Grp Demog, Philadelphia, PA 19104 USA. [Chang, Virginia W.] Univ Penn, Dept Sociol, Philadelphia, PA 19104 USA. [Chang, Virginia W.] Univ Penn, Sch Med, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Chang, Virginia W.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. RP Mehta, NK (reprint author), Univ Penn, Ctr Populat Studies, Grad Grp Demog, 239 MvNeil Bldg,3718 Locust Walk, Philadelphia, PA 19104 USA. EM nmehta@sas.upenn.edu FU NIA NIH HHS [T32 AG000177-19, T32 AG000177]; NICHD NIH HHS [K12 HD043459, K12HD043459] NR 43 TC 120 Z9 124 U1 4 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD FEB PY 2008 VL 34 IS 2 BP 127 EP 133 DI 10.1016/j.amepre.2007.09.031 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 256VP UT WOS:000252758300006 PM 18201642 ER PT J AU Nuechterlein, KH Green, MF Kern, RS Baade, LE Barch, DM Cohen, JD Essock, S Fenton, WS Frese, FJ Gold, JM Goldberg, T Heaton, RK Keefe, RSE Kraemer, H Mesholam-Gately, R Seidman, LJ Stover, E Weinberger, DR Young, AS Zalcman, S Marder, SR AF Nuechterlein, Keith H. Green, Michael F. Kern, Robert S. Baade, Lyle E. Barch, Deanna M. Cohen, Jonathan D. Essock, Susan Fenton, Wayne S. Frese, Frederick J., III Gold, James M. Goldberg, Terry Heaton, Robert K. Keefe, Richard S. E. Kraemer, Helena Mesholam-Gately, Raquelle Seidman, Larry J. Stover, Ellen Weinberger, Daniel R. Young, Alexander S. Zalcman, Steven Marder, Stephen R. TI The MATRICS consensus cognitive battery, part 1: Test selection, reliability, and validity SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID SEVERE MENTAL-ILLNESS; IMPROVE COGNITION; SCHIZOPHRENIA; SUPPORT; REHABILITATION; PERFORMANCE; PROGRAMS; MEMORY; SCALE AB Objective: The lack of an accepted standard for measuring cognitive change in schizophrenia has been a major obstacle to regulatory approval of cognition-enhancing treatments. A primary mandate of the National institute of Mental Health's Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative was to develop a consensus cognitive battery for clinical trials of cognition-enhancing treatments for schizophrenia through a broadly based scientific evaluation of measures. Method: The MATRICS Neurocognition Committee evaluated more than 90 tests in seven cognitive domains to identify the 36 most promising measures. A separate expert panel evaluated the degree to which each test met specific selection criteria. Twenty tests were selected as a beta battery. The beta battery was administered to 176 individuals with schizophrenia and readministered to 167 of them 4 weeks later so that the 20 tests could be compared directly. Results: The expert panel ratings are presented for the initially selected 36 tests. For the beta battery tests, data on test-retest reliability, practice effects, relationships to functional status, practicality, and tolerability are presented. Based on these data, 10 tests were selected to represent seven cognitive domains in the MATRICS Consensus Cognitive Battery. Conclusions: The structured consensus method was a feasible and fair mechanism for choosing candidate tests, and direct comparison of beta battery tests in a common sample allowed selection of a final consensus battery. The MATRICS Consensus Cognitive Battery is expected to be the standard tool for assessing cognitive change in clinical trials of cognition-enhancing drugs for schizophrenia. it may also aid evaluation of cognitive remediation strategies. C1 [Nuechterlein, Keith H.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Geffen Sch Med, Dept Psychol, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Kansas, Sch Med, Wichita, KS 67214 USA. Washington Univ, Dept Psychol, St Louis, MO 63130 USA. Washington Univ, Dept Psychiat, St Louis, MO 63130 USA. Princeton Univ, Dept Psychol, Princeton, NJ 08544 USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr, Bronx, NY USA. NIMH, Bethesda, MD 20892 USA. Northeastern Ohio Univ Coll Med & Pharm, Dept Psychiat, Rootstown, OH 44272 USA. Univ Maryland, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. Zucker Hillside Hosp, Psychiat Res Div, Glen Oaks, NY USA. Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA. Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. Beth Israel Deaconess Med Ctr, Div Publ Psychiat, Massachusetts Mental Hlth Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Nuechterlein, KH (reprint author), Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Geffen Sch Med, 300 Med Plaza,Rm 2251, Los Angeles, CA 90095 USA. EM keithn@ucla.edu RI Barch, Deanna/G-8638-2013; Young, Alexander/A-1523-2009 OI Young, Alexander/0000-0002-9367-9213 FU NIMH NIH HHS [N01MH22006] NR 37 TC 607 Z9 624 U1 5 U2 46 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD FEB PY 2008 VL 165 IS 2 BP 203 EP 213 DI 10.1176/appi.ajp.2007.07010042 PG 11 WC Psychiatry SC Psychiatry GA 260ZV UT WOS:000253049800012 PM 18172019 ER PT J AU Kern, RS Nuechterlein, KH Green, MF Laade, LE Fenton, WS Gold, JM Keefe, RSE Mesholam-Gately, R Mintz, J Seidman, LJ Stover, E Marder, SR AF Kern, Robert S. Nuechterlein, Keith H. Green, Michael F. Laade, Lyle E. Fenton, Wayne S. Gold, James M. Keefe, Richard S. E. Mesholam-Gately, Raquelle Mintz, Jim Seidman, Larry J. Stover, Ellen Marder, Stephen R. TI The MATRICS consensus cognitive battery, part 2: Co-norming and standardization SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID CLINICAL-TRIALS; SCHIZOPHRENIA; NEUROPSYCHOLOGISTS; PERFORMANCE AB Objective: The consensus cognitive battery developed by the National Institute of Mental Health's (NIMH's) Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative includes 10 independently developed tests that are recommended as the standard battery for clinical trials of cognition-enhancing interventions for schizophrenia. To facilitate interpretation of results from the MATRICS Consensus Cognitive Battery using a common scaling across tests, normative data were obtained from a single representative U.S. community sample with the battery administered as a unit. Method: The MATRICS Consensus Cognitive Battery was administered to 300 individuals from the general community at five sites in differing geographic regions. For each site, recruitment was stratified by age, gender, and education. A scientific survey sampling method was used to help avoid sampling bias. The battery was administered in a standard order to each participant in a single session lasting approximately 60 minutes. Descriptive data were generated, and age, gender, and education effects on performance were examined. Results: Prominent age and education effects were observed across tests. The results for gender differed by measure, suggesting the need for age and gender corrections in clinical trials. The MATRICS Consensus Cognitive Battery components were co-normed, with allowance for demographic corrections. Conclusions: Co-norming a battery such as the MATRICS Consensus Cognitive Battery, comprising tests from independent test developers each with their own set of norms, facilitates valid interpretation of test scores and communication of findings across studies. These normative data will aid in estimating the magnitude of change during clinical trials of cognition-enhancing agents and make it possible to derive more directly interpretable composite scores. C1 Univ Calif Los Angeles, Geffen Sch Med, Dept Psychol, Los Angeles, CA USA. Univ Calif Los Angeles, Geffen Sch Med, Semel Inst Neurosci & Human Behav, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Kansas, Sch Med, Wichita, KS 67214 USA. Univ Maryland, Dept Psychiat, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. NIMH, Bethesda, MD 20892 USA. Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA. Beth Israel Deaconess Med Ctr, Div Publ Psychiat, Massachusetts Mental Hlth Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Kern, RS (reprint author), VA Greater Los Angeles Healthcare Ctr, MIRECC 210 A,Bldg 210,Rm 116,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM rkern@ucla.edu FU NIMH NIH HHS [N01MH22006] NR 28 TC 183 Z9 195 U1 3 U2 12 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD FEB PY 2008 VL 165 IS 2 BP 214 EP 220 DI 10.1176/appi.ajp.2007.07010043 PG 7 WC Psychiatry SC Psychiatry GA 260ZV UT WOS:000253049800013 PM 18172018 ER PT J AU Green, MF Nuechterlein, KH Kern, RS Baade, LE Fenton, WS Gold, JM Keefe, RSE Mesholam-Gately, R Seidman, L Stover, E Marder, SR AF Green, Michael F. Nuechterlein, Keith H. Kern, Robert S. Baade, Lyle E. Fenton, Wayne S. Gold, James M. Keefe, Richard S. E. Mesholam-Gately, Raquelle Seidman, LarryJ Stover, Ellen Marder, Stephen R. TI Functional co-primary measures for clinical trials in schizophrenia: Results from the MATRICS psychometric and standardization study SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID COGNITION; PERFORMANCE; PROGRAMS; CAPACITY; WORKSHOP; SUPPORT; SCALE AB Objective: During the consensus meetings of the National Institute of Mental Health Measurement and Treatment Research to Improve Cognition in Schizophrenia (NIMH-MATRICS) Initiative, the U.S. Food and Drug Administration took the position that a drug for this purpose should show changes on 1) an accepted consensus cognitive performance measure and 2) an additional measure (i. e., a co-primary) that is considered functionally meaningful. The goal of the current study was to describe steps to evaluate four potential co-primary measures for psychometric properties and validity. Method: As part of the five-site MATRICS Psychometric and Standardization Study (PASS), two measures of functional capacity and two interview-based measures of cognition were evaluated in 176 patients with schizophrenia (167 of these patients were retested 4 weeks later). Results: Data are presented for each co-primary measure for test-retest reliability, utility as a repeated measure, relationship to cognitive performance, relationship to functioning, tolerability/practicality, and number of missing data. Conclusions: Psychometric properties of all of the measures were considered acceptable, and the measures were generally comparable across the various criteria, except that the functional capacity measures had stronger relationships to cognitive performance and fewer missing data. The development and evaluation of potential co-primary measures is still at an early stage, and it was decided not to endorse a single measure for clinical trials at this point. The current findings offer the initial steps to identify functionally meaningful co-primary measures in this area and will help to guide further evaluation of such measures. C1 [Green, Michael F.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Geffen Sch Med, Dept Psychol, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Kansas, Sch Med, Wichita, KS 67214 USA. NIMH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA. Beth Israel Deaconess Med Ctr, Dept Psychiat, Massachusetts Mental Hlth Ctr, Publ Psychiat Div, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Green, MF (reprint author), Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Geffen Sch Med, 300 Med Plaza,Rm 2263, Los Angeles, CA 90095 USA. EM mgreen@ucla.edu FU NIMH NIH HHS [N01MH22006] NR 21 TC 112 Z9 119 U1 5 U2 11 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD FEB PY 2008 VL 165 IS 2 BP 221 EP 228 DI 10.1176/appi.ajp.2007.07010089 PG 8 WC Psychiatry SC Psychiatry GA 260ZV UT WOS:000253049800014 PM 18172017 ER PT J AU Eddy, KT Dorer, DL Franko, DL Tahilani, K Thompson-Brenner, H Herzog, DB AF Eddy, Kamryn T. Dorer, David. L. Franko, Debra L. Tahilani, Kavita Thompson-Brenner, HeathEr Herzog, David B. TI Diagnostic crossover in anorexia nervosa and bulimia nervosa: Implications for DSM-V SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 160th Annual Meeting of the American-Psychiatric-Association CY MAY 19-24, 2007 CL San Diego, CA SP Amer Psychiat Assoc ID EATING-DISORDERS; FOLLOW-UP; OUTCOME PREDICTORS; 12-YEAR COURSE; RECOVERY; RELAPSE; WOMEN; IV AB Objective: The Diagnostic and Statistical Manual of Mental Disorders (DSM) is designed primarily as a clinical tool. Yet high rates of diagnostic "crossover" among the anorexia nervosa subtypes and bulimia nervosa may reflect problems with the validity of the current diagnostic schema, thereby limiting its clinical utility. This study was designed to examine diagnostic crossover longitudinally in anorexia nervosa and bulimia nervosa to inform the validity of the DSM-IV-TR eating disorders classification system. Method: A total of 216 women with a diagnosis of anorexia nervosa or bulimia nervosa were followed for 7 years; weekly eating disorder symptom data collected using the Eating Disorder Longitudinal interval Follow-Up Examination allowed for diagnoses to be made throughout the follow-up period. Results: Over 7 years, the majority of women with anorexia nervosa experienced diagnostic crossover: more than half crossed between the restricting and binge eating/purging anorexia nervosa subtypes over time; one-third crossed over to bulimia nervosa but were likely to relapse into anorexia nervosa. Women with bulimia nervosa were unlikely to cross over to anorexia nervosa. Conclusions: These findings support the longitudinal distinction of anorexia nervosa and bulimia nervosa but do not support the anorexia nervosa subtyping schema. C1 [Eddy, Kamryn T.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02214 USA. Northeastern Univ, Dept Counseling & Appl Educ Psychol, Boston, MA 02115 USA. Boston Univ, Ctr Anxiety & Related Disorders, Boston, MA 02215 USA. RP Eddy, KT (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 2 Longfellow Pl,Suite 200, Boston, MA 02214 USA. EM keddy@partners.org FU NIDDK NIH HHS [P30 DK040561, P30 DK040561-12]; NIMH NIH HHS [5R01-MH-38333-05, R01 MH038333] NR 19 TC 151 Z9 154 U1 6 U2 39 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD FEB PY 2008 VL 165 IS 2 BP 245 EP 250 DI 10.1176/appi.ajp.2007.07060951 PG 6 WC Psychiatry SC Psychiatry GA 260ZV UT WOS:000253049800017 PM 18198267 ER PT J AU Bluthenthal, RN Heinzerling, KG Anderson, R Flynn, NM Kral, AH AF Bluthenthal, Ricky N. Heinzerling, Keith G. Anderson, Rachel Flynn, Neil M. Kral, Alex H. TI Approval of syringe exchange programs in California: Results from a local approach to HIV prevention SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID UNITED-STATES; NEEDLE-EXCHANGE; ACCESS; INFECTIONS; RISK AB Objectives. We studied the effect of local approval of syringe exchange programs in California (through Assembly AB136) on program availability and performance. Methods. We determined the number of active syringe exchange programs in California by conducting Internet searches and obtaining information from the state and from local programs. To track changes in program availability and performance between 2000 and 2002, we interviewed 24 program directors annually for 3 years about program characteristics, syringe exchange policies, law enforcement contact, and other issues. We conducted multivariate analyses to determine whether AB136 approval status was associated with changes in performance. Results. Fifteen local governments (13 counties and 2 cities) enacted the new law by 2002, and operating syringe exchange programs increased from 24 to 35. The proportion of these programs that were not locally approved declined from 54% to 40%. No new approved programs were started in high-need counties. Total syringes exchanged increased by more than 1 million per year, average annual budgets increased by more than 50%, and police harassment of the program volunteers, clients, and operators declined. Improvements at approved syringe exchange programs accounted for these changes. Conclusions. Statewide approval and funding appears necessary to further syringe exchange availability in California. C1 [Bluthenthal, Ricky N.] RAND Corp, Hlth Program, Santa Monica, CA 90407 USA. [Bluthenthal, Ricky N.] RAND Corp, Drug Policy Res Ctr, Santa Monica, CA 90407 USA. [Bluthenthal, Ricky N.] Calif State Univ Dominguez Hills, Dept Sociol, Carson, CA 90747 USA. [Heinzerling, Keith G.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Heinzerling, Keith G.] Univ Calif Los Angeles, Integrated Substance Abuse Res Programs, Los Angeles, CA 90024 USA. [Heinzerling, Keith G.] Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. [Anderson, Rachel; Flynn, Neil M.] Univ Calif Davis, Sch Med, Div Internal Med, Dept Infect Dis, Davis, CA 95616 USA. [Kral, Alex H.] RTI Int, Urban Hlth Program, San Francisco, CA USA. [Kral, Alex H.] Univ Calif San Francisco, Dept Family & Community Med, San Francisco, CA 94143 USA. RP Bluthenthal, RN (reprint author), RAND Corp, Hlth Program, 1776 Main S,POB 2138, Santa Monica, CA 90407 USA. EM rickyb@rand.org OI Bluthenthal, Ricky/0000-0003-3491-1702 FU NIDA NIH HHS [R01 DA014210, R01 DA14210]; PHS HHS [R06/CCR918667] NR 34 TC 11 Z9 11 U1 1 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD FEB PY 2008 VL 98 IS 2 BP 278 EP 283 DI 10.2105/AJPH.2005.080770 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 257XU UT WOS:000252833400020 PM 17538068 ER PT J AU Musch, G Bellani, G Melo, MFV Harris, RS Winkler, T Schroeder, T Venegas, JG AF Musch, Guido Bellani, Giacomo Melo, Marcos F. Vidal Harris, R. Scott Winkler, Tilo Schroeder, Tobias Venegas, Jose G. TI Relation between shunt, aeration, and perfusion in experimental acute lung injury SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE artificial respiration; adult respiratory distress syndrome; positron emission tomography; mechanical ventilators; X-ray computed tomography ID END-EXPIRATORY PRESSURE; RESPIRATORY-DISTRESS-SYNDROME; REGIONAL PULMONARY PERFUSION; BLOOD-FLOW REDISTRIBUTION; GAS-EXCHANGE; MECHANICAL VENTILATION; GENERAL-ANESTHESIA; DYNAMIC CT; RECRUITMENT; VOLUME AB Rationale. In a pulmonary process characterized by spatially heterogeneous loss of aeration, the impairment of gas exchange is expected to depend on the regional distribution of perfusion relative to that of aeration. Objectives: To investigate how regional aeration, shunt, and perfusion are interrelated at different levels of end-expiratory pressure and how their interplay relates to global shunt fraction in acute lung injury. Methods: Regional shunt and perfusion were assessed by imaging with positron emission tomography the pulmonary kinetics of [N-13]nitrogen infused in saline solution in five sheep after lung lavage. The lung field was divided in six horizontal regions. Measurements and Main Results: Each animal showed an inverse relation between regional shunt (Fs) and gas (FG) fractions: Fs = -m . FG + Fs(0). This relation was similar among animals (m = 1.25 +/- 0.14, Fs(0) = 0.75 +/- 0.15) and invariant with end-expiratory pressure, despite lack of correlation between global shunt and gas fractions and large interanimal variability in global shunt fraction. When this relation was used to estimate global shunt fraction as a perfusion-weighted average of the estimates of regional shunt fraction derived from regional gas fraction, 72% of the interanimal variability in global shunt fraction could be explained. Conclusions: Despite large interanimal variability in global shunt fraction, there was a consistent inverse relation between regional shunt and gas fractions, independent of end-expiratory pressure. Most of the interanimal variability in global shunt fraction could be explained by the combined effect of this relation and the distribution of perfusion on regional shunt, rather than by differences in global aeration. C1 [Musch, Guido; Bellani, Giacomo; Melo, Marcos F. Vidal; Winkler, Tilo; Schroeder, Tobias; Venegas, Jose G.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Musch, Guido; Bellani, Giacomo; Melo, Marcos F. Vidal; Harris, R. Scott; Winkler, Tilo; Schroeder, Tobias; Venegas, Jose G.] Harvard Univ, Sch Med, Boston, MA USA. [Bellani, Giacomo] Univ Milan, Monza, Italy. [Bellani, Giacomo] Osped San Gerado, Dept Expt Med, Monza, Italy. [Harris, R. Scott] Massachusetts Gen Hosp, Dept Med Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Musch, G (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM gmusch@partners.org RI Bellani, Giacomo/D-2379-2010; Winkler, Tilo/B-5337-2009; OI Bellani, Giacomo/0000-0002-3089-205X; Winkler, Tilo/0000-0002-7276-5550; Schroeder, Tobias/0000-0002-4439-8060 FU NHLBI NIH HHS [R01 HL086827-02, HL086827, HL076464, R01 HL086827] NR 52 TC 27 Z9 27 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD FEB 1 PY 2008 VL 177 IS 3 BP 292 EP 300 DI 10.1164/rccm.200703-484OC PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 255IC UT WOS:000252650600009 PM 17932380 ER PT J AU Wang, X Zhang, HX Sun, BX Dai, HL Hang, JQ Eisen, E Su, L Christiani, DC AF Wang, Xiaorong Zhang, Hong-Xi Sun, Bi-Xiong Dai, He-Lian Hang, Jin-Qing Eisen, Ellen Su, Li Christiani, David C. TI Cross-shift airway responses and long-term decline in FEV1 in cotton textile workers SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE cross-shift FEV1 change; chronic changes in lung function; cotton textile workers; cotton dust; occupational lung disease ID RESPIRATORY SYMPTOMS; LUNG-FUNCTION; EXPERIMENTAL CARDROOM; PULMONARY-FUNCTION; DUST EXPOSURE; ENDOTOXIN; BRONCHOCONSTRICTION; FEV(1) AB Rationale Acute airway response, measured as cross-shift change in FEV1, to cotton dust may lead to subsequent chronic loss of lung function in exposed workers. Objectives: To explore the association between the magnitude and frequency of cross-shift change and chronic loss of FEV1. Methods: Four hundred eight cotton workers and 417 silk workers from Shanghai textile mills were observed prospectively for 20 years, with cross-shift measurements at baseline and follow-up surveys at approximate 5-year intervals. To account for repeated measures of 5-year change, generalized estimating equations were used to estimate the relationship between the magnitude of cross-shift change in FEV1 (Delta FEV1) and subsequent 5-year annualized change. Linear regression models were used to examine the association between the number of drops in cross-shift FEV1 (Delta FEV1 < 0) and annualized change over the entire study period. Measurements and Main Results: Exposure to cotton dust was associated with a 10 ml/year decrement in 5-year annualized FEV1 decline. In addition, every 10 ml in Delta FEV1 drop was associated with an additional 1.5 ml/year loss in annualized FEV1 decline. The association between the frequency of drops and annualized decline was stronger for cotton workers than for silk workers over the entire study period. Conclusions: Cotton workers had larger and more frequent drops, as well as excessive chronic declines in FEV1, than did silk workers. The magnitude and frequency of cross-shift drops were associated with chronic loss in FEV1 over the entire 20-year period examined. C1 [Wang, Xiaorong; Eisen, Ellen; Su, Li; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, Boston, MA 02115 USA. [Wang, Xiaorong] Chinese Univ Hong Kong, Dept Community & Family Med, Hong Kong, Hong Kong, Peoples R China. [Zhang, Hong-Xi; Sun, Bi-Xiong; Dai, He-Lian; Hang, Jin-Qing] Shanghai Putuo Dist Peoples Hosp, Shanghai, Peoples R China. [Christiani, David C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Christiani, David C.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, 665 Huntington Ave,Bldg 1-1407, Boston, MA 02115 USA. EM dchris@hsph.harvard.edu RI Lin, Sihao/A-8412-2012 FU NIEHS NIH HHS [ES00002]; NIOSH CDC HHS [R01OH02421] NR 19 TC 18 Z9 22 U1 0 U2 3 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD FEB 1 PY 2008 VL 177 IS 3 BP 316 EP 320 DI 10.1164/rccm.200702-318OC PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 255IC UT WOS:000252650600012 PM 17975204 ER PT J AU Jonsson, S Varella-Garcia, M Miller, YE Wolf, HJ Byers, T Braudrick, S Kiatsimkul, P Lewis, M Kennedy, TC Keith, RL Bjornsson, J Mcwilliams, A Lam, S Hirsch, FR Franklin, WA AF Jonsson, Steinn Varella-Garcia, Marileila Miller, York E. Wolf, Holly J. Byers, Tim Braudrick, Sarah Kiatsimkul, Porntip Lewis, Marina Kennedy, Timothy C. Keith, Robert L. Bjornsson, Johannes Mcwilliams, Annette Lam, Stephen Hirsch, Fred R. Franklin, Wilbur A. TI Chromosomal aneusomy in bronchial high-grade lesions is associated with invasive lung cancer SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE chromosomal aneusomy; fluorescence in situ hybridization; carcinoma in situ; premalignancy ID IN-SITU HYBRIDIZATION; PRENEOPLASTIC LESIONS; COMPUTED-TOMOGRAPHY; FLUORESCENCE; CARCINOMA; CYTOLOGY; SMOKERS; RISK; ABNORMALITIES; ORGANIZATION AB Rationale: The development of lung cancer (LC) is accompanied by field changes in the airway mucosa that may have prognostic importance. Objectives: To compare patients with prevalent LC to control subjects regarding their histologic dysplasia scores and chromosomal aneusomy as measured by fluorescence in situ hybridization (FISH). Methods: The most advanced bronchial histology lesion was assessed from each of 44 LC cases and 90 cancer-free control subjects using a four-color FISH probe set encompassing the chromosome 6 centromere, 5p15.2, 7p12 (epidermal growth factor receptor), and 8q24 v-myc myelocytomatosis viral oncogene homolog (MYC) sequences. Histology grades were coded as dysplasia (moderate or severe) or carcinoma in situ (CIS). Measurements and Main Results: CIS was the highest histologic grade for 32 subjects, and dysplasia was the highest grade for 102 subjects (54 moderate, 48 severe). Chromosomal aneusomy was seen in 64% of the LC cases, but in only 31% of the control subjects (odds ratio [OR], 4.68; 95% confidence interval [CI]. 1.97-11.04). Among those with any level of dysplasia, the OR for positive FISH and LC was 2.28 (95% Cl, 0.75-6.86). Among those with CIS, the OR for positive FISH and LC was 5.84 (95% Cl, 1.31-26.01). Conclusions: Chromosomal aneusomy is associated with LC. Prospective examination of aneusomy as a precursor lesion that predicts LC is needed. C1 [Jonsson, Steinn; Varella-Garcia, Marileila; Miller, York E.; Kiatsimkul, Porntip; Lewis, Marina; Keith, Robert L.; Hirsch, Fred R.] Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO USA. [Jonsson, Steinn] Univ Iceland, Dept Med, Reykjavik, Iceland. [Miller, York E.; Keith, Robert L.] Denver Vet Affairs Med Ctr, Div Pulm, Denver, CO USA. [Byers, Tim; Braudrick, Sarah] Univ Colorado, Hlth Sci Ctr, Dept Prevent Med & Biostat, Denver, CO 80045 USA. [Kennedy, Timothy C.] Presbyterian St Lukes Med Ctr 1, Dept Med, Div Pulm, Denver, CO USA. [Bjornsson, Johannes] Univ Iceland Hosp, Dept Pathol, Reykjavik, Iceland. [Mcwilliams, Annette; Lam, Stephen] British Columbia Canc Agcy, Dept Resp Med, Vancouver, BC V5Z 4E6, Canada. [Hirsch, Fred R.; Franklin, Wilbur A.] Univ Colorado, Hlth Sci Ctr, Dept Pathol, Denver, CO USA. RP Varella-Garcia, M (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Med Med Oncol, Campus Box 6511,Mail Box 8117, Aurora, CO 80045 USA. EM marileila.garcia@uchsc.edu FU NCI NIH HHS [P30-CA46934, P01-CA58187, U01-CA85070] NR 30 TC 24 Z9 24 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD FEB 1 PY 2008 VL 177 IS 3 BP 342 EP 347 DI 10.1164/rccm.200708-1142OC PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 255IC UT WOS:000252650600016 PM 17989344 ER PT J AU Streblow, DN Kreklywich, CN Andoh, T Moses, AV Dumortier, J Smith, PP Defilippis, V Fruh, K Nelson, JA Orloff, SL AF Streblow, D. N. Kreklywich, C. N. Andoh, T. Moses, A. V. Dumortier, J. Smith, P. P. Defilippis, V. Fruh, K. Nelson, J. A. Orloff, S. L. TI The role of angiogenic and wound repair factors during CMV-accelerated transplant vascular sclerosis in rat cardiac transplants SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE accelerated rejection; allograft vasculopathy; angiogenesis; arrays; cardiac allograft rejection; cardiac allograft vasculopathy; chronic allograft rejection; cyclosporine A; cytomegalovirus (CMV); cytomegalovirus infection; transplant vascular sclerosis; virus ID CYTOMEGALO-VIRUS INFECTION; CHRONIC REJECTION; SMALL-BOWEL; CORONARY-ARTERIES; HEART-TRANSPLANTS; GROWTH-FACTORS; ELUTING STENT; ATHEROSCLEROSIS; EXPRESSION; DISEASE AB Human cytomegalovirus (HCMV) accelerates transplant vascular sclerosis (TVS), a consequence of angiogenesis (AG) and wound repair (WR). While HCMV can be localized to TVS lesions, the low number of infected cells suggests a global effect on target tissues. We used microarray analysis followed by real-time-polymerase chain reaction (RT-PCR) in an RCMV-accelerated TVS rat cardiac transplant model to determine whether CMV activates host WR and AG factors. Dysregulated cellular genes in allografts from RCMV-infected recipients were compared to those from uninfected recipients and native hearts. We demonstrated that RCMV upregulates the genes involved in WR and AG, which was highest during the critical time of TVS acceleration (21-28 days). Using a standard in vitro AG assay, virus and serum-free supernatants collected at 48 h postinfection significantly induced endothelial cell (EC) migration, branching and tubule formation compared to supernatants from mock-infected cells. Supernatants from ultraviolet (UV)-inactivated RCMV-infected cells failed to induce AG, indicating that virus replication is required. Upregulation of WR and AG genes occurs during the critical period of CMV-accelerated TVS. Targeting these genes may prevent this process and improve allograft survival. C1 [Orloff, S. L.] Portland VA Med Ctr, Portland, OR 97239 USA. [Kreklywich, C. N.; Andoh, T.; Fruh, K.; Nelson, J. A.; Orloff, S. L.] Oregon Hlth & Sci Univ, Dept Med Microbiol & Immunol, Portland, OR 97201 USA. [Orloff, S. L.] Oregon Hlth & Sci Univ, Dept Surg, Portland, OR 97201 USA. [Streblow, D. N.; Moses, A. V.; Dumortier, J.; Smith, P. P.; Defilippis, V.; Fruh, K.; Nelson, J. A.] Oregon Hlth & Sci Univ, Vaccine& Gene Therapy Inst, Portland, OR 97201 USA. RP Orloff, SL (reprint author), Portland VA Med Ctr, Portland, OR 97239 USA. EM orloffs@ohsu.edu FU NCRR NIH HHS [P51 RR000163-496162, P51 RR000163-486828, P51 RR000163]; NHLBI NIH HHS [HL66238-01, HL083194, R01 HL085451]; NIAID NIH HHS [R01 AI070890-01A2, R01 AI070890] NR 31 TC 28 Z9 28 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD FEB PY 2008 VL 8 IS 2 BP 277 EP 287 DI 10.1111/j.1600-6143.2007.02062.x PG 11 WC Surgery; Transplantation SC Surgery; Transplantation GA 252DD UT WOS:000252424300005 PM 18093265 ER PT J AU Spaniolas, K Velmahos, GC Wicky, S Nussbaumer, K Petrovick, L Gervasini, A De Moya, M Alam, HB AF Spaniolas, Konstantinos Velmahos, George C. Wicky, Stephan Nussbaumer, Karen Petrovick, Laurie Gervasini, Alice De Moya, Marc Alam, Hasan B. TI Is upper extremity deep venous thrombosis underdiagnosed in trauma patients? SO AMERICAN SURGEON LA English DT Article ID PULMONARY-EMBOLISM; VEIN-THROMBOSIS; RISK-FACTORS; THROMBOEMBOLISM; MORTALITY; DIAGNOSIS; THROMBOPROPHYLAXIS; ULTRASONOGRAPHY; ANGIOGRAPHY; VENOGRAPHY AB It has been suggested that upper extremity deep venous thrombosis (UEDVT) is as common and dangerous as lower extremity deep venous thrombosis. Pulmonary embolism (PE) is often found with no evidence of associated lower extremity deep venous thrombosis and could have originated from UEDVT. Routine screening is well accepted for lower extremity deep venous thrombosis but not for UEDVT. We hypothesized that UEDVT in trauma is frequent but undetected; therefore, routine screening of trauma patients at risk will increase the UEDVT rate and decrease the PE rate due to early diagnosis and treatment. We evaluated the incidence of UEDVT and PE over 6 months before (Group BEFORE) and 6 months after (Group AFTER) implementing a policy of screening patients at high risk for deep venous thrombosis with Duplex ultrasonography. Group BEFORE was evaluated retrospectively and group AFTER prospectively. There were 1110 BEFORE and 911 AFTER patients. The two groups were similar. Of the AFTER patients, 86 met predetermined screening criteria and were evaluated routinely by a total of 130 Duplex exams. One patient in each group developed UEDVT (0.09% vs 0.11%, P=1.00). The brachial vein was involved in both patients. Six BEFORE (0.54%) and I AFTER (0.11%) patients developed PE (P=0.137). The single AFTER patient with PE was not screened for UEDVT because he had no high-risk criteria. UEDVT is an uncommon event with unclear significance in trauma. Aggressive screening did not result in a higher rate of UEDVT diagnosis, nor an opportunity to prevent PE. C1 [Spaniolas, Konstantinos; Velmahos, George C.; Petrovick, Laurie; Gervasini, Alice; De Moya, Marc; Alam, Hasan B.] Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [Wicky, Stephan; Nussbaumer, Karen] Massachusetts Gen Hosp, Dept Radiol, Div Cardiovasc Imaging & Intervent, Boston, MA 02114 USA. [Spaniolas, Konstantinos; Velmahos, George C.; Wicky, Stephan; Nussbaumer, Karen; Petrovick, Laurie; Gervasini, Alice; De Moya, Marc; Alam, Hasan B.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Velmahos, GC (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM gvelmahos@partners.org NR 30 TC 6 Z9 6 U1 0 U2 0 PU SOUTHEASTERN SURGICAL CONGRESS PI ATLANTA PA 141 WEST WIEUCA RD, STE B100, ATLANTA, GA 30342 USA SN 0003-1348 J9 AM SURGEON JI Am. Surg. PD FEB PY 2008 VL 74 IS 2 BP 124 EP 128 PG 5 WC Surgery SC Surgery GA 260KN UT WOS:000253009300006 PM 18306861 ER PT J AU Cooper, JB Blum, RH Carroll, JS Dershwitz, M Feinstein, DM Gaba, DM Morey, JC Singla, AK AF Cooper, Jeffrey B. Blum, Richard H. Carroll, John S. Dershwitz, Mark Feinstein, David M. Gaba, David M. Morey, John C. Singla, Aneesh K. TI Differences in safety climate among hospital anesthesia departments and the effect of a realistic simulation-based training program SO ANESTHESIA AND ANALGESIA LA English DT Article ID CRISIS RESOURCE-MANAGEMENT; OPERATING-ROOM; ORGANIZATIONAL CULTURE; PATIENT SAFETY; HEALTH-CARE; TEAMWORK; ATTITUDES; PHYSICIANS; PERSONNEL; NURSES AB BACKGROUND: Safety climate is often measured via surveys to identify appropriate patient safety interventions. The introduction of an insurance premium incentive for simulation-based anesthesia crisis resource management (CRM) training motivated our naturalistic experiment to compare the safety climates of several departments and to assess the impact of the training. METHODS: We administered a 59-item survey to anesthesia providers in six academic anesthesia programs (Phase 1). Faculty in four of the programs subsequently participated in a CRM program using simulation. The survey was readministered 3 yr later (Phase 2). Factor analysis was used to create scales regarding common safety themes. Positive safety climate (% of respondents with positive safety attitudes) was computed for the scales to indicate the safety climate levels. RESULTS: The usable response rate was 44% (309/708) and 38% (293/772) in Phases 1 and 2 respectively. There was wide variation in response rates among hospitals and providers. Eight scales were identified. There were significantly different climate scores among hospitals but no difference between the trained and untrained cohorts. The positive safety climate scores varied from 6% to 94% on specific survey questions. Faculty and residents had significantly different perceptions of the degree to which residents are debriefed about their difficult clinical situations. CONCLUSIONS: Safety climate indicators can. vary substantially among anesthesia practice groups. Scale scores and responses to specific questions can suggest practices for improvement. Overall safety climate is probably not a good criterion for assessing the impact of simulation-based CRM training. Training alone was insufficient to alter engrained behaviors in the absence of further reinforcing actions. C1 [Cooper, Jeffrey B.; Singla, Aneesh K.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Cooper, Jeffrey B.; Blum, Richard H.; Feinstein, David M.; Singla, Aneesh K.] Harvard Univ, Sch Med, Boston, MA USA. [Blum, Richard H.] Childrens Hosp, Dept Anesthesia Perioperat & Pain Med, Boston, MA 02115 USA. [Carroll, John S.] MIT, Sloan Sch Management, Cambridge, MA 02139 USA. [Carroll, John S.] Engn Syst Div, Cambridge, MA USA. [Dershwitz, Mark] Univ Massachusetts, Med Ctr, Dept Anesthesiol, Worcester, MA USA. [Feinstein, David M.] Beth Israel Deaconess Med Ctr, Dept Anesthesia & Crit Care, Boston, MA 02215 USA. [Gaba, David M.] VA Palo Alto Hlth Care Syst, Stanford, CA USA. [Gaba, David M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. RP Cooper, JB (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St,RSL 335, Boston, MA 02114 USA. EM jcooper@partners.org NR 28 TC 17 Z9 17 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD FEB PY 2008 VL 106 IS 2 BP 574 EP 584 DI 10.1213/01.ane.0000296462.39953.d3 PG 11 WC Anesthesiology SC Anesthesiology GA 254ZE UT WOS:000252625700035 PM 18227319 ER PT J AU Campbell, MK McLerran, D Turner-McGrievy, G Feng, Z Havas, S Sorensen, G Buller, D Beresford, SAA Nebeling, L AF Campbell, Marci Kramish McLerran, Dale Turner-McGrievy, Gabrielle Feng, Ziding Havas, Stephen Sorensen, Glorian Buller, David Beresford, Shirley A. A. Nebeling, Linda TI Mediation of adult fruit and vegetable consumption in the national 5 a day for better health community studies SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Article DE cancer prevention; fruit and vegetable consumption; health promotion; mediation ID DIETARY CHANGE; NUTRITION INTERVENTION; PSYCHOSOCIAL FACTORS; PROMOTION PROGRAM; INCREASING FRUIT; PREVENTION; WORKSITE; PREDICTORS; MODERATORS; AWARENESS AB Background The 5 A Day for Better Health community studies demonstrated in randomized trials the efficacy of population-based strategies to increase fruit and vegetable consumption in diverse geographic areas and settings. Purpose Mediation analysis can help to elucidate the theoretical basis of changing dietary habits. This is important for informing more powerful cancer prevention and control interventions to achieve broad public health impact. Methods Five sites that focused on adults were included in mediation analyses to determine whether theoretically derived constructs assessed at baseline and follow-up contributed to explaining change in fruit and vegetable (F&V) consumption. These variables were knowledge, self-efficacy, and autonomy/responsibility. Stage of change also was considered as a potential moderating variable. Results Self-efficacy and knowledge of the 5 A Day recommendation increased in those who received the interventions and were positively associated with higher F&V. Mediation of intervention effect was demonstrated for these variables. Autonomy/responsibility did not meet the criteria for mediation. There was no evidence of differential effect of mediators according to baseline stage. Conclusions The present study findings provide strong support for mediation of F&V consumption by two variables: self-efficacy and knowledge. The authors discuss the findings in relation to study limitations and future research directions. C1 [Campbell, Marci Kramish; Turner-McGrievy, Gabrielle] Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA. [McLerran, Dale; Feng, Ziding] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Havas, Stephen] Amer Med Assoc, Chicago, IL 60610 USA. [Sorensen, Glorian] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Sorensen, Glorian] Dana Farber Canc Inst, Boston, MA 02115 USA. [Buller, David] Klein Buendel Inc, Golden, CO 80401 USA. [Beresford, Shirley A. A.] Univ Washington, Grp Hlth Cooperat, Dept Hlth Serv, Seattle, WA 98101 USA. [Beresford, Shirley A. A.] Univ Washington, Grp Hlth Cooperat, Ctr Hlth Studies, Seattle, WA 98101 USA. [Nebeling, Linda] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Campbell, MK (reprint author), Univ N Carolina, Dept Nutr, Campus Box 7461, Chapel Hill, NC 27599 USA. EM marci_campbell@unc.edu OI Turner-McGrievy, Gabrielle/0000-0002-1683-5729 FU NCI NIH HHS [R01 CA 98014]; NIDDK NIH HHS [P30 DK056350, DK 56350] NR 37 TC 21 Z9 21 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD FEB PY 2008 VL 35 IS 1 BP 49 EP 60 DI 10.1007/s12160-007-9002-y PG 12 WC Psychology, Multidisciplinary SC Psychology GA 268IQ UT WOS:000253573900006 PM 18347904 ER PT J AU Sayers, SL Riegel, B Pawlowski, S Coyne, JC Samaha, FF AF Sayers, Steven L. Riegel, Barbara Pawlowski, Stephanie Coyne, James C. Samaha, Frederick F. TI Social support and self-care of patients with heart failure SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Article DE heart failure; social support; self-care ID MULTIDIMENSIONAL SCALE; COGNITIVE IMPAIRMENT; ENHANCING RECOVERY; HEALTH BEHAVIORS; VALIDATION; MANAGEMENT; ADHERENCE; DISEASE; KIN; DEPRESSION AB Background Social support can influence treatment adherence of patients with chronic illnesses, which may explain the positive effects of social support on heart failure (HF) outcomes. Purpose To investigate the effects of social support among patients with HF, we examined whether aspects of social support were associated with self-care, including medication adherence, dietary adherence, and HF symptom monitoring functions. Methods We recruited 74 patients with HF from cardiology clinics of a Veterans Affairs Medical Center and a university-affiliated hospital, and tested the relationships between social support and the patients' self-care. Results Consistent with previous research in older adults, family members, especially spouses, were often involved in the medical care of patients with chronic HF and provided a range of levels of support to patients. Self-care was generally poor, as measured across several self-care domains. Perceived social support was moderately associated with relatively better self-reported medication and dietary adherence, and other aspects of self-care such as daily weighing. Conclusions These findings suggest that a relatively higher level of self-care is an important correlate of social support and may explain how social support influences HF outcomes. This study also suggests that family members should play a greater part in clinical care focused on improving self-care. C1 [Sayers, Steven L.; Pawlowski, Stephanie; Coyne, James C.; Samaha, Frederick F.] Univ Penn, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Riegel, Barbara; Pawlowski, Stephanie; Coyne, James C.] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. RP Sayers, SL (reprint author), Univ Penn, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. EM steven.sayers@va.gov NR 51 TC 93 Z9 98 U1 7 U2 15 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD FEB PY 2008 VL 35 IS 1 BP 70 EP 79 DI 10.1007/s12160-007-9003-x PG 10 WC Psychology, Multidisciplinary SC Psychology GA 268IQ UT WOS:000253573900008 PM 18347906 ER PT J AU Stewart, SE Stack, DE Wilhelm, S AF Stewart, S. Evelyn Stack, Denise Egan Wilhelm, Sabine TI Severe Obsessive-Compulsive Disorder with and without Body Dysmorphic Disorder: Clinical Correlates and Implications SO ANNALS OF CLINICAL PSYCHIATRY LA English DT Article DE Obsessive-compulsive disorder; Body dysmorphic disorder; Comorbidity; Prevalence; Severe; Phenomenology; Hoarding ID SYMPTOM DIMENSIONS; MAJOR DEPRESSION; COMORBIDITY; SCALE; ONSET; PREVALENCE; PREDICTORS; ANXIETY; FAMILY; TRIAL AB Objective. Body Dysmorphic Disorder is a putative obsessive-compulsive spectrum disorder. This exploratory study systematically examined prevalence and clinical correlates of Body Dysmorphic Disorder (BDD) comorbidity in an inpatient Obsessive-Compulsive Disorder (OCD) population. Method. Consecutive patients from an OCD Intensive Residential Treatment program were included (N = 275). Clinician-rated and patient-rated measures were administered at baseline and repeated at discharge. The prevalence of BDD was determined and clinical characteristics were statistically compared between groups with (N = 42) and without (N = 233) comorbid BDD. Results. The prevalence of BDD among residential patients with OCD was 15.3% (N = 42), Those with comorbid BDD were younger (p = 0.007) and more predominantly female (p = 0.02), with lower marriage rates (p = 0.006), more severe depression (p = 0.003) and increased self-reported illicit substance use histories (p = 0.003) versus those without BDD. This cohort also had earlier onset OCD (p = 0.02) and more severe hoarding (p = 0.01), symmetry (p = 0.01), reassurance-seeking (p = 0.01) and checking symptoms (p = 0,01) than patients without comorbid BDD. OCD treatment response was unaffected by the presence of BDD. Conclusion. BDD is a common comorbidity in severe OCD. Younger women and those with early-onset OCD appear more likely to have BDD. OCD patients with BDD also have increased hoarding, symmetry, reassurance-seeking and checking severity, which requires consideration in treatment planning. C1 [Stewart, S. Evelyn; Wilhelm, Sabine] Massachusetts Gen Hosp, OCD Clin, Boston, MA 02114 USA. [Stewart, S. Evelyn; Stack, Denise Egan] McLean Hosp, Obsess Compuls Disorder Inst, Belmont, MA 02178 USA. [Stewart, S. Evelyn; Wilhelm, Sabine] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Wilhelm, S (reprint author), Massachusetts Gen Hosp, OCD Clin, Simches Res Bldg,2nd Floor,185 Cambridge St, Boston, MA 02114 USA. EM sabinewilhelmwilhelm@earthlink.net RI Stewart, Evelyn/K-6961-2014; OI Stewart, S. Evelyn/0000-0002-0994-6383 FU Obsessive-Compulsive Foundation; McLean Hospital Research Fellowship (SES); Harvard 50th Anniversary Scholar in Medicine Award (SES); McIngvale Foundation FX This work was supported by grants from an Obsessive-Compulsive Foundation research award (SES), a McLean Hospital Research Fellowship (SES), a Harvard 50th Anniversary Scholar in Medicine Award (SES) and funding from the McIngvale Foundation. The authors thank all staff and patients of the OCD Institute, Eric Jenike and Erin Hendrickson for their assistance with manuscript preparation. NR 47 TC 17 Z9 18 U1 3 U2 7 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1040-1237 J9 ANN CLIN PSYCHIATRY JI Ann. Clin. Psychiatry PD FEB PY 2008 VL 20 IS 1 BP 33 EP 38 DI 10.1080/10401230701844463 PG 6 WC Psychiatry SC Psychiatry GA 382FQ UT WOS:000261591200006 PM 18297584 ER PT J AU Albers, MW Marder, KS AF Albers, Mark W. Marder, Karen S. TI A tale of two etiologies: Loss and recovery of olfactory function SO ANNALS OF NEUROLOGY LA English DT Editorial Material ID PARKINSONS-DISEASE; DYSFUNCTION; IDENTIFICATION C1 [Albers, Mark W.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis,Dept Neurol, Boston, MA 02115 USA. [Marder, Karen S.] Columbia Univ Coll Phys & Surg, Taub Inst Res Alzheimers Dis & Aging Brain, Gertrude H Sergievsky Ctr, Dept Neurol, New York, NY 10032 USA. RP Albers, MW (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis,Dept Neurol, Boston, MA 02115 USA. NR 14 TC 1 Z9 1 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD FEB PY 2008 VL 63 IS 2 BP 132 EP 134 DI 10.1002/ana.21330 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 270AG UT WOS:000253691500006 PM 18306414 ER PT J AU Harris, S Sheth, SA Cohen, MS AF Harris, Sam Sheth, Sameer A. Cohen, Mark S. TI Functional neuroimaging of belief, disbelief, and uncertainty SO ANNALS OF NEUROLOGY LA English DT Article ID MEDIAL PREFRONTAL CORTEX; BASAL GANGLIA; NEURAL RESPONSE; FMRI; BRAIN; INFORMATION; REGIONS; PAIN; MODULATION; EXPERIENCE AB Objective: The difference between believing and disbelieving a proposition is one of the most potent regulators of human behavior and emotion. When one accepts a statement as true, it becomes the basis for further thought and action; rejected as false, it remains a string of words. The purpose of this study was to differentiate belief, disbelief, and uncertainty at the level of the brain. Methods: We used functional magnetic resonance imaging (fMRI) to study the brains of 14 adults while they judged written statements to be "true" (belief), "false" (disbelief), or "undecidable" (uncertainty). To characterize belief, disbelief, and uncertainty in a content-independent manner, we included statements from a wide range of categories: autobiographical, mathematical, geographical, religious, ethical, semantic, and factual. Results: The states of belief, disbelief, and uncertainty differentially activated distinct regions of the prefrontal and parietal cortices, as well as the basal ganglia. Interpretation: Belief and disbelief differ from uncertainty in that both provide information that can subsequently inform behavior and emotion. The mechanism underlying this difference appears to involve the anterior cingulate cortex and the caudate. Although many areas of higher cognition are likely involved in assessing the truth-value of linguistic propositions, the final acceptance of a statement as "true" or its rejection as "false" appears to rely on more primitive, hedonic processing in the medial prefrontal cortex and the anterior insula. Truth may be beauty, and beauty truth, in more than a metaphorical sense, and false propositions may actually disgust us. C1 [Cohen, Mark S.] Univ Calif Los Angeles, Ctr Cognit Neurosci, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Cohen, Mark S.] Univ Calif Los Angeles, Ctr Cognit Neurosci, Dept Neurol, Los Angeles, CA 90095 USA. [Cohen, Mark S.] Univ Calif Los Angeles, Ctr Cognit Neurosci, Dept Radiol Sci, Los Angeles, CA 90095 USA. [Cohen, Mark S.] Univ Calif Los Angeles, Ctr Cognit Neurosci, Dept Biomed Phys, Los Angeles, CA 90095 USA. [Cohen, Mark S.] Univ Calif Los Angeles, Ctr Cognit Neurosci, Dept Psychol, Los Angeles, CA 90095 USA. [Harris, Sam] Univ Calif Los Angeles, Brain Mapping Ctr, Los Angeles, CA 90095 USA. [Sheth, Sameer A.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Cohen, MS (reprint author), Univ Calif Los Angeles, Ctr Cognit Neurosci, Dept Psychiat & Biobehav Sci, Suite C8-881,740 Westwood Plaza, Los Angeles, CA 90095 USA. EM mscohen@ucla.edu RI Cohen, Mark/C-6610-2011 OI Cohen, Mark/0000-0001-6731-4053 NR 38 TC 56 Z9 57 U1 10 U2 37 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD FEB PY 2008 VL 63 IS 2 BP 141 EP 147 DI 10.1002/ana.21301 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 270AG UT WOS:000253691500008 PM 18072236 ER PT J AU Dzhala, VI Brumback, AC Staley, KJ AF Dzhala, Volodymyr I. Brumback, Audrey C. Staley, Kevin J. TI Bumetanide enhances phenobarbital efficacy in a neonatal seizure model SO ANNALS OF NEUROLOGY LA English DT Article ID K-CL COTRANSPORTER; CATION-CHLORIDE COTRANSPORTERS; GAMMA-AMINOBUTYRIC ACID; RAT HIPPOCAMPAL SLICE; STRUCTURES IN-VITRO; EPILEPTIFORM ACTIVITY; ANTIEPILEPTIC DRUGS; EXCITATORY ACTIONS; DEVELOPING BRAIN; CORTICOHIPPOCAMPAL FORMATION AB Objectives: High levels of expression of the Na+-K+-2Cl(-) (NKCC1) cotransporter in immature neurons cause the accumulation of intracellular chloride and, therefore, a depolarized Cl- equilibrium potential (E-Cl). This results in the outward flux of Cl- through GABA, channels, the opposite direction compared with mature neurons, in which GABA(A) receptor activation is inhibitory because Cl- flows into the cell. This outward flow of Cl- in neonatal neurons is excitatory and contributes to a greater seizure propensity and poor electroencephalographic response to GABAergic anticonvulsants such as phenobarbital and benzodiazepines. Blocking the NKCC1 transporter with bumetanide prevents outward Cl- flux and causes a more negative GABA equilibrium potential (E-GABA) in immature neurons. We therefore tested whether bumetanide enhances the anticonvulsant action of phenobarbital in the neonatal brain. Methods: Recurrent seizures were induced in the intact hippocampal preparation in vitro by continuous 5-hour exposure to low-Mg2+ solution. The anticonvulsant efficacy of phenobarbital, bumetanide, and the combination of these drugs was studied. Results: Phenobarbital failed to abolish or depress recurrent seizures in 70% of hippocampi. In contrast, phenobarbital in combination with bumetanide abolished seizures in 70% of hippocampi and significantly reduced the frequency, duration, and power of seizures in the remaining 30%. Interpretation: Thus, alteration of Cl- transport by bumetanide enables the anticonvulsant action of phenobarbital in immature brain. This is a mechanistic demonstration of rational anticonvulsant polypharmacy. The combination of these agents may comprise an effective therapy for early-life seizures. C1 [Dzhala, Volodymyr I.; Staley, Kevin J.] Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Sch Med, Boston, MA 02114 USA. [Dzhala, Volodymyr I.; Brumback, Audrey C.; Staley, Kevin J.] Univ Colorado Denver, Dept Neurol, Denver, CO USA. [Dzhala, Volodymyr I.; Brumback, Audrey C.; Staley, Kevin J.] Univ Colorado Denver, Dept Pediat, Denver, CO USA. [Dzhala, Volodymyr I.; Brumback, Audrey C.; Staley, Kevin J.] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. RP Staley, KJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Sch Med, 55 Fruit St,VBK 910, Boston, MA 02114 USA. EM kstalev@partners.org OI Brumback, Audrey/0000-0002-4904-4368 FU NINDS NIH HHS [R01 NS40109] NR 80 TC 122 Z9 124 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD FEB PY 2008 VL 63 IS 2 BP 222 EP 235 DI 10.1002/ana.21229 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 270AG UT WOS:000253691500017 PM 17918265 ER PT J AU Mann, M Tendulkar, A Birger, N Howard, C Ratcliffe, MB AF Mann, Michael Tendulkar, Amod Birger, Noy Howard, Cheryl Ratcliffe, Mark B. TI National institutes of health funding for surgical research SO ANNALS OF SURGERY LA English DT Article ID TRANSLATIONAL RESEARCH; PHYSICIAN-SCIENTIST; SURGEON; TRENDS AB Objective: The objective was to compare National Institutes of Health (NIH) funding rates and application success rates among surgeon and nonsurgeon-scientists over the past 2 decades. Summary Background Data: Surgeons may be capable of accelerating the translation of basic research into new clinical therapies. Nevertheless, most surgeon-scientists believe they are at a disadvantage in competing for peer-reviewed funding, despite a recent emphasis on "translational science" by organizations such as the NIH. Methods: We accessed databases from the NIH and the American Association of Medical Colleges. Results: Although total competing NIH awards rose 79.2% from 5608 to 10,052, the much smaller number of surgical awards increased only by 41.4% from 157 to 222. There was a small but statistically significant difference between total NIH and surgical application success rates (29% vs. 25%, P < 0.01). However, the persistently low percent of NIH funding going to surgical investigators was due primarily to the very small number of surgical applications, and to a much smaller increase in the absolute number of applications over time (464 vs. 23,847). As a result, the number of grants per 100 faculty members, was more than 4 times higher among nonsurgical than surgical faculties at US medical schools. Conclusion: NIH funding to academic surgeons is declining relative to their nonsurgical colleagues. This trend will likely be reversed only by an increase in the number of grant applications submitted by surgeon-scientists. Structural changes in surgical training programs, and in the economics of academic surgery, may support a greater contribution of surgeon-scientists to the success of translational research. C1 [Mann, Michael; Birger, Noy; Ratcliffe, Mark B.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Mann, Michael; Tendulkar, Amod; Ratcliffe, Mark B.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. [Howard, Cheryl] NHLBI, Div Sci Program Operat, Bethesda, MD 20892 USA. RP Ratcliffe, MB (reprint author), San Francisco VA Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA. EM mark.ratcliffe@med.va.gov NR 15 TC 52 Z9 52 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD FEB PY 2008 VL 247 IS 2 BP 217 EP 221 DI 10.1097/SLA.0b013e3181568e26 PG 5 WC Surgery SC Surgery GA 256VR UT WOS:000252758500003 PM 18216525 ER PT J AU Rodriguez, JR Razo, AS Targarona, J Thayer, SP Rattner, DW Warshaw, AL Castillo, CFD AF Rodriguez, J. Ruben Razo, A. Swaldo Targarona, Javier Thayer, Sarah P. Rattner, David W. Warshaw, Andrew L. Castillo, Carlos Fernandez-del TI Debridement and closed packing for sterile or infected necrotizing pancreatitis - Insights into indications and outcomes in 167 patients SO ANNALS OF SURGERY LA English DT Article ID NECROSIS; NECROSECTOMY; MANAGEMENT; THERAPY; MORTALITY AB Objective: To examine the surgical indications and clinical outcomes of a large cohort of patients with necrotizing pancreatitis. Summary Background Data: Mortality after debridement for necrotizing pancreatitis continues to be inordinately high. The clinical experience with patients who underwent uniform surgical treatment for necrotizing pancreatitis at the Massachusetts General Hospital over a 15-year period is described. Methods: Retrospective review of 167 patients with necrotizing pancreatitis who required intervention and were treated with single stage debridement and a closed packing technique. Particular emphasis was placed on the indication for surgery and the presence of infected necrosis. Multiple logistic regression models were used to identify predictors of mortality. Results: The primary preoperative indication for operation was infected necrosis (51%), but intraoperative cultures proved that 72% of the entire cohort was infected. The rate of reoperation was 12.6%, and 29.9% of patients required percutaneous interventional radiology drainage after initial debridement. Overall operative mortality was 11.4% (19/167), but higher in patients who were operated upon before 28 days (20.3% vs. 5.1%, P = 0.002). Other important predictors of mortality included organ failure >= 3 (OR = 2.4, P = 0.001), postoperative intensive care unit stay >= 6 days (OR = 15.9, P = 0.001), and female gender (OR = 5.41, P = 0.02). Conclusions: Open, transperitoneal debridement followed by closed packing and drainage results in the lowest reported mortality and reoperation rates, and provides a standard for comparing other methods of treatment. A negative FNA does not reliably rule out infection. The clinical status of the patients and not proof of infection should determine the need for debridement. C1 [Rodriguez, J. Ruben; Razo, A. Swaldo; Targarona, Javier; Thayer, Sarah P.; Rattner, David W.; Warshaw, Andrew L.; Castillo, Carlos Fernandez-del] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Castillo, CFD (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St,WACC 460, Boston, MA 02114 USA. EM cfemandez@partners.org FU NIDDK NIH HHS [K08 DK071329] NR 27 TC 120 Z9 145 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD FEB PY 2008 VL 247 IS 2 BP 294 EP 299 DI 10.1097/SLA.0b013e31815b6976 PG 6 WC Surgery SC Surgery GA 256VR UT WOS:000252758500014 PM 18216536 ER PT J AU Nathan, NR Michaelson, JS Cady, B AF Nathan, N. R. Michaelson, J. S. Cady, B. TI Matched pair analysis of stage 4 breast cancer with resection of primary breast site SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 61st Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 13-16, 2008 CL Chicago, IL SP Soc Surg Oncol C1 [Nathan, N. R.; Michaelson, J. S.; Cady, B.] Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2008 VL 15 SU 2 BP 2 EP 2 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 258RT UT WOS:000252887900003 ER PT J AU Wapnir, IL Zahrieh, D Aebi, S AF Wapnir, I. L. Zahrieh, D. Aebi, S. TI Progress on BIG 1-02/IBCSG 27-02/NSABP B-37, a prospective randomized trial evaluating chemotherapy after local therapy for isolated locoregional recurrences SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 61st Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 13-16, 2008 CL Chicago, IL SP Soc Surg Oncol C1 [Wapnir, I. L.] Stanford Univ, Stanford, CA USA. [Zahrieh, D.] Dana Farber Canc Inst, Boston, MA USA. [Aebi, S.] Univ Bern Inselspital, Bern, Switzerland. RI Aebi, Stefan/F-2004-2010 OI Aebi, Stefan/0000-0002-3383-9449 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2008 VL 15 SU 2 BP 9 EP 9 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 258RT UT WOS:000252887900024 ER PT J AU Kraybill, WG Harris, IJ Spiro, IJ Ettinger, DS Letson, GD DeLaney, TF Blum, RH Lucas, DR Harmon, DC Eisenberg, B AF Kraybill, W. G. Harris, I. J. Spiro, I. J. Ettinger, D. S. Letson, G. D. DeLaney, T. F. Blum, R. H. Lucas, D. R. Harmon, D. C. Eisenberg, B. TI Updated analysis of a phase II study of neoadjuvant chemotherapy and radiation therapy in the management of high-risk, high-grade, soft tissue sarcomas of the extremities and body wall: Radiation therapy oncology group trial 9514 SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 61st Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 13-16, 2008 CL Chicago, IL SP Soc Surg Oncol C1 [Kraybill, W. G.] Univ Missouri, St Lukes Hosp, Kansas City, MO USA. [Harris, I. J.] Radiat Therapy Oncol Grp, Philadelphia, PA USA. [Harris, I. J.; Spiro, I. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ettinger, D. S.] Johns Hopkins Oncol Ctr, Baltimore, MD USA. [Letson, G. D.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Blum, R. H.] Beth Israel Hosp Canc Ctr, New York, NY USA. [Lucas, D. R.] Univ Michigan, Hlth Sci Ctr, Ann Arbor, MI USA. [Eisenberg, B.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2008 VL 15 SU 2 BP 17 EP 17 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 258RT UT WOS:000252887900051 ER PT J AU Bilimoria, KY Bentrem, DJ Feinglass, JM Stewart, AK Winchester, DP Talamonti, MS Ko, CY AF Bilimoria, K. Y. Bentrem, D. J. Feinglass, J. M. Stewart, A. K. Winchester, D. P. Talamonti, M. S. Ko, C. Y. TI Directing surgical quality improvement initiatives in the United States: Comparison of perioperative mortality and long-term survival for cancer surgery SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 61st Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 13-16, 2008 CL Chicago, IL SP Soc Surg Oncol C1 [Bilimoria, K. Y.; Stewart, A. K.] Amer Coll Surg, Canc Programs, Chicago, IL USA. [Bentrem, D. J.; Feinglass, J. M.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Chicago, IL USA. [Winchester, D. P.; Talamonti, M. S.] Evanston Northwest Healthcare, Dept Surg, Evanston, IL USA. [Ko, C. Y.] Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2008 VL 15 SU 2 BP 18 EP 19 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA 258RT UT WOS:000252887900056 ER PT J AU Glass, E Iker, E AF Glass, E. Iker, E. TI The role of SPECT-CT in lymphatic mapping SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 6th Biennial International-Sentinel-Node-Society Meeting CY FEB 18-20, 2008 CL Sydney, AUSTRALIA SP Int Sentinel Node Soc C1 [Glass, E.] John Wayne Canc Inst, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Iker, E.] Lymphedema Ctr So Calif, Santa Monica, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2008 VL 15 SU 1 BP 19 EP 19 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 263DK UT WOS:000253197600048 ER PT J AU Bilimoria, KY Bentrem, DJ Ko, CY Winchester, DP Stewart, AK Talamonti, MS Halverson, A AF Bilimoria, K. Y. Bentrem, D. J. Ko, C. Y. Winchester, D. P. Stewart, A. K. Talamonti, M. S. Halverson, A. TI Anal cancer in the United States: Utilization and outcomes of recommended treatment SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 61st Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 13-16, 2008 CL Chicago, IL SP Soc Surg Oncol C1 [Bilimoria, K. Y.; Winchester, D. P.; Stewart, A. K.] Northwestern Univ, Amer Coll Surg, Feinberg Sch Med, Dept Surg,Canc Programs, Chicago, IL USA. [Bentrem, D. J.; Talamonti, M. S.; Halverson, A.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Chicago, IL USA. [Ko, C. Y.] Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2008 VL 15 SU 2 BP 21 EP 22 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA 258RT UT WOS:000252887900065 ER PT J AU Eisenberg, BL Harris, J Blanke, C Demetri, G Von Mehren, M Heinrich, M Watson, J Okuno, S Kane, J Hoffman, J AF Eisenberg, B. L. Harris, J. Blanke, C. Demetri, G. Von Mehren, M. Heinrich, M. Watson, J. Okuno, S. Kane, J. Hoffman, J. TI Phase II trial of Neoadjuvant/Adjuvant imatinib mesylate (IM) for advanced primary and recurrent operable GI stromal tumor (GIST) - early results of RTOG 0132 SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 61st Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 13-16, 2008 CL Chicago, IL SP Soc Surg Oncol C1 [Eisenberg, B. L.] Norris Cotton Canc Ctr, Lebanon, NH USA. [Harris, J.] Amer Coll Radiol, Philadelphia, PA USA. [Blanke, C.; Heinrich, M.] Oregon Hlth & Sci Univ, Portland, OR USA. [Demetri, G.] Dana Farber Canc Inst, Boston, MA USA. [Von Mehren, M.; Watson, J.; Hoffman, J.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Kane, J.] Roswell Pk Canc Inst, Buffalo, NY USA. [Okuno, S.] Mayo Clin, Rochester, MN USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2008 VL 15 SU 2 BP 26 EP 26 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 258RT UT WOS:000252887900081 ER PT J AU Murphy, CD Lee, JM Drohan, B Lawrence, CJ Kopans, DB Moore, RH Javid, SH Gadd, MA Specht, MC Hughes, KS AF Murphy, C. D. Lee, J. M. Drohan, B. Lawrence, C. J. Kopans, D. B. Moore, R. H. Javid, S. H. Gadd, M. A. Specht, M. C. Hughes, K. S. TI Cost analysis of the American Cancer Society (ACS) guidelines for breast screening with MRI: An alternative strategy versus the 20% solution SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 61st Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 13-16, 2008 CL Chicago, IL SP Soc Surg Oncol C1 [Murphy, C. D.; Lee, J. M.; Lawrence, C. J.; Kopans, D. B.; Moore, R. H.; Javid, S. H.; Gadd, M. A.; Specht, M. C.; Hughes, K. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Drohan, B.] Univ Massachusetts Lowell, Lowell, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2008 VL 15 SU 2 BP 43 EP 43 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 258RT UT WOS:000252887900130 ER PT J AU Schwab, JH Healey, JH Boland, PJ AF Schwab, J. H. Healey, J. H. Boland, P. J. TI The surgical management of sacral chordoma SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 61st Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 13-16, 2008 CL Chicago, IL SP Soc Surg Oncol C1 [Healey, J. H.; Boland, P. J.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Schwab, J. H.] Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2008 VL 15 SU 2 BP 65 EP 66 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA 258RT UT WOS:000252887900202 ER PT J AU Rocha, FG George, S Fletcher, C Bertagnolli, MM Butrynski, J Demetri, G Morgan, J Wagner, A Raut, CP AF Rocha, F. G. George, S. Fletcher, C. Bertagnolli, M. M. Butrynski, J. Demetri, G. Morgan, J. Wagner, A. Raut, C. P. TI Pregnancy-associated desmoid tumors: A distinct clinical entity SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 61st Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 13-16, 2008 CL Chicago, IL SP Soc Surg Oncol C1 [Rocha, F. G.; Fletcher, C.; Bertagnolli, M. M.; Raut, C. P.] Brigham & Womens Hosp, Boston, MA USA. [George, S.; Butrynski, J.; Demetri, G.; Morgan, J.; Wagner, A.] Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2008 VL 15 SU 2 BP 66 EP 66 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 258RT UT WOS:000252887900205 ER PT J AU Pessler, F Ogdie, A Diaz-Torne, C Dai, L Yu, X Einhorn, E Gay, S Schumacher, HR AF Pessler, F. Ogdie, A. Diaz-Torne, C. Dai, L. Yu, X. Einhorn, E. Gay, S. Schumacher, H. R. TI Subintimal Ki-67 as a synovial tissue biomarker for inflammatory arthropathies SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID HISTOPATHOLOGICAL GRADING SYSTEM; RHEUMATOID-ARTHRITIS; IMMUNOHISTOCHEMICAL ANALYSIS; REACTIVE ARTHRITIS; EXPRESSION; CELLS; PROLIFERATION; IGV(H) AB Objectives: Ki-67 is expressed in the nuclei of dividing cells and can be used to assess proliferation of synovial inflammatory and stromal cells. We evaluated subintimal Ki-67+ cell density as a tissue biomarker for inflammatory arthropathies and compared it to subintimal CD68, a synovial biomarker of RA. Methods: Subintimal Ki-67+ and CD68+ cell densities were measured immunohistochemically in synovial specimens obtained from patients with rheumatoid arthritis (RA; n = 19), osteoarthritis (OA; n = 18), "non-inflammatory'' orthopaedic arthropathies ( avascular necrosis, meniscus injury, femur fracture; n = 16), chronic septic arthritis ( n = 9), and histologically normal synovium (n = 10). Results were correlated with a histological synovitis score. Utilising the areas under receiver operating characteristic curves (AUCs), we compared the abilities of Ki-67 and CD68 to differentiate among these arthropathies. Results: Ki-67 was expressed widely in the subintima of inflamed specimens and in RA pannus invading hard tissues. Compared to normal controls, it was highly overexpressed in RA (26.6-fold) and chronic septic arthritis (55-fold), and mildly elevated in OA ( 3.9-fold) and orthopaedic arthropathies (2.1-fold). Ki-67 and CD68 differentiated similarly well between RA and OA (AUC: Ki-67 = 0.91, CD68 = 0.94), Ki-67 better between chronic septic arthritis and RA, and CD68 better between OA and normal controls. Ki-67 (r = 0.80) and CD68 (r = 0.79) correlated positively with the synovitis score. Conclusions: Subintimal Ki-67 was overexpressed in inflammatory arthropathies, distinguished among differentially inflamed arthropathies, and correlated positively with the histological severity of synovitis. It may prove useful in synovial tissue classification and as a synovial marker of disease activity in clinical trials when biopsies are available. C1 [Pessler, F.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Ogdie, A.; Diaz-Torne, C.; Dai, L.; Yu, X.; Schumacher, H. R.] Univ Penn, Sch Med, Div Rheumatol, Philadelphia, PA 19104 USA. [Einhorn, E.] Philadelphia VA Med Ctr, Dept Pathol, Philadelphia, PA USA. [Gay, S.] Univ Zurich, WHO Collaborating Ctr Mol Biol & Novel Therapeut, CH-8006 Zurich, Switzerland. RP Pessler, F (reprint author), Tech Univ Dresden, Klin & Poliklin Kinder & Jugendmed, Dresden, Germany. EM frank.pessler@uniklinikum-dresden.de OI Cesar, Diaz-Torne/0000-0001-6275-7699; Ogdie, Alexis/0000-0002-4639-0775 FU NCI NIH HHS [T32-CA 09140]; NIAMS NIH HHS [T32-AR 007442] NR 22 TC 21 Z9 22 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD FEB PY 2008 VL 67 IS 2 BP 162 EP 167 DI 10.1136/ard.2007.071670 PG 6 WC Rheumatology SC Rheumatology GA 250LN UT WOS:000252301700005 PM 17613556 ER PT J AU Wright, CD Choi, NC Wain, JC Mathisen, DJ Lynch, TJ Fidias, P AF Wright, Cameron D. Choi, Noah C. Wain, John C. Mathisen, Douglas J. Lynch, Thomas J. Fidias, Panos TI Induction chemoradiotherapy followed by resection for locally advanced masaoka stage III and IVA thymic tumors SO ANNALS OF THORACIC SURGERY LA English DT Article ID LUNG-CANCER; MULTIMODALITY TREATMENT; SURGICAL RESECTION; RADIATION-THERAPY; INVASIVE THYMOMA; SUPERIOR SULCUS; PHASE-II; CHEMOTHERAPY; CHEMORADIATION; CARCINOMAS AB Background. The treatment of locally advanced thymic tumors is not uniform. Recently, several centers have reported the results of induction chemotherapy followed by resection and then radiation. Our center adopted an alternative strategy and treated locally advanced thymic tumors with induction chemoradiotherapy in an effort to maximize the intensity of the induction therapy. Methods. A retrospective review was performed of 10 patients with locally advanced thymic tumors treated from 1997 to 2006. Seven patients were clinically staged as Masaoka stage III and 3 as stage IVA. The treatment plan included two cycles of cisplatin and etoposide with concurrent radiation. Patients then had resection followed by postoperative chemotherapy if they were judged to be at high risk for relapse. Results. Four patients had a partial radiographic response to induction therapy and 6 had no response. Eight patients had a R0 resection and 2 had a R1 resection. Four patients had substantial (> 90%) necrosis in the resected specimen. There was no postoperative mortality. Seven patients had two more cycles of chemotherapy. The median follow-up was 41 months. Three patients had recurrences. The 5-year estimated survival was 69% (95% confidence interval: 32% to 100%). Conclusions. Induction therapy for locally advanced thymic tumors with cisplatin, etoposide, and radiation is well tolerated, with many patients having a partial radiographic response. The majority of patients can undergo a complete resection with this treatment. The survival of these patients compares favorably with those undergoing other induction regimens. Further efforts to maximize the intensity of induction therapy for locally advanced thymic tumors is warranted. We have initiated a multicenter phase 2 clinical trial (NCT00387868) to prospectively test this concept. C1 [Wright, Cameron D.] Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Med Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Radiat Oncol, Boston, MA 02114 USA. RP Wright, CD (reprint author), Massachusetts Gen Hosp, Div Thorac Surg, Blake 1570,55 Fruit St, Boston, MA 02114 USA. EM wright.cameron@mgh.harvard.edu NR 16 TC 68 Z9 72 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD FEB PY 2008 VL 85 IS 2 BP 385 EP 389 DI 10.1016/j.athoracsur.2007.08.051 PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 255NO UT WOS:000252664900005 PM 18222230 ER PT J AU Olenchock, SA Karmpaliotis, D Gibson, WJ Murphy, SA Southard, MC Ciaglo, L Buros, J Mack, MJ Alexander, JH Harrington, RA Califf, RM Kouchoukos, NT Ferguson, TB Gibson, CM AF Olenchock, Stephen A., Jr. Karmpaliotis, Dimitri Gibson, William J. Murphy, Sabina A. Southard, Matthew C. Ciaglo, Lauren Buros, Jacqueline Mack, Michael J. Alexander, John H. Harrington, Robert A. Califf, Robert M. Kouchoukos, Nicholas T. Ferguson, T. Bruce, Jr. Gibson, C. Michael TI Impact of saphenous vein graft radiographic markers on clinical events and angiographic parameters SO ANNALS OF THORACIC SURGERY LA English DT Article ID MYOCARDIAL-INFARCTION; FRAME COUNT; PREVENT-IV; MORTALITY; FAILURE; TRIAL AB Background. Use of saphenous vein graft (SVG) radiographic markers has been associated with shorter cardiac catheterization procedure times and reduced contrast agent volume for postoperative coronary artery bypass graft (CABG) catheterizations. Use of such markers is varied and often operator-dependent, as the effect of SVG markers has not been fully evaluated. The goal of the present analysis was to evaluate the association of SVG markers with clinical outcomes and graft patency. Methods. Data were drawn from the Project of Ex-vivo Vein Graft Engineering via Transfection (PREVENT) IV trial of patients undergoing CABG at 107 hospitals across the United States. Repeat angiography was performed within 12 to 18 months after CABG. The SVG markers were used at the discretion of the surgeon and were identified on the follow-up angiogram as any device used to mark the ostium, regardless of shape. Results. The SVG markers were present in 51.2% of evaluable patients (910 of 1,778) and 52.3% of SVGs (2,228 of 4,240). Among patients with totally occluded SVGs (n = 911), visual identification of the SVG was obtained more frequently in those with an SVG marker (90.7% vs 72.1%, p < 0.001). The SVG stenosis 70% or greater at follow-up did not differ by use of markers (25.8% with marker vs 24.4% without marker, p = not significant). These findings were also consistent in ostial lesions (n = 942). Long-term death or myocardial infarction (MI) was similar by use of marker. The perioperative CABG MI was higher in patients with SVG markers (10.1% vs 5.5%, odds ratio adjusted 1.86, p = 0.021). Conclusions. Saphenous vein graft radiographic markers were associated with higher rates of direct visualization of totally occluded SVGs without an adverse effect on graft patency or long-term clinical outcomes, but the association of SVG markers with increased perioperative CABG MI warrants further examination. C1 [Olenchock, Stephen A., Jr.] Tufts Univ, Sch Med, Dept Cardiothorac Surg, Boston, MA 02111 USA. Caritas St Elizabeths Med Ctr, Boston, MA USA. Piedmont Hosp, Fuqua Heart Ctr, Atlanta, GA USA. MIT, Cambridge, MA 02139 USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiovasc, Boston, MA 02215 USA. Inst Sci & Technol, Dallas, TX USA. Harvard Univ, Sch Med, Boston, MA USA. Duke Univ, Clin Res Inst, Durham, NC USA. Missouri Baptist Med Ctr, St Louis, MO USA. E Carolina Univ, E Carolina Heart Inst, Brody Sch Med, Greenville, NC USA. RP Gibson, CM (reprint author), TIMI Data Coordinating Ctr, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM mgibson@perfuse.org OI Buros, Jacqueline/0000-0001-9588-4889 NR 17 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD FEB PY 2008 VL 85 IS 2 BP 520 EP 524 DI 10.1016/j.athoracsur.2007.10.061 PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 255NO UT WOS:000252664900027 PM 18222256 ER PT J AU Kontoyiannis, DP Lewis, RE Alexander, BD Lortholary, O Dromer, F Gupta, KL John, GT del Busto, R Klintmalm, GB Somani, J Lyon, GM Pursell, K Stosor, V Munoz, P Limaye, AP Kalil, AC Pruett, TL Garcia-Diaz, J Humar, A Houston, S House, AA Wray, D Orloff, S Dowdy, LA Fisher, RA Heitman, J Albert, ND Wagener, MM Singh, N AF Kontoyiannis, Dimitrios P. Lewis, Russell E. Alexander, Barbara D. Lortholary, Olivier Dromer, Francoise Gupta, Krishan L. John, George T. del Busto, Ramon Klintmalm, Goran B. Somani, Jyoti Lyon, G. Marshall Pursell, Kenneth Stosor, Valentina Munoz, Patricia Limaye, Ajit P. Kalil, Andre C. Pruett, Timothy L. Garcia-Diaz, Julia Humar, Atul Houston, Sally House, Andrew A. Wray, Dannah Orloff, Susan Dowdy, Lorraine A. Fisher, Robert A. Heitman, Joseph Albert, Nathaniel D. Wagener, Marilyn M. Singh, Nina TI Calcineurin inhibitor agents interact synergistically with antifungal agents in vitro against Cryptococcus neoformans isolates: Correlation with outcome in solid organ transplant recipients with Cryptococcosis SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID CANDIDA-ALBICANS; SUSCEPTIBILITY; FLUCONAZOLE; VORICONAZOLE; COMBINATION; VIRULENCE; TOR AB Synergistic interactions were observed between CIs and antifungal agents against 53 (90%) of 59 Cryptococcus neoformans isolates from solid organ transplant recipients with cryptococcosis and may account for better outcomes in patients with cryptococcosis receiving these immunosuppressive agents. C1 [Kontoyiannis, Dimitrios P.; Lewis, Russell E.; Albert, Nathaniel D.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Alexander, Barbara D.] Duke Univ, Med Ctr, Durham, NC USA. [Lortholary, Olivier; Dromer, Francoise; Heitman, Joseph] Inst Pasteur, Paris, France. [Lortholary, Olivier; Heitman, Joseph] Hop Necker Enfants Malad, Fac Med Paris Descartes, Paris, France. [Gupta, Krishan L.] Postgrad Inst Med Educ & Res, Chandigarh 160012, India. [John, George T.] Christian Med Coll & Hosp, Vellore 632004, Tamil Nadu, India. [del Busto, Ramon] Henry Ford Hosp, Detroit, MI 48202 USA. [Klintmalm, Goran B.] Baylor Univ, Med Ctr, Dallas, TX USA. [Somani, Jyoti; Lyon, G. Marshall] Emory Univ, Atlanta, GA 30322 USA. [Pursell, Kenneth] Univ Chicago, Chicago, IL 60637 USA. [Stosor, Valentina] Northwestern Univ, Chicago, IL 60611 USA. [Munoz, Patricia] Hosp Gen Univ Gregorio Maranon, Madrid, Spain. [Limaye, Ajit P.] Univ Washington, Seattle, WA 98195 USA. [Kalil, Andre C.] Univ Nebraska, Omaha, NE 68182 USA. [Pruett, Timothy L.] Univ Virginia, Charlottesville, VA USA. [Garcia-Diaz, Julia] Alton Ochsner Med Fdn & Ochsner Clin, New Orleans, LA 70121 USA. [Humar, Atul] Toronto Gen Hosp, Univ Hlth Network, Toronto, ON, Canada. [Houston, Sally] Univ S Florida, Tampa, FL USA. [House, Andrew A.] Univ Western Ontario, London, ON, Canada. [Wray, Dannah] Med Univ S Carolina, Charleston, SC 29425 USA. [Orloff, Susan] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Dowdy, Lorraine A.] Univ Miami, Miami, FL 33152 USA. [Fisher, Robert A.] Virginia Commonwealth Univ, Richmond, VA USA. [Wagener, Marilyn M.; Singh, Nina] VA Med Ctr, Pittsburgh, PA USA. [Wagener, Marilyn M.; Singh, Nina] Univ Pittsburgh, Med Ctr, VA Pittsburgh Healthcare Syst, Infect Dis Sect 2A 137, Pittsburgh, PA 15240 USA. RP Kontoyiannis, DP (reprint author), Univ Texas MD Anderson Canc Ctr, 1515 Holcombe Blvd,Box 402, Houston, TX 77030 USA. EM dkontoyi@mdanderson.org; nis5@pitt.edu RI Garcia-Diaz, Julia/D-3555-2011; OI Munoz Garcia, Patricia Carmen/0000-0001-5706-5583; Lewis, Russell/0000-0002-2002-4339 FU NIAID NIH HHS [R01 AI054719, R01 AI 054719-01] NR 23 TC 42 Z9 43 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD FEB PY 2008 VL 52 IS 2 BP 735 EP 738 DI 10.1128/AAC.00990-07 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 256JN UT WOS:000252724800051 PM 18070977 ER PT J AU Isenbarger, TA Finney, M Rios-Velazquez, C Handelsman, J Ruvkun, G AF Isenbarger, Thomas A. Finney, Michael Rios-Velazquez, Carlos Handelsman, Jo Ruvkun, Gary TI Miniprimer PCR, a new lens for viewing the microbial world SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID RIBOSOMAL-RNA GENES; BACTERIAL DIVERSITY; HALOBACTERIUM-HALOBIUM; COMMUNITY STRUCTURE; MULTITEMPLATE PCR; 16S; BIAS; IDENTIFICATION; AMPLIFICATION; ENVIRONMENT AB Molecular methods based on the 16S rRNA gene sequence are used widely in microbial ecology to reveal the diversity of microbial populations in environmental samples. Here we show that a new PCR method using an engineered polymerase and 10-nucleotide 'miniprimers" expands the scope of detectable sequences beyond those detected by standard methods using longer primers and Taq polymerase. After testing the method in silico to identify divergent ribosomal genes in previously cloned environmental sequences, we applied the method to soil and microbial mat samples, which revealed novel 16S rRNA gene sequences that would not have been detected with standard primers. Deeply divergent sequences were discovered with high frequency and included representatives that define two new division-level taxa, designated CRI and CR2, suggesting that miniprimer PCR may reveal new dimensions of microbial diversity. C1 [Isenbarger, Thomas A.; Handelsman, Jo] Univ Wisconsin, Dept Bacteriol, Madison, WI 53706 USA. [Isenbarger, Thomas A.; Handelsman, Jo] Univ Wisconsin, Dept Plant Pathol, Madison, WI 53706 USA. [Isenbarger, Thomas A.; Finney, Michael; Ruvkun, Gary] Harvard Univ, Dept Genet, Boston, MA 02114 USA. [Isenbarger, Thomas A.; Finney, Michael; Ruvkun, Gary] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Rios-Velazquez, Carlos] Univ Puerto Rico, Dept Biol, Mayaguez, PR USA. RP Handelsman, J (reprint author), Univ Wisconsin, Dept Bacteriol, 1550 Linden Dr, Madison, WI 53706 USA. EM joh@bact.wisc.edu FU NIAID NIH HHS [F32 AI065067, F32AI065067] NR 41 TC 52 Z9 55 U1 1 U2 13 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD FEB PY 2008 VL 74 IS 3 BP 840 EP 849 DI 10.1128/AEM.01933-07 PG 10 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 260OG UT WOS:000253019000036 PM 18083877 ER PT J AU Schultz, MK Cessna, JT Anderson, TL Ponto, JA Petry, N Kowalsky, RJ Palmer, MR Beinlich, UF Baker, W Hinkle, GH Hung, JC Quinton, T Rice, PA Divgi, C Norenberg, JP AF Schultz, Michael K. Cessna, Jeffrey T. Anderson, Tamara L. Ponto, James A. Petry, Neil Kowalsky, Richard J. Palmer, Matthew R. Beinlich, Uwe F. Baker, William Hinkle, George H. Hung, Joseph C. Quinton, Timothy Rice, Peter A. Divgi, Chaitanya Norenberg, Jeffrey P. TI A performance evaluation of Y-90 dose-calibrator measurements in nuclear pharmacies and clinics in the United States SO APPLIED RADIATION AND ISOTOPES LA English DT Article DE (90)Yttrium; radiopharmacy; ibritumomab tiuxetan; dose calibrator; measurement assurance ID NON-HODGKINS-LYMPHOMA; RADIONUCLIDE CALIBRATORS; ASSURANCE PROGRAM; RADIOIMMUNOTHERAPY; MEDICINE; STANDARD AB A blind performance test was conducted to evaluate dose-calibrator measurements at nuclear pharmacies in the United States (US). Two test-sample geometries were chosen to represent those used for measurements of Y-90-ibritumomab tiuxetan (ZEVALINO(R)). The radioactivity concentration of test-samples was verified by the US National Institute of Standards and Technology. Forty-five results were reported by 10 participants. Eighty percent of reported values were within the US Pharmacopoeia content standard ( 10%) for Y-90-ZEVALIN(R). All results were within US Nuclear Regulatory Commission conformance limits (+/-20%) for defining therapeutic misadministrations. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Schultz, Michael K.; Cessna, Jeffrey T.] NIST, Nucl Med Standards Program, Gaithersburg, MD 20899 USA. [Anderson, Tamara L.; Norenberg, Jeffrey P.] Univ New Mexico, Hlth Sci Ctr, Coll Pharm, New Mexico Ctr Isotopes Med, Albuquerque, NM 87131 USA. [Ponto, James A.] Univ Iowa Hosp & Clin, Dept Nucl Med, Dept Radiol, Iowa City, IA 52242 USA. [Petry, Neil] Duke Univ, Med Ctr, Dept Nucl Med, Dept Radiol, Durham, NC 27710 USA. [Kowalsky, Richard J.] Univ N Carolina, Dept Radiol, Chapel Hill, NC 27599 USA. [Palmer, Matthew R.] Beth Israel Deaconess Med Ctr, Div Nucl Med, Dept Radiol, Boston, MA 02215 USA. [Beinlich, Uwe F.] QSA Global Inc, Auriga Med Div, Burlington, MA 01803 USA. [Baker, William] Pharmaceut & Diagnost Serv, W Valley City, UT 84119 USA. [Hinkle, George H.] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. [Hung, Joseph C.] Mayo Clin, Div Nucl Med, Dept Radiol, Rochester, MN 55905 USA. [Quinton, Timothy] Radiopharm Inc, Evansville, IN 47711 USA. [Rice, Peter A.] Massachusetts Gen Hosp, Div Nucl Med, Boston, MA 02114 USA. [Divgi, Chaitanya] Univ Penn, Hosp Univ Penn, Div Nucl Med & Clin Mol Imaging, Philadelphia, PA 19104 USA. RP Schultz, MK (reprint author), NIST, Nucl Med Standards Program, 100 Bur Dr,MS 8462, Gaithersburg, MD 20899 USA. EM michael-schultz@uiowa.edu NR 25 TC 3 Z9 3 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0969-8043 J9 APPL RADIAT ISOTOPES JI Appl. Radiat. Isot. PD FEB PY 2008 VL 66 IS 2 BP 252 EP 260 DI 10.1016/j.apradiso.2007.09.002 PG 9 WC Chemistry, Inorganic & Nuclear; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Chemistry; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 261TO UT WOS:000253103100021 PM 17933545 ER PT J AU Kouba, DJ Fincher, EF Moy, RL AF Kouba, David J. Fincher, Edgar F. Moy, Ronald L. TI Nevus of Ota successfully treated by fractional photothermolysis using a fractionated 1440-nm Nd : YAG laser SO ARCHIVES OF DERMATOLOGY LA English DT Article ID SWITCHED RUBY-LASER; ACQUIRED BILATERAL NEVUS; DERMAL MELANOCYTOSIS; ALEXANDRITE; TRIAL; MACULES C1 [Kouba, David J.] Henry Ford Hlth Syst, Detroit, MI USA. [Fincher, Edgar F.; Moy, Ronald L.] W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. [Fincher, Edgar F.; Moy, Ronald L.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Moy, RL (reprint author), Moy Fincher Med Grp, 100 UCLA Med Plaza,Suite 590, Los Angeles, CA 90024 USA. EM rmoy@ucla.edu NR 24 TC 29 Z9 30 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD FEB PY 2008 VL 144 IS 2 BP 156 EP 158 DI 10.1001/archdermatol.2007.49 PG 3 WC Dermatology SC Dermatology GA 262RE UT WOS:000253164900002 PM 18283171 ER PT J AU Kimball, AB Gordon, KB Langley, RG Menter, A Chartash, EK Valdes, J AF Kimball, Alexa B. Gordon, Kenneth B. Langley, Richard G. Menter, Alan Chartash, Elliot K. Valdes, Joaquin CA ABT-874 Psoriasis Study Investigat TI Safety and efficacy of ABT-874, a fully human interleukin 12/23 monoclonal antibody, in the treatment of moderate to severe chronic plaque psoriasis SO ARCHIVES OF DERMATOLOGY LA English DT Article; Proceedings Paper CT Summer Meeting of the American-Academy-of-Dermatology CY AUG 02-04, 2007 CL New York, NY SP Amer Acad Dermatol ID QUALITY-OF-LIFE; DOUBLE-BLIND; CLINICAL-RESPONSE; THERAPY; TRIAL; SKIN; PATHOGENESIS; EXPRESSION; DISTINCT; LINEAGE AB Objective: To investigate the efficacy and safety of ABT-874, an interleukin 12/23 monoclonal antibody, in psoriasis. Design: Phase 2, 12-week, multicenter, randomized, double-blind, placebo-controlled trial. Setting: Outpatient dermatology clinics. Patients: One hundred eighty patients with clinically stable moderate to severe chronic plaque psoriasis. Interventions: Patients were randomized in groups of 30 to receive 1 of 6 treatments with ABT-874 provided as a subcutaneous injection: one 200-mg dose at week 0; 100 mg every other week for 12 weeks; 200 mg weekly for 4 weeks; 200 mg every other week for 12 weeks; 200 mg weekly for 12 weeks; or placebo. Main Outcome Measure: At least a 75% reduction in the Psoriasis Area and Severity Index. Results: The percentage of patients achieving a 75% reduction in the Psoriasis Area and Severity Index at week 12 was statistically significantly greater in all of the ABT-874 treatment groups than in the placebo group (200 mg once, 63% [19 of 30]; 100 mg every other week for 12 weeks, 93% [28 of 30]; 200 mg weekly for 4 weeks, 90% [27 of 30]; 200 mg every other week for 12 weeks, 93% [28 of 30]; 200 mg weekly for 12 weeks, 90% [27 of 301; placebo, 3% [1 of 301; P <.001). Treatment with ABT-874 was well tolerated. The most common adverse event was injection-site reaction, and the most common infectious adverse events were nasopharyngitis and upper respiratory tract infection. There were no serious infectious adverse events. Conclusions: ABT-874, an interleukin 12/23 monoclonal antibody, was highly effective and well tolerated in the treatment of psoriasis. Longer-term studies are required to confirm these findings. Trial Registration: clinical trials. gov Identifier: NCT00292396. C1 [Kimball, Alexa B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Clin Unit Res Trials Skin, Boston, MA 02114 USA. [Kimball, Alexa B.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Clin Unit Res Trials Skin, Boston, MA 02114 USA. [Gordon, Kenneth B.] Evanston NW Healthcare, Div Dermatol, Evanston, IL USA. [Langley, Richard G.] Dalhousie Univ, Dept Med, Div Dermatol, Halifax, NS, Canada. [Menter, Alan] Baylor Res Inst, Dept Internal Med, Div Dermatol, Dallas, TX USA. [Chartash, Elliot K.] Abbott Labs, Parsippany, NJ USA. [Valdes, Joaquin] Abbott Labs, Abbott Pk, IL 60064 USA. RP Kimball, AB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Clin Unit Res Trials Skin, 50 Staniford St,246, Boston, MA 02114 USA. EM harvardskinstudies@partners.org RI menter md, alan/A-8250-2009 NR 32 TC 136 Z9 142 U1 0 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD FEB PY 2008 VL 144 IS 2 BP 200 EP 207 DI 10.1001/archdermatol.2007.63 PG 8 WC Dermatology SC Dermatology GA 262RE UT WOS:000253164900007 PM 18283176 ER PT J AU Gunzler, SA Koudelka, C Carlson, NE Pavel, M Nutt, JG AF Gunzler, Steven A. Koudelka, Caroline Carlson, Nichole E. Pavel, Misha Nutt, John G. TI Effect of low concentrations of apomorphine on parkinsonism in a randomized, placebo-controlled, crossover study SO ARCHIVES OF NEUROLOGY LA English DT Article ID MOTOR FLUCTUATIONS; IN-VIVO; DISEASE; LEVODOPA; RECEPTORS; DETERIORATION; PERGOLIDE; MICE AB Objective: To determine whether low concentrations of a dopamine agonist worsen parkinsonism, which would suggest that activation of presynaptic dopamine autoreceptors causes a super-off state. Design: Randomized, double-blind, placebo-controlled, crossover clinical trial. Setting: Academic movement disorders center. Patients: Patients with Parkinson disease and motor fluctuations. Intervention: Fourteen patients with Parkinson disease and motor fluctuations were randomized to receive 1 of 6 possible sequences of placebo, low-dose (subthreshold) apomorphine hydrochloride, and high-dose (threshold to suprathreshold) apomorphine hydrochloride infusions. Subthreshold doses of apomorphine hydrochloride (12.5 mu g/kg/h every 2 hours and 25 mu g/kg/h every 2 hours), threshold to suprathreshold doses of apomorphine hydrochloride (50 mu g/kg/h every 2 hours and 100 mu g/kg/h every 2 hours), and placebo were infused for 4 hours daily for 3 consecutive days. Main Outcome Measures: Finger and foot tapping rates. Results: There was no decline in finger or foot tapping rates during the low-dose apomorphine hydrochloride infusions relative to placebo. The high-dose infusions increased foot tapping (P < .001) and trended toward increasing finger tapping compared with placebo infusions. Conclusions: Subthreshold concentrations of apomorphine did not worsen parkinsonism, suggesting that presynaptic dopamine autoreceptors are not important to the motor response in moderate to advanced Parkinson disease. Trial Registration: clinicaltrials.gov Identifier: NCT00472355. C1 [Gunzler, Steven A.] Univ Hosp Case Med Ctr, Neurol Inst, Movement Disorders Ctr, Cleveland, OH 44106 USA. [Gunzler, Steven A.] Case Western Reserve Univ, Sch Med, Cleveland, OH 44106 USA. [Gunzler, Steven A.; Nutt, John G.] Portland VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Portland, OR USA. [Gunzler, Steven A.; Nutt, John G.] Oregon Hlth & Sci Univ, Parkinson Ctr Oregon, Portland, OR 97201 USA. [Koudelka, Caroline] Oregon Hlth & Sci Univ, Oregon Clin & Translat Res Inst, Portland, OR 97201 USA. [Carlson, Nichole E.] Oregon Hlth & Sci Univ, Div Biostat, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. [Pavel, Misha] Oregon Hlth & Sci Univ, Dept Biomed Engn, Portland, OR 97201 USA. RP Gunzler, SA (reprint author), Univ Hosp Case Med Ctr, Neurol Inst, Movement Disorders Ctr, 11100 Euclid Ave, Cleveland, OH 44106 USA. EM steven.gunzler@uhhospitals.org FU NCRR NIH HHS [UL1 RR 024140-01, UL1 RR024140]; NINDS NIH HHS [R01 NS021062-22, R01 NS021062] NR 21 TC 4 Z9 4 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD FEB PY 2008 VL 65 IS 2 BP 193 EP 198 DI 10.1001/archneurol.2007.58 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 261DH UT WOS:000253058800004 PM 18268187 ER PT J AU Sundelof, J Giedraitis, V Irizarry, MC Sundstrom, J Ingelsson, E Ronnemaa, E Arnlov, J Gunnarsson, MD Hyman, BT Basun, H Ingelsson, M Lannfelt, L Kilander, L AF Sundelof, Johan Giedraitis, Vilmantas Irizarry, Michael C. Sundstrom, Johan Ingelsson, Erik Ronnemaa, Elina Arnlov, Johan Gunnarsson, Malin Degerman Hyman, Bradley T. Basun, Hans Ingelsson, Martin Lannfelt, Lars Kilander, Lena TI Plasma beta amyloid and the risk of Alzheimer disease and dementia in elderly men SO ARCHIVES OF NEUROLOGY LA English DT Article ID MILD COGNITIVE IMPAIRMENT; CEREBROSPINAL-FLUID LEVELS; APOLIPOPROTEIN-E GENOTYPE; PROTEIN A-BETA; CLINICAL-DIAGNOSIS; DOWN-SYNDROME; CELL BIOLOGY; PEPTIDE 1-42; A-BETA-40; BLOOD AB Background: beta Amyloid (A beta) protein accumulates in the brains of individuals with Alzheimer disease (AD) and is detectable in cerebrospinal fluid and plasma. Objective: To examine plasma levels of A beta peptides A beta(40) and A beta(42) as predictors of incident AD and other types of dementia. Design: Prospective, population-based cohort study. Setting: The Uppsala Longitudinal Study of Adult Men. Participants: Plasma A beta(40) and A beta(42) levels were analyzed as predictors of incident AD in 1045 men at age 70 years and 680 men at age 77 years using Cox proportional hazards analyses. Alzheimer disease and other types of dementia were diagnosed by standardized screening, clinical evaluation, and medical record review. Main Outcome Measures: Hazard ratios of AD (primary outcome) and vascular dementia or other dementia (secondary outcomes) according to baseline levels of plasma A beta(40) and A beta(42). Results: From the age of 77 years at baseline, 46 individuals developed AD at follow-up (median, 5.3 years). A low plasma A beta(40) level at age 77 years was associated with higher incidence of AD. The multivariate-adjusted hazard ratio was 4.87 (95% confidence interval, 1.63-14.6) for the lowest A beta(40) tertile compared with the highest tertile. On follow-up from age 70 years at baseline (median, 11.2 years), 82 individuals developed AD. Plasma A beta(40) and A beta(42) levels measured at age 70 years were not significantly associated with incident AD. Conclusions: Low plasma A beta(40) levels predicted incident AD in elderly men independently of potential confounders. Plasma A beta 42 levels were not significantly associated with AD incidence. The clinical value of A beta measurement in plasma remains to be established in future studies. C1 [Sundelof, Johan; Giedraitis, Vilmantas; Ingelsson, Erik; Ronnemaa, Elina; Arnlov, Johan; Gunnarsson, Malin Degerman; Basun, Hans; Ingelsson, Martin; Lannfelt, Lars; Kilander, Lena] Uppsala Univ, Dept Publ Hlth & Geriatr, S-75185 Uppsala, Sweden. [Sundstrom, Johan] Uppsala Univ, Dept Med Sci, S-75185 Uppsala, Sweden. [Irizarry, Michael C.; Hyman, Bradley T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Basun, Hans] AstraZeneca, Sodertalje, Sweden. [Irizarry, Michael C.] GlaxoSmithKline Inc, WW Eipdemiol, Res Triangle Pk, NC USA. RP Lannfelt, L (reprint author), Uppsala Univ, Dept Publ Hlth & Geriatr, Uppsala Sci Pk,Dag Hammarskolds Vag 14B, S-75185 Uppsala, Sweden. EM lars.lannfelt@pubcare.uu.se RI Sundstrom, Johan/A-6286-2009; Arnlov, Johan/N-9886-2013 OI Sundstrom, Johan/0000-0003-2247-8454; FU NIA NIH HHS [AG 05134]; NINDS NIH HHS [1T32 NS 048005-01, T32 NS048005, T32 NS048005-04, T32 NS048005-05] NR 41 TC 75 Z9 77 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD FEB PY 2008 VL 65 IS 2 BP 256 EP 263 DI 10.1001/archneurol.2007.57 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 261DH UT WOS:000253058800015 PM 18268197 ER PT J AU Rashid, S Jin, YP Ecoiffier, T Barabino, S Schaumberg, DA Dana, R AF Rashid, Saadia Jin, Yiping Ecoiffier, Tatiana Barabino, Stefano Schaumberg, Debra A. Dana, Reza TI Topical omega-3 and omega-6 fatty acids for treatment of dry eye SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; ALPHA-LINOLENIC ACID; SJOGRENS-SYNDROME; DENDRITIC CELLS; OCULAR SURFACE; TEAR FLUID; INTERLEUKIN-1; INFLAMMATION; POPULATION; EPITHELIUM AB Objective: To study the efficacy of topical application of alpha-linolenic acid (ALA) and linoleic acid (LA) for dry eye treatment. Methods: Formulations containing ALA, LA, combined ALA and LA, or vehicle alone, were applied to dry eyes induced in mice. Corneal fluorescein staining and the number and maturation of corneal CD11b(+) cells were determined by a masked observer in the different treatment groups. Real-time polymerase chain reaction was used to quantify expression of inflammatory cytokines in the cornea and conjunctiva. Results: Dry eye induction significantly increased corneal fluorescein staining; CD11b(+) cell number and major histocompatibility complex Class II expression; corneal IL-1 alpha and tumor necrosis factor alpha (TNF-alpha) expression; and conjunctival IL-1 alpha, TNF-alpha, interferon gamma, IL-2, IL- and IL-10 expression. Treatment with ALA significantly decreased corneal fluorescein staining compared with both vehicle and untreated controls. Additionally, ALA treatment was associated with a significant decrease in CD11b(+) cell number, expression of corneal IL-1 alpha and TNF-alpha, and conjunctival TNF-alpha. Conclusions: Topical ALA treatment led to a significant decrease in dry eye signs and inflammatory changes at both cellular and molecular levels. Clinical Relevance: Topical application of ALA omega-3 fatty acid may be a novel therapy to treat the clinical signs and inflammatory changes accompanying dry eye syndrome. C1 [Rashid, Saadia; Jin, Yiping; Ecoiffier, Tatiana; Barabino, Stefano; Schaumberg, Debra A.; Dana, Reza] Schepens Eye Res Inst, Boston, MA 02114 USA. [Rashid, Saadia; Jin, Yiping; Ecoiffier, Tatiana; Barabino, Stefano; Schaumberg, Debra A.; Dana, Reza] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Barabino, Stefano] Univ Genoa, Dept Neurosci Ophthalmol & Genet, Genoa, Italy. [Schaumberg, Debra A.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Dana, Reza] Massachusetts Eye & Ear Infirm, Cornea Serv, Boston, MA 02114 USA. RP Dana, R (reprint author), Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM reza.dana@schepens.harvard.edu FU NEI NIH HHS [K23 EY000365, K23 EY000365-04, K23 EY000365-05] NR 45 TC 106 Z9 108 U1 2 U2 14 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD FEB PY 2008 VL 126 IS 2 BP 219 EP 225 DI 10.1001/archophthalmol.2007.61 PG 7 WC Ophthalmology SC Ophthalmology GA 261DQ UT WOS:000253059700009 PM 18268213 ER PT J AU Harris, GF Anderson, ME Lee, JH AF Harris, George F. Anderson, Mary E. Lee, John H. TI The effect of proteasome inhibition on p53 degradation and proliferation in tonsil epithelial cells SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Head-and-Neck-Society/Research Workshop on the Biology, Prevention and Treatment of Head and Neck Cancer CY AUG 17-20, 2006 CL Chicago, IL SP Amer Head & Neck Soc ID HUMAN-PAPILLOMAVIRUS TYPE-16; NECK-CANCER; MEDIATED DEGRADATION; HEAD; E6; CARCINOMA; COMPLEX; RISK; IMMORTALIZATION; UBIQUITINATION AB Objective: To determine whether proteasome inhibition could reverse E6-mediated p53 degradation, cause selective growth inhibition, and induce apoptosis in human papillomavirus E6-transformed primary tonsil epithelial cells. Design: Primary human and mouse tonsil epithelial cell lines were transformed with a retrovirus containing human papillomavirus 16 oncogenes. MG132 was used to inhibit proteasome degradation in vitro and in vivo, and biochemical assays regarding p53 and apoptosis were performed. Results: In cells that express E6, proteasome inhibition with MG132 restored p53 protein levels and decreased proliferation in a dose-dependent fashion that was significantly more pronounced compared with controls. However, inhibition of proliferation occurred at a lower concentration than restoration of p53 protein expression. Also, wild-type and p53 knockout mouse tonsil epithelial cells that express E6 had near-identical inhibition of growth, suggesting that growth inhibition was p53 independent. In vivo studies did not demonstrate any growth inhibition. Conclusion: The findings suggest that proteasome inhibition preferentially inhibits proliferation in cells expressing E6 through a p53-independent mechanism. C1 [Harris, George F.; Lee, John H.] Univ Iowa, Dept Otolaryngol Head & Neck Surg, Iowa City, IA 52242 USA. [Anderson, Mary E.; Lee, John H.] Vet Hlth Adm, Dept Otolaryngol, US Dept Vet Affairs, Iowa City, IA USA. RP Lee, JH (reprint author), Univ Iowa, Dept Otolaryngol Head & Neck Surg, 200 Hawkins Dr, Iowa City, IA 52242 USA. EM john-h-lee@uiowa.edu FU NIDCD NIH HHS [1-K08-DC0005627-1, 5-T32-DC000040] NR 27 TC 4 Z9 4 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD FEB PY 2008 VL 134 IS 2 BP 157 EP 163 DI 10.1001/archoto.2007.37 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 262RG UT WOS:000253165100008 PM 18283158 ER PT J AU Bair-Merritt, MH Feudtner, C Localio, AR Feinstein, JA Rubin, D Holmes, WC AF Bair-Merritt, Megan H. Feudtner, Chris Localio, A. Russell Feinstein, Jamie A. Rubin, David Holmes, William C. TI Health care use of children whose female caregivers have intimate partner violence histories SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID MATERNAL DEPRESSIVE SYMPTOMS; DOMESTIC VIOLENCE; YOUNG-CHILDREN; WOMEN; EMERGENCY; EXPERIENCES; PREVALENCE; INJURIES; EXPOSURE; ASTHMA AB Objective: To determine whether prior exposure to intimate partner violence ( IPV) is associated with children's subsequent emergency department ( ED) visits and hospitalizations. Design: Retrospective cohort study. Setting: The National Survey of Child and Adolescent Well-Being, a nationally representative sample of children reported to Child Protective Services between 1999 and 2000. Participants: Families of children reported to Child Protective Services who were assessed through comprehensive caregiver interviews at baseline and 18 and 36 months. Main Exposure: Severe or minor IPV, as measured by the Conflict Tactics Scale 1. Main Outcome Measures: Number of ED visits or hospitalizations from baseline to the 18-month assessment ( interval 1, n= 2689) and from the 18-month to the 36-month assessment ( interval 2, n= 2546). Results: Compared with children whose female caregivers reported no IPV at baseline, children whose female caregivers disclosed severe IPV at baseline had significantly higher rates of ED visits over both subsequent intervals ( interval 1, incidence rate ratio [ IRR], 2.0; 95% confidence interval [ CI], 1.3-2.9; interval 2, IRR, 1.9; 95% CI, 1.2-3.0). In contrast, rates of hospitalizations were lower in the second interval for children whose female caregivers disclosed minor IPV as compared with no IPV at baseline ( IRR, 0.2; 95% CI, 0.1-0.6). Conclusions: Further research is required to elucidate the complex relationship between IPV and child health care use. Such an understanding will facilitate identification of sites within the health care system where effective interventions for children exposed to IPV, and their caregivers, might be located. C1 [Bair-Merritt, Megan H.] Johns Hopkins Sch Med, Div Gen Pediat & Adolescent Med, Baltimore, MD 21287 USA. [Bair-Merritt, Megan H.; Feudtner, Chris; Feinstein, Jamie A.; Rubin, David] Univ Penn, Childrens Hosp Philadelphia, Div Gen Pediat, Pediat Generalist Res Grp, Philadelphia, PA 19104 USA. [Holmes, William C.] Univ Penn, Vet Adm Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA 19104 USA. [Holmes, William C.] Univ Penn, Dept Med, Hosp Univ Penn, Philadelphia, PA 19104 USA. [Feudtner, Chris; Localio, A. Russell; Rubin, David; Holmes, William C.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Feudtner, Chris] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Bair-Merritt, MH (reprint author), Johns Hopkins Sch Med, Div Gen Pediat & Adolescent Med, 200 N Wolfe St,Off 2021, Baltimore, MD 21287 USA. EM mbairme1@jhmi.edu OI Bair-Merritt, Megan/0000-0002-1876-9817; Feinstein, James/0000-0003-3074-8805 FU PHS HHS [2T32 HP 10026-10] NR 34 TC 5 Z9 5 U1 2 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD FEB PY 2008 VL 162 IS 2 BP 134 EP 139 DI 10.1001/archpediatrics.2007.32 PG 6 WC Pediatrics SC Pediatrics GA 258HU UT WOS:000252859800006 PM 18250237 ER PT J AU Cowan, RE Boninger, ML Sawatzky, BJ Mazoyer, BD Cooper, RA AF Cowan, Rachel E. Boninger, Michael L. Sawatzky, Bonita J. Mazoyer, Brian D. Cooper, Rory A. TI Preliminary outcomes of the SmartWheel Users' Group database: a proposed framework for clinicians to objectively evaluate manual wheelchair propulsion SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE biomechanics; engineering; insurance; rehabilitation; wheelchairs ID SPINAL-CORD INJURIES; PUSHRIM FORCES; SEAT POSITION; ENERGY-COST; BIOMECHANICS; MOBILITY; LEVEL; DISABILITY; KINETICS; HEALTH AB Objectives: To describe a standard clinical protocol for the objective assessment of manual wheelchair propulsion; to establish preliminary values for temporal and kinetic parameters derived from the protocol; and to develop graphical references and a proposed application process for use by clinicians. Design: Case series. Setting: Six research institutions that collect kinetic wheelchair propulsion data and contribute that data to an international data pool. Participants: Subjects with spinal cord injury (N= 128). Interventions: Subjects propelled a wheelchair from a stationary position to a self-selected velocity across a hard tile surface, a low pile carpet, and up an Americans with Disabilities Act-compliant ramp. Unilateral kinetic data were obtained from subjects using a force and moment sensing pushrim. Main Outcome Measures: Differences in self-selected velocity, peak resultant force, push frequency, and stroke length across all surfaces, relationship between (1) weight-normalized peak resultant force and self-selected velocity and (2) push frequency and self-selected velocity. Results: Graphical references were generated for potential clinical use based on the relation between body weight-normalized peak resultant force, push frequency, and velocity. Self-selected velocity decreased (ramp < carpet < tile), peak resultant forces increased (ramp > carpet > tile), and push frequency and stroke length remained unchanged when compared across the different surfaces. Weight-normalized peak resultant force was a significant predictor of velocity on tile and ramp. Push frequency was a significant predictor of velocity on tile, car-pet, and ramp. Conclusions: We present preliminary data generated from a clinically practical manual wheelchair propulsion evaluation protocol and we describe a proposed method for clinicians to objectively evaluate manual wheelchair propulsion. C1 [Cowan, Rachel E.; Boninger, Michael L.; Cooper, Rory A.] VA Pittsburgh Hlth Care Syst, Human Engn Res Lab, Ctr Excellence Wheelchairs & Related Technol, Pittsburgh, PA 15206 USA. [Cowan, Rachel E.; Boninger, Michael L.; Cooper, Rory A.] Univ Pittsburgh, Human Engn Res Labs, Pittsburgh, PA USA. [Boninger, Michael L.; Cooper, Rory A.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Boninger, Michael L.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Cowan, Rachel E.; Boninger, Michael L.; Cooper, Rory A.] Univ Pittsburgh, Sch Hlth & Rehabil Sci, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. [Sawatzky, Bonita J.] Univ British Columbia, Fac Med, Dept Orthopaed, Vancouver, BC, Canada. [Mazoyer, Brian D.] Banner Good Samaritan Rehabil Inst, Phoenix, AZ USA. RP Boninger, ML (reprint author), VA Pittsburgh Hlth Care Syst, Human Engn Res Lab, Ctr Excellence Wheelchairs & Related Technol, 5180 Highland Dr,151R-1, Pittsburgh, PA 15206 USA. EM boninger@pitt.edu RI Mazoyer, Bernard/B-6303-2012; OI Mazoyer, Bernard/0000-0003-0970-2837; Boninger, Michael/0000-0001-6966-919X FU NICHD NIH HHS [1 F31 HD053986-01]; PHS HHS [H133N000019] NR 40 TC 37 Z9 37 U1 1 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD FEB PY 2008 VL 89 IS 2 BP 260 EP 268 DI 10.1016/j.apmr.2007.08.141 PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 260OD UT WOS:000253018700009 PM 18226649 ER PT J AU Hussain, R Cevallos, ME Darouiche, RO Trautner, BW AF Hussain, Rahat Cevallos, Manuel E. Darouiche, Rabih O. Trautner, Barbara W. TI Gram-negative intravascular catheter-related bacteremia in patients with spinal cord injury SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the Infectious-Diseases-Society-of-America CY OCT 12-15, 2006 CL Toronto, CANADA SP Infect Dis Soc Amer DE bacteremia; rehabilitation; spinal cord injuries ID BLOOD-STREAM INFECTIONS; INTENSIVE-CARE UNITS; DECUBITUS ULCERS; BACTERIURIA; PATHOGENESIS; MORTALITY AB Objective: To determine whether the prevalence of gram-negative catheter-related bloodstream infection (CRBSI) is higher in patients with spinal cord injury (SCI) than in patients without SCI. Design: Retrospective chart review from August 1998 to August 2006. Setting: A Veterans Affairs medical center, which serves as a tertiary care medical center to over 500 veterans with SCI and is the primary Source of health care for veterans in southeast Texas. Participants: All hospitalized patients who had an International Classification of Diseases, Ninth Revision, code for bacteremia associated with their hospital stay. Interventions: Not applicable. Main Outcome Measure: The proportion of CRBSI caused by gram-negative organisms in the SCI patients to the proportion of CRBSI caused by gram-negative organisms in the non-SCI patients. Results: Eight (42%) of 19 episodes of CRBSI in the SCI were caused by a gram-negative organism as compared with 4 (11%) of 36 infections in the non-SCI group (P<.01). Factors associated with having a grain-negative organism rather than a grain-positive organism as the causative agent of CRBSI were SCI, femoral catheter site, prolonged hospitalization, decubitus Ulcer, and urinary catheter. Conclusions: In Our medical center, patients with SCI who develop CRBSI are more likely to have an infection with a gram-negative organism than are patients without SCI. This knowledge may guide initial empirical therapy of suspected bloodstream infection. C1 [Hussain, Rahat] Univ Texas Houston, Hlth Sci Ctr, Dept Internal Med, Houston, TX 77225 USA. [Cevallos, Manuel E.; Darouiche, Rabih O.; Trautner, Barbara W.] Baylor Coll Med, Infect Dis Sect, Dept Med, Houston, TX 77030 USA. [Darouiche, Rabih O.; Trautner, Barbara W.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Trautner, BW (reprint author), MEDVAMC, Spinal Cord Injury 128, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM trautner@bcm.edu FU NICHD NIH HHS [HD42014]; VA [VA B4087R] NR 23 TC 5 Z9 5 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD FEB PY 2008 VL 89 IS 2 BP 339 EP 342 DI 10.1016/j.apmr.2007.08.151 PG 4 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 260OD UT WOS:000253018700020 PM 18226660 ER PT J AU Chauhan, AK Kisucka, J Cozzi, MR Walsh, MT Moretti, FA Battiston, M Mazzucato, M De Marco, L Baralle, FE Wagner, DD Muro, AF AF Chauhan, Anil K. Kisucka, Janka Cozzi, Maria R. Walsh, Meghan T. Moretti, Federico A. Battiston, Monica Mazzucato, Mario De Marco, Luigi Baralle, Francisco E. Wagner, Denisa D. Muro, Andres F. TI Prothrombotic effects of fibronectin Isoforms containing the EDA domain SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE plasma fibronectin; fibronectin splice variants isoforms; arterial thrombosis; intravital microscopy; thromboembolism; arterial and venous injury ID VON-WILLEBRAND-FACTOR; PLATELET THROMBUS FORMATION; CELLULAR-FIBRONECTIN; INJURED ARTERIOLES; VASCULAR INJURY; PLASMA-LEVELS; MATRIX; FIBRIN; GENE; EXON AB Objective-Fibronectin (FN) plays an important role in the formation of stable arterial thrombi at the site of vascular injury. FN containing Extra Domain A (EDA(+)FN) is absent from normal plasma, but elevated plasma levels of EDA(+)FN are found in several pathological conditions. We hypothesized that EDA(+)FN plays a special role in thrombosis. Methods and Results-We used mouse strains constitutively including (EDA(-/-)) or excluding (EDA(-/-)) the EDA domain in all tissues and plasma. Using a flow chamber and the ferric-chloride injury model we found that EDA(+)FN accelerates thrombosis both in vitro and in vivo at arterial shear rates. In EDA(-/-) mice thrombi (> 30 mu m) grew faster when compared with EDA(WT/WT) (6.6 +/- 0.2 minutes versus 8.3 +/- 0.6 minutes, P < 0.05) and the mean vessel occlusion time was shorter (9.9 +/- 0.4 minutes versus 14.6 +/- 1.7 minutes, P < 0.05). However, the presence of EDA(+)FN affected neither single platelet adhesion to subendothelium nor thrombosis in veins. In addition, the mortality rate of EDA(-/-) mice after collagen/epinephrine infusion was twice that of EDA(WT/WT) or EDA(-/-) mice. Conclusions-Our findings reveal that EDA(+)FN has prothrombotic activity, and its presence in plasma may worsen pathological conditions in which this form is elevated. C1 [Chauhan, Anil K.; Kisucka, Janka; Walsh, Meghan T.; Wagner, Denisa D.] Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. [Chauhan, Anil K.; Kisucka, Janka; Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Cozzi, Maria R.; Battiston, Monica; Mazzucato, Mario; De Marco, Luigi] Natl Canc Inst, Ctr Riferimento Oncol, Ist Ric & Cura Carattere Sci, Aviano, Italy. [Moretti, Federico A.; Baralle, Francisco E.; Muro, Andres F.] Int Ctr Genet Engn & Biotechnol, I-34012 Trieste, Italy. RP Muro, AF (reprint author), Int Ctr Genet Engn & Biotechnol, Padriciano 99, I-34012 Trieste, Italy. EM wagner@cbr.med.harvard.edu; muro@icgeb.org RI Muro, Andres/K-3156-2016; OI Muro, Andres/0000-0002-9628-0494; Mazzucato, Mario/0000-0001-8319-053X FU NHLBI NIH HHS [R37 HL041002, R37 HL41002]; Telethon [GGP06147] NR 36 TC 29 Z9 29 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD FEB 1 PY 2008 VL 28 IS 2 BP 296 EP 301 DI 10.1161/ATVBAHA.107.149146 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 256DH UT WOS:000252707400015 PM 17991876 ER PT J AU Hazen, MM Woodward, AL Hofmann, I Degar, BA Grom, A Filipovich, AH Binstadt, BA AF Hazen, Melissa M. Woodward, Amy L. Hofmann, Inga Degar, Barbara A. Grom, Alexei Filipovich, AJexandra H. Binstadt, Bryce A. TI Mutations of the hemophagocytic lymphohistiocytosis-associated gene UNC13D in a patient with systemic juvenile idiopathic arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID MACROPHAGE ACTIVATION SYNDROME; RHEUMATOID-ARTHRITIS; EXPRESSION; BLOCKADE; MUNC13-4; CHILDREN; LINKAGE; FHL AB The clinical syndromes of hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are both characterized by dysregulated inflammation with prolonged fever, hepatosplenomegaly, coagulopathy, hematologic cytopenias, and evidence of hemophagocytosis in the bone marrow or liver. While HLH is either inherited or acquired, children with severe rheumatic diseases, most notably systemic juvenile idiopathic arthritis, are at risk for MAS. The phenotypic similarity between HLH and NUS raises the possibility that they share common pathogenetic mechanisms. Familial forms of HLH have been attributed to mutations in the genes encoding perforin (PRF1) and Munc13-4 (UNC13D), among others, and are characterized by defective cytotoxic lymphocyte function. While some patients with systemic RA have decreased levels of perforin protein expression and natural killer (NK) cell function, mutations of HLH-associated genes in patients with systemic RA have not been reported. We report the case of an 8-year-old girl with systemic RA without MAS who was found to have compound heterozygous mutations of UNC13D and reduced NK cell cytotoxic function. This case broadens the range of clinical phenotypes attributable to UNC13D mutations and offers new insights into the etiology and pathogenesis of systemic RA. C1 [Binstadt, Bryce A.] Univ Minnesota, Minneapolis, MN 55455 USA. [Grom, Alexei; Filipovich, AJexandra H.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. [Hofmann, Inga; Degar, Barbara A.] Dana Farber Canc Ctr, Boston, MA USA. [Woodward, Amy L.] Indiana Univ, Sch Med, Indianapolis, IN 46204 USA. [Hazen, Melissa M.] Childrens Hosp, Boston, MA 02115 USA. RP Binstadt, BA (reprint author), Univ Minnesota, 420 Delaware St SE,MMC 296, Minneapolis, MN 55455 USA. EM binstadt@umn.edu RI Binstadt, Bryce/N-1305-2013 OI Binstadt, Bryce/0000-0003-3127-3856 FU NIAID NIH HHS [T32-AI-007512] NR 15 TC 46 Z9 52 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD FEB PY 2008 VL 58 IS 2 BP 567 EP 570 DI 10.1002/art.23199 PG 4 WC Rheumatology SC Rheumatology GA 264BR UT WOS:000253260700026 PM 18240215 ER PT J AU Chen, YL Leask, A Abraham, DJ Pala, D Xu, SW Khan, K Liu, SX Carter, DE Wilcox-Adelman, S Goetinck, P Denton, CP Black, CM Pitsillides, AA Sarraf, CE Eastwood, M AF Chen, Yunliang Leask, Andrew Abraham, David J. Pala, Daphne Xu Shiwen Khan, Korsa Liu, Shangxi Carter, David E. Wilcox-Adelman, Sarah Goetinck, Paul Denton, Christopher P. Black, Carol M. Pitsillides, Andrew A. Sarraf, Catherine E. Eastwood, Mark TI Heparan sulfate-dependent ERK activation contributes to the overexpression of fibrotic proteins and enhanced contraction by scleroderma fibroblasts SO ARTHRITIS AND RHEUMATISM LA English DT Article ID TISSUE GROWTH-FACTOR; SMOOTH-MUSCLE-CELLS; FACTOR-BETA; PROTEOGLYCAN SYNTHESIS; DERMAL FIBROBLASTS; SYSTEMIC-SCLEROSIS; MATRIX CONTRACTION; TGF-BETA; COLLAGEN; FIBROSIS AB Objective. To investigate the contribution of heparan sulfate proteoglycan and Ras/MEK/ERK to the overexpression of profibrotic proteins and the enhanced contractile ability of dermal fibroblasts from patients with systemic sclerosis (SSc; scleroderma). Methods. The effects of the MEK/ERK inhibitor U0126, the heparan sulfate side chain formation inhibitor beta-xyloside, and soluble heparin on the overexpression of profibrotic genes were compared in fibroblasts from lesional skin of patients with diffuse SSc and fibroblasts from healthy control subjects. Identified protein expressions were compared with the contractile abilities of fibroblasts while they resided within a collagen lattice. Forces generated were measured using a culture force monitor. Results. Inhibiting MEK/ERK with U0126 significantly reduced expression of a cohort of proadhesive and procontractile proteins that normally are overexpressed by scleroderma fibroblasts, including integrin alpha 4 and integrin beta 1. Antagonizing heparan sulfate side chain formation with beta-xyloside or the addition of soluble heparin prevented ERK activation, in addition to reducing the expression of these proadhesive/contractile proteins. Treatment with either U0126, beta-xyloside, or heparin resulted in a reduction in the overall peak contractile force generated by dermal fibroblasts. Blocking platelet-derived growth factor receptor with Gleevec (imatinib mesylate) reduced overall contractile ability and the elevated syndecan 4 expression and ERK activation in SSc fibroblasts. Conclusion. The results of this study suggest that heparan sulfate-dependent ERK activation contributes to the enhanced contractile ability demonstrated by dermal fibroblasts from lesional skin of patients with scleroderma. These results are consistent with the notion that the MEK/ERK procontractile pathway is dysregulated in scleroderma dermal fibroblasts. Additionally, the results suggest that antagonizing the MEK/ERK pathway is likely to modulate heparan sulfate proteoglycan activity, which in turn may have a profound effect on the fibrotic response in SSc. C1 [Sarraf, Catherine E.; Eastwood, Mark] Univ Westminster, Sch Biosci, London W1W 6UW, England. [Chen, Yunliang] UCL, London WC1E 6BT, England. [Leask, Andrew; Pala, Daphne; Liu, Shangxi] Univ Western Ontario, Schulich Sch Dent, London, ON N6A 3K7, Canada. [Carter, David E.] London Reg Genom Ctr, London, ON, Canada. [Wilcox-Adelman, Sarah; Goetinck, Paul] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Wilcox-Adelman, Sarah; Goetinck, Paul] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pitsillides, Andrew A.] Univ London Royal Vet Coll, London NW1 0TU, England. RP Eastwood, M (reprint author), Univ Westminster, Sch Biosci, 115 New Cavendish St, London W1W 6UW, England. EM eastwood@wmin.ac.uk RI Leask, Andrew/G-5217-2015 FU Arthritis Research UK; British Heart Foundation NR 44 TC 20 Z9 20 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD FEB PY 2008 VL 58 IS 2 BP 577 EP 585 DI 10.1002/art.23146 PG 9 WC Rheumatology SC Rheumatology GA 264BR UT WOS:000253260700028 PM 18240216 ER PT J AU Keenan, HA Poznik, GD Varo, N Schneider, J Almasy, L Warram, JH Duggirala, R Schoenbeck, U Krolewski, AS Doria, A AF Keenan, Hillary A. Poznik, G. David Varo, Nerea Schneider, Jennifer Almasy, Laura Warram, James H. Duggirala, Ravindranath Schoenbeck, Uwe Krolewski, Andrzej S. Doria, Alessandro TI Identification of a locus modulating serum C-reactive protein levels on chromosome 5p15 SO ATHEROSCLEROSIS LA English DT Article DE CRP; genome-wide scan; diabetes; insulin-resistance; linkage ID TRAIT LINKAGE ANALYSIS; PLASMA CRP LEVELS; POSTMENOPAUSAL WOMEN; VARIANCE-COMPONENTS; DIABETES-MELLITUS; GENETIC-LINKAGE; PROMOTER REGION; INFLAMMATION; POLYMORPHISMS; ASSOCIATION AB Objective: Individual propensity to chronic, low-grade inflammation-a determinant of atherosclerosis-is in part under the control of genetic factors. To identify genes involved in this modulation, we performed a 10 cM genome screen for linkage with plasma C-reactive protein in 38 extended families including 317 non-diabetic and 177 type 2 diabetic family members (2547 relative pairs). Methods and results: In a variance component analysis, heritability of CRP values was significant (h(2)=0.39, p < 0.0001). This effect was independent of BMI and was present in both diabetic (h(2)=0.42, p=0.003) and non-diabetic (h(2)=0.34, p=0.0015) relatives. The strongest evidence of linkage with CRP was on chromosome 5p15, where the LOD score reached genome-wide significance (LOD=3.41, genome-wide p=0.013). Both diabetic and non-diabetic family members contributed to linkage at this location. Smaller linkage peaks were detected on chromosomes 5q35 (LOD=1.35) and 17p11 (LOD=1.33). When the analysis was restricted to diabetic family members, another peak of moderate intensity (LOD=2.17) was evident at 3p21. Conclusions: A major gene influencing CRP levels appears to be located on chromosome 5p15, with an effect that is independent of diabetes. Another gene on 3p21 may control CRP variation but only in the presence of a diabetic or insulin-resistant environment. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Keenan, Hillary A.; Poznik, G. David; Warram, James H.; Krolewski, Andrzej S.; Doria, Alessandro] Joslin Diabet Ctr, Div Res, Sect Genet & Epidemiol, Boston, MA 02215 USA. [Keenan, Hillary A.; Krolewski, Andrzej S.; Doria, Alessandro] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Varo, Nerea] Univ Navarra, Ctr Appl Med Res, Div Cardiovasc Sci, Navarra, Spain. [Schneider, Jennifer; Almasy, Laura; Duggirala, Ravindranath] SW Fdn Biomed Res, Dept Genet, San Antonio, TX USA. [Schoenbeck, Uwe] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA. RP Doria, A (reprint author), Joslin Diabet Ctr, Div Res, Sect Genet & Epidemiol, 1 Joslin Pl, Boston, MA 02215 USA. EM alessandro.doria@joslin.harvard.edu FU NHLBI NIH HHS [HL73168, R01 HL073168, R01 HL073168-03, R01 HL073168-04]; NIDDK NIH HHS [P30 DK036836-19, DK36836, P30 DK036836, R01 DK047475, R01 DK047475-05, T32 DK007260, T32 DK007260-30, T32 DK07260] NR 36 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD FEB PY 2008 VL 196 IS 2 BP 863 EP 870 DI 10.1016/j.atherosclerosis.2007.01.036 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 270TT UT WOS:000253743800048 PM 17343862 ER PT J AU Putnam, KM McSweeney, LB AF Putnam, Katherine M. McSweeney, Lauren B. TI Depressive symptoms and baseline prefrontal EEG alpha activity: A study utilizing ecological momentary assessment SO BIOLOGICAL PSYCHOLOGY LA English DT Article; Proceedings Paper CT 19th Annual Meeting of the Society-for-Research-in-Psychopathology CY OCT 07-10, 2004 CL St Louis, MO SP Soc Res Psychopathol DE depression; electroencephalography (EEG); ecological momentary assessment (EMA); prefrontal cortex (PFC) ID SELF-ESTEEM; RUMINATION; ASYMMETRIES; HOPELESSNESS; EMOTION; BRAIN AB Prefrontal cortex (PFC) electroencephalography (EEG) alpha asymmetry has been found in individuals with major depression. However, EEG activity has never been examined in regard to specific depressive symptoms. We examine the relationship between resting baseline PFC alpha activity and both rumination and self-esteem in a depressed outpatient group (N = 6) and a healthy control group (N = 7) using high-density EEG sampling and multiple longitudinal self report measures, i.e. Ecological Momentary Assessment (EMA). Symptom measures were collected five times daily for 7 days, i.e. 35 assessments. Using a mixed-level analysis, significant Group x Hemisphere interactions for PFC sites and both rumination and self-esteem were found. Within the depressed group, lower bilateral PFC activity predicted higher levels of rumination, and lower right PFC activity predicted higher levels of self-esteem. There were no significant effects for the control group. Results indicate that specific symptoms of depression are uniquely associated with patterns of PFC EEG alpha activity. Published by Elsevier B.V. C1 [Putnam, Katherine M.; McSweeney, Lauren B.] Natl Ctr PTSD, Boston VA Healthcare Syst, Boston, MA 02130 USA. [Putnam, Katherine M.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Putnam, KM (reprint author), Natl Ctr PTSD, Boston VA Healthcare Syst, 150 S Huntington Ave,116B-2, Boston, MA 02130 USA. EM katherine.putnam@va.gov FU NIMH NIH HHS [P50 MH052354, P50-MH069315, P50-MH52354, R37-MH43454, T32-MH18931] NR 36 TC 27 Z9 28 U1 6 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0511 J9 BIOL PSYCHOL JI Biol. Psychol. PD FEB PY 2008 VL 77 IS 2 BP 237 EP 240 DI 10.1016/j.biopsycho.2007.10.010 PG 4 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA 266BV UT WOS:000253407200015 PM 18079035 ER PT J AU Ofran, Y Brusic, V Soiffer, RJ Antin, JH Ritz, J AF Ofran, Y. Brusic, V Soiffer, R. J. Antin, J. H. Ritz, J. TI IDENTIFICATION OF HUMAN MINOR HISTOCOMPATIBILTY ANTIGENS (MHA) BY COMBINING BIOINFORMATIC PREDICTION OF PEPTIDE EPITOPES WITH VALIDATION OF T CELL REACTIVITY IN PATIENT BLOOD SAMPLES AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation CY FEB 13-17, 2008 CL San Diego, CA SP Amer Soc Blood & Marrow Transplantat C1 [Ofran, Y.; Brusic, V; Soiffer, R. J.; Antin, J. H.; Ritz, J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2008 VL 14 IS 2 MA 2 BP 1 EP 1 DI 10.1016/j.bbmt.2007.12.008 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 364IT UT WOS:000260330100003 ER PT J AU Gorgun, G Philpot, PA Naxerova, K Kohane, IS Nadler, LM Guinan, EC AF Gorgun, G. Philpot, P. A. Naxerova, K. Kohane, I. S. Nadler, L. M. Guinan, E. C. TI COSTIMULATORY BLOCKADE (CSB) DURING MIXED LYMPHOCYTE REACTION (MLR) PREVENTS IL27 UPREGULATION AND SIGNALLING SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation CY FEB 13-17, 2008 CL San Diego, CA SP Amer Soc Blood & Marrow Transplantat C1 [Gorgun, G.; Philpot, P. A.; Nadler, L. M.; Guinan, E. C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Naxerova, K.; Kohane, I. S.] Childrens Hosp, Boston, MA 02115 USA. RI Kohane, Isaac Kohane/K-3716-2012 OI Kohane, Isaac Kohane/0000-0003-2192-5160 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2008 VL 14 IS 2 MA 10 BP 6 EP 6 DI 10.1016/j.bbmt.2007.12.018 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 364IT UT WOS:000260330100011 ER PT J AU Mullally, A Kim, H Li, C Mohseni, M Ho, V Alyea, EP Soiffer, RJ Ritz, J AF Mullally, A. Kim, H. Li, C. Mohseni, M. Ho, V Alyea, E. P. Soiffer, R. J. Ritz, J. TI COMPREHENSIVE TYPING OF 1143 SINGLE NUCLEOTIDE POLYMORPHISMS (SNP) IN 220 IMMUNOREGULATORY GENES DEMONSTRATES THAT POLYMORPHISMS IN CCL3, CCL4 AND CCL27 MODULATE THE RISK OF ACUTE GRAFT VERSUS HOST DISEASE (GVHD) SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation CY FEB 13-17, 2008 CL San Diego, CA SP Amer Soc Blood & Marrow Transplantat C1 [Mullally, A.; Kim, H.; Li, C.; Mohseni, M.; Ho, V; Alyea, E. P.; Soiffer, R. J.; Ritz, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2008 VL 14 IS 2 MA 31 BP 14 EP 14 DI 10.1016/j.bbmt.2007.12.039 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 364IT UT WOS:000260330100032 ER PT J AU Sarantopoulos, S Bhuiya, NS Cutler, CS Wu, CJ Brusic, V Soiffer, RJ Antin, JH Ritz, J AF Sarantopoulos, S. Bhuiya, N. S. Cutler, C. S. Wu, C. J. Brusic, V Soiffer, R. J. Antin, J. H. Ritz, J. TI CHARACTERIZATION OF B CELL TARGET ANTIGENS IN PATIENTS WITH CHRONIC GRAFT VERSUS HOST DISEASE SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation/Meeting on Center for International Blood and Marrow Transplant Research Tandem CY FEB 13-17, 2008 CL San Diego, CA SP Amer Soc Blood & Marrow Transplantat, Ctr Int Blood & Marrow Transplant Res Tandem C1 [Wu, C. J.; Brusic, V] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2008 VL 14 IS 2 SU 2 MA 34 BP 15 EP 15 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 364IT UT WOS:000260330100035 ER PT J AU Sarantopoulos, S Stevenson, KE Kim, HT Bhuiya, NS Cutler, CS Alyea, EP Ho, VT Soiffer, RJ Antin, JH Ritz, J AF Sarantopoulos, S. Stevenson, K. E. Kim, H. T. Bhuiya, N. S. Cutler, C. S. Alyea, E. P. Ho, V. T. Soiffer, R. J. Antin, J. H. Ritz, J. TI HIGH BAFF AND BCR-ACTIVATED B CELLS IN PATIENTS WITH PROGRESSIVE CHRONIC GRAFT VERSUS HOST DISEASE AFTER RITUXIMAB TREATMENT SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation/Meeting on Center for International Blood and Marrow Transplant Research Tandem CY FEB 13-17, 2008 CL San Diego, CA SP Amer Soc Blood & Marrow Transplantat, Ctr Int Blood & Marrow Transplant Res Tandem C1 [Stevenson, K. E.; Kim, H. T.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2008 VL 14 IS 2 SU 2 MA 35 BP 15 EP 15 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 364IT UT WOS:000260330100036 ER PT J AU Davies, J Gribbeny, J Brennan, L Nadler, L Guinan, E AF Davies, J. Gribbeny, J. Brennan, L. Nadler, L. Guinan, E. TI ALLOANERGIZED HLA-MISMATCHED BONE MARROW TRANSPLANTATION - LOW INCIDENCE OF CLINICALLY SIGNIFICANT GVHD AND VIRAL INFECTION RESULTING IN LONG TERM DISEASE FREE SURVIVAL SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation CY FEB 13-17, 2008 CL San Diego, CA SP Amer Soc Blood & Marrow Transplantat C1 [Davies, J.; Gribbeny, J.; Brennan, L.; Nadler, L.; Guinan, E.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2008 VL 14 IS 2 MA 38 BP 16 EP 17 DI 10.1016/j.bbmt.2007.12.046 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 364IT UT WOS:000260330100039 ER PT J AU Davies, J Yuk, D Brennan, L Nadler, L Guinan, E AF Davies, J. Yuk, D. Brennan, L. Nadler, L. Guinan, E. TI IN VIVO EXPANSION OF CD4+FOXP3+REGULATORY T CELLS MAY CONTRIBUTE TO CONTROL OF ACUTE GVHD AFTER HLA-MISMATCHED ALLOANERGIZED HSCT SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation CY FEB 13-17, 2008 CL San Diego, CA SP Amer Soc Blood & Marrow Transplantat C1 [Davies, J.; Yuk, D.; Brennan, L.; Nadler, L.; Guinan, E.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2008 VL 14 IS 2 MA 42 BP 18 EP 18 DI 10.1016/j.bbmt.2007.12.050 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 364IT UT WOS:000260330100043 ER PT J AU Armand, P Gannamaneni, S Kim, HT Cutler, CS Ho, VT Koreth, J Alyea, EP LaCasce, AS Jacobsen, ED Fisher, DC Brown, JR Canellos, GP Freedman, AS Soiffer, RJ Antin, JH AF Armand, P. Gannamaneni, S. Kim, H. T. Cutler, C. S. Ho, V. T. Koreth, J. Alyea, E. P. LaCasce, A. S. Jacobsen, E. D. Fisher, D. C. Brown, J. R. Canellos, G. P. Freedman, A. S. Soiffer, R. J. Antin, J. H. TI INCLUSION OF SIROLIMUS IN THE GVHD PROPHYLAXIS REGIMEN IS ASSOCIATED WITH IMPROVED SURVIVAL IN PATIENTS WITH LYMPHOMA UNDERGOING ALLOGENEIC TRANSPLANTATION SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation CY FEB 13-17, 2008 CL San Diego, CA SP Amer Soc Blood & Marrow Transplantat C1 [Armand, P.; Kim, H. T.; Cutler, C. S.; Ho, V. T.; Koreth, J.; Alyea, E. P.; LaCasce, A. S.; Jacobsen, E. D.; Fisher, D. C.; Brown, J. R.; Canellos, G. P.; Freedman, A. S.; Soiffer, R. J.; Antin, J. H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gannamaneni, S.] Cambridge Hlth Alliance, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2008 VL 14 IS 2 MA 54 BP 22 EP 23 DI 10.1016/j.bbmt.2007.12.062 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 364IT UT WOS:000260330100055 ER PT J AU Rosenblatt, J Vasir, B Wu, Z Bissonnette, A MacNamara, C Uhl, L Lenahan, C Miller, K Joyce, R Levine, JD Lowe, K Dombagoda, D Richardson, P Anderson, K Munshi, N Kufe, D Avigan, D AF Rosenblatt, J. Vasir, B. Wu, Z. Bissonnette, A. MacNamara, C. Uhl, L. Lenahan, C. Miller, K. Joyce, R. Levine, J. D. Lowe, K. Dombagoda, D. Richardson, P. Anderson, K. Munshi, N. Kufe, D. Avigan, D. TI VACCINATION WITH DC/MM FUSIONS IN CONJUNCTION WITH STEM CELL TRANSPLANTATION SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation CY FEB 13-17, 2008 CL San Diego, CA SP Amer Soc Blood & Marrow Transplantat C1 [Rosenblatt, J.; Uhl, L.; Lenahan, C.; Miller, K.; Joyce, R.; Levine, J. D.; Lowe, K.; Dombagoda, D.; Avigan, D.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Vasir, B.; Wu, Z.; Bissonnette, A.; MacNamara, C.; Richardson, P.; Anderson, K.; Munshi, N.; Kufe, D.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2008 VL 14 IS 2 MA 56 BP 23 EP 23 DI 10.1016/j.bbmt.2007.12.064 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 364IT UT WOS:000260330100057 ER PT J AU Jacobsohn, DA Browning, B Gilman, A Lehmann, L Nemecek, E Thormann, K Vogelsang, GB AF Jacobsohn, D. A. Browning, B. Gilman, A. Lehmann, L. Nemecek, E. Thormann, K. Vogelsang, G. B. TI MULTI-INSTITUTIONAL PHASE II STUDY OF PENTOSTATIN FOR THE TREATMENT OF REFRACTORY CHRONIC GVHD (cGVHD) IN CHILDREN: A PEDIATRIC BLOOD AND MARROW TRANSPLANT CONSORTIUM (PBMTC) STUDY SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation CY FEB 13-17, 2008 CL San Diego, CA SP Amer Soc Blood & Marrow Transplantat C1 [Jacobsohn, D. A.; Browning, B.; Thormann, K.] Northwestern Univ, Childrens Mem Hosp, Chicago, IL 60614 USA. [Gilman, A.] UNC Sch Med, Chapel Hill, NC USA. [Lehmann, L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Nemecek, E.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Vogelsang, G. B.] Sidney Kimmel Comprehens Canc Ctr John Hopkins, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2008 VL 14 IS 2 MA 61 BP 25 EP 25 DI 10.1016/j.bbmt.2007.12.069 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 364IT UT WOS:000260330100062 ER PT J AU Midura, B Lehmann, L Duncan, C AF Midura, B. Lehmann, L. Duncan, C. TI CLINICAL OUTCOMES OF ADOLESCENT PATIENTS UNDERGOING HEMATOPOIETIC STEM CELL TRANSPLANT SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation CY FEB 13-17, 2008 CL San Diego, CA SP Amer Soc Blood & Marrow Transplantat C1 [Lehmann, L.; Duncan, C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Midura, B.] Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2008 VL 14 IS 2 MA 67 BP 27 EP 27 DI 10.1016/j.bbmt.2007.12.075 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 364IT UT WOS:000260330100068 ER PT J AU Rosenblatt, J Wu, Z Lenaban, C Bissonnette, A Vasir, B Miller, K Joyce, R Levine, JD Galinsky, I Stone, R Kufe, D Avigan, D AF Rosenblatt, J. Wu, Z. Lenaban, C. Bissonnette, A. Vasir, B. Miller, K. Joyce, R. Levine, J. D. Galinsky, I. Stone, R. Kufe, D. Avigan, D. TI TARGETING MUC I AS A MARKER FOR MYELOID LEUKEMIA STEM CELLS BY DC/AML FUSIONS SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation CY FEB 13-17, 2008 CL San Diego, CA SP Amer Soc Blood & Marrow Transplantat C1 [Rosenblatt, J.; Lenaban, C.; Miller, K.; Joyce, R.; Levine, J. D.; Avigan, D.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Wu, Z.; Bissonnette, A.; Vasir, B.; Galinsky, I.; Stone, R.; Kufe, D.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2008 VL 14 IS 2 SU 2 MA 74 BP 30 EP 30 DI 10.1016/j.bbmt.2007.12.082 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 364IT UT WOS:000260330100075 ER PT J AU Cutler, C Kao, G Ho, V Alyea, E Koreth, J Armand, P Dey, B Spitzer, T Soiffer, R Antin, JH Ballen, K AF Cutler, C. Kao, G. Ho, V. Alyea, E. Koreth, J. Armand, P. Dey, B. Spitzer, T. Soiffer, R. Antin, J. H. Ballen, K. TI DOUBLE UMBILICAL CORD BLOOD TRANSPLANTATION WITH REDUCED INTENSITY CONDITIONING AND SIROLIMUS-BASED GVHD PROPHYLAXIS SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation CY FEB 13-17, 2008 CL San Diego, CA SP Amer Soc Blood & Marrow Transplantat C1 [Cutler, C.; Kao, G.; Ho, V.; Alyea, E.; Koreth, J.; Armand, P.; Soiffer, R.; Antin, J. H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Dey, B.; Spitzer, T.; Ballen, K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2008 VL 14 IS 2 MA 130 BP 49 EP 50 DI 10.1016/j.bbmt.2007.12.139 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 364IT UT WOS:000260330100131 ER PT J AU Koreth, J Kim, HT Ho, VT Cutler, CS Soiffer, RJ Antin, JH Alyea, EP AF Koreth, J. Kim, H. T. Ho, V. T. Cutler, C. S. Soiffer, R. J. Antin, J. H. Alyea, E. P. TI BORTEZOMIB PLUS TACROLIMUS/METHOTREXATE FOR PROPHYLAXIS OF ACUTE GVHD AFTER HLA MISMATCHED ALLOGENEIC NON-MYELOABLATIVE TRANSPLANTATION: RESULTS OF A DOSE FINDING PHASE I STUDY SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation CY FEB 13-17, 2008 CL San Diego, CA SP Amer Soc Blood & Marrow Transplantat C1 [Koreth, J.; Kim, H. T.; Ho, V. T.; Cutler, C. S.; Soiffer, R. J.; Antin, J. H.; Alyea, E. P.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2008 VL 14 IS 2 MA 140 BP 53 EP 53 DI 10.1016/j.bbmt.2007.12.149 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 364IT UT WOS:000260330100141 ER PT J AU Avigan, D Rosenblatt, J Vasir, B Wu, Z Bissonnette, A MacNamara, C Ubl, L Lenahan, C Miller, K Joyce, R Levine, JD Lowe, K Donbagoda, D Richardson, P Anderson, K Munshi, N Kufe, D AF Avigan, D. Rosenblatt, J. Vasir, B. Wu, Z. Bissonnette, A. MacNamara, C. Ubl, L. Lenahan, C. Miller, K. Joyce, R. Levine, J. D. Lowe, K. Donbagoda, D. Richardson, P. Anderson, K. Munshi, N. Kufe, D. TI PHASE I STUDY OF VACCINATION WITH DENDRITIC CELL MYELOMA FUSIONS SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation CY FEB 13-17, 2008 CL San Diego, CA SP Amer Soc Blood & Marrow Transplantat C1 [Avigan, D.; Rosenblatt, J.; MacNamara, C.; Ubl, L.; Lenahan, C.; Miller, K.; Joyce, R.; Levine, J. D.; Lowe, K.; Donbagoda, D.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Vasir, B.; Wu, Z.; Bissonnette, A.; Richardson, P.; Anderson, K.; Munshi, N.; Kufe, D.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2008 VL 14 IS 2 MA 172 BP 64 EP 64 DI 10.1016/j.bbmt.2007.12.181 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 364IT UT WOS:000260330100173 ER PT J AU Biernacki, MA Marina, O Liu, F Soiffer, RJ Ritz, J Anderson, KC Wu, CJ AF Biernacki, M. A. Marina, O. Liu, F. Soiffer, R. J. Ritz, J. Anderson, K. C. Wu, C. J. TI IDENTIFICATION OF GRAFT-VERSUS-MYELOMA TARGET ANTIGENS FOLLOWING SYNGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation CY FEB 13-17, 2008 CL San Diego, CA SP Amer Soc Blood & Marrow Transplantat C1 [Biernacki, M. A.; Marina, O.; Soiffer, R. J.; Ritz, J.; Anderson, K. C.; Wu, C. J.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2008 VL 14 IS 2 MA 181 BP 67 EP 67 DI 10.1016/j.bbmt.2007.12.190 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 364IT UT WOS:000260330100182 ER PT J AU Vrooman, L Duncan, C Eaton, M Silverman, LB Lehmann, L AF Vrooman, L. Duncan, C. Eaton, M. Silverman, L. B. Lehmann, L. TI OSTEONECROSIS IN PEDIATRIC HEMATOPOIETIC STEM CELL TRANSPLANTATION SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation CY FEB 13-17, 2008 CL San Diego, CA SP Amer Soc Blood & Marrow Transplantat C1 [Vrooman, L.; Duncan, C.; Eaton, M.; Silverman, L. B.; Lehmann, L.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2008 VL 14 IS 2 MA 193 BP 71 EP 71 DI 10.1016/j.bbmt.2007.12.202 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 364IT UT WOS:000260330100194 ER PT J AU Friedrich-Medina, PM Duncan, CN Lehmann, LE AF Friedrich-Medina, P. M. Duncan, C. N. Lehmann, L. E. TI INFLUENCE OF DONOR AGE ON RISK OF CHRONIC GVHD IN SEX-MISMATCHED PEDIATRIC ALLOGENIC HEMATOPOIETIC STEM CELL TRANSPLANT SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation CY FEB 13-17, 2008 CL San Diego, CA SP Amer Soc Blood & Marrow Transplantat C1 [Duncan, C. N.; Lehmann, L. E.] Childrens Hosp Boston, Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2008 VL 14 IS 2 MA 195 BP 72 EP 72 DI 10.1016/j.bbmt.2007.12.204 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 364IT UT WOS:000260330100196 ER PT J AU Lehmann, LE Buonanno, M Duncan, CN AF Lehmann, L. E. Buonanno, M. Duncan, C. N. TI OUTCOMES OF SECOND MYELOABLATIVE HEMATOPOIETIC STEM CELL TRANSPLANTS IN PEDIATRIC PATIENTS WITH RECURRENT HEMATOLOGIC MALIGNANCIES SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation CY FEB 13-17, 2008 CL San Diego, CA SP Amer Soc Blood & Marrow Transplantat C1 [Lehmann, L. E.; Buonanno, M.; Duncan, C. N.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lehmann, L. E.; Buonanno, M.; Duncan, C. N.] Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2008 VL 14 IS 2 MA 200 BP 74 EP 74 DI 10.1016/j.bbmt.2007.12.209 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 364IT UT WOS:000260330100201 ER PT J AU Barry, EV Chirnomas, D Barry, K Duncan, CN Lehmann, L AF Barry, E., V Chirnomas, D. Barry, K. Duncan, C. N. Lehmann, L. TI IRON OVERLOAD IN PEDIATRIC HEMATOPOIETIC STEM CELL TRANSPLANT (HSCT) PATIENTS SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation CY FEB 13-17, 2008 CL San Diego, CA SP Amer Soc Blood & Marrow Transplantat C1 [Barry, E., V; Chirnomas, D.; Duncan, C. N.; Lehmann, L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Barry, E., V; Chirnomas, D.; Barry, K.; Duncan, C. N.; Lehmann, L.] Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2008 VL 14 IS 2 MA 216 BP 80 EP 81 DI 10.1016/j.bbmt.2007.12.225 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 364IT UT WOS:000260330100217 ER PT J AU O'Connor, MR Duncan, C Myers, K Lehmann, L AF O'Connor, M. R. Duncan, C. Myers, K. Lehmann, L. TI TOLERABILITY OF DAPSONE IN PEDIATRIC HEMATOPOIETIC STEM CELL TRANSPLANT SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation CY FEB 13-17, 2008 CL San Diego, CA SP Amer Soc Blood & Marrow Transplantat C1 [O'Connor, M. R.; Duncan, C.; Myers, K.; Lehmann, L.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2008 VL 14 IS 2 MA 220 BP 82 EP 82 DI 10.1016/j.bbmt.2007.12.229 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 364IT UT WOS:000260330100221 ER PT J AU Duncan, C Buonanno, M Clark, J Lehmann, L AF Duncan, C. Buonanno, M. Clark, J. Lehmann, L. TI INTENSIVE CARE UNIT ADMISSION OF PEDIATRIC HSCT PATIENTS FOLLOWING INITIAL TRANSPLANT DISCHARGE SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation CY FEB 13-17, 2008 CL San Diego, CA SP Amer Soc Blood & Marrow Transplantat C1 [Duncan, C.; Buonanno, M.; Clark, J.; Lehmann, L.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2008 VL 14 IS 2 MA 231 BP 86 EP 86 DI 10.1016/j.bbmt.2007.12.240 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 364IT UT WOS:000260330100232 ER PT J AU Kao, G Gatzo, L Madison, H Daley, H Perzepiorka, D Burger, S Kelley, L Vierra-Green, C Flesch, S Spellman, S Miller, J Confer, D AF Kao, G. Gatzo, L. Madison, H. Daley, H. Perzepiorka, D. Burger, S. Kelley, L. Vierra-Green, C. Flesch, S. Spellman, S. Miller, J. Confer, D. TI IMPACT OF STORAGE CONDITIONS ON MARROW AND PERIPHERAL BLOOD STEM CELL PRODUCTS STORED OVER 72 HOURS SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation CY FEB 13-17, 2008 CL San Diego, CA SP Amer Soc Blood & Marrow Transplantat C1 [Kao, G.; Gatzo, L.; Madison, H.; Daley, H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Perzepiorka, D.] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. [Burger, S.] Adv Cell & Gene Therapy LLC, Chapel Hill, NC USA. [Kelley, L.] Univ Utah, Salt Lake City, UT USA. [Vierra-Green, C.; Flesch, S.; Spellman, S.; Miller, J.; Confer, D.] Natl Marrow Donor Program, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2008 VL 14 IS 2 MA 251 BP 93 EP 93 DI 10.1016/j.bbmt.2007.12.260 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 364IT UT WOS:000260330100252 ER PT J AU Toro, JJ Westbrook, SD Kirkpatrick, WR Fothergill, AW Patterson, TF Redding, SW Freytes, CO AF Toro, J. J. Westbrook, S. D. Kirkpatrick, W. R. Fothergill, A. W. Patterson, T. F. Redding, S. W. Freytes, C. O. TI CURRENT EPIDEMIOLOGY OF ORAL CANDIDA COLONIZATION IN PATIENTS WITH HEMATOLOGIC MALIGNANCIES UNDERGOING HEMATOPOIETIC STEM CELL TRANSPLANTATION: A LONGITUDINAL, PROSPECTIVE STUDY SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation CY FEB 13-17, 2008 CL San Diego, CA SP Amer Soc Blood & Marrow Transplantat C1 [Toro, J. J.; Westbrook, S. D.; Patterson, T. F.; Redding, S. W.; Freytes, C. O.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Toro, J. J.; Westbrook, S. D.; Kirkpatrick, W. R.; Fothergill, A. W.; Patterson, T. F.; Redding, S. W.; Freytes, C. O.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2008 VL 14 IS 2 SU 2 MA 263 BP 97 EP 97 DI 10.1016/j.bbmt.2007.12.272 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 364IT UT WOS:000260330100264 ER PT J AU Oliansky, DM Appelbaum, F Cassileth, PA Keating, A Kerr, F Nieto, Y Stewart, S Stone, RM Tallman, MS McCarthy, PL Hahn, T AF Oliansky, Denise M. Appelbaum, Frederick Cassileth, Peter A. Keating, Armand Kerr, Famie Nieto, Yago Stewart, Susan Stone, Richard M. Tallman, Martin S. McCarthy, Philip L. Fr. Hahn, Theresa TI The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of acute myelogenous leukemia in adults: An evidence-based review SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review DE acute myeloid leukemia; hematopoietic stem cell transplantation; therapy; adult ID ACUTE MYELOID-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; TOTAL-BODY IRRADIATION; 1ST COMPLETE REMISSION; ACUTE MYELOBLASTIC-LEUKEMIA; HIGH-DOSE CYTARABINE; ACUTE LYMPHOBLASTIC-LEUKEMIA; VERSUS-HOST-DISEASE; QUALITY-OF-LIFE; TERM-FOLLOW-UP AB Clinical research examining the role of hematopoietic stem cell transplantation (HSCT) in the therapy of acute myelogenous leukemia (AML) in adults is presented and critically evaluated in this systematic evidence-based review. Specific criteria were used for searching the published literature and for grading the quality and strength of the evidence and the strength of the treatment recommendations. Treatment recommendations based on the evidence are presented in Table 3, entitled Summary of Treatment Recommendations Made by the Expert Panel for Adult Acute Myelogenous Leukemia, and were reached unanimously by a panel of AML experts. The identified priority areas of needed future research in adult AML include: (1) What is the role of HSCT in treating patients with specific molecular markers (eg, FLT3, NPM1, CEBPA, BAALC, MLL, NRAS, etc.) especially in patients with normal cytogenetics? (2) What is the benefit of using HSCT to treat different cytogenetic subgroups? (3) What is the impact on survival outcomes of reduced intensity or nonmyeloablative versus conventional conditioning in older (> 60 years) and intermediate (40-60 years) aged adults? (4) What is the impact on survival outcomes of unrelated donor HSCT vesus chemotherapy in younger (< 40 years) adults with high risk disease? (c) 2008 American Society for Blood and Marrow Transplantation. C1 [Oliansky, Denise M.; McCarthy, Philip L. Fr.; Hahn, Theresa] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Appelbaum, Frederick] Fred Hutchinson Canc Inst, Seattle, WA USA. [Cassileth, Peter A.] Univ Miami, Sylvester Canc Ctr, Miami, FL 33152 USA. [Keating, Armand] Univ Toronto, Toronto, ON, Canada. [Kerr, Famie] Excellus Blue Cross Blue Shield, New York, NY USA. [Nieto, Yago] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Stewart, Susan] BMT Infonet, Chicago, IL USA. [Stone, Richard M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Tallman, Martin S.] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. RP Hahn, T (reprint author), Roswell Pk Canc Inst, Elm & Carlton St, Buffalo, NY 14263 USA. EM Theresa.hahn@roswellpark.org NR 144 TC 38 Z9 42 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2008 VL 14 IS 2 BP 137 EP 180 DI 10.1016/j.bbmt.2007.11.002 PG 44 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 264FH UT WOS:000253271100001 PM 18215777 ER PT J AU Materazzo, M Lehmann, L Duncan, C AF Materazzo, M. Lehmann, L. Duncan, C. TI A SPECIALTY CLINIC FOR PEDIATRIC HEMATOPOIETIC STEM CELL TRANSPLANT PATIENTS WITH CHRONIC GRAFT-VERSUS-HOST DISEASE SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation CY FEB 13-17, 2008 CL San Diego, CA SP Amer Soc Blood & Marrow Transplantat C1 [Materazzo, M.; Lehmann, L.; Duncan, C.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2008 VL 14 IS 2 MA 444 BP 157 EP 158 DI 10.1016/j.bbmt.2007.12.454 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 364IT UT WOS:000260330100445 ER PT J AU Schlenk, RF Pasquini, MC Perez, WS Zhang, MJ Krauter, J Antin, JH Bashey, A Bolwell, BJ Buchner, T Cahn, JY Cairo, MS Copelan, EA Cutler, CS Dohner, H Gale, RP Ilhan, O Lazarus, HM Liesveld, JL Litzow, MR Marks, DI Maziarz, RT McCarthy, PL Nimer, SD Sierra, J Tallman, MS Weisdorf, DJ Horowitz, MM Ganser, A AF Schlenk, Richard F. Pasquini, Marcelo C. Perez, Waleska S. Zhang, Mei-Jie Krauter, Juergen Antin, Joseph H. Bashey, Asad Bolwell, Brian J. Buechner, Thomas Cahn, Jean-Yves Cairo, Mitchell S. Copelan, Edward A. Cutler, Corey S. Doehner, Hartmut Gale, Robert Peter Ilhan, Osman Lazarus, Hillard M. Liesveld, Jane L. Litzow, Mark R. Marks, David I. Maziarz, Richard T. McCarthy, Philip L. Nimer, Stephen D. Sierra, Jorge Tallman, Martin S. Weisdorf, Daniel J. Horowitz, Mary M. Ganser, Arnold CA CIBMTR Acute Leukemia Working Comm TI HLA-identical sibling allogeneic transplants versus chemotherapy in acute myelogenous leukemia with t(8;21) in first complete remission: Collaborative study between the German AML intergroup and CIBMTR SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article; Proceedings Paper CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol DE t(8;21); AML; hematopoietic stem cell transplantation; chemotherapy ID ACUTE MYELOID-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; PERIPHERAL-BLOOD CELLS; HIGH-DOSE CYTARABINE; POSTREMISSION THERAPY; INTENSIVE CHEMOTHERAPY; PROGNOSTIC FACTOR; GROUP-B; TRIAL; SURVIVAL AB We studied the role of HLA-matched sibling hematopoietic cell transplantation (HCT) in treating t(8;21) acute myelogenous leukemia (AML) in first remission. Outcomes of 118 patients receiving HCT and reported to the Center for International Blood and Marrow Transplant Research were compared with 132 similar patients receiving chemotherapy selected from 8 German AML Intergroup multicenter trials. Characteristics of the cohorts were similar except that chemotherapy recipients were significantly older. To adjust for time to treatment bias, outcomes were compared using left-truncated Cox regression models. Transplants were associated with higher treatment-related mortality (TRM; relative risk [RR] 6.76, 95% confidence interval [CI] 2.95-15.45, P < .001), lower relapse (RR0.47,95% CI0.25-0.85,P = .01), and similar relapse-free survival (P =.2). Loss of sexchromosomes (LOS) in addition to t(8;2 1) had a negative impact on overall survival (OS) in patients receiving chemotherapy. Patients without LOS experienced shorter survival after HCT comparing to chemotherapy (RR 3.05, P = .02), whereas patients with LOS had similar survival regardless of postremission therapy. In both cohorts, white blood cell count (WBC) at diagnosis > 25 x 10(9)/L was associated with a higher relapse risk (RR = 2.09, P = .03), lower relapse-free (RR = 1.9, P =.008), and OS (RR = 1.91, P = .01). In this cohort of patients with t(8;21) AML, HCT did not improve OS, because reduction of relapse was offset by high TRM. In the group without LOS, survival after chemotherapy was far superior to HCT. These results suggest that patients with t(8;2 1) AML without poor prognostic factors have higher rates of survival after chemotherapy as a post remission therapy compared to HCT. C1 [Pasquini, Marcelo C.; Perez, Waleska S.; Zhang, Mei-Jie; Horowitz, Mary M.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Schlenk, Richard F.; Doehner, Hartmut] Univ Ulm, Ulm, Germany. [Krauter, Juergen; Ganser, Arnold] Hannover Med Sch, D-3000 Hannover, Germany. [Antin, Joseph H.; Cutler, Corey S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bashey, Asad] BMT Grp Georgia, Atlanta, GA USA. [Bolwell, Brian J.; Copelan, Edward A.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Buechner, Thomas] Univ Munster, Munster, Germany. [Cahn, Jean-Yves] CHU Grenoble, F-38043 Grenoble, France. [Cairo, Mitchell S.] Columbia Univ, Med Ctr, New York, NY USA. [Gale, Robert Peter] Ctr Adv Studies Leukemia, Los Angeles, CA USA. [Ilhan, Osman] Ibni Sinai Hosp, Ankara, Turkey. [Lazarus, Hillard M.] Univ Hosp Cleveland, Cleveland, OH 44106 USA. [Liesveld, Jane L.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Litzow, Mark R.] Mayo Clin, Rochester, MN USA. [Marks, David I.] Bristol Childrens Hosp, Bristol, Avon, England. [Maziarz, Richard T.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [McCarthy, Philip L.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Nimer, Stephen D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Sierra, Jorge] Hosp Santa Creu & Sant Pau, Barcelona, Spain. [Tallman, Martin S.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Weisdorf, Daniel J.] Univ Minnesota, Minneapolis, MN USA. RP Pasquini, MC (reprint author), Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, 8701 Watertown Plank Rd,POB 26509, Milwaukee, WI 53226 USA. EM mpasquin@mcw.edu RI Lopez, Dulce/A-7700-2013; Cahn, Jean-Yves/M-6493-2014 FU NCI NIH HHS [U24-CA76518, U24 CA076518, U24 CA076518-08, U24 CA076518-09, U24 CA076518-10] NR 37 TC 31 Z9 33 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2008 VL 14 IS 2 BP 187 EP 196 DI 10.1016/j.bbmt.2007.10.006 PG 10 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 264FH UT WOS:000253271100003 PM 18215779 ER PT J AU Saito, AM Cutler, C Zahrieh, D Soiffer, RJ Ho, VT Alyea, EP Koreth, J Antin, JH Lee, SJ AF Saito, Akiko M. Cutler, Corey Zahrieh, David Soiffer, Robert J. Ho, Vincent T. Alyea, Edwin P. Koreth, John Antin, Joseph H. Lee, Stephanie J. TI Costs of allogeneic hematopoietic cell transplantation with high-dose regimens SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE costs; outcomes research; hematopoietic cell transplantation with high-dose regimens; hematological malignancies ID BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; UNRELATED DONOR TRANSPLANTATION; DIFFUSE ALVEOLAR HEMORRHAGE; LUNG TRANSPLANTATION; AUTOLOGOUS TRANSPLANTATION; RISK-FACTORS; THERAPY; GRAFT; RECIPIENTS AB To characterize the costs of allogeneic hematopoietic cell transplantation with high-dose regimens (HDCT), we analyzed clinical information and costs of 315 HDCT recipients during a 4-year study period beginning in 2000. Multivariate analyses were performed to identify pre- and/or post-HDCT factors predicting higher costs within the first year. Overall survival (OS) at 100 days and I year were 80% and 58%, respectively. The median cost and days of hospitalization were $102,574 in 2004 US dollars and 36 days in the hospital for 100 days, and $128,800 and 39 days in the hospital for I year. Early costs, defined as costs within the first 100 days, accounted for 84% of total costs within the first year. Inpatient costs comprise 94% of the early costs, but only 61% of the later costs defined as costs incurred between 10 1 days and I year. Of the pre-HDCT factors, unrelated donors and advanced disease risk were significantly associated with increased cost. When post-HDCT events were also considered, these pre-HDCT factors were no longer independently predictive of high cost. Instead, severe complications post-HDCT were associated with higher costs, increasing total costs $20,228 on average. If no complications occurred, the mean cost within the first year was $79,222. These results provide cost estimates for complicated and uncomplicated HDCT procedures, as well as costs for management of specific transplant complications. (c) 2008 American Society for Blood and Marrow Transplantation. C1 [Saito, Akiko M.; Cutler, Corey; Soiffer, Robert J.; Ho, Vincent T.; Alyea, Edwin P.; Koreth, John; Antin, Joseph H.] Dana Farber Canc Inst, Dept Med Oncol, Div Med Oncol, Boston, MA 02115 USA. [Saito, Akiko M.; Cutler, Corey; Soiffer, Robert J.; Ho, Vincent T.; Alyea, Edwin P.; Koreth, John; Antin, Joseph H.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Zahrieh, David] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. RP Saito, AM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Div Med Oncol, 44 Binney St,SM 277, Boston, MA 02115 USA. EM akiko_saito@dfci.harvard.edu FU NHLBI NIH HHS [P01 HL070149-03, P01 HL070149, P01 HL070149-01A1, P01 HL070149-01A10001, P01 HL070149-02, P01 HL070149-020001, P01 HL070149-030001, P01 HL070149-04, P01 HL070149-040001, P01 HL070149-05, P01 HL070149-050001] NR 47 TC 32 Z9 33 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2008 VL 14 IS 2 BP 197 EP 207 DI 10.1016/j.bbmt.2007.10.010 PG 11 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 264FH UT WOS:000253271100004 PM 18215780 ER PT J AU Laport, GG Sandmaier, BM Storer, BE Scott, BL Stuart, MJ Lange, T Maris, MB Agura, ED Chauncey, TR Wong, RM Forman, SJ Petersen, FB Wade, JC Epner, E Bruno, B Bethge, WA Curtin, PT Maloney, DG Blume, KG Storb, RF AF Laport, Ginna G. Sandmaier, Brenda M. Storer, Barry E. Scott, Bart L. Stuart, Monic J. Lange, Thoralf Maris, Michael B. Agura, Edward D. Chauncey, Thomas R. Wong, Ruby M. Forman, Stephen J. Petersen, Finn B. Wade, James C. Epner, Elliot Bruno, Benedetto Bethge, Wolfgang A. Curtin, Peter T. Maloney, David G. Blume, Karl G. Storb, Rainer F. TI Reduced-intensity conditioning follow by allogeneic hematopoietic cell transplantation for adult patients with myelodysplastic syndrome and myeloproliferative disorders SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE reduced-intensity conditioning; nonmyeloablative transplantation; myelodysplastic syndrome; myeloproliferative disorders; allogeneic ID ACUTE MYELOID-LEUKEMIA; CHRONIC MYELOMONOCYTIC LEUKEMIA; BONE-MARROW-TRANSPLANTATION; ACUTE MYELOGENOUS LEUKEMIA; HLA-IDENTICAL SIBLINGS; EUROPEAN GROUP; WORKING PARTY; MULTILINEAGE DYSPLASIA; RETROSPECTIVE ANALYSIS; MYCOPHENOLATE-MOFETIL AB Allogeneic hematopoietic cell transplantation (HCT) is the only curative strategy for patients with myelodysplastic syndrome (MDS) and myeloproliferative disorders (MPD). We report the results of 148 patients (median age = 59 years old) with de novo MDS (n = 40), acute myelogenous leukemia (AML) after antecedent MDS/MPD (n = 49), treatment-related MDS (t-MDS) (n = 25), MPD (n = 27), and chronic myelomonocytic leukemia (CMML) (n = 7) who underwent allogeneic HCT using a conditioning regimen of low-dose total body irradiation (TBI) alone (200 cGy) on day 0 (n = 5) or with the addition of fludarabine (Flu) 30 mg/m(2)/day on days -4 to -2 (n = 143). Postgrafting immunosuppression consisted of cyclosporine and mycophenolate mofetil (AIMF). Seventy-five patients (51%) received an allograft from a matched related donor (MRD), and 73 patients (49%) were recipients of unrelated donor (URD) grafts. There was no significant difference in the incidence of acute (gr II-IV) and chronic extensive graft-versus-host disease (aGVHD, cGVHD) between the recipients of related and unrelated donor grafts. By day +28, 75% of patients demonstrated mixed T cell chimerism. Graft rejection was seen in 15% of patients. With a median follow-up of 47 (range: 6-89) months, the 3-year relapse-free survival (RFS) and overall survival (OS) are both 27% for all patients, with a relapse incidence of 41%. The 3-year RFS for the patients with de novo MDS, AML after antecedent MDS/MPD, t-MDS, MPD, and CMML were 22%, 20%, 29%, 37%, and 43%, respectively, and the 3-year OS was 20%, 23%, 27%, 43%, and 43%, respectively. The 3-year nonrelapse mortality (NRM) was 32%. Factors associated with a lower risk of relapse were the development of extensive cGVHD and having a low risk or intermediate-1 risk International Prognostic Score for the de novo AIDS patients. Nonmyeloablative HCT confers remissions in patients who otherwise were not eligible for conventional HCT but for whom relapse is the leading cause of treatment failure. (c) 2008 American Society for Blood and Marrow Transplantation. C1 [Laport, Ginna G.; Stuart, Monic J.; Wong, Ruby M.; Blume, Karl G.] Stanford Univ, Med Ctr, Div Blood & Marrow Transplantat, 300 Pasteur Dr,Rm H3249, Stanford, CA 94305 USA. [Sandmaier, Brenda M.; Storer, Barry E.; Scott, Bart L.; Maloney, David G.; Storb, Rainer F.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Maris, Michael B.; Chauncey, Thomas R.] Vet Affairs Puget Sound Hlth Care syst, Seattle, WA USA. [Wade, James C.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Petersen, Finn B.] Univ Utah, Salt Lake City, UT USA. [Bethge, Wolfgang A.] Univ Tubingen, Tubingen, Germany. [Epner, Elliot] Univ Arizona, Tucson, AZ USA. [Bruno, Benedetto] Univ Turin, Turin, Italy. [Curtin, Peter T.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Forman, Stephen J.] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Lange, Thoralf] Univ Leipzig, Leipzig, Germany. [Agura, Edward D.] Baylor Univ, Med Ctr, Dallas, TX USA. RP Laport, GG (reprint author), Stanford Univ, Med Ctr, Div Blood & Marrow Transplantat, 300 Pasteur Dr,Rm H3249, Stanford, CA 94305 USA. EM glaport@stanford.edu FU NCI NIH HHS [P01 CA018029-270047, CA15704, CA18029, CA78902, CA92058, K23 CA092058, K23 CA092058-01, P01 CA018029, P01 CA018029-250002, P01 CA049605, P01 CA049605-14, P01 CA078902, P01 CA078902-09, P01-CA 49605, P30 CA015704, P30 CA015704-31]; NHLBI NIH HHS [HL36444, P01 HL036444, P01 HL036444-27] NR 35 TC 90 Z9 93 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2008 VL 14 IS 2 BP 246 EP 255 DI 10.1016/j.bbmt.2007.11.012 PG 10 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 264FH UT WOS:000253271100009 PM 18215785 ER PT J AU Law, B Tung, CH AF Law, Benedict Tung, Ching-Hsuan TI Structural modification of protease inducible preprogrammed nanofiber precursor SO BIOMACROMOLECULES LA English DT Article ID UROKINASE PLASMINOGEN-ACTIVATOR; PEPTIDE SCAFFOLDS; PROGENITOR CELLS; DELIVERY; HYDROGEL; DIFFERENTIATION; BIOMATERIALS; DESIGN; GROWTH AB As many proteases such as urokinase plasminogen activator (uPA) are overexpressed in various tumors, a new type of peptide-based smart delivery system (hydrogel matrix) that could be degraded by uPA was previously described (Law, B.; Weissleder, R.; Tung, C. H. Peptide-based biornaterials for protease-enhanced drug delivery. Biomacromolecules 2006, 7 (4), 1261-1265). Subsequently, we designed nanometer-sized fluorescent nanofibers by introducing a hydrophilic component (methoxyl polyethylene glycol) to the core peptide [MPEG(2000)-BK(FITC)SGRSANA-kldlkldlkldl-NH2]. Preliminary studies showed that these nanofibers could detect uPA activity by optical imaging in vitro (Law, B.; Weissleder, R.; Tung, C. H. Protease-sensitive fluorescent nanofibers. Bioconjugate Chem. 2007, 18 (6), 1701-1704). Here, we further extend our studies to the structural responses of these nanofiber precursors (NFP). In the presence of a model protease, the FITC-containing hydrophilic fragments were released from the NFPs that contributed to fluorescence amplification. Simultaneously, the remaining self-assembling residues were mechanically driven to transform into interfibril networking of micrometer size hydrogel. These unique morphological changes, together with the optical property, may have considerable biomedical applications as diagnostic sensors for specific protease or dual systemic and functional delivery nanoplatforms to target protease-associated diseases. C1 [Law, Benedict; Tung, Ching-Hsuan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA 02129 USA. RP Law, B (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA 02129 USA. EM Shek.law@ndsu.edu OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [R01 CA099385, R33 CA114149] NR 23 TC 10 Z9 10 U1 2 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1525-7797 J9 BIOMACROMOLECULES JI Biomacromolecules PD FEB PY 2008 VL 9 IS 2 BP 421 EP 425 DI 10.1021/bm7012026 PG 5 WC Biochemistry & Molecular Biology; Chemistry, Organic; Polymer Science SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA 261TE UT WOS:000253102100001 PM 18177006 ER PT J AU Janorkar, AV Rajagopalan, P Yarmush, ML Megeed, Z AF Janorkar, Amol V. Rajagopalan, Padmavathy Yarmush, Martin L. Megeed, Zaki TI The use of elastin-like polypeptide-polyelectrolyte complexes to control hepatocyte morphology and function in vitro SO BIOMATERIALS LA English DT Article DE elastin; hepatocyte; polyelectrolyte; liver; tissue engineering ID EXTRACELLULAR-MATRIX; SANDWICH CONFIGURATION; SPHEROIDS; PROTEINS; BEHAVIOR; CULTURE; CHAIN; PURIFICATION; EXPRESSION; MONOLAYER AB Both tissue engineering and biological science will benefit from improved methods to control the morphology, differentiated state, and function of primary cells. In this paper, we show that surface modification of tissue culture polystyrene (TCPS) with chemically derivatized elastin-like polypeptides (ELPs) enables control over the in vitro morphology and liver-specific function of primary rat hepatocytes. The ELP (VPGVG)(40) was produced in Escherichia coli and conjugated with polyacrylic acid (PAA) and polyethyleneimine (PEI) using carbodiimide activation chemistry. These conjugates were characterized by transmission Fourier transform infrared (FTIR) spectroscopy, mass spectroscopy, and the ninhydrin assay. We demonstrated that the ELP-polyelectrolyte conjugates profoundly influenced the morphology, aggregation, and differentiated function of primary rat hepatocytes, where hepatocytes plated on the ELP-PAA and ELP-PEI surfaces formed spread and spheroidal morphologies with corresponding low and high liver-specific function, respectively. These materials may have utility as substrata for in vitro studies of hepatocyte biology and tissue engineering applications. (c) 2007 Elsevier Ltd. All rights reserved. C1 [Janorkar, Amol V.; Yarmush, Martin L.; Megeed, Zaki] Harvard Univ, Sch Med, Ctr Engn Med, Massachusetts Gen Hosp,Shriners Burns Hosp, Boston, MA 02114 USA. [Rajagopalan, Padmavathy] Lehigh Univ, Dept Chem Engn, Bethlehem, PA 18015 USA. RP Megeed, Z (reprint author), Harvard Univ, Sch Med, Ctr Engn Med, Massachusetts Gen Hosp,Shriners Burns Hosp, 51 Blossom St, Boston, MA 02114 USA. EM zmegeed@hms.harvard.edu FU NIBIB NIH HHS [P41EB002503]; NIDDK NIH HHS [F32DK070496] NR 37 TC 39 Z9 39 U1 2 U2 22 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD FEB PY 2008 VL 29 IS 6 BP 625 EP 632 DI 10.1016/j.biomaterials.2007.10.022 PG 8 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 249ON UT WOS:000252238400001 PM 18006054 ER PT J AU Park, J Li, Y Berthiaume, F Toner, M Yarmush, ML Tilles, AW AF Park, Jaesung Li, Yawen Berthiaume, Francois Toner, Mehmet Yarmush, Martin L. Tilles, Arno W. TI Radial flow hepatocyte bioreactor using stacked microfabricated grooved substrates SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE radial flow bioreactor; stacked microgrooved substrates; microfabrication; perfusion; hepatocyte; bioartificial liver ID ACUTE LIVER-FAILURE; FIBER BIOARTIFICIAL LIVER; CONTROLLED-TRIAL; PORCINE HEPATOCYTES; GENE-EXPRESSION; RAT HEPATOCYTES; OXYGEN-TRANSFER; SUPPORT; CELLS; MECHANOTRANSDUCTION AB Bioartificial liver (BAL) devices with fully functioning hepatocytes have the potential to provide temporary hepatic support for patients with liver failure. The goal of this study was to optimize the flow environment for the cultured hepatocytes in a stacked substrate, radial flow bioreactor. Photolithographic techniques were used to microfabricate concentric grooves onto the underlying glass substrates. The microgrooves served to protect the seeded hepatocytes from the high shear stresses caused by the volumetric flow rates necessary for adequate convective oxygen delivery. Finite element analysis was used to analyze the shear stresses and oxygen concentrations in the bioreactor. By employing high volumetric flow rates, sufficient oxygen supply to the hepatocytes was possible without an integrated oxygen permeable membrane. To implement this concept, 18 microgrooved glass substrates, seeded with rat hepatocytes cocultured with 3T3-J2 fibroblasts, were stacked in the bioreactor, creating a channel height of 100 mu m between each substrate. In this bioreactor configuration, liver-specific functions (i.e., albumin and urea synthesis rates) of the hepatocytes remained stable over 5 days of perfusion, and were significantly increased compared to those in the radial flow bioreactor with stacked substrates without microgrooves. This study suggests that this radial flow bioreactor with stacked microgrooved substrates is scalable and may have potential as a BAL device in the treatment of liver failure. C1 [Park, Jaesung; Li, Yawen; Berthiaume, Francois; Toner, Mehmet; Yarmush, Martin L.; Tilles, Arno W.] Shriners Hosp Children, Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. [Park, Jaesung; Li, Yawen; Berthiaume, Francois; Toner, Mehmet; Yarmush, Martin L.; Tilles, Arno W.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Tilles, AW (reprint author), Shriners Hosp Children, Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. EM arno_tilles@hms.harvard.edu FU NIBIB NIH HHS [P41 EB002503, P41 EB02503]; NIDDK NIH HHS [K08 DK66040, R01 DK43371] NR 37 TC 47 Z9 53 U1 3 U2 24 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD FEB 1 PY 2008 VL 99 IS 2 BP 455 EP 467 DI 10.1002/bit.21572 PG 13 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 249ZR UT WOS:000252270300020 PM 17626294 ER PT J AU Sachs, G Berk, M Ng, F Ferrier, N Wilting, I Cassidy, F Beaulieu, S Yatham, L AF Sachs, G. Berk, M. Ng, F. Ferrier, N. Wilting, I. Cassidy, F. Beaulieu, S. Yatham, L. TI Safety monitoring of bipolar disorder treatment: ISBD consensus guidelines SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 3rd Biennial Conference of the International-Society-for-Bipolar-Disorders CY JAN 27-30, 2008 CL New Delhi, INDIA C1 [Sachs, G.; Ng, F.; Ferrier, N.; Cassidy, F.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Berk, M.] Univ Melbourne, Geelong, Vic, Australia. [Wilting, I.] Univ Utrecht, Div Pharmacoepidemiol & Pharmacotheraphy, NL-3508 TC Utrecht, Netherlands. [Beaulieu, S.] McGill Univ, Douglas Mental Hlth Univ Inst, Verdun, PQ H4H 1R3, Canada. [Yatham, L.] Univ British Columbia, Dept Psychiat, Vancouver, BC V5Z 1M9, Canada. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD FEB PY 2008 VL 10 SU 1 BP 1 EP 1 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 256ES UT WOS:000252711100004 ER PT J AU Nierenberg, AA Ketter, TA AF Nierenberg, A. A. Ketter, T. A. TI Bipolar II depression: A critical review SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 3rd Biennial Conference of the International-Society-for-Bipolar-Disorders CY JAN 27-30, 2008 CL New Delhi, INDIA C1 [Nierenberg, A. A.] Massachusetts Gen Hosp, Bipolar Clin & Res Program, Boston, MA 02114 USA. [Ketter, T. A.] Stanford Univ, Med Ctr, Bipolar Disorders Clin, Palo Alto, CA 94304 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD FEB PY 2008 VL 10 SU 1 BP 4 EP 4 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 256ES UT WOS:000252711100010 ER PT J AU Nierenberg, AA Marangell, LB Bowden, CL Ketter, TA Calabrese, JR Thase, ME Friedman, E Ostacher, MJ Reilly-Harrington, N Iosifescu, D Leon, AC AF Nierenberg, A. A. Marangell, L. B. Bowden, C. L. Ketter, T. A. Calabrese, J. R. Thase, M. E. Friedman, E. Ostacher, M. J. Reilly-Harrington, N. Iosifescu, D. Leon, A. C. TI Lithium use for bipolar disorder study (litmus): Rationale, design, and innovations SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 3rd Biennial Conference of the International-Society-for-Bipolar-Disorders CY JAN 27-30, 2008 CL New Delhi, INDIA C1 [Nierenberg, A. A.; Ostacher, M. J.; Reilly-Harrington, N.; Iosifescu, D.] Massachusetts Gen Hosp, Bipolar Clin & Res Program, Boston, MA 02114 USA. [Marangell, L. B.] Eli Lilly & Co, Indianapolis, IN USA. [Bowden, C. L.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX USA. [Ketter, T. A.] Stanford Univ, Bipolar Disorders Clin, Palo Alto, CA USA. [Calabrese, J. R.] Case Western Reserve Univ, Bipolar Disorder Res Ctr, Cleveland, OH 44106 USA. [Thase, M. E.] Univ Penn, Mood & Anxiety Disorders Res & Treatment Program, Philadelphia, PA 19104 USA. [Friedman, E.] Univ Pittsburgh, Western Psychiat Inst & Clin, Mood Disorders Treatment & Res Program, Pittsburgh, PA 15260 USA. [Leon, A. C.] Weill Cornell Med Coll, Psychiat & Publ Hlth Dept, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD FEB PY 2008 VL 10 SU 1 BP 8 EP 9 PG 2 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 256ES UT WOS:000252711100020 ER PT J AU Dias, RS Sachs, GS Lafer, B DelDebbio, A Nierenberg, AA Joffe, H AF Dias, R. S. Sachs, G. S. Lafer, B. DelDebbio, A. Nierenberg, A. A. Joffe, H. TI Clinical correlates of premenstrual worsening of mood in women with bipolar disorder SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 3rd Biennial Conference of the International-Society-for-Bipolar-Disorders CY JAN 27-30, 2008 CL New Delhi, INDIA C1 [Dias, R. S.; Sachs, G. S.; Lafer, B.; DelDebbio, A.; Nierenberg, A. A.] Massachusetts Gen Hosp, Bipolar Clin & Res Program, Boston, MA 02114 USA. [Dias, R. S.] State Univ Sao Paulo, Inst Psychiat, Bipolar Res Program, BR-05508 Sao Paulo, Brazil. [DelDebbio, A.] Univ Pisa, Neurobiol & Clin Affect Disorders Postdoctoral Fe, I-56100 Pisa, Italy. [Joffe, H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Perinatal Psychiat Res Unit, Boston, MA USA. RI Lafer, Beny/C-1055-2012; Lafer, Beny/F-9390-2015; Dias, Rodrigo/N-8985-2013 OI Lafer, Beny/0000-0002-6132-9999; Lafer, Beny/0000-0002-6132-9999; Dias, Rodrigo/0000-0002-1315-7205 NR 0 TC 0 Z9 0 U1 2 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD FEB PY 2008 VL 10 SU 1 BP 33 EP 33 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 256ES UT WOS:000252711100079 ER PT J AU Mynderse, L Mclaren, R Larson, B Jaff, M Somers, V Evans, W Larson, T AF Mynderse, L. Mclaren, R. Larson, B. Jaff, M. Somers, V. Evans, W. Larson, T. TI Blood pressure (BP) surges during trans-urethral microwave thermotherapy (TUMT) of the prostate SO BJU INTERNATIONAL LA English DT Meeting Abstract CT 61st Annual Scientific Meeting of the Urological-Society-of-Australia-and-New-Zealand CY FEB 24-28, 2008 CL Hong Kong, PEOPLES R CHINA SP Urol Soc Australia & New Zealand C1 [Mynderse, L.; Mclaren, R.; Somers, V.; Larson, T.] Mayo Clin, Rochester, MN USA. [Larson, B.] Cleveland Clin, Lerner Coll Med, Cleveland, OH USA. [Jaff, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Evans, W.] SW Florida Urol Assoc, Ft Myers, FL USA. [Larson, T.] Inst Med Res, Scottsdale, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1464-4096 J9 BJU INT JI BJU Int. PD FEB PY 2008 VL 101 SU 1 BP 42 EP 42 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 257RF UT WOS:000252815500139 ER PT J AU Nakabayashi, M Sartor, O Jacobus, S Regan, MM McKearn, D Ross, RW Kantoff, PW Taplin, ME Oh, WK AF Nakabayashi, Mari Sartor, Oliver Jacobus, Susanna Regan, Meredith M. McKearn, David Ross, Robert W. Kantoff, Philip W. Taplin, Mary-Ellen Oh, William K. TI Response to docetaxel/carboplatin-based chemotherapy as first- and second-line therapy in patients with metastatic hormone-refractory prostate cancer SO BJU INTERNATIONAL LA English DT Article DE carboplatin; docetaxel; chemotherapy; hormone-refractory prostate cancer ID PHASE-II; ESTRAMUSTINE PHOSPHATE; WEEKLY DOCETAXEL; OVARIAN-CANCER; CARBOPLATIN; PACLITAXEL; MITOXANTRONE; GUIDELINES; PREDNISONE; CARCINOMA AB OBJECTIVES To evaluate the efficacy of docetaxel/carboplatin (DC)-based chemotherapy as first- and second-line chemotherapy for patients with hormone-refractory prostate cancer (HRPC). PATIENTS AND METHODS We retrospectively identified all patients with HRPC treated with DC-based chemotherapy at the Dana-Farber Cancer Institute. Regimens either included estramustine (EDC) or not (DC). We identified patients who received EDC as first-line chemotherapy and patients who received DC as second-line or subsequent chemotherapy. Patients treated with EDC received 20-70 mg/m(2) docetaxel every 1-4 weeks, estramustine 140 mg three times daily and carboplatin (area under the curve, AUC), (4-6) every 3-4 weeks. Patients treated with DC received docetaxel 50-70 mg/m(2) and carboplatin AUC (4-6) every 3-4 weeks. RESULTS In all, the study included 54 patients; 24 received EDC and 30 DC (median age 62.8 and 66.9 years, respectively); their prostate-specific antigen (PSA) level at the start of chemotherapy was 112.7 and 213.3 ng/mL, respectively. There were declines of >= 50% in PSA level in 88% and 20% in the two groups, respectively. The median overall survival was 17.7 and 14.9 months in the EDC and DC groups, respectively. The most common reversible grade 4 toxicity with either regimen was neutropenia (4% and 7% in EDC and DC, respectively). CONCLUSIONS DC-based chemotherapy is well tolerated and active in HRPC. Adding carboplatin to docetaxel provides an additional activity in 20% of patients as a second-line or subsequent chemotherapy. C1 [Oh, William K.] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Dept Med Oncol, Boston, MA 02115 USA. [Jacobus, Susanna; Regan, Meredith M.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Oh, WK (reprint author), Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM william_oh@dfci.harvard.edu RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 26 TC 22 Z9 22 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1464-4096 J9 BJU INT JI BJU Int. PD FEB PY 2008 VL 101 IS 3 BP 308 EP 312 DI 10.1111/j.1464-410X.2007.07331.x PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 247YZ UT WOS:000252119800012 PM 18184327 ER PT J AU Wu, Q Shi, JD Chen, LF Wang, CY Park, I Lee, C Zhang, J AF Wu, Quan Shi, Jiandang Chen, Linfeng Wang, Chun-Yu Park, Irwin Lee, Chung Zhang, Ju TI Regulation of proliferation and differentiation of prostatic stromal cells by oestradiol through prostatic epithelial cells in a paracrine manner SO BJU INTERNATIONAL LA English DT Article DE epithelial-stromal interactions; oestradiol; proliferation; differentiation; extracellular matrix ID SMOOTH-MUSCLE; TGF-BETA; ANDROGEN RECEPTOR; ESTROGEN; HYPERPLASIA; EXPRESSION; INDUCTION; PHENOTYPE; DISEASE AB To characterize a paracrine effect of prostatic epithelial cells in the presence or absence of oestradiol on the differentiation and proliferation of prostatic stromal cells. Conditioned media (CM) collected from a prostatic epithelial cell line (BPH-1), which was pre-treated with different concentration of oestradiol, were added to cultures of primary prostatic stromal cells. The proliferation rates of stromal cells were determined using a tetrazolium assay. The mRNA level was analysed by real-time reverse transcription-polymerase chain reaction (RT-PCR), and the protein level of smooth muscle myosin heavy chain (SM-MHC), fibronectin and collagen IV were determined with Western blotting, enzyme-linked immunosorbent assay and radioimmunoassay, respectively. The expression of transforming growth factor beta 1 (TGF beta 1) in the BPH-1 cell line was analysed. The rate of proliferation of stromal cells increased when they were cultured with CM harvested from oestradiol-treated BPH-1 cells, but there was no remarkable change when they were cultured with CM from untreated cells. The level of smoothelin mRNA and SM-MHC protein increased after treatment with CM from BPH-1. The CM from BPH-1 with oestradiol stimulation was more effective in stimulating smoothelin mRNA and SM-MHC protein level. The protein level of collagen type IV, but not fibronectin, was up-regulated in the supernatants and cell extracts of CM-treated stromal cells. Oestradiol enhanced the expression and secretion of TGF beta 1 in BPH-1 cells. TGF beta 1-neutralizing antibody abrogated the effect of BPH-1 CM on the synthesis of collagen IV and SM-MHC in stromal cells. These results suggest that oestradiol-stimulated proliferation and differentiation of prostatic stromal cells could be regulated by factors secreted from prostatic epithelial cells. C1 [Wu, Quan; Shi, Jiandang; Chen, Linfeng; Wang, Chun-Yu; Zhang, Ju] Nankai Univ, Inst Mol Biol, Minist Educ, Bioact Mat Key Lab, Tianjin 300071, Peoples R China. [Chen, Linfeng] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Park, Irwin; Lee, Chung] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. RP Zhang, J (reprint author), Nankai Univ, Inst Mol Biol, Minist Educ, Bioact Mat Key Lab, Tianjin 300071, Peoples R China. EM zhangju@nankai.cdu.cn NR 26 TC 12 Z9 12 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1464-4096 J9 BJU INT JI BJU Int. PD FEB PY 2008 VL 101 IS 4 BP 497 EP 502 DI 10.1111/j.1464-410X.2007.07340.x PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 256EU UT WOS:000252711300019 PM 18190643 ER PT J AU Hochhaus, A Druker, B Sawyers, C Guilhot, F Schiffer, CA Cortes, J Niederwieser, DW Gambacorti, C Stone, RM Goldman, J Fischer, T O'Brien, SG Reiffers, JJ Mone, M Krahnke, T Talpaz, M Kantarjian, HM AF Hochhaus, Andreas Druker, Brian Sawyers, Charles Guilhot, Francois Schiffer, Charles A. Cortes, Jorge Niederwieser, Dietger W. Gambacorti, Carlo Stone, Richard M. Goldman, John Fischer, Thomas O'Brien, Stephen G. Reiffers, Jose J. Mone, Manisha Krahnke, Tillmann Talpaz, Moshe Kantarjian, Hagop M. TI Favorable long-term follow-up results over 6 years for response, survival, and safety with imatinib mesylate therapy in chronic-phase chronic myeloid leukemia after failure of interferon-alpha treatment SO BLOOD LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; PATIENTS RECEIVING IMATINIB; PHILADELPHIA-CHROMOSOME; CYTOGENETIC RESPONSES; MOLECULAR RESPONSES; PLUS CYTARABINE; TYROSINE KINASE; PROGNOSIS AB Imatinib mesylate, a targeted inhibitor of BCR-ABL tyrosine kinase, is the standard of care for chronic myeloid leukemia (CML). A phase 2 trial of imatinib in late chronic-phase (CP) CML after interferon-a (IFN alpha) failure enrolled 532 patients, 454 with a confirmed diagnosis of CP CML. Median time from diagnosis was 34 months; median duration of imatinib treatment was 65 months. Cumulative best rates of major cytogenetic response (MCyR) and complete cytogenetic response (CCyR) were 67% and 57%, respectively. At the 5-year landmark, 184 (41 %) of the 454 patients are in CCyR. At more than 6 years, 199 (44%) of the 454 patients remain on imatinib. Most responses occurred within 12 months of starting imatinib; however, some patients achieved initial MCyR and CCyR more than 5 years after imatinib initiation. Estimated rates of freedom from progression to accelerated phase (AP) and blastic phase (BP) and overall survival at 6 years were 61% and 76%, respectively. Both freedom from progression to AP/BP and overall survival (OS) were associated with cytogenetic response level at 12 months. No increase in rates of serious adverse events was observed with continuous use of imatinib for up to 6.5 years, compared with earlier time points. Imatinib continues to be an effective and safe therapy for patients with CP CML after failure of IFN. C1 [Hochhaus, Andreas] Univ Heidelberg, Fak Klin Med Mannheim, D-6800 Mannheim, Germany. [Druker, Brian] Oregon Hlth & Sci Univ, Inst Canc, Portland, OR USA. [Sawyers, Charles] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Guilhot, Francois] CHU Poiters, Poitiers, France. [Schiffer, Charles A.] Karmanos Canc Inst, Detroit, MI USA. [Cortes, Jorge; Kantarjian, Hagop M.] Univ Texas MD Anderson Canc Ctr Houston, Houston, TX USA. [Niederwieser, Dietger W.] Univ Leipzig, D-7010 Leipzig, Germany. [Gambacorti, Carlo] Inst Natl Tumuri, Milan, Italy. [Stone, Richard M.] Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Goldman, John] Univ London Imperial Coll Sci & Technol, London, England. [Fischer, Thomas] Johannes Gutenberg Univ Mainz, D-6500 Mainz, Germany. [O'Brien, Stephen G.] Univ Newcastle, Newcastle Upon Tyne, Tyne & Wear, England. [Reiffers, Jose J.] Univ Victor Segalen, Lab Greffe Moelle, Bordeaux, France. [Mone, Manisha; Krahnke, Tillmann] Novartis Pharmaceut, E Hanover, NJ USA. [Talpaz, Moshe] Univ Michigan, Ann Arbor, MI 48109 USA. RP Hochhaus, A (reprint author), Univ Heidelberg, Fak Klin Med Mannheim, D-6800 Mannheim, Germany. RI Sawyers, Charles/G-5327-2016; OI Hochhaus, Andreas/0000-0003-0626-0834 NR 19 TC 149 Z9 155 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 1 PY 2008 VL 111 IS 3 BP 1039 EP 1043 DI 10.1182/blood-2007-07-103523 PG 5 WC Hematology SC Hematology GA 257IR UT WOS:000252792900021 PM 17932248 ER PT J AU Doolittle, ND Abrey, LE Shenkier, TN Siegal, T Bromberg, JEC Neuwelt, EA Soussain, C Jahnke, K Johnston, P Illerhaus, G Schiff, D Batchelor, T Montoto, S Kraemer, DF Zucca, E AF Doolittle, Nancy D. Abrey, Lauren E. Shenkier, Tamara N. Siegal, Tali Bromberg, Jacoline E. C. Neuwelt, Edward A. Soussain, Carole Jahnke, Kristoph Johnston, Patrick Illerhaus, Gerald Schiff, David Batchelor, Tracy Montoto, Silvia Kraemer, Dale F. Zucca, Emanuele TI Brain parenchyma involvement as isolated central nervous system relapse of systemic non-Hodgkin lymphoma: an International Primary CNS Lymphoma Collaborative Group report SO BLOOD LA English DT Article; Proceedings Paper CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol ID HIGH-DOSE METHOTREXATE; B-CELL LYMPHOMA; RISK-FACTORS; INTERMEDIATE-GRADE; RITUXIMAB THERAPY; ELDERLY-PATIENTS; CHEMOTHERAPY; PROPHYLAXIS; RECURRENCE; DIAGNOSIS AB Isolated central nervous system (CNS) relapse involving the brain parenchyma is a rare complication of systemic non-Hodgkin lymphoma. We retrospectively analyzed patient characteristics, management, and outcomes of this complication. After complete response to initial non-Hodgkin lymphoma treatment, patients with isolated CNS relapse with the brain parenchyma as initial relapse site were eligible. Patients with isolated CNS relapse involving only the cerebrospinal fluid were not eligible. Information on 113 patients was assembled from 13 investigators; 94 (83%) had diffuse large B-cell lymphoma. Median time to brain relapse was 1.8 years (range, 0.25-15.9 years). Brain relapse was identified by neuroimaging in all patients; in 54 (48%), diagnostic brain tumor specimen was obtained. Median overall survival from date of brain relapse was 1.6 years (95% confidence interval, 0.9-2.6 years); 26 (23%) have survived 3 years or more. Median time to progression was 1.0 year (95% confidence interval, 0.7-1.7 years). Age less than 60 years (P =.006) at relapse and methotrexate use (P =.008) as frontline treatment for brain relapse were significantly associated with longer survival in a multivariate model. Our results suggest systemic methotrexate is the optimal treatment for isolated CNS relapse involving the brain parenchyma. Long-term survival is possible in some patients. C1 [Doolittle, Nancy D.; Neuwelt, Edward A.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Abrey, Lauren E.] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA. [Shenkier, Tamara N.] British Columbia Canc Agcy, Div Med Oncol, Vancouver, BC V5Z 4E6, Canada. [Shenkier, Tamara N.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Siegal, Tali] Hadassah Hebrew Univ Hosp, Leslie & Michael Gaffin Ctr Neuro Oncol, Jerusalem, Israel. [Bromberg, Jacoline E. C.] Erasmus MC Univ, Med Ctr, Dr Daniel Den Hoed Canc Ctr, Dept Neuro Oncol, Rotterdam, Netherlands. [Neuwelt, Edward A.] Oregon Hlth & Sci Univ, Dept Neurosurg, Portland, OR 97201 USA. [Neuwelt, Edward A.] Portland VA Med Ctr, Portland, OR USA. [Johnston, Patrick] Ctr Rene Huguenin, Dept Hematol, St Cloud, France. [Illerhaus, Gerald] Univ Med Berlin, Charite, Dept Hematol Oncol & Transfus Med, Berlin, Germany. [Schiff, David] Univ Virginia, Neuro Oncol Ctr, Charlottesville, VA USA. [Batchelor, Tracy] Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neuro Oncol, Boston, MA 02114 USA. [Montoto, Silvia] Barts & London, Canc Res United Kingdom, Med Oncol Unit, London, England. [Kraemer, Dale F.] Oregon State Univ, Dept Pharm Practice, Portland, OR USA. [Zucca, Emanuele] Oncol Inst So Switzerland, Bellinzona, Switzerland. RP Doolittle, ND (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, L 603,3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. EM doolittl@ohsu.edu NR 45 TC 42 Z9 43 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 1 PY 2008 VL 111 IS 3 BP 1085 EP 1093 DI 10.1182/blood-2007-07-101402 PG 9 WC Hematology SC Hematology GA 257IR UT WOS:000252792900027 PM 17962515 ER PT J AU Cervi, D Yip, TT Bhattacharya, N Podust, VN Peterson, J Abou-Slaybi, A Naumov, GN Bender, E Almog, N Italiano, JE Folkman, J Klement, GL AF Cervi, David Yip, Tai-Tung Bhattacharya, Nandita Podust, Vladimir N. Peterson, Jon Abou-Slaybi, Abdo Naumov, George N. Bender, Elise Almog, Nava Italiano, Joseph E., Jr. Folkman, Judah Klement, Giannoula L. TI Platelet-associated PF-4 as a biomarker of early tumor growth SO BLOOD LA English DT Article ID GENE-EXPRESSION PROFILES; FACTOR-IV; CANCER-PATIENTS; COLORECTAL-CANCER; ANGIOGENIC FACTORS; ENDOTHELIAL-CELLS; SERUM PROTEOMICS; FACTOR VEGF; IN-VIVO; MICROSATELLITE INSTABILITY AB Early tumor detection and intervention are important determinants of survival in patients with cancer. We have recently reported that the "platelet angiogenesis proteome" may be used to detect microscopic tumors in mice. We now present evidence that changes in platelet-associated platelet factor-4 (PF-4) detect malignant growth across a spectrum of human cancers in mice. A deregulated expression of an 8206-Da protein was observed by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-ToF MS) proteomic comparison of platelets from normal and tumor-bearing mice. The differentially expressed protein was identified as PF-4 by tandem mass spectrometry and ProteinChip immunoassay using anti-PF-4 antibody. The platelet-associated PF-4 appeared to be up-regulated in early growth of human liposarcoma, mammary adenocarcinoma, and osteosarcoma. A 120-day follow-up study of liposarcoma revealed a sustained 2-fold or higher increase of platelet-associated PF-4 at 19, 30, and 120 days. In contrast, only an insignificant change of PF-4 was observed in the plasma of mice bearing the different human tumor xenografts, and throughout the 120 days of the liposarcoma study. We conclude that platelet-associated PF-4, but not its plasma counterpart, may represent a potential biomarker of early tumor presence. C1 [Cervi, David; Bhattacharya, Nandita; Peterson, Jon; Abou-Slaybi, Abdo; Naumov, George N.; Bender, Elise; Almog, Nava; Folkman, Judah; Klement, Giannoula L.] Childrens Hosp, Karp Family Res Labs, Boston, MA 02115 USA. [Yip, Tai-Tung; Podust, Vladimir N.] Ciphergen Biosyst, Fremont, CA USA. [Peterson, Jon] Ortho Clin Diagnost, Rochester, NY USA. [Italiano, Joseph E., Jr.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Klement, Giannoula L.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Klement, GL (reprint author), Childrens Hosp, Karp Family Res Labs, Rm 11-211,One Blackfan Circle, Boston, MA 02115 USA. EM giannoula.klement@childrens.harvard.edu NR 79 TC 70 Z9 78 U1 0 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 1 PY 2008 VL 111 IS 3 BP 1201 EP 1207 DI 10.1182/blood-2007-04-084798 PG 7 WC Hematology SC Hematology GA 257IR UT WOS:000252792900042 PM 17914028 ER PT J AU Italiano, JE Richardson, JL Patel-Hett, S Battinelli, E Zaslavsky, A Short, S Ryeom, S Folkman, J Klement, GL AF Italiano, Joseph E., Jr. Richardson, Jennifer L. Patel-Hett, Sunita Battinelli, Elisabeth Zaslavsky, Alexander Short, Sarah Ryeom, Sandra Folkman, Judah Klement, Giannoula L. TI Angiogenesis is regulated by a novel mechanism: pro- and antiangiogenic proteins are organized into separate platelet alpha granules and differentially released SO BLOOD LA English DT Article ID MOLECULAR-WEIGHT HEPARIN; VIII-RELATED ANTIGEN; GROWTH-FACTOR; ENDOTHELIAL-CELLS; ADVANCED MALIGNANCY; TUMOR ANGIOGENESIS; BLOOD PLATELETS; MEGAKARYOCYTES; THROMBIN; GEL AB Platelets, in addition to their function in hemostasis, play an important role in wound healing and tumor growth. Because platelets contain angiogenesis stimulators and inhibitors, the mechanisms by which platelets regulate angiogenesis remain unclear. As platelets adhere to activated endothelium, their action can enhance or inhibit local angiogenesis. We therefore suspected a higher organization of angiogenesis regulators in platelets. Using double immunofluorescence and immunoelectron microscopy, we show that pro- and antiangiogenic proteins are separated in distinct sub-populations of a-granules in platelets and megakaryocytes. Double immunofluorescence labeling of vascular endothelial growth factor (VEGF) (an angiogenesis stimulator) and endostatin (an angiogenesis inhibitor), or for thrombospondin-1 and basic fibroblast growth factor, confirms the segregation of stimulators and inhibitors into separate and distinct alpha-granules. These observations motivated the hypothesis that distinct populations of ot-granules could undergo selective release. The treatment of human platelets with a selective PAR4 agonist (AYPGKF-NH2) resulted in release of endostatin-containing granules, but not VEGF-containing granules, whereas the selective PAR1 agonist (TFLLR-NH2) liberated VEGF, but not endostatin-containing granules. In conclusion, the separate packaging of angiogenesis regulators into pharmacologically and morphologically distinct populations of a-granules in megakaryocytes and platelets may provide a mechanism by which platelets can locally stimulate or inhibit anglogenesis. C1 [Italiano, Joseph E., Jr.; Richardson, Jennifer L.; Patel-Hett, Sunita] Brigham & Womens Hosp, Translat Med Div, Boston, MA 02115 USA. [Italiano, Joseph E., Jr.; Patel-Hett, Sunita; Zaslavsky, Alexander; Short, Sarah; Ryeom, Sandra; Folkman, Judah; Klement, Giannoula L.] Childrens Hosp, Vasc Biol Program, Dept Surg, Boston, MA USA. [Battinelli, Elisabeth] Beth Israel Deaconess Med Ctr, Dept Hematol & Oncol, Boston, MA USA. [Klement, Giannoula L.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Italiano, JE (reprint author), Brigham & Womens Hosp, Translat Med Div, One Blackfan Circle, Boston, MA 02115 USA. EM jitaliano@rics.bwh.harvard.edu; giannoula.klement@childrens.harvard.edu FU NHLBI NIH HHS [HL068130, R01 HL068130] NR 41 TC 374 Z9 380 U1 7 U2 29 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 1 PY 2008 VL 111 IS 3 BP 1227 EP 1233 DI 10.1182/blood-2007-09-113837 PG 7 WC Hematology SC Hematology GA 257IR UT WOS:000252792900045 PM 17962514 ER PT J AU Au, P Daheron, LM Duda, DG Cohen, KS Tyrrell, JA Lanning, RM Fukumura, D Scadden, DT Jain, RK AF Au, Patrick Daheron, Laurence M. Duda, Dan G. Cohen, Kenneth S. Tyrrell, James A. Lanning, Ryan M. Fukumura, Dai Scadden, David T. Jain, Rakesh K. TI Differential in vivo potential of endothelial progenitor cells from human umbilical cord blood and adult peripheral blood to form functional long-lasting vessels SO BLOOD LA English DT Article ID EXPRESSION; LIFE AB Tissue engineering requires formation of a de novo stable vascular network. Because of their ability to proliferate, differentiate into endothelial cells, and form new vessels, blood-derived endothelial progenitor cells (EPCs) are attractive source of cells for use in engineering blood vessels. However, the durability and function of EPC-derived vessels implanted in vivo are unclear. To this end, we directly compared formation and functions of tissue-engineered blood vessels generated by peripheral blood- and umbilical cord blood-derived EPCs in a model of in vivo vasculogenesis. We found that adult peripheral blood EPCs form blood vessels that are unstable and regress within 3 weeks. In contrast, umbilical cord blood EPCs form normal-functioning blood vessels that last for more than 4 months. These vessels exhibit normal blood flow, perm-selectivity to macromolecules, and induction of leukocyte-endothelial interactions in response to cytokine activation similar to normal vessels. Thus, umbilical cord blood EPCs hold great therapeutic potential, and their use should be pursued for vascular engineering. C1 [Au, Patrick; Duda, Dan G.; Tyrrell, James A.; Lanning, Ryan M.; Fukumura, Dai; Jain, Rakesh K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Edwin L Steel Lab, Boston, MA 02114 USA. [Au, Patrick; Lanning, Ryan M.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Daheron, Laurence M.; Cohen, Kenneth S.; Scadden, David T.] Harvard Univ, Massachusetts Gen Hosp, Ctr Regenerat Med, Sch Med, Cambridge, MA 02138 USA. [Daheron, Laurence M.; Cohen, Kenneth S.; Scadden, David T.] Harvard Stem Cell Inst, Cambridge, MA USA. RP Jain, RK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Edwin L Steel Lab, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu RI Tyrrell, James/A-6359-2010 FU NCI NIH HHS [R01CA115767, P01 CA080124, R01 CA096915, R01 CA085140, R01 CA115767, R01CA96915, R01CA85140, P01CA80124]; NIGMS NIH HHS [T32 GM007753] NR 14 TC 180 Z9 187 U1 0 U2 18 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 1 PY 2008 VL 111 IS 3 BP 1302 EP 1305 DI 10.1182/blood-2007-06-094318 PG 4 WC Hematology SC Hematology GA 257IR UT WOS:000252792900056 PM 17993613 ER PT J AU Rastelli, J Homig-Holzel, C Seagal, J Muller, W Hermann, AC Rajewsky, K Zimber-Strobl, U AF Rastelli, Julia Hoemig-Hoelzel, Cornelia Seagal, Jane Mueller, Werner Hermann, Andrea C. Rajewsky, Klaus Zimber-Strobl, Ursula TI LMP1 signaling can replace CD40 signaling in B cells in vivo and has unique features of inducing class-switch recombination to IgG1 SO BLOOD LA English DT Article ID EPSTEIN-BARR-VIRUS; MEMBRANE-PROTEIN 1; MICE; EXPRESSION; TRANSDUCTION; LYMPHOCYTES; ACTIVATION; RESPONSES; SURVIVAL; SYSTEM AB The Epstein-Barr virus (EBV) protein LMP1 is considered to be a functional homologue of the CD40 receptor. However, in contrast to the latter, LMP1 is a constitutively active signaling molecule. To compare B cell-specific LMP1 and CD40 signaling in an unambiguous manner, we generated transgenic mice conditionally expressing a CD40/LMP1 fusion protein, which retained the LMP1 cyto-plasmic tail but has lost the constitutive activity of LMP1 and needs to be activated by the CD40 ligand. We show that LMP1 signaling can completely substitute CD40 signaling in B cells, leading to normal B-cell development, activation, and immune responses including class-switch recombination, germinal center formation, and somatic hypermutation. In addition, the LMP1-signaling domain has a unique property in that it can induce class-switch recombination to IgG1 independent of cytokines. Thus, our data indicate that LMP1 has evolved to imitate T-helper cell function allowing activation, proliferation, and differentiation of EBV-infected B cells independent of T cells. C1 [Rastelli, Julia; Hoemig-Hoelzel, Cornelia; Zimber-Strobl, Ursula] Natl Res Ctr Environm & Hlth, GSF, Inst Clin Mol Biol & Tumor Genet, D-81377 Munich, Germany. [Seagal, Jane] Harvard Univ, Sch Med, Ctr Blood Res, Inst Biomed Res, Cambridge, MA 02138 USA. [Mueller, Werner] Helmholtz Ctr Infect Res, Dept Expt Immunol, Braunschweig, Germany. [Hermann, Andrea C.] Natl Res Ctr Environm & Hlth, GSF, Inst Stem Cell Res, Neuherberg, Germany. RP Zimber-Strobl, U (reprint author), Natl Res Ctr Environm & Hlth, GSF, Inst Clin Mol Biol & Tumor Genet, Marchioninistr 25, D-81377 Munich, Germany. EM strobl@gsf.de RI Muller, Werner/B-9044-2008 OI Muller, Werner/0000-0002-1297-9725 NR 31 TC 48 Z9 49 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 1 PY 2008 VL 111 IS 3 BP 1448 EP 1455 DI 10.1182/blood-2007-10-117655 PG 8 WC Hematology SC Hematology GA 257IR UT WOS:000252792900073 PM 18006702 ER PT J AU Chauhan, D Singh, A Brahmandam, M Podar, K Hideshirna, T Richardson, P Munshi, N Palladino, MA Anderson, KC AF Chauhan, Dharminder Singh, Ajita Brahmandam, Mohan Podar, Klaus Hideshirna, Teru Richardson, Paul Munshi, Nikhil Palladino, Michael A. Anderson, Kenneth C. TI Combination of proteasome inhibitors bortezomib and NPI-0052 trigger in vivo synergistic cytotoxicity in multiple myeloma SO BLOOD LA English DT Article ID MOLECULAR-WEIGHT PROTEASES; OVERCOMES DRUG-RESISTANCE; NF-KAPPA-B; PROTEIN BREAKDOWN; HEMATOLOGIC MALIGNANCIES; INDUCED APOPTOSIS; UBIQUITIN SYSTEM; ACTIVE-SITES; CELL-GROWTH; DEGRADATION AB Our recent study demonstrated that a novel proteasome inhibitor NPI-0052 triggers apoptosis in multiple myeloma (MM) cells, and importantly, that is distinct from bortezomib (Velcade) in its chemical structure, effects on proteasome activities, and mechanisms of action. Here, we demonstrate that combining NPI-0052 and bortezomb induces synergistic anti-MM activity both in vitro using MM cell lines or patient CD138(+) MM cells and in vivo in a human plasmacytoma xenograft mouse model. NPI-0052 plus bortezomib-induced synergistic apoptosis is associated with: (1) activation of caspase-8, caspase-9, caspase-3, and PARP; (2) induction of endoplasmic reticulum (ER) stress response and JNK; (3) inhibition of migration of MM cells and angiogenesis; (4) suppression of chymotrypsin-like (CT-L), caspase-like (C-L), and trypsin-like (T-L) proteolytic activities; and (5) blockade of NF-kappa B signaling. Studies in a xenograft model show that low dose combination of NPI-0052 and bortezomib is well tolerated and triggers synergistic inhibition of tumor growth and CT-L, C-L, and T-L proteasome activities in tumor cells. Immununostaining of MM tumors from NPI-0052 plus bortezomib-treated mice showed growth inhibition, apoptosis, and a decrease in associated angiogenesis. Taken together, our study provides the preclinical rationale for clinical protocols evaluating bortezomib together with NPI-0052 to improve patient outcome in MM. C1 [Chauhan, Dharminder; Singh, Ajita; Brahmandam, Mohan; Podar, Klaus; Hideshirna, Teru; Richardson, Paul; Anderson, Kenneth C.] Harvard Univ, Jerome Lipper Ctr Myeloma Res, Sch Med, LeBow Inst Myeloma Therapeuat,Dana Farber Canc I, Boston, MA USA. [Munshi, Nikhil] Harvard Univ, Sch Med, Vet Adm Boston Healthcare Syst, Boston, MA USA. [Palladino, Michael A.] Nereus Pharmaceut, San Diego, CA USA. RP Chauhan, D (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM dharminder_hauhan@dfci.harvard.edu FU NCI NIH HHS [CA 10070, CA 50947, CA 78373, R01 CA050947] NR 70 TC 149 Z9 156 U1 0 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 1 PY 2008 VL 111 IS 3 BP 1654 EP 1664 DI 10.1182/blood-2006-10-050476 PG 11 WC Hematology SC Hematology GA 257IR UT WOS:000252792900098 PM 18006697 ER PT J AU Ho, VT Revta, C Richardson, PG AF Ho, V. T. Revta, C. Richardson, P. G. TI Hepatic veno-occlusive disease after hematopoietic stem cell transplantation: update on defibrotide and other current investigational therapies SO BONE MARROW TRANSPLANTATION LA English DT Review DE veno-occlusive disease; sinusoidal obstruction syndrome; defibrotide; SCT ID BONE-MARROW-TRANSPLANTATION; TISSUE-PLASMINOGEN-ACTIVATOR; SINUSOIDAL OBSTRUCTION SYNDROME; MOLECULAR-WEIGHT HEPARIN; GEMTUZUMAB OZOGAMICIN EXPOSURE; REGIMEN-RELATED TOXICITY; HIGH-RISK POPULATION; LOW-DOSE HEPARIN; ENDOTHELIAL-CELLS; RANDOMIZED-TRIAL AB Hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), remains one of the most serious and common complications after myeloablative hematopoietic stem cell transplantation (HSCT). Clinical diagnosis of hepatic VOD is based on the clinical triad of (1) painful hepatomegaly, (2) \hyperbilirubinemia and (3) unexplained fluid retention. While milder cases usually resolve spontaneously, severe VOD is associated with a grim prognosis. Defibrotide (DF), a polydisperse mixture of single-stranded oligonucleotide with antithrombotic and fibrinolytic effects on microvascular endothelium, has emerged as an effective and safe therapy for patients with severe VOD. Multiple studies, including a recent large international multicenter phase II clinical trial, have demonstrated 30-60% complete remission rates with DF, even among patients with severe VOD and multiorgan failure. This article will review our current understanding of hepatic VOD, and update the clinical trial experience with DF and other potential therapies for this feared transplant complication. C1 [Ho, V. T.; Revta, C.; Richardson, P. G.] Harvard Univ, Sch Med, Dana Farber Canc Inst,Ctr Hematol Oncol, Brigham & Womens Hosp,Dept Adult Oncol, Boston, MA 02115 USA. RP Ho, VT (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst,Ctr Hematol Oncol, Brigham & Womens Hosp,Dept Adult Oncol, 44 Binney St,D1B06, Boston, MA 02115 USA. EM vincent_ho@dfci.harvard.edu NR 104 TC 61 Z9 66 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD FEB PY 2008 VL 41 IS 3 BP 229 EP 237 DI 10.1038/sj.bmt.1705899 PG 9 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 261ZH UT WOS:000253118000001 PM 17994121 ER PT J AU Riest, G Peters, J Weiss, M Dreyer, S Klassen, PD Stegen, B Bello, A Eikermann, M AF Riest, G. Peters, J. Weiss, M. Dreyer, S. Klassen, P. D. Stegen, B. Bello, A. Eikermann, M. TI Preventive effects of perioperative parecoxib on post-discectomy pain SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Article DE analgesics non-opioid; analgesics opioid, morphine; pain, mechanism; pain, postoperative ID PRODUCE MATRIX METALLOPROTEINASES; GYNECOLOGIC LAPAROTOMY SURGERY; POSTOPERATIVE PAIN; PREEMPTIVE ANALGESIA; COX-2 INHIBITORS; ABDOMINAL HYSTERECTOMY; CENTRAL SENSITIZATION; ORTHOPEDIC-SURGERY; PROSTAGLANDIN E(2); NITRIC-OXIDE AB Background. Cyclooxygenase inhibitor treatment is viewed increasingly critical because of safety considerations, and there are several open questions on their optimal use. Methods. In a randomized placebo-controlled study in 320 patients undergoing discectomy, we administered parecoxib 40 mg either perioperatively (before operation and after operation), after operation (first dose given in the evening after surgery), or before operation (single parecoxib dose given 45 min before surgery). We measured the main outcome variables: average pain score, morphine consumption, and opioid-related symptom distress at 25, 49, and 73 h after surgery. Results. Perioperative parecoxib significantly (i) improved the pain score compared with both placebo and postoperative parecoxib, (ii) decreased morphine consumption, and (iii) reduced the opioid-related symptom distress score. Neither a single preoperative dose nor postoperative parecoxib (first dose given in the evening after surgery) significantly improved morphine's analgesic effectiveness. Conclusions. Perioperative parecoxib compared with postoperative parecoxib improves post-discectomy pain and results in a reduction in adverse effects associated with opioid therapy. Postoperative parecoxib, or a single pre-incisional parecoxib dose, does not significantly improve post-discectomy pain or opioid side-effects up to 3 days after surgery. C1 [Riest, G.; Peters, J.; Weiss, M.; Dreyer, S.; Stegen, B.; Eikermann, M.] Univ Klinikum Essen, Klin Anasthesiol & Intens Med, Essen, Germany. [Klassen, P. D.] Univ Klinikum Essen, Neurochirurg Klin, Essen, Germany. [Bello, A.] Pfizer Inc, New York, NY USA. RP Eikermann, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM meikermann@partners.org NR 37 TC 11 Z9 22 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0007-0912 J9 BRIT J ANAESTH JI Br. J. Anaesth. PD FEB PY 2008 VL 100 IS 2 BP 256 EP 262 DI 10.1093/bja/aem345 PG 7 WC Anesthesiology SC Anesthesiology GA 256GQ UT WOS:000252716400017 PM 18079431 ER PT J AU O'Cleirigh, C Ironson, G Fletcher, MA Schneiderman, N AF O'Cleirigh, Conall Ironson, Gail Fletcher, Mary Ann Schneiderman, Neil TI Written emotional disclosure and processing of trauma are associated with protected health status and immunity in people living with HIV/AIDS SO BRITISH JOURNAL OF HEALTH PSYCHOLOGY LA English DT Article ID CD4 AB Objective. This study compared written emotional disclosure and processing of trauma among a relatively rare group of people with AIDS with atypically favourable disease status with an HIV+ comparison group. The study also examined the mediational role of emotional/cognitive processing and natural killer (NK) cells. Design. This study utilized a cross-sectional group comparison design. Method. Two HIV+ groups, the Healthy Survivors (N = 37; > 9-months with < 50 CD4 cells/mm(3) and asymptomatic), and an HIV+ comparison groups (N = 100) wrote essays describing their reactions to past traumas; these were scored for emotional disclosure/processing. Results. Healthy survivors had higher levels of emotional disclosure and emotional/cognitive processing than the comparison group. Emotional/cognitive processing mediated the relationship between emotional disclosure and group membership. NK cell number mediated the relationship between emotional/cognitive processing and 'healthy survival'. Conclusions. The results suggest that higher levels of emotional disclosure and processing of trauma may confer health and immunological benefits to people living with HIV/AIDS. C1 [O'Cleirigh, Conall; Ironson, Gail; Fletcher, Mary Ann; Schneiderman, Neil] Univ Miami, Dept Psychol, Coral Gables, FL 33124 USA. [O'Cleirigh, Conall; Ironson, Gail; Fletcher, Mary Ann; Schneiderman, Neil] Univ Miami, Dept Psychiat, Coral Gables, FL 33124 USA. [O'Cleirigh, Conall; Ironson, Gail; Fletcher, Mary Ann; Schneiderman, Neil] Univ Miami, Dept Med, Coral Gables, FL 33124 USA. RP O'Cleirigh, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, 1,Bowdoin Sq BS-07B, Boston, MA 02114 USA. EM cocleirigh@partners.org FU NIMH NIH HHS [R01 MH066697, R01 MH066697-05, R01 MH53791, T32 MH018917, T32 MH18917] NR 4 TC 12 Z9 12 U1 1 U2 6 PU BRITISH PSYCHOLOGICAL SOC PI LEICESTER PA ST ANDREWS HOUSE, 48 PRINCESS RD EAST, LEICESTER LE1 7DR, LEICS, ENGLAND SN 1359-107X J9 BRIT J HEALTH PSYCH JI Br. J. Health Psychol. PD FEB PY 2008 VL 13 BP 81 EP 84 DI 10.1348/135910707X250884 PN 1 PG 4 WC Psychology, Clinical SC Psychology GA 265SN UT WOS:000253381300017 PM 18230237 ER PT J AU Zhang, Y Mashimo, H Paterson, WG AF Zhang, Y. Mashimo, H. Paterson, W. G. TI Regional differences in nitrergic innervation of the smooth muscle of murine lower oesophageal sphincter SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE ATP; niflumic acid; neuronal nitric oxide synthase; circular smooth muscle; long-lasting slow IJP ID INHIBITORY JUNCTION POTENTIALS; VASOACTIVE-INTESTINAL-PEPTIDE; NITRIC-OXIDE SYNTHASE; GUINEA-PIG ILEUM; INTERSTITIAL-CELLS; OPOSSUM ESOPHAGUS; MOTOR-NEURONS; SLING MUSCLE; CL-CHANNELS; CAJAL AB Background and purpose: Anatomical and pharmacological studies have demonstrated that the lower oesophageal sphincter (LES) is not a simple homogenous circular muscle with uniform innervation. Regional differences have been demonstrated in several species including humans. We investigated, for the first time in mice LES, regionally distinct physiological and pharmacological characteristics of the neuromusculature. Experimental approach: Conventional intracellular recordings and pharmacological techniques were employed to evaluate electrical properties and functional innervation of smooth muscle cells. Results from CD1 (control), nNOS((-/-)) and eNOS((-/-)) genetic knockout mice were compared. Key results: Smooth muscle of sling and clasp LES displayed unitary membrane potentials of 1-4 mV. Transmural nerve stimulation produced a monophasic inhibitory junction potential (IJP) in the sling, whereas in the clasp a biphasic IJP, consisting of a brief IJP followed by a long-lasting slow IJP (lsIJP), was induced. Pharmacological interventions and genetically modified mice were used to demonstrate a monophasic apamin-sensitive (purinergic) component in both LES regions. However, the nitrergic IJP was monophasic in the sling and biphasic in the clasp. Unitary membrane potentials and IJPs were not different in CD1 and eNOS((-/-)) mice, suggesting no involvement of myogenic NOS. Conclusion and implications: These data in mouse LES indicate that there are previously unreported regional differences in the IJP and that both the apamin-resistant monophasic and biphasic IJPs are mediated primarily by nitrergic innervation. C1 [Zhang, Y.; Paterson, W. G.] Queens Univ, Dept Physiol, Gastrointestinal Dis Res Unit, Kingston, ON K7L 3N6, Canada. [Mashimo, H.] Harvard Univ, Sch Med, Ctr Swallowing & Motil Disorders, VA Boston Healthcare, Boston, MA USA. [Paterson, W. G.] Queens Univ, Dept Med, Kingston, ON K7L 3N6, Canada. [Paterson, W. G.] Queens Univ, Dept Biol, Kingston, ON K7L 3N6, Canada. RP Paterson, WG (reprint author), Hop Hotel Dieu, Div Gastroenterol, 166 Brock St, Kingston, ON, Canada. EM patersow@hdh.kari.net NR 55 TC 11 Z9 11 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD FEB PY 2008 VL 153 IS 3 BP 517 EP 527 DI 10.1038/sj.bjp.0707573 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 258QW UT WOS:000252884000014 PM 18037919 ER PT J AU Dewey, CM Coverdale, JH Ismail, NJ Culberson, JW Thompson, BM Patton, CS Friedland, JA AF Dewey, Charlene M. Coverdale, John H. Ismail, Nadia J. Culberson, John W. Thompson, Britta M. Patton, Cynthia S. Friedland, Joan A. TI Residents-as-teachers programs in psychiatry: A systematic review SO CANADIAN JOURNAL OF PSYCHIATRY-REVUE CANADIENNE DE PSYCHIATRIE LA English DT Review DE residents; teaching skills; residents as teachers; psychiatry; assessments ID MEDICAL-STUDENTS; RANDOMIZED-TRIAL; TRAINING-PROGRAM; TEACHING SKILLS; ATTITUDES; INSTRUMENT AB Objectives: Because psychiatry residents have important roles as teachers and significant opportunities to contribute to medical student education, we set out to: identify all randomized control trials (RCT) for residents' teaching skills programs in psychiatry and to identify the efficacy of those interventions for improving teaching skills; identify the strengths and weaknesses of the available studies across medical disciplines; and identify currently available methods for enhancing residents' teaching skills for residents training in psychiatry. Methods: The published English-language literature was searched using PubMed, Social Sciences Index, and PsycINFO databases, with key search words including: residents, teaching skills, residents as teachers, psychiatry, and assessments. Both RCT and controlled, nonrandomized trials of residents' teaching programs directed to enhance residents' teaching skills were selected and critically appraised. Results: Of 13 trials identified and reviewed, most included residents in internal medicine. Only one included psychiatry residents and assessed their ability to teach interviewing skills to medical students. Along with other studies, this study demonstrated improvement in residents' teaching skills. Overall, interventions and outcome measures were heterogeneous while the quality of methodologies varied. Five studies were of higher quality, representing examples of quality educational research. Several described group differences, blinding, good follow-up, and use of valid, reliable tools. Conclusions: Only one trial exists that incorporated psychiatry residents. Significant opportunity to advance educational research in this field exists. Psychiatry residency program directors should incorporate high-quality methodologies and can benefit from the findings of trials in other disciplines. C1 [Dewey, Charlene M.] Vanderbilt Univ, Sch Med, Off Teaching & Learning Med, Nashville, TN 37232 USA. [Coverdale, John H.] Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA. [Coverdale, John H.] Baylor Coll Med, Ctr Eth, Houston, TX 77030 USA. [Ismail, Nadia J.] Baylor Coll Med, Dept Med, Gen Internal Med Sect, Houston, TX 77030 USA. [Culberson, John W.] Baylor Coll Med, Dept Med, Sect Geriatr, Houston, TX USA. [Thompson, Britta M.; Patton, Cynthia S.] Baylor Coll Med, Off Curriculum, Relationship Ctr Transformat Curriculum, Houston, TX USA. [Friedland, Joan A.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. RP Dewey, CM (reprint author), Vanderbilt Univ, Sch Med, Off Teaching & Learning Med, 3402 MRB-4, Nashville, TN 37232 USA. EM charlene.dewey@vanderbilt.edu FU NHLBI NIH HHS [5 K07 HL082629-01] NR 36 TC 19 Z9 19 U1 0 U2 3 PU CANADIAN PSYCHIATRIC ASSOC PI OTTAWA PA 141 LAURIER AVENUE WEST, STE 701, OTTAWA, ONTARIO K1P 5J3, CANADA SN 0706-7437 J9 CAN J PSYCHIAT JI Can. J. Psychiat.-Rev. Can. Psychiat. PD FEB PY 2008 VL 53 IS 2 BP 77 EP 84 PG 8 WC Psychiatry SC Psychiatry GA 269RS UT WOS:000253667900002 PM 18357925 ER PT J AU Ross, RW Beer, TM Jacobus, S Bubley, GJ Taplin, ME Ryan, CW Huang, J Oh, WK AF Ross, Robert W. Beer, Tomasz M. Jacobus, Susanna Bubley, Glenn J. Taplin, Mary-Ellen Ryan, Christopher W. Huang, Jiaoti Oh, William K. CA Prostate Canc Clin Trials Conso TI A phase 2 study of carboplatin plus docetaxel in men with metastatic hormone-refractory prostate cancer who are refractory to docetaxel SO CANCER LA English DT Article DE carboplatin; chromogranin A; docetaxel-refractory; prostate cancer ID ESTRAMUSTINE; CHEMOTHERAPY; MITOXANTRONE; GUIDELINES; PREDNISONE AB BACKGROUND. Prostate cancer is the second leading cause of cancer mortality among men in the U.S. To the authors' knowledge, there is no proven, effective, second-line therapy for docetaxel-refractory disease. Recent data suggest that platinum salts may be effective when combined with taxanes in metastatic hormone-refractory prostate cancer (HRPC). The authors conducted a phase 2 trial of docetaxel plus carboplatin chemotherapy in this disease setting. METHODS. Eligible men had metastatic HRPC that had progressed during or within 45 days after the completion of docetaxel-based chemotherapy. Patients were treated with intravenous docetaxel at a dose of 60 mg/m(2) plus carboplatin at an area under the curve of 4 once every 21 days until they had either disease progression or unacceptable toxicity. RESULTS. Thirty-four patients were enrolled. Therapy was tolerated reasonably well; Grade 3 leukopenia (graded according to the Common Toxicity Criteria grading system) was the most common adverse event (experienced by 56% of patients), but there was only 1 episode of febrile neutropenia reported. Prostate-specific antigen (PSA) declines >= 50% were noted in 18% of patients, and measurable responses were observed in 14%. The median duration of PSA response was 5.7 months. The median progression -free survival was 3 months, and the median overall survival was 12.4 months. Patients were more likely to respond to the combination if they previously had responded to docetaxel. CONCLUSIONS. In men with HRPC who developed progressive disease during or shortly after treatment with docetaxel, the addition of carboplatin resulted in modest additional activity. Taxane- refractory HRPC is an area of unmet need, and the current trial has provided evidence that platinum chemotherapy may be an important therapeutic option. C1 [Ross, Robert W.; Jacobus, Susanna; Taplin, Mary-Ellen; Oh, William K.] Lank Ctr Genitourinary Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Beer, Tomasz M.; Ryan, Christopher W.] Oregon Hlth & Sci Univ, Inst Canc, Portland, OR 97201 USA. [Beer, Tomasz M.; Ryan, Christopher W.] Oregon Hlth & Sci Univ, Div Hematol & Med Oncol, Portland, OR 97201 USA. [Bubley, Glenn J.] Beth Israel Deaconess Med Ctr, Dept Med Oncol, Boston, MA 02215 USA. [Huang, Jiaoti] Univ Rochester, Sch Med, Dept Pathol, Rochester, NY USA. RP Oh, WK (reprint author), Lank Ctr Genitourinary Oncol, Dana Farber Canc Inst, Dana 1230,44 Binney St, Boston, MA 02115 USA. EM william_oh@dfci.harvard.edu RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 20 TC 56 Z9 61 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD FEB 1 PY 2008 VL 112 IS 3 BP 521 EP 526 DI 10.1002/cncr.23195 PG 6 WC Oncology SC Oncology GA 256XR UT WOS:000252763700011 PM 18085595 ER PT J AU Come, SE Buzdar, AU Ingle, JN Johnston, SRD Brodie, AM Coombes, RC Miller, WR Pritchard, KI Winer, EP Zujewski, JA Goss, PE AF Come, Steven E. Buzdar, Aman U. Ingle, James N. Johnston, Stephen R. D. Brodie, Angela M. Coombes, R. Charles Miller, William R. Pritchard, Kathleen I. Winer, Eric P. Zujewski, Jo Anne Goss, Paul E. TI Endocrine and Targeted Manipulation of Breast Cancer: Summary statement for the Sixth Cambridge Conference SO CANCER LA English DT Article; Proceedings Paper CT 6th Cambridge Conference on Endocrine and Targeted Manipulation of Breast Cancer CY APR 30-MAY 01, 2007 CL Cambridge, MA DE endocrine therapy; breast cancer; estrogen; aromatase inhibitors; tamoxifen ID THERAPY AB The Sixth Cambridge Conference on Endocrine and Targeted Manipulation of Breast Cancer was convened in Cambridge, Massachusetts on April 30 and May 1, 2007. The purpose of this multidisciplinary meeting of leaders in clinical and basic research and patient treatment was to assess the most recent data in the field, articulate current best practices, and identify the next steps to advance both patient care and research. Topics included a review of data from major recent and ongoing trials of endocrine treatment in patients with early breast cancer and from studies combining endocrine therapy with other treatment. The current status of breast cancer prevention efforts was examined. Preclinical models of response and resistance, initial efforts to profile tumor response and resistance during endocrine therapy in patients, and new developments in pharmacogenomics were also highlighted. In this article, a synopsis of the key issues discussed, conclusions, and recommendations are summarized; these are presented at greater length in the individual articles and accompanying Open Discussions that comprise the full conference proceedings. In the 2 years since the Fifth Conference, we have gained valuable follow-up data from key trials in early breast cancer, which have helped to clarify both the efficacy and safety and tolerability of the available strategies for endocrine therapy. Observations using endocrine agents in combination with other treatment have been similarly extended. More detailed analysis of preclinical models has improved our understanding of resistance to endocrine therapy, and efforts to explore these and other mechanisms in the clinic are now underway. All of this has and continues to contribute to a growing understanding of how to optimize the use of endocrine agents in both treating and preventing breast cancer. C1 [Come, Steven E.] Beth Israel Deaconess Med Ctr, Breast Cancer Program, Boston, MA 02215 USA. [Buzdar, Aman U.] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX USA. [Ingle, James N.] Mayo Clin, Div Med Oncol, Rochester, MN USA. [Johnston, Stephen R. D.] Royal Marsden Hosp, Dept Med, London, England. [Brodie, Angela M.] Univ Maryland, Sch Med, Dept Pharmacol & Expt Therapeut, Baltimore, MD 21201 USA. [Coombes, R. Charles] Imperial Coll Sch Med, Dept Med, Breast Unit, London, England. [Miller, William R.] Univ Edinburgh, Breast Res Grp, Edinburgh, Midlothian, Scotland. [Pritchard, Kathleen I.] Univ Toronto, Toronto Sunnybrool Reg Canc Ctr, Clin Trial & Epidemiol, Toronto, ON, Canada. [Winer, Eric P.] Dana Farber Canc Inst, Breast Oncol Ctr, Boston, MA USA. [Zujewski, Jo Anne] Natl Canc Inst, Canc Therapy Evaluat Program, Bethesda, MD USA. [Goss, Paul E.] Massachusetts Gen Canc Ctr, Breast Canc Res, Boston, MA USA. RP Come, SE (reprint author), Beth Israel Deaconess Med Ctr, Breast Cancer Program, 330 Brookline Ave,Room CC-913, Boston, MA 02215 USA. EM scome@caregroup.harvard.edu NR 2 TC 7 Z9 7 U1 1 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD FEB 1 PY 2008 VL 112 IS 3 SU S BP 673 EP 678 DI 10.1002/cncr.23194 PG 6 WC Oncology SC Oncology GA 258QN UT WOS:000252882800001 PM 18072254 ER PT J AU Buzdar, AU Coombes, RC Goss, PE Winer, EP AF Buzdar, Aman U. Coombes, R. Charles Goss, Paul E. Winer, Eric P. TI Summary of aromatase inhibitor clinical trials in postmenopausal women with early breast cancer SO CANCER LA English DT Article; Proceedings Paper CT 6th Cambridge Conference on Endocrine and Targeted Manipulation of Breast Cancer CY APR 30-MAY 01, 2007 CL Cambridge, MA DE aromatase inhibitor; breast cancer; endocrine therapy; clinical trial ID QUALITY-OF-LIFE; ADJUVANT TREATMENT; RANDOMIZED-TRIAL; COMBINATION TRIAL; TAMOXIFEN THERAPY; ATAC ARIMIDEX; ANASTROZOLE; COMPLETION; EXEMESTANE; LETROZOLE AB Five years of adjuvant therapy with tamoxifen was considered the gold-standard treatment for postmenopausal women with estrogen receptor-positive breast cancer for many years. Data from a core group of clinical trials investigating the safety and efficacy of aromatase inhibitors (AIs) have challenged this perception. These studies were designed to evaluate the safety and efficacy of AIs in the following clinical settings: 1) as initial adjuvant therapy (the Arimidex, Tamoxifen, Alone or in Combination trial, Breast International Group Trial 1-98), 2) in a "switched setting" after 2 to 3 years of treatment with tamoxifen (Arimidex-Nolvadex 95, the Austrian Breast and Colorectal Cancer Study Group 8 [ABCSG 8] trial, the Italian Tamoxifen Anastrozole study the Intergroup Exemestane Study), and 3) in extended settings (National Cancer Institute of Canada Trial MA.17, ABCSG 6a, National Surgical Adjuvant Breast and Bowel Project 33). The efficacy data from these studies suggested that AIs have added substantial benefit in terms of disease outcome. AIs were tolerated well, and patients who received them experienced fewer thrombolic events and less endometrial cancer, hot flashes, night sweats, and vaginal bleeding compared with patients who receive tamoxifen. However, patients who received tamoxifen had less skeletal events and accelerated bone resorption compared with women who received AIs. AIs should be considered when planning a patient's endocrine therapy, taking into account the differences in tolerability and end-organ effects of the classes of endocrine therapy. Outstanding issues to optimize AI therapy include identifying the optimal duration, agent, and patients for these therapies. C1 [Buzdar, Aman U.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA. [Coombes, R. Charles] Imperial Coll Sch Med, Dept Med Oncol, London, England. [Goss, Paul E.] Massachusetts Gen Hosp, Ctr Canc, Dept Breast Canc Res, Boston, MA USA. [Winer, Eric P.] Dana Farber Canc Inst, Breast Oncol Ctr, Boston, MA USA. RP Buzdar, AU (reprint author), Univ Texas Houston, MD Anderson Canc Ctr, Dept Breast Med Oncol, 1515 Holcombe Blvd,Unit 1354, Houston, TX 77030 USA. EM abuzdar@mdanderson.org NR 19 TC 28 Z9 28 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD FEB 1 PY 2008 VL 112 IS 3 SU S BP 700 EP 709 DI 10.1002/cncr.23193 PG 10 WC Oncology SC Oncology GA 258QN UT WOS:000252882800005 PM 18072256 ER PT J AU Sakamoto, H Friel, AM Wood, AW Guo, L Ilic, A Seiden, MV Chung, DC Lynch, MP Serikawa, T Munro, E Oliva, E Orsulic, S Kirley, SD Foster, R Zukerberg, LR Rueda, BR AF Sakamoto, Hideo Friel, Anne M. Wood, Antony W. Guo, Lankai Ilic, Ana Seiden, Michael V. Chung, Daniel C. Lynch, Maureen P. Serikawa, Takehiro Munro, Elizabeth Oliva, Esther Orsulic, Sandra Kirley, Sandra D. Foster, Rosemary Zukerberg, Lawrence R. Rueda, Bo R. TI Mechanisms of Cables 1 gene inactivation in human ovarian cancer development SO CANCER BIOLOGY & THERAPY LA English DT Article DE ovarian cancer; tumor suppressor; cell cycle; gene inactivation ID FULL-LENGTH HUMAN; CHROMOSOME 18Q; IN-VIVO; PROTEIN; KINASE; CELLS; PHOSPHORYLATION; IK3-1/CABLES; PROGRESSION; QUALITY AB Cables 1, a cyclin-dependent kinase binding protein, is primarily involved in cell cycle regulation. Loss of nuclear Cables 1 expression is observed in human colon, lung and endometrial cancers. We previously reported that loss of nuclear Cables 1 expression was also observed with high frequency in a limited sample set of human ovarian carcinomas, although the mechanisms under lying loss of nuclear Cables 1 expression remained unknown. Our present objective was to examine Cables 1 expression in ovarian cancer in greater detail, and determine the predominant mechanisms of Cables 1 loss. We assessed potential genetic and epigenetic modifications of the Cables 1 locus through analyses of mutation, polymorphisms, loss of heterozygosity and DNA methylation. We observed a marked loss of nuclear Cables 1 expression in serous and endometrioid ovarian carcinomas that correlated with decreased Cables 1 mRNA levels. Although we detected no Cables 1 mutations, there was evidence of LOH at the Cables 1 locus and epigenetic modification of the Cables 1 promoter region in a subset of ovarian carcinomas and established cancer cell lines. From a functional perspective, over-expression of Cables 1 induced apoptosis, whereas, knockdown of Cables 1 negated this effect. Together these findings suggest that multiple mechanisms underlie the loss of Cables 1 expression in ovarian cancer cells, supporting the hypothesis that Cables 1 is a tumor suppressor in human ovarian cancer. C1 [Sakamoto, Hideo; Friel, Anne M.; Wood, Antony W.; Guo, Lankai; Ilic, Ana; Lynch, Maureen P.; Serikawa, Takehiro; Munro, Elizabeth; Oliva, Esther; Zukerberg, Lawrence R.; Rueda, Bo R.] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. [Sakamoto, Hideo; Friel, Anne M.; Wood, Antony W.; Seiden, Michael V.; Lynch, Maureen P.; Serikawa, Takehiro; Munro, Elizabeth; Rueda, Bo R.] Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA. [Chung, Daniel C.] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. [Oliva, Esther; Orsulic, Sandra; Kirley, Sandra D.; Zukerberg, Lawrence R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Seiden, Michael V.; Foster, Rosemary] Massachusetts Gen Hosp, Ctr Canc, Div Canc Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Rueda, BR (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, THR 901A,55 Fruit St, Boston, MA 02114 USA. EM brueda@partners.org FU NCI NIH HHS [R01 CA098333, K24-CA109416] NR 27 TC 8 Z9 8 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD FEB PY 2008 VL 7 IS 2 BP 180 EP 188 DI 10.4161/cbt.7.2.5253 PG 9 WC Oncology SC Oncology GA 312GZ UT WOS:000256658500004 PM 18059193 ER PT J AU Wu, JQ Williams, JP Rizvi, TA Kordich, JJ Witte, D Meijer, D Stemmer-Rachamimov, AO Cancelas, JA Ratner, N AF Wu, Jianqiang Williams, Jon P. Rizvi, Tilat A. Kordich, Jennifer J. Witte, David Meijer, Dies Stemmer-Rachamimov, Anat O. Cancelas, Jose A. Ratner, Nancy TI Plexiform and dermal neurofibromas and pigmentation are caused by Nf1 loss in desert hedgehog-expressing cells SO CANCER CELL LA English DT Article ID CREST STEM-CELLS; GROWTH-FACTOR RECEPTOR; NERVE SHEATH TUMORS; NEURAL CREST; SCHWANN-CELLS; PERIPHERAL-NERVES; MOUSE MODELS; GLIAL-CELLS; MAST-CELLS; ADULT SKIN C1 [Wu, Jianqiang; Williams, Jon P.; Rizvi, Tilat A.; Kordich, Jennifer J.; Cancelas, Jose A.; Ratner, Nancy] Univ Cincinnati, Coll Med,Div Expt Hematol & Canc Biol, Cincinnati Childrens Hosp Med Ctr, Cincinnati Childrens Res Fdn, Cincinnati, OH 45229 USA. [Witte, David] Univ Cincinnati, Coll Med,Div Pathol, Cincinnati Childrens Hosp Med Ctr, Cincinnati Childrens Res Fdn, Cincinnati, OH 45229 USA. [Cancelas, Jose A.] Univ Cincinnati, Coll Med,Hoxworth Blood Ctr, Cincinnati Childrens Hosp Med Ctr, Cincinnati Childrens Res Fdn, Cincinnati, OH 45229 USA. [Stemmer-Rachamimov, Anat O.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02129 USA. [Stemmer-Rachamimov, Anat O.] Harvard Univ, Sch Med, Boston, MA 02129 USA. [Meijer, Dies] Erasmus Univ, Ctr Med, Dept Cell Biol, NL-3000 DR Rotterdam, Netherlands. [Meijer, Dies] Erasmus Univ, Ctr Med, Dept Genet, NL-3000 DR Rotterdam, Netherlands. RP Ratner, N (reprint author), Univ Cincinnati, Coll Med,Div Expt Hematol & Canc Biol, Cincinnati Childrens Hosp Med Ctr, Cincinnati Childrens Res Fdn, Cincinnati, OH 45229 USA. EM nancy.ratner@cchmc.org RI Meijer, Dies/C-7786-2012 OI Meijer, Dies/0000-0002-8461-6341 FU NINDS NIH HHS [1R01 NS28840, R01 NS028840, R01 NS028840-15] NR 48 TC 81 Z9 82 U1 2 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD FEB PY 2008 VL 13 IS 2 BP 105 EP 116 DI 10.1016/j.ccr.2007.12.027 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 260QW UT WOS:000253026200006 PM 18242511 ER PT J AU Kouros-Mehr, H Bechis, SK Slorach, EM Littlepage, LE Egeblad, M Ewald, AJ Pai, SY Ho, IC Werb, Z AF Kouros-Mehr, Hosein Bechis, Seth K. Slorach, Euan M. Littlepage, Laurie E. Egeblad, Mikala Ewald, Andrew J. Pai, Sung-Yun Ho, I-Cheng Werb, Zena TI GATA-3 links tumor differentiation and dissemination in a luminal breast cancer model SO CANCER CELL LA English DT Article ID GENE-EXPRESSION PROFILES; ACUTE PROMYELOCYTIC LEUKEMIA; MAMMARY-GLAND; ESTROGEN-RECEPTOR; TRANSGENIC MICE; RETINOIC ACID; STEM-CELL; PROGNOSIS; IDENTIFICATION; METASTASIS AB How breast cancers are able to disseminate and metastasize is poorly understood. Using a hyperplasia transplant system, we show that tumor dissemination and metastasis occur in discrete steps during tumor progression. Bioinformatic analysis revealed that loss of the transcription factor GATA-3 marked progression from adenoma to early carcinoma and onset of tumor dissemination. Restoration of GATA-3 in late carcinomas induced tumor differentiation and suppressed tumor dissemination. Targeted deletion of GATA-3 in early tumors led to apoptosis of differentiated cells, indicating that its loss is not sufficient for malignant conversion. Rather, malignant progression occurred with an expanding GATA-3-negative tumor cell population. These data indicate that GATA-3 regulates tumor differentiation and suppresses tumor dissemination in breast cancer. C1 [Kouros-Mehr, Hosein; Bechis, Seth K.; Slorach, Euan M.; Littlepage, Laurie E.; Egeblad, Mikala; Ewald, Andrew J.; Werb, Zena] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. [Kouros-Mehr, Hosein; Bechis, Seth K.; Werb, Zena] Univ Calif San Francisco, Program Biomed Sci, San Francisco, CA 94143 USA. [Pai, Sung-Yun] Childrens Hosp, Combined Dept Pediat Hematol Oncol, Boston, MA 02115 USA. [Pai, Sung-Yun] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ho, I-Cheng] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Werb, Z (reprint author), Univ Calif San Francisco, Dept Anat, 513 Parnassus Ave, San Francisco, CA 94143 USA. EM zena.werb@ucsf.edu OI Egeblad, Mikala/0000-0002-3371-1445 FU NCI NIH HHS [R01 CA057621, CA057621, CA105379, R01 CA057621-10, R01 CA057621-11, R01 CA057621-12, R01 CA057621-13, R01 CA057621-14, R01 CA057621-15, U01 CA105379, U01 CA105379-01, U01 CA105379-02, U01 CA105379-03, U01 CA105379-04, U01 CA105379-05]; NIEHS NIH HHS [ES012801, U01 ES012801, U01 ES012801-010001, U01 ES012801-05] NR 47 TC 178 Z9 180 U1 1 U2 13 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD FEB PY 2008 VL 13 IS 2 BP 141 EP 152 DI 10.1016/j.ccr.2008.01.011 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 260QW UT WOS:000253026200009 PM 18242514 ER PT J AU Hazra, A Chanock, S Giovannucci, E Cox, DG Niu, T Fuchs, C Willett, WC Hunter, DJ AF Hazra, Aditi Chanock, Stephen Giovannucci, Edward Cox, David G. Niu, Tianhua Fuchs, Charles Willett, Walter C. Hunter, David J. TI Large-scale evaluation of genetic variants in candidate genes for colorectal cancer risk in the Nurses' Health Study and the Health Professionals' Follow-up Study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CATECHOL-O-METHYLTRANSFERASE; SINGLE-NUCLEOTIDE POLYMORPHISMS; O-6-METHYLGUANINE-DNA METHYLTRANSFERASE; SEQUENCE VALIDATION; ASSAY DEVELOPMENT; PUBLIC RESOURCE; COLON-CANCER; SNP500CANCER; ASSOCIATION; ILLUMINA AB Advances in genomics offer new strategies for assessing the association of common genetic variations at multiple loci and risk of many diseases, including colorectal cancer. Low-penetrance alleles of genes in many biological pathways, such as DNA repair, metabolism, inflammation, cell cycle, apoptosis, and Wnt signaling, may influence the risk of nonfamilial colorectal cancer. To identify susceptibility genes for colorectal cancer, we designed a large-scale case-control association study nested within the Nurses' Health Study (190 cases and 190 controls) and the Health Professionals' Follow-up Study (168 cases and 168 controls). We used a custom Golden Gate (Illumina) oligonucleotide pool assay including 1,536 single nucleotide polymorphisms (SNP) selected in candidate genes from cancer-related pathways, which have been sequenced and genotyped in the SNP500Cancer project; 1,412 of the 1,536 (92%) of the SNPs were genotyped successfully within 388 genes. SNPs in high linkage disequilibrium (r(2) >= 0.90) with another assayed SNP were excluded from further analyses. As expected by chance (and not significant compared with a corrected Bonferroni P = 0.00004), in the additive model, 11 of 1,253 (0.9%) SNPs had a P-trend < 0.01 and 38 of 1,253 (3.0%) SNPs had a P-trend >= 0.01 and P-trend < 0.05. Of note, the MGMT Lys(178) Arg (rs2308237) SNP, in linkage disequilibrium with the previously reported MGMT Ile(143) Val SNP, had an inverse association with colorectal cancer risk (MGMT Lys(178) Arg: odds ratio, 0.52; 95% confidence interval, 0.35-0.78; unadjusted P-trend = 0.0003 for the additive model; gene-based test global P = 0.00003). The SNP500Cancer database and the Illumina Golden Gate Assay allowed us to test a larger number of SNPs than previously possible. We identified several SNPs worthy of investigation in larger studies. C1 [Giovannucci, Edward; Cox, David G.; Fuchs, Charles; Willett, Walter C.; Hunter, David J.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Giovannucci, Edward; Cox, David G.; Fuchs, Charles; Willett, Walter C.; Hunter, David J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hazra, Aditi; Giovannucci, Edward; Cox, David G.; Niu, Tianhua; Willett, Walter C.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Cambridge, MA 02138 USA. [Giovannucci, Edward; Willett, Walter C.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Cambridge, MA 02138 USA. [Fuchs, Charles] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chanock, Stephen] NCI, Core Genotype Facil, Adv Technol Ctr, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Chanock, Stephen] NCI, Div Canc Epidemiol & Genet, Adv Technol Ctr, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Hazra, A (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM ahazra@hsph.harvard.edu RI Cox, David/A-2023-2009 OI Cox, David/0000-0002-2152-9259 FU NCI NIH HHS [CA55075, CA70817, CA87969, T32- CA 09001-30] NR 32 TC 9 Z9 11 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD FEB PY 2008 VL 17 IS 2 BP 311 EP 319 DI 10.1158/1055-9965.EPI-07-0195 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 263ZR UT WOS:000253255500009 PM 18268114 ER PT J AU Lin, WM Baker, AC Beroukhim, R Winckler, W Feng, W Marmion, JM Laine, E Greulich, H Tseng, H Gates, C Hodi, FS Dranoff, G Sellers, WR Thomas, RK Meyerson, M Golub, TR Dummer, R Herlyn, M Getz, G Garraway, LA AF Lin, William M. Baker, Alissa C. Beroukhim, Rameen Winckler, Wendy Feng, Whei Marmion, Jennifer M. Laine, Elisabeth Greulich, Heidi Tseng, Hsiuyi Gates, Casey Hodi, F. Stephen Dranoff, Glenn Sellers, William R. Thomas, Roman K. Meyerson, Matthew Golub, Todd R. Dummer, Reinhard Herlyn, Meenhard Getz, Gad Garraway, Levi A. TI Modeling genomic diversity and tumor dependency in malignant melanoma SO CANCER RESEARCH LA English DT Article ID NUCLEOTIDE POLYMORPHISM ARRAYS; LOSS-OF-HETEROZYGOSITY; CELL LUNG-CANCER; COPY NUMBER; CUTANEOUS MELANOMA; IMATINIB MESYLATE; MUTATIONS; GENE; INACTIVATION; GEFITINIB AB The classification of human tumors based on molecular criteria offers tremendous clinical potential; however, discerning critical and "druggable" effectors on a large scale will also require robust experimental models reflective of tumor genomic diversity. Here, we describe a comprehensive genomic analysis of 101 melanoma short-term cultures and cell lines. Using an analytic approach designed to enrich for putative "driver" events, we show that cultured melanoma cells encompass the spectrum of significant genomic alterations present in primary tumors. When annotated according to these lesions, melanomas cluster into subgroups suggestive of distinct oncogenic mechanisms. Integrating gene expression data suggests novel candidate effector genes linked to recurrent copy gains and losses, including both phosphatase and tensin homologue (PTEN)-dependent and PTEN-independent tumor suppressor mechanisms associated with chromosome 10 deletions. Finally, sample-matched pharmacologic data show that FGFR1 mutations and extracellular signal-regulated kinase (ERK) activation may modulate sensitivity to mitogen-activated protein kinase/ERK kinase inhibitors. Genetically defined cell culture collections therefore offer a rich framework for systematic functional studies in melanoma and other tumors. C1 [Lin, William M.; Baker, Alissa C.; Beroukhim, Rameen; Winckler, Wendy; Feng, Whei; Greulich, Heidi; Tseng, Hsiuyi; Meyerson, Matthew; Golub, Todd R.; Getz, Gad; Garraway, Levi A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Lin, William M.; Baker, Alissa C.; Beroukhim, Rameen; Winckler, Wendy; Feng, Whei; Greulich, Heidi; Tseng, Hsiuyi; Hodi, F. Stephen; Dranoff, Glenn; Sellers, William R.; Meyerson, Matthew; Garraway, Levi A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Golub, Todd R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Lin, William M.; Beroukhim, Rameen; Winckler, Wendy; Feng, Whei; Greulich, Heidi; Gates, Casey; Meyerson, Matthew; Golub, Todd R.; Getz, Gad; Garraway, Levi A.] MIT & Harvard, Broad Inst, Cambridge, MA 02139 USA. [Sellers, William R.] Novartis Inst Biomed Res, Cambridge, MA 02139 USA. [Marmion, Jennifer M.; Herlyn, Meenhard] Wistar Inst Anat & Biol, Div Canc Biol, Philadelphia, PA 19104 USA. [Laine, Elisabeth] Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland. [Thomas, Roman K.] Max Planck Soc, Klaus Joachim Zulch Labs, Max Planck Inst Neurol Res, Cologne, Germany. [Thomas, Roman K.] Univ Cologne, Fac Med, Cologne, Germany. [Thomas, Roman K.] Univ Cologne, Ctr Integrated Oncol, Cologne, Germany. [Thomas, Roman K.] Univ Cologne, Dept Internal Med 1, Cologne, Germany. RP Garraway, LA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. EM levi_garraway@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012 FU NCI NIH HHS [K08CA115927, K08 CA115927, K08 CA122833, K08 CA122833-01A1, P50CA93683, R01 CA085912] NR 49 TC 176 Z9 179 U1 1 U2 12 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 2008 VL 68 IS 3 BP 664 EP 673 DI 10.1158/0008-5472.CAN-07-2615 PG 10 WC Oncology SC Oncology GA 259QD UT WOS:000252952900008 PM 18245465 ER PT J AU Suswam, E Li, YY Zhang, XW Gillespie, GY Li, XL Shacka, JJ Lu, L Zheng, L King, PH AF Suswam, Esther Li, Yanyan Zhang, Xiaowen Gillespie, G. Yancey Li, Xuelin Shacka, John J. Lu, Liang Zheng, Lei King, Peter H. TI Tristetraprolin down-regulates interleukin-8 and vascular endothelial growth factor in malignant glioma cells SO CANCER RESEARCH LA English DT Article ID ACTIVATED PROTEIN-KINASE; TUMOR-NECROSIS-FACTOR; MESSENGER-RNA STABILITY; RICH ELEMENT; POSTTRANSCRIPTIONAL REGULATION; BINDING PROTEINS; UP-REGULATION; BRAIN-TUMORS; FACTOR-ALPHA; TNF-ALPHA AB Malignant gliomas are highly aggressive tumors of the central nervous system that rely on production of growth factors for tumor progression. Vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), and tumor necrosis factor-alpha, for example, are up-regulated in these tumors to promote angiogenesis and proliferation. RNA stability, mediated through adenine and uridine-rich elements (ARE) in the 3' untranslated region, is a critical control point for regulating these growth factors. RNA half-life is predominantly governed by a balance between stabilizing and destabilizing factors that bind to ARE. We have previously shown that the stabilizing factor HuR is overexpressed in malignant gliomas and linked to RNA stabilization of angiogenic growth factors. Here, we report that the destabilizing factor tristetraprolin (TTP) is also ubiquitously expressed in primary malignant glioma tissues and cell lines. In contrast to benign astrogliotic tissues, however, the protein was hyperphosphorylated, with evidence implicating the p38/mitogen-activated protein kinase (MAPK) pathway. Conditional overexpression of TTP as a transgene in malignant glioma cells led to RNA destabilization of IL-8 and VEGF and down-regulation of protein production. Analysis of in vivo RNA binding indicated a shift of mRNA toward ectopic TTP and away from endogenous HuR. This biochemical phenotype was associated with a decrease in cell proliferation, loss of cell viability, and apoptosis. We postulate that hyperphosphorylation of TTP via p38/MAPK promotes progression of malignant gliomas by negatively regulating its RNA destabilizing function. C1 [Suswam, Esther; Li, Yanyan; Zhang, Xiaowen; Li, Xuelin; Lu, Liang; Zheng, Lei; King, Peter H.] Univ Alabama, Dept Neurol, Birmingham, AL 35294 USA. [King, Peter H.] Univ Alabama, Dept Genet, Birmingham, AL 35294 USA. [King, Peter H.] Univ Alabama, Dept Physiol & Biophys, Birmingham, AL 35294 USA. [Gillespie, G. Yancey] Univ Alabama, Dept Cell Biol, Birmingham, AL 35294 USA. [Shacka, John J.] Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. [Gillespie, G. Yancey] Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. [Li, Yanyan; Zhang, Xiaowen; Li, Xuelin; Shacka, John J.; Lu, Liang; Zheng, Lei; King, Peter H.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP King, PH (reprint author), Univ Alabama, Dept Neurol, SC 200,1530 3rd Ave S, Birmingham, AL 35294 USA. EM pking@uab.edu FU NCI NIH HHS [P50 CA097247, P50 CA097247-04S1] NR 48 TC 71 Z9 76 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 2008 VL 68 IS 3 BP 674 EP 682 DI 10.1158/0008-5472.CAN-07-2751 PG 9 WC Oncology SC Oncology GA 259QD UT WOS:000252952900009 PM 18245466 ER PT J AU Contreras, CM Gurumurthy, S Haynie, JM Shirley, LJ Akbay, EA Wingo, SN Schorge, JO Broaddus, RR Wong, KK Bardeesy, N Castrillon, DH AF Contreras, Cristina M. Gurumurthy, Sushma Haynie, J. Marshall Shirley, Lane J. Akbay, Esra A. Wingo, Shana N. Schorge, John O. Broaddus, Russell R. Wong, Kwok-Kin Bardeesy, Nabeel Castrillon, Diego H. TI Loss of Lkb1 provokes highly invasive endometrial adenocarcinomas SO CANCER RESEARCH LA English DT Article ID ACTIVATED PROTEIN-KINASE; PEUTZ-JEGHERS-SYNDROME; EPITHELIAL-CELLS; PTEN(+/-) MICE; TRANSFORMATION; INACTIVATION; POLARIZATION; NEOPLASIA; CANCER; PTEN AB Mutations in the LKB1 tumor suppressor gene result in the Peutz-Jeghers syndrome, an autosomal dominant condition characterized by hamartomatous polyps of the gastrointestinal tract and a dramatically increased risk of epithelial malignancies at other sites, including the female reproductive tract. Here we show that female mice heterozygous for a null Lkb1 allele spontaneously develop highly invasive endometrial adenocarcinomas. To prove that these lesions were indeed due to Lkb1 inactivation, we introduced an adenoviral Cre vector into the uterine lumen of mice harboring a conditional allele of Lkb1. This endometrial-specific deletion of the Lkb1 gene provoked highly invasive and sometimes metastatic endometrial adenocarcinomas closely resembling those observed in Lkb1 heterozygotes. Tumors were extremely well differentiated and histopathologically distinctive and exhibited alterations in AMP-dependent kinase signaling. Although Lkb1 has been implicated in the establishment of cell polarity, and loss of polarity defines most endometrial cancers, Lkb1-driven endometrial cancers paradoxically exhibit (given their highly invasive phenotype) normal cell polarity and apical differentiation. In human endometrial cancers, Lkb1 expression was inversely correlated with tumor grade and stage, arguing that Lkb1 inactivation or down-regulation also contributes to endometrial cancer progression in women. This study shows that Lkb1 plays an important role in the malignant transformation of endometrium and that Lkb1 loss promotes a highly invasive phenotype. C1 [Contreras, Cristina M.; Haynie, J. Marshall; Shirley, Lane J.; Akbay, Esra A.; Castrillon, Diego H.] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA. [Contreras, Cristina M.; Haynie, J. Marshall; Shirley, Lane J.; Akbay, Esra A.; Schorge, John O.; Castrillon, Diego H.] Univ Texas SW Med Ctr Dallas, Simmons Comprehens Canc Ctr, Dallas, TX 75390 USA. [Wingo, Shana N.; Schorge, John O.] Univ Texas SW Med Ctr Dallas, Dept Obstet & Gynecol, Div Gynecol & Oncol, Dallas, TX 75390 USA. [Schorge, John O.] Univ Texas SW Med Ctr Dallas, Hamon Ctr Therapeut Oncol Res, Dallas, TX 75390 USA. [Gurumurthy, Sushma; Bardeesy, Nabeel] Massachusetts Gen Hosp, Ctr Canc, Dept Med, Boston, MA USA. [Gurumurthy, Sushma; Wong, Kwok-Kin; Bardeesy, Nabeel] Harvard Univ, Sch Med, Boston, MA USA. [Wong, Kwok-Kin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Broaddus, Russell R.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. RP Castrillon, DH (reprint author), Univ Texas SW Med Ctr Dallas, Dept Pathol, 6000 Harry Hines Blvd, Dallas, TX 75390 USA. EM diego.castrillon@utsouthwestern.edu OI wong, kwok kin/0000-0001-6323-235X FU NCI NIH HHS [1P50CA098258-01]; NCRR NIH HHS [K26RR024196] NR 34 TC 65 Z9 67 U1 2 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 2008 VL 68 IS 3 BP 759 EP 766 DI 10.1158/0008-5472.CAN-07-5014 PG 8 WC Oncology SC Oncology GA 259QD UT WOS:000252952900019 PM 18245476 ER PT J AU Roodman, GD Dougall, WC AF Roodman, G. David Dougall, William C. TI RANK ligand as a therapeutic target for bone metastases and multiple myeloma SO CANCER TREATMENT REVIEWS LA English DT Review DE RANK; RANKL; OPG; bone metastasis; osteoclast; skeletal complications; breast cancer; prostate cancer; multiple myeloma ID FACTOR-KAPPA-B; OSTEOCLAST DIFFERENTIATION FACTOR; SOLUBLE RECEPTOR ACTIVATOR; SKELETAL TUMOR BURDEN; PROSTATE-CANCER BONE; FORMATION IN-VITRO; NF-KB LIGAND; BREAST-CANCER; OSTEOPROTEGERIN LIGAND; SERUM OSTEOPROTEGERIN AB Osteoclastic bone resorption is a critical component of sketetal. complications of malignancy including fracture, bone pain, hypercalcemia, and spinal cord compression. Three proteins, RANKL, RANK, and OPG have been recently identified as key determinants of osteoclastogenesis and the regulation of bone resorption. Both RANKL and OPG can be aberrantly regulated in the cancer setting and function as important gatekeepers of tumor-induced osteolytic bone disease. RANKL-induced osteoclastogenesis not only mediates osteolytic bone disease, but also contributes to the pathogenesis of osteoblastic bone disease resulting from tumors. In addition, an important role was recently described for bone marrow derived RANKL to mediate the bone-specific tropism of RANK-expressing tumor cells. This manuscript will review how RANKL contributes to skeletal complications of cancer and the development of targeted, mechanism-based drugs that inhibit RANKL. (c) 2007 Elsevier Ltd. All rights reserved. C1 [Dougall, William C.] Amgen Washington, Dept Canc Biol, Seattle, WA 98119 USA. [Roodman, G. David] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15240 USA. [Roodman, G. David] VA Pittsburgh Healthcare Syst, Vet Adm Med Ctr, Res & Dev 151U, Pittsburgh, PA 15240 USA. RP Dougall, WC (reprint author), Amgen Washington, Dept Canc Biol, 1201 Amgen Court W, Seattle, WA 98119 USA. EM roodmangd@upmc.edu; dougattw@amgen.com NR 95 TC 60 Z9 67 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0305-7372 J9 CANCER TREAT REV JI Cancer Treat. Rev. PD FEB PY 2008 VL 34 IS 1 BP 92 EP 101 DI 10.1016/j.ctrv.2007.09.002 PG 10 WC Oncology SC Oncology GA 267YG UT WOS:000253544500008 PM 17964729 ER PT J AU Wu, L Rajamani, S Shryock, JC Li, H Ruskin, J Antzelevitch, C Belardinelli, L AF Wu, Lin Rajamani, Sridharan Shryock, John C. Li, Hong Ruskin, Jeremy Antzelevitch, Charles Belardinelli, Luiz TI Augmentation of late sodium current unmasks the proarrhythmic effects of amiodarone SO CARDIOVASCULAR RESEARCH LA English DT Article DE antiarrhythmic agents; arrhythmia (mechanism); ion channels; long QT syndrome; membrane potentials ID LONG-QT SYNDROME; TORSADE-DE-POINTES; TRANSMURAL DISPERSION; SHORT-TERM; REPOLARIZATION RESERVE; ANTIARRHYTHMIC-DRUGS; CANINE HEART; RABBIT HEART; CHANNEL; MODEL AB Aim Clinical use of amiodarone is associated with occasional development of torsade de pointes (TdP). However, preclinical models have failed to demonstrate the proarrhythmic potential of amiodarone. The objective of this study was to reveal and explain the pro- and anti-arrhythmic effects of acute exposure to amiodaron in an animal model. Methods and results Endo- and epicardial monophasic action potentials (MAPs) and 12-lead electrocardiogram were recorded in female rabbit isolated hearts. Ion channel currents were measured in human embryonic kidney cells expressing SCN5A Na+ and HERG K+ channels. Acute amiodarone alone caused an insignificant increase in duration of MAP (MAPD(90)) without causing TdP. In the presence of 3 nM sea anemone toxin (ATX-II), amiodarone (1-30 nM) prolonged MAPD(90) from 217 +/- 5 to 250 +/- 8 ms (n = 16, P < 0.01), increased transmural dispersion of repolarization (TDR) from 59 +/- 9 to 70 +/- 10 ms and beat-to-beat variability (BVR) of MAPD(90) from 0.75 +/- 0.03 to 1.06 +/- 0.13 ms (P < 0.05). At 30-300 nM, amiodarone induced TdP in 16 out of 17 hearts. A further increase of amiodarone concentration to 1-10 mu M abbreviated MAPD90 to 211 +/- 9 ms, decreased BVR to 0.5 +/- 0.01 ms, decreased TDR (n = 7, P < 0.05), and suppressed TdP. Amiodarone inhibited HERG K+ and late Na+ currents with IC50s of 0.8 +/- 0.1 and 3.0 +/- 0.9 mu M, respectively. Conclusion In hearts in which late l(Na) is augmented to mimic congenital or acquired pathological conditions, amiodarone has a concentration-dependent biphasic effect to induce and then suppress arrhythmic activity, secondary to inhibition of HERG K+ and late Na+ currents. This is the first preclinical model demonstrating the potential for amiodarone to induce TdP. C1 [Wu, Lin; Rajamani, Sridharan; Shryock, John C.; Li, Hong; Belardinelli, Luiz] CV Therapeut Inc, Dept Pharmacol Sci, Palo Alto, CA 94304 USA. [Ruskin, Jeremy] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA USA. [Antzelevitch, Charles] Masonic Med Res Lab, Utica, NY USA. RP Wu, L (reprint author), CV Therapeut Inc, Dept Pharmacol Sci, 3172 Porter Dr, Palo Alto, CA 94304 USA. EM lin971@yahoo.com OI Antzelevitch, Charles/0000-0001-5215-4667; Antzelevitch, Charles/0000-0001-7349-1582 FU NHLBI NIH HHS [R01 HL047678, R01 HL047678-15] NR 36 TC 35 Z9 40 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD FEB 1 PY 2008 VL 77 IS 3 BP 481 EP 488 DI 10.1093/cvr/cvm069 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 269AO UT WOS:000253622100007 PM 18006430 ER PT J AU Schainfeld, RM AF Schainfeld, Robert M. TI Cutting balloon angioplasty: Is it the key to access? SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Editorial Material ID PERCUTANEOUS ANGIOPLASTY C1 [Schainfeld, Robert M.] Massachusetts Gen Hosp, Sect Vasc Med, Boston, MA 02114 USA. RP Schainfeld, RM (reprint author), 52 2nd Ave,Suite 2100, Waltham, MA USA. EM rschainfeld@partners.org NR 9 TC 0 Z9 2 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD FEB 1 PY 2008 VL 71 IS 2 BP 255 EP 257 DI 10.1002/ccd.21487 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 258QG UT WOS:000252882000025 PM 18327844 ER PT J AU Biddinger, SB Hernandez-Ono, A Rask-Madsen, C Haas, JT Aleman, JO Suzuki, R Scapa, EF Agarwal, C Carey, MC Stephanopoulos, G Cohen, DE King, GL Ginsberg, HN Kahn, CR AF Biddinger, Sudha B. Hernandez-Ono, Antonio Rask-Madsen, Christian Haas, Joel T. Aleman, Jose O. Suzuki, Ryo Scapa, Erez F. Agarwal, Chhavi Carey, Martin C. Stephanopoulos, Gregory Cohen, David E. King, George L. Ginsberg, Henry N. Kahn, C. Ronald TI Hepatic insulin resistance is sufficient to produce dyslipidemia and susceptibility to atherosclerosis SO CELL METABOLISM LA English DT Article ID ELEMENT-BINDING PROTEIN-1C; STEAROYL-COA DESATURASE-1; CORONARY-HEART-DISEASE; FATTY-ACID SYNTHESIS; LIVER-X-RECEPTOR; METABOLIC SYNDROME; LIPOPROTEIN METABOLISM; APOLIPOPROTEIN-B; PHOSPHATIDYLINOSITOL 3-KINASE; SELECTIVE DEFICIENCY AB Insulin resistance plays a central role in the development of the metabolic syndrome, but how it relates to cardiovascular disease remains controversial. Liver insulin receptor knockout (LIRKO) mice have pure hepatic insulin resistance. On a standard chow diet, LIRKO mice have a proatherogenic lipoprotein profile with reduced high-density lipoprotein (HDL) cholesterol and very low-density lipoprotein (VLDL) particles that are markedly enriched in cholesterol. This is due to increased secretion and decreased clearance of apolipoprotein B-containing lipoproteins, coupled with decreased triglyceride secretion secondary to increased expression of Pgc-1 beta (Ppargc-1b), which promotes VLDL secretion, but decreased expression of Srebp-1c (Srebf1), Srebp-2 (Srebf2), and their targets, the lipogenic enzymes and the LDL receptor. Within 12 weeks on an atherogenic diet, LIRKO mice show marked hypercholesterolemia, and 100% of LIRKO mice, but 0% of controls, develop severe atherosclerosis. Thus, insulin resistance at the level of the liver is sufficient to produce the dyslipidemia and increased risk of atherosclerosis associated with the metabolic syndrome. C1 [Biddinger, Sudha B.; Rask-Madsen, Christian; Haas, Joel T.; Suzuki, Ryo; King, George L.; Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Hernandez-Ono, Antonio; Agarwal, Chhavi; Ginsberg, Henry N.] Columbia Univ, Dept Med, New York, NY 10032 USA. [Aleman, Jose O.; Stephanopoulos, Gregory] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Scapa, Erez F.; Carey, Martin C.; Cohen, David E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. EM crkahn@joslin.harvard.edu FU NHLBI NIH HHS [HL55368, HL73030, R01 HL073030]; NIDDK NIH HHS [DK75850, DK036588, DK053105, DK073687, DK31036, DK45935, DK59637-01, K08DK073358, K12 DK063696, P30 DK036836, P30 DK36836, R01 DK031036, R01 DK036588, R01 DK045935, R01 DK048873, R01 DK053105, R01 DK056626, R01 DK073687, R01 DK075850, R37 DK031036, R37 DK036588, R37 DK048873, U24 DK059637] NR 75 TC 225 Z9 229 U1 1 U2 15 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD FEB PY 2008 VL 7 IS 2 BP 125 EP 134 DI 10.1016/j.cmet.2007.11.013 PG 10 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 259WG UT WOS:000252971000007 PM 18249172 ER PT J AU White, RM Sessa, A Burke, C Bowman, T LeBlanc, J Ceol, C Bourque, C Dovey, M Goessling, W Burns, CE Zon, LI AF White, Richard Mark Sessa, Anna Burke, Christopher Bowman, Teresa LeBlanc, Jocelyn Ceol, Craig Bourque, Caitlin Dovey, Michael Goessling, Wolfram Burns, Caroline Erter Zon, Leonard I. TI Transparent adult zebrafish as a tool for in vivo transplantation analysis SO CELL STEM CELL LA English DT Article ID TUMOR-INITIATING CELLS; TOMOGRAPHY; METASTASIS; MODEL; IDENTIFICATION; PROLIFERATION; ENGRAFTMENT; EXPRESSION; PROTEINS; SURVIVAL AB The zebrafish is a useful model for understanding normal and cancer stem cells, but analysis has been limited to embryogenesis due to the opacity of the adult fish. To address this, we have created a transparent adult zebrafish in which we transplanted either hematopoietic stem/progenitor cells or tumor cells. In a hematopoiesis radiation recovery assay, transplantation of GFP-labeled marrow cells allowed for striking in vivo visual assessment of engraftment from 2 hr-5 weeks posttransplant. Using FACS analysis, both transparent and wild-type fish had equal engraftment, but this could only be visualized in the transparent recipient. In a tumor engraftment model, transplantation of RAS-melanoma cells allowed for visualization of tumor engraftment, proliferation, and distant metastases in as little as 5 days, which is not seen in wild-type recipients until 3 to 4 weeks. This transparent adult zebrafish serves as the ideal combination of both sensitivity and resolution for in vivo stem cell analyses. C1 [White, Richard Mark; Zon, Leonard I.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [White, Richard Mark; Sessa, Anna; Burke, Christopher; Bowman, Teresa; LeBlanc, Jocelyn; Ceol, Craig; Bourque, Caitlin; Dovey, Michael; Goessling, Wolfram; Zon, Leonard I.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [White, Richard Mark; Dovey, Michael; Goessling, Wolfram; Zon, Leonard I.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Burns, Caroline Erter] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Zon, LI (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM zon@enders.tch.harvard.edu OI Goessling, Wolfram/0000-0001-9972-1569 FU Howard Hughes Medical Institute; NCI NIH HHS [R01 CA103846, R01 CA103846-04, R01 CA103846-05]; NIDDK NIH HHS [R01 DK053298, R01 DK053298-10, R01 DK053298-11] NR 31 TC 352 Z9 358 U1 3 U2 58 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD FEB PY 2008 VL 2 IS 2 BP 183 EP 189 DI 10.1016/j.stem.2007.11.002 PG 7 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 264PW UT WOS:000253301900013 PM 18371439 ER PT J AU Das, F Ghosh-Choudhury, N Mahimainathan, L Venkatesan, B Feliers, D Riley, DJ Kasinath, BS Choudhury, GG AF Das, Falguni Ghosh-Choudhury, Nandini Mahimainathan, Lenin Venkatesan, Balachandar Feliers, Denis Riley, Daniel J. Kasinath, Balakuntalam S. Choudhury, Goutam Ghosh TI Raptor-rictor axis in TGF beta-induced protein synthesis SO CELLULAR SIGNALLING LA English DT Article DE mTORC1; mTORC2; tuberin; 4EBP-1; eIF4E; S6 kinase; Akt ID MESSENGER-RNA TRANSLATION; TUBEROUS SCLEROSIS COMPLEX; GROWTH-FACTOR RECEPTOR; TUMOR-SUPPRESSOR PTEN; INDUCED DNA-SYNTHESIS; CELL-GROWTH; MESANGIAL CELLS; DIABETIC-NEPHROPATHY; PHOSPHOINOSITIDE 3-KINASE; SIGNALING PATHWAY AB Transforming growth factor-beta (TGF beta) stimulates pathological renal cell hypertrophy for which increased protein synthesis is critical. The mechanism of TGF beta-induced protein synthesis is not known, but PI 3 kinase-dependent Akt kinase activity is necessary. We investigated the contribution of downstream effectors of Akt in TGF beta-stimulated protein synthesis. TGF beta increased inactivating phosphorylation of Akt substrate tuberin in a PI 3 kinase/Akt dependent manner, resulting in activation of mTOR kinase. mTOR activity increased phosphorylation of S6 kinase and the translation repressor 4EBP-1, which were sensitive to inhibition of both PI 3 kinase and Akt. mTOR inhibitor rapamycin and a dominant negative mutant of mTOR suppressed TGF beta-induced phosphorylation of S6 kinase and 4EBP-1. PI 3 kinase/Akt and mTOR regulated dissociation of 4EBP-1 from eIF4E to make the latter available for binding to eIF4E. mTOR and 4EBP-1 modulated TGF beta-induced protein synthesis. mTOR is present in two multi protein complexes, mTORCI and mTORC2. Raptor and rictor are part of mTORCI and mTORC2, respectively. shRNA-mediated downregulation of raptor inhibited TGF beta-stimulatcd mTOR kinase activity, resulting in inhibition of phosphorylation of S6 kinase and 4EBP-1. Raptor shRNA also prevented protein synthesis in response to TGF. Downregulation of rictor inhibited serine 473 phosphorylation of Akt without any effect on phosphorylation of its substrate, tuberin. Furthermore, rictor shRNA increased phosphorylation of S6 kinase and 4EBP-1 in TGF beta -independent manner, resulting in increased protein synthesis. Thus mTORC1 function is essential for TGF beta-induced protein synthesis. Our data also provide novel evidence that rictor negatively regulates TORC1 activity to control basal protein synthesis, thus conferring tight control on cellular hypertrophy. (C) 2007 Elsevier Inc. All rights reserved. C1 [Das, Falguni; Mahimainathan, Lenin; Venkatesan, Balachandar; Feliers, Denis; Riley, Daniel J.; Kasinath, Balakuntalam S.; Choudhury, Goutam Ghosh] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Ghosh-Choudhury, Nandini] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Ghosh-Choudhury, Nandini; Kasinath, Balakuntalam S.; Choudhury, Goutam Ghosh] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Kasinath, Balakuntalam S.; Choudhury, Goutam Ghosh] Univ Texas Hlth Sci Ctr San Antonio, George OBrien Kidney Ctr, San Antonio, TX 78229 USA. [Choudhury, Goutam Ghosh] Ctr Geriatr Res Educ & Clin, San Antonio, TX USA. RP Choudhury, GG (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Mail Code 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM choudhuryg@uthscsa.edu FU NIAMS NIH HHS [NIH R01 AR52425]; NIDDK NIH HHS [R01 DK50190, NIH R01 DK077295] NR 91 TC 50 Z9 52 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD FEB PY 2008 VL 20 IS 2 BP 409 EP 423 DI 10.1016/j.cellsig.2007.10.027 PG 15 WC Cell Biology SC Cell Biology GA 260RH UT WOS:000253027400014 PM 18068336 ER PT J AU Nagano, S Bush, AI AF Nagano, Seiichi Bush, Ashley I. TI Sensitive, selective, and irreversible inhibition of cyclooxygenase-2 activity by copper SO CHEMMEDCHEM LA English DT Article DE copper; cyclooxygenase-2; indomethacin; inflammation; prostaglandin ID PROSTAGLANDIN H SYNTHASE-1; SUPEROXIDE-DISMUTASE; RHEUMATOID-ARTHRITIS; ALZHEIMERS-DISEASE; MEDIATED METABOLISM; PEROXIDASE-ACTIVITY; OXIDATIVE STRESS; TRACE-ELEMENT; EXPRESSION; BETA C1 [Nagano, Seiichi; Bush, Ashley I.] Harvard Univ, Sch Med, Massachusetts Gen Hosp East, Lab Oxidat Biol,Genet & Aging Res Unit, Charlestown, MA 02129 USA. [Nagano, Seiichi; Bush, Ashley I.] Harvard Univ, Sch Med, Massachusetts Gen Hosp East, Dept Psychiat, Charlestown, MA 02129 USA. [Bush, Ashley I.] Univ Melbourne, Mental Hlth Res Inst Victoria, Parkville, Vic 3052, Australia. [Bush, Ashley I.] Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. RP Bush, AI (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp East, Lab Oxidat Biol,Genet & Aging Res Unit, Bldg 114 16th St, Charlestown, MA 02129 USA. EM bush@helix.mgh.harvard.edu RI Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 FU NIA NIH HHS [R01-AG12686] NR 35 TC 1 Z9 1 U1 1 U2 3 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1860-7179 J9 CHEMMEDCHEM JI ChemMedChem PD FEB PY 2008 VL 3 IS 2 BP 223 EP 225 DI 10.1002/cmdc.200700217 PG 3 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 274SY UT WOS:000254022600002 PM 18000939 ER PT J AU Okamoto, Y Folco, EJ Minami, M Wara, AK Feinberg, MW Sukhova, GK Colvin, RA Kihara, S Funahashi, T Luster, AD Libby, P AF Okamoto, Yoshihisa Folco, Eduardo J. Minami, Manabu Wara, A. K. Feinberg, Mark W. Sukhova, Galina K. Colvin, Richard A. Kihara, Shinji Funahashi, Tohru Luster, Andrew D. Libby, Peter TI Adiponectin inhibits the production of CXC receptor 3 chemokine ligands in macrophages and reduces T-lymphocyte recruitment in atherogenesis SO CIRCULATION RESEARCH LA English DT Article DE adiponectin; atherogenesis; chemokine; macrophage; T lymphocyte ID C-REACTIVE PROTEIN; INDUCED INSULIN-RESISTANCE; METABOLIC SYNDROME; APOLIPOPROTEIN-E; PLASMA-PROTEIN; ADIPOSE-TISSUE; CXC CHEMOKINES; OBESE ADULTS; EXPRESSION; ATHEROSCLEROSIS AB Obese individuals often have low plasma adiponectin and concomitant chronic inflammation with a predisposition to metabolic and cardiovascular diseases. The present study reports a novel antiinflammatory action of adiponectin in human monocyte-derived macrophages (M Phi) suppressing T-lymphocyte accumulation in atherogenesis. RNA profiling of lipopolysaccharide-stimulated human M Phi identified CXC chemokine ligands (CXCLs), such as IP-10 (interferon [IFN]-inducible protein 10) (CXCL10), I-TAC (IFN-inducible T-cell alpha chemoattractant) ( CXCL11), and Mig (monokine induced by IFN-gamma) (CXCL9), T-lymphocyte chemoattractants associated with atherogenesis, among the top 14 transcripts suppressed by adiponectin. Real-time quantitative RT-PCR and ELISA verified that adiponectin inhibited expression of these chemokines at both the mRNA and protein levels in a concentration-dependent manner. Adiponectin reduced the release by lipopolysaccharide-stimulated M Phi of chemoattractant activity for CXC chemokine receptor 3-transfected (receptor for IP-10, Mig, and I-TAC) lymphocytes. Adiponectin decreased lipopolysaccharide-inducible IP-10 promoter activity in promoter-transfected THP-1 M Phi but did not change IP-10 mRNA stability. In lipopolysaccharide-stimulated M Phi, reduction of IFN-beta by adiponectin preceded inhibition of IP-10 mRNA expression. Immunoblot and chromatin immunoprecipitation analyses demonstrated that adiponectin attenuated activation of the transcription factor IFN regulatory factor 3, involved in the MyD88-independent pathway of Toll-like receptor 4 signaling, and subsequent IFN regulatory factor 3 binding to IFN-beta promoter. In vivo studies further demonstrated that apolipoprotein E/adiponectin double-deficient (apoE(-/-) APN(-/-)) mice had increased plasma IP-10 levels, accelerated T-lymphocyte accumulation in atheromata, and augmented atherogenesis compared with apoE single-deficient (apoE(-/-) APN(-/-)) mice. This study establishes that low levels of adiponectin associated with obesity, the metabolic syndrome, and diabetes favor T-lymphocyte recruitment and contribute to adaptive immune response during atherogenesis. C1 [Okamoto, Yoshihisa; Folco, Eduardo J.; Minami, Manabu; Wara, A. K.; Feinberg, Mark W.; Sukhova, Galina K.; Libby, Peter] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Colvin, Richard A.; Luster, Andrew D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Rheumatol, Charlestown, MA USA. [Kihara, Shinji; Funahashi, Tohru] Osaka Univ, Dept Metab Med, Grad Sch Med, Suita, Osaka, Japan. RP Libby, P (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc Med, NRB 741,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM plibby@rics.bwh.harvard.edu OI Minami, Manabu/0000-0003-0052-398X FU NHLBI NIH HHS [HL-34636] NR 38 TC 104 Z9 104 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD FEB 1 PY 2008 VL 102 IS 2 BP 218 EP 225 DI 10.1161/CIRCRESAHA.107.164988 PG 8 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 257VA UT WOS:000252825600015 PM 17991878 ER PT J AU Kay, J AF Kay, Jonathan TI Gadolinium and nephrogenic systemic fibrosis: The evidence of things not seen SO CLEVELAND CLINIC JOURNAL OF MEDICINE LA English DT Editorial Material ID DERMOPATHY; SCLEROMYXEDEMA C1 [Kay, Jonathan] Massachusetts Gen Hosp, Rheumatol Unit, Boston, MA 02114 USA. [Kay, Jonathan] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Kay, J (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, 55 Fruit St,Yawkey 2-174, Boston, MA 02114 USA. EM jkay@partners.org NR 11 TC 9 Z9 9 U1 0 U2 0 PU CLEVELAND CLINIC PI CLEVELAND PA 9500 EUCLID AVE, CLEVELAND, OH 44106 USA SN 0891-1150 J9 CLEV CLIN J MED JI Clevel. Clin. J. Med. PD FEB PY 2008 VL 75 IS 2 BP 112 EP + PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 260QB UT WOS:000253023900004 PM 18290354 ER PT J AU Siuss, PM Hayes, FJ Adams, JM Barnes, W Williams, G Frost, S Ramp, J Pacenti, D Lehotay, DC George, S Ramsay, C Doss, RC Crowley, WF AF Siuss, Patrick M. Hayes, Frances J. Adams, Judith M. Barnes, Wayne Williams, Gregg Frost, Stephen Ramp, John Pacenti, David Lehotay, Denis C. George, Sabu Ramsay, Carol Doss, Robert C. Crowley, William F., Jr. TI Mass spectrometric and physiological validation of a sensitive, automated, direct immunoassay for serum estradiol using the Architect (R) SO CLINICA CHIMICA ACTA LA English DT Article DE estradiol; measurement; immunoassay; mass spectrometry; reference intervals ID GAS CHROMATOGRAPHY/MASS SPECTROMETRY; FOLLICLE-STIMULATING-HORMONE; MENOPAUSAL TRANSITION; POSTMENOPAUSAL WOMEN; MENSTRUAL CYCLES; BREAST-CANCER; RISK; PLASMA; ASSAY; LIMITATIONS AB Background: Measurement of estradiol (E-2) plays a critical role in the diagnosis and clinical management of reproductive disorders. The challenge for all currently available direct methods for measuring E-2 is to provide accuracy and precision across a wide dynamic range. Methods: We describe the development and multi-site performance evaluation of a direct E-2 assay on the Architect i2000 (R). Assay performance and method comparisons were performed by testing specimens from men, healthy women with regular menstrual cycles, and post-menopausal women using the Architect assay and isotope dilution, gas chromatography-mass spectrometry (ID/GC-MS). Reference intervals were established by testing prospectively collected daily blood draws from 42 healthy women, 72 postmenopausal women and 101 males. Results: No unexpected cross-reactivity or interference was observed for over 40 compounds tested. Recovery was 100 +/- 10% in the presence of estrone and estriol. Functional sensitivity (%CV< 20%) was < 15 pg/ml. 1 The imprecision of the assay was <7.1% (total CV), <2.5%, and <2.3% for control sera containing 45, 190, and 600 pg/ml estradiol, respectively. The assay had a correlation of y= 1.033 x+0.3156, r(2) = 0.99, n=131 compared to ID/GC-MS. Reference intervals for the current Architect Estradiol assay are reported. Conclusions: Format changes resulted in dramatic improvement in the performance and accuracy of this direct, fully automated assay. The assay is standardized by ID/GC-MS. The assay is clinically useful for serum concentrations from 15 to >4000 pg/ml. (c) 2007 Elsevier B.V All rights reserved. C1 [Siuss, Patrick M.; Hayes, Frances J.; Adams, Judith M.; Crowley, William F., Jr.] Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. [Barnes, Wayne; Williams, Gregg; Frost, Stephen; Ramp, John; Pacenti, David; Ramsay, Carol; Doss, Robert C.] Abbott Labs, Div Diagnost, Abbott Pk, IL 60064 USA. [Lehotay, Denis C.; George, Sabu] Univ Saskatchewan, Coll Med, Provinc Lab, Saskatoon, SK S4S 5W6, Canada. RP Siuss, PM (reprint author), Immunodiagnost Lab, Bulfinch Bldg,Suite 051,55 Fruit St, Boston, MA 02114 USA. EM Sluss.Patrick@mgh.harvard.edu NR 34 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD FEB PY 2008 VL 388 IS 1-2 BP 99 EP 105 DI 10.1016/j.cca.2007.10.020 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 257AK UT WOS:000252770800017 ER PT J AU Partridge, AH Gelber, S Peppercorn, J Ginsburg, E Sampson, E Rosenberg, R Przypyszny, M Winer, EP AF Partridge, Ann H. Gelber, Shari Peppercorn, Jeffrey Ginsburg, Elizabeth Sampson, Ebonie Rosenberg, Randi Przypyszny, Michele Winer, Eric P. TI Fertility and menopausal outcomes in young breast cancer survivors SO CLINICAL BREAST CANCER LA English DT Article DE amenorrhea; early-stage breast cancer; menopause; pregnancy ID PROGNOSTIC IMPACT; TRIAL-VI; WOMEN; PREGNANCY; CARCINOMA; CHEMOTHERAPY; CHILDBEARING; AMENORRHEA; DIAGNOSIS; THERAPY AB Background: Following treatment for breast cancer, many young women are interested in having a child. There are few data available regarding actual fertility and menopausal outcomes in young breast cancer survivors. We evaluated these outcomes among young breast cancer survivors in collaboration with the Young Survival Coalition, an international advocacy group for young women with breast cancer. Patients and Methods: All registered Young Survival Coalition survivor members were sent a link to the survey about fertility issues for women with early-stage breast cancer via e-mail; 440 women who completed the survey were eligible for this analysis. Survey respondents were a median of 2.8 years from diagnosis. Mean age at breast cancer diagnosis was 32.6 years. Results: Of the 440 women in this cohort, 247 women (56%) recalled that they had desired a future pregnancy at diagnosis, and 43 women (10%) took steps to preserve fertility. A total of 384 women (87%) received chemotherapy. A total of 295 women (67%) reported that they remained premenopausal, and an additional 33 women (8%) were receiving ovarian suppression therapy at the time of the survey. Since diagnosis, 70 women (16%) had been pregnant >= 1 time; 40 women (9%) had >= 1 live birth. Out of the 247 women who reported wanting a future pregnancy at diagnosis, 59 (24%) had become pregnant. Of the 60 women who reported having tried to become pregnant since diagnosis, 34 (57%) were successful. Conclusion: Most young women remain premenopausal after breast cancer treatment, including chemotherapy. A relatively small percentage of women in this series had become pregnant; however, the median time since diagnosis was relatively short. C1 [Partridge, Ann H.; Gelber, Shari; Ginsburg, Elizabeth; Sampson, Ebonie; Winer, Eric P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, Boston, MA 02115 USA. [Peppercorn, Jeffrey] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Rosenberg, Randi; Przypyszny, Michele] Young Survival Coalit, New York, NY USA. RP Partridge, AH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, 44 Binney St,D1210, Boston, MA 02115 USA. EM ahpartridge@partners.org NR 24 TC 38 Z9 39 U1 0 U2 2 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1526-8209 J9 CLIN BREAST CANCER JI Clin. Breast Cancer PD FEB PY 2008 VL 8 IS 1 BP 65 EP 69 DI 10.3816/CBC.2008.n.004 PG 5 WC Oncology SC Oncology GA 267IP UT WOS:000253503000006 PM 18501060 ER PT J AU Gagnon, A Kim, JH Schorge, JO Ye, B Liu, B Hasselblatt, K Welch, WR Bandera, CA Mok, SC AF Gagnon, Audrey Kim, Jae-Hoon Schorge, John O. Ye, Bin Liu, Brian Hasselblatt, Kathleen Welch, William R. Bandera, Christina A. Mok, Samuel C. TI Use of a combination of approaches to identify and validate relevant tumor-associated antigens and their corresponding autoantibodies in ovarian cancer patients SO CLINICAL CANCER RESEARCH LA English DT Article ID ACID-BINDING PROTEIN; PSORIASIN S100A7; P53 AUTOANTIBODIES; BREAST-CARCINOMA; IMMUNE-RESPONSE; EXPRESSION; MARKERS; IDENTIFICATION; DIAGNOSIS; ANTIBODIES AB Purpose: Novel biomarkers are urgently needed to increase the sensitivity of CA125 for the early detection of ovarian cancer. Indeed, it has been shown that as much as 20% of early-stage patients do not express significant levels of this biomarker.Therefore, the possibility of using autoantibodies directed against tumor-associated antigens as putative cancer markers is being more examined. Indeed, many autoantibodies have recently been shown to correlate with cancer patient prognosis or to be suitable for detection of the disease. Experimental Design: In this study, we have used a new approach involving the use of proteomics, immunology, and ELISA methods to identify relevant autoantibodies in the plasma of ovarian cancer patients. To do so, we developed an innovative technique called two-dimensional differential gel electrophoresis analysis of immunoprecipitated tumor antigens. Results: This strategy allowed us to successfully identify novel circulating autoantibodies directed against the S100A7 protein in the plasma of ovarian cancer patients. Further real-time reverse transcription-PCR and immunohistochemical studies confirmed that the S100A7 mRNA and protein were highly expressed in ovarian tumors but absent in normal and benign tissues. Moreover, a preliminary study involving 138 patients confirmed that the plasma levels of anti-S100A7 antibodies are significantly elevated in early- and late-stage ovarian cancer patients compared with healthy controls and with patients with benign gynecologic diseases. Conclusions: This shows that our approach is a valuable tool to successfully identify autoantibodies and tumor-associated antigens in cancer patients and that future research assessing their putative clinical usefulness would be worthwhile. C1 [Gagnon, Audrey; Hasselblatt, Kathleen; Mok, Samuel C.] Harvard Univ, Brigham & Womens Hosp, Sch Med,Div Gynecol Oncol, Dept Obstet Gynecol & Reprod Biol,Lab Gynecol Onc, Boston, MA 02115 USA. [Liu, Brian] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Urol, Boston, MA 02115 USA. [Welch, William R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Ye, Bin] Harvard Univ, Brigham & Womens Hosp, Dept Obstet & Gynecol, Sch Med,Dana Farber Harvard Canc Ctr, Boston, MA 02115 USA. [Kim, Jae-Hoon] Yonsei Univ, Coll Med, Dept Obstet & Gynecol, Yongdong Severance Hosp, Seoul, South Korea. [Schorge, John O.] Univ Texas SW Med Ctr Dallas, Dept Obstet & Gynecol, Div Gynecol Oncol, Dallas, TX 75390 USA. [Bandera, Christina A.] Brown Univ, Sch Med, Women & Infants Hosp, Program Womens Oncol, Providence, RI 02912 USA. RP Mok, SC (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med,Div Gynecol Oncol, Dept Obstet Gynecol & Reprod Biol,Lab Gynecol Onc, Boston, MA 02115 USA. EM scmok@rics.bwh.harvard.edu FU NCI NIH HHS [R33CA103595, P50CA105009, UO1CA86381] NR 40 TC 34 Z9 37 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB 1 PY 2008 VL 14 IS 3 BP 764 EP 771 DI 10.1158/1078-0432.CCR-07-0856 PG 8 WC Oncology SC Oncology GA 258QK UT WOS:000252882400021 PM 18245537 ER PT J AU Huston, A Leleu, X Jia, XY Moreau, AS Ngo, HT Runnels, J Anderson, J Alsayed, Y Roccaro, A Vallet, S Hatjiharissi, E Tai, YT Sportelli, P Munshi, N Richardson, P Hideshima, T Roodman, DG Anderson, KC Ghobrial, IM AF Huston, Alissa Leleu, Xavier Jia, Xiaoying Moreau, Anne-Sophie Ngo, Hai T. Runnels, Judith Anderson, Judy Alsayed, Yazan Roccaro, Aldo Vallet, Sonia Hatjiharissi, Evdoxia Tai, Yu-Tsu Sportelli, Peter Munshi, Nikhil Richardson, Paul Hideshima, Teru Roodman, David G. Anderson, Kenneth C. Ghobrial, Irene M. TI Targeting Akt and heat shock protein 90 produces synergistic multiple myeloma cell cytotoxicity in the bone marrow microenvironment SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR-I; MAMMALIAN TARGET; PHOSPHATIDYLINOSITOL 3-KINASE/AKT; CLINICAL-APPLICATIONS; MTOR INHIBITORS; STROMAL CELLS; PATHWAY; SURVIVAL; EXPRESSION; KINASE AB Purpose: We hypothesized that targeting both Akt and heat shock protein (HSP) 90 would induce cytotoxic activity against multiple myeloma (MM) cells and target the bone marrow (BM) microenvironment to inhibit angiogenesis, osteoclast formation, as well as migration and adhesion of MM cells. Experimental Design: MM cell lines were incubated with perifosine (5 and 10 mu mol/L) and 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG; 50 and 100 nmol/L) alone and in combination. Results: The combination of Akt inhibitor perifosine and HSP90 inhibitor 17-DMAG was synergistic in inducing MM cell cytotoxicity, evidenced by inhibition of DNA synthesis and induction of apoptosis. In addition, perifosine and 17-DMAG almost completely inhibited osteoclast formation: perifosine interfered with both early and late stages of osteoclast progenitor development, whereas 17-DMAG targeted only early stages: We next showed that combined therapy overcomes tumor growth and resistance induced by BM stromal cells and endothelial cells as well as the proliferative effect of exogenous interleukin-6, insulin-like growth factor-I, and vascular endothelial growth factor. Moreover, the combination also induced apoptosis and growth inhibition in endothelial cells and inhibited angiogenesis. Finally, we showed that the two agents prevented migration of MM cells toward stromal-derived factor-1 and vascular endothelial growth factor, which are present in the BM milieu, and also prevented adhesion of MM cells to fibronectin. Conclusions: This study provides the preclinical framework for treatment protocols targeting both the Akt and HSP pathways in MM. C1 [Leleu, Xavier; Jia, Xiaoying; Moreau, Anne-Sophie; Ngo, Hai T.; Runnels, Judith; Roccaro, Aldo; Vallet, Sonia; Hatjiharissi, Evdoxia; Tai, Yu-Tsu; Munshi, Nikhil; Richardson, Paul; Hideshima, Teru; Anderson, Kenneth C.; Ghobrial, Irene M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Huston, Alissa; Anderson, Judy; Alsayed, Yazan] Univ Rochester, James P Wilmot Canc Ctr, Rochester, NY USA. [Leleu, Xavier; Jia, Xiaoying; Moreau, Anne-Sophie; Ngo, Hai T.; Runnels, Judith; Roccaro, Aldo; Vallet, Sonia; Hatjiharissi, Evdoxia; Tai, Yu-Tsu; Munshi, Nikhil; Richardson, Paul; Hideshima, Teru; Anderson, Kenneth C.; Ghobrial, Irene M.] Harvard Univ, Sch Med, Boston, MA USA. [Leleu, Xavier; Moreau, Anne-Sophie] CHRU, Serv Malad Sang, Lille, France. [Leleu, Xavier; Moreau, Anne-Sophie] CHRU, Immunol Lab, Lille, France. [Roodman, David G.] Univ Pittsburgh, Pittsburgh Canc Inst, Pittsburgh, PA USA. [Sportelli, Peter] Keryx Biopharmaceut, New York, NY USA. RP Ghobrial, IM (reprint author), Dana Farber Canc Inst, 44 Binney St,Mayer 548A, Boston, MA 02115 USA. EM irene_ghobrial@dfci.harvard.edu OI Roccaro, Aldo/0000-0002-1872-5128 NR 45 TC 40 Z9 43 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB 1 PY 2008 VL 14 IS 3 BP 865 EP 874 DI 10.1158/1078-0432.CCR-07-1299 PG 10 WC Oncology SC Oncology GA 258QK UT WOS:000252882400034 PM 18245550 ER PT J AU Brugge, WR AF Brugge, William R. TI The incidental pancreatic cyst on abdominal computerized tomography imaging: Diagnosis and management SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Editorial Material ID CLINICOPATHOLOGICAL FEATURES; NEOPLASMS C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NR 10 TC 8 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD FEB PY 2008 VL 6 IS 2 BP 140 EP 144 DI 10.1016/j.cgh.2007.11.024 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 261YF UT WOS:000253115200006 PM 18237864 ER PT J AU Lindsay, KL Morishima, C Wright, EC Dienstag, JL Shiffman, ML Everson, GT Lok, ASF Bonkovsky, HLR Lee, WM Morgan, TR Ghany, MG AF Lindsay, Karen L. Morishima, Chihiro Wright, Elizabeth C. Dienstag, Jules L. Shiffman, Mitchell L. Everson, Gregory T. Lok, Anna S. F. Bonkovsky, Herbert L. R. Lee, William M. Morgan, Timothy R. Ghany, Marc G. TI Blunted cytopenias and weight loss: New correlates of virologic null response to re-treatment of chronic hepatitis C SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID PEGINTERFERON ALPHA-2A; PEGYLATED INTERFERON; PLUS RIBAVIRIN; HCV-RNA; COMBINATION THERAPY; TREATMENT DURATION; ANTIVIRAL THERAPY; AMERICAN PATIENTS; AFRICAN-AMERICAN; VIRAL DYNAMICS AB Background & Aims: Peginterferon with ribavirin therapy for chronic hepatitis C leads to sustained loss of serum hepatitis C virus (HCV) RNA in half of treated patients. Although viral kinetic profiles in treatment responders shed light on the mechanism of action of interferon and ribavirin, minimal information is available to explain why some patients experience little or no virologic suppression. Methods: We evaluated factors that might be associated with the lack of a week-20 virologic response in previous nonresponder patients undergoing peginterferon and ribavirin retreatment. Among 1145 patients enrolled in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis Trial's lead-in treatment phase, 588 who received more than 80% of prescribed therapy for 20 weeks were analyzed. Results: By week 20, 245 patients (41.7%) had undetectable HCV RNA (full response), 186 (31.6%) had a 1 log(10) or greater decrease in HCV RNA (partial response), and 157 (26.7%) had less than a 1 log(10) decrease (null response) in HCV RNA. Null response was associated independently with African American race, genotype-1 infection, and less reduction in body weight, platelets, and white blood cells during treatment. Conclusions: On-treatment variables associated with null response suggest a blunted systemic response to interferon. These observations have important implications for the design and analysis of trial results in which novel agents are evaluated. Further studies are needed to discern whether host interferon resistance, viral drug resistance, or both are playing a role in patients who have no virologic response to interferon treatment. C1 [Lindsay, Karen L.] Univ So Calif, Keck Sch Med, Div Gastrointestinal & Liver Dis, Los Angeles, CA 90033 USA. [Morishima, Chihiro] Univ Washington, Dept Lab Med, Div Virol, Seattle, WA 98195 USA. [Wright, Elizabeth C.] New England Res Inst, Watertown, MA 02172 USA. [Dienstag, Jules L.] Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. [Dienstag, Jules L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Shiffman, Mitchell L.] Virginia Commonwealth Univ Hlth Syst, Div Gastroenterol, Richmond, VA USA. [Everson, Gregory T.] Univ Colorado, Sch Med, Div Gastroenterol & Hepatol, Sect Hepatol, Denver, CO USA. [Lok, Anna S. F.] Univ Michigan, Med Ctr, Div Gastroenterol, Ann Arbor, MI USA. [Bonkovsky, Herbert L. R.] Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA. [Bonkovsky, Herbert L. R.] Univ Connecticut, Ctr Hlth, Dept Biol Mol & Struct, Farmington, CT USA. [Bonkovsky, Herbert L. R.] Univ Connecticut, Ctr Hlth, Liver Biliary Pancreat Ctr, Farmington, CT USA. [Lee, William M.] Univ Texas SW Med Ctr Dallas, Div Digest & Liver Dis, Dallas, TX 75390 USA. [Morgan, Timothy R.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. [Morgan, Timothy R.] VA Long Beach Healthcare Syst, Gastroenterol Serv, Long Beach, CA USA. [Ghany, Marc G.] NIDDK, Liver Dis Branch, Div Digest Dis & Nutr, NIH,Dept Hlth & Human Serv, Bethesda, MD USA. RP Lindsay, KL (reprint author), Univ So Calif, Div GI Liver Dis, Dept Med, 1640 Marengo St,Suite 103, Los Angeles, CA 90033 USA. EM klindsay@usc.edu RI Lok, Anna /B-8292-2009; OI Yang, Shuman/0000-0002-9638-0890 FU NCRR NIH HHS [M01RR-00042, M01RR-00043, M01RR-00051, M01RR-00065, M01RR-00633, M01RR-00827, M01RR-01066, M01RR-06192]; NIDDK NIH HHS [N01-DK-9-2322, N01 DK092323, N01-DK-9-2318, N01-DK-9-2319, N01-DK-9-2320, N01-DK-9-2321, N01-DK-9-2323, N01-DK-9-2324, N01-DK-9-2325, N01-DK-9-2326, N01-DK-9-2327, N01-DK-9-2328] NR 37 TC 18 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD FEB PY 2008 VL 6 IS 2 BP 234 EP 241 DI 10.1016/j.cgh.2007.11.020 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 261YF UT WOS:000253115200018 PM 18237873 ER PT J AU Ansaria, MJI Fiorina, P Dada, S Guleria, I Ueno, T Yuan, X Trikudanathan, S Smith, RN Freeman, G Sayegh, MH AF Ansaria, Mohammed Javeed I. Fiorina, Paolo Dada, Shirine Guleria, Indira Ueno, Takuya Yuan, Xueli Trikudanathan, Subbulaxmi Smith, R. Neal Freeman, Gordon Sayegh, Mohamed H. TI Role of ICOS pathway in autoimmune and alloimmune responses in NOD mice SO CLINICAL IMMUNOLOGY LA English DT Article DE ICOS; costimulation; sirolimus; autoimmune diabetes; NOD mice; islet transplantation ID INDUCIBLE COSTIMULATOR ICOS; CHRONIC ALLOGRAFT-REJECTION; TYPE-1 DIABETES-MELLITUS; MONOCLONAL-ANTIBODY; ISLET ALLOGRAFTS; SIMULTANEOUS BLOCKADE; COMBINATION THERAPY; T-CELLS; TRANSPLANTATION; TOLERANCE AB Islet allografts are subject to alloimmune and autoimmune destruction when transplanted into autoimmune prone animals or humans. The ICOS-B7h pathway plays a role in alloimmune responses, but its function in autoimmunity against islet cells is controversial. We investigated the role of ICOS signaling in autoimmune and alloimmune responses in NOD mice. ICOS blockade prevents development of spontaneous disease in pre-diabetic NOD mice. Furthermore, while ICOS blockade prolongs graft survival in a fully mismatched non-autoimmune islet allograft model in C57BL/6 recipients, it has no beneficial effect in reversing diabetes in models of islet transplantation in NOD mice involving autoimmunity alone or both allo- and autoimmunity. Interestingly, ICOS blockade is effective in prolonging heart allograft (not subject to tissue-specific autoimmunity) survival in NOD mice. We conclude that in islet transplantation and autoimmune diabetes, ICOS blockade can be effective in inhibiting alloimmunity and preventing autoimmunity but is ineffective in inhibiting recurrence of autoimmunity. (c) 2007 Elsevier Inc. All rights reserved. C1 [Ansaria, Mohammed Javeed I.; Fiorina, Paolo; Dada, Shirine; Guleria, Indira; Ueno, Takuya; Yuan, Xueli; Trikudanathan, Subbulaxmi; Sayegh, Mohamed H.] Brigham & Womens Hosp, Div Renal, Transplantat Res Ctr, Boston, MA 02115 USA. [Ansaria, Mohammed Javeed I.; Fiorina, Paolo; Dada, Shirine; Guleria, Indira; Ueno, Takuya; Yuan, Xueli; Trikudanathan, Subbulaxmi; Sayegh, Mohamed H.] Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. [Fiorina, Paolo] Ist Sci San Raffaele, I-20132 Milan, Italy. [Ueno, Takuya] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Freeman, Gordon] Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Sayegh, MH (reprint author), Brigham & Womens Hosp, Div Renal, Transplantat Res Ctr, Boston, MA 02115 USA. EM msayegh@rics.harvard.edu FU NIAID NIH HHS [P01 AI041521, P01 AI056299] NR 33 TC 33 Z9 40 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD FEB PY 2008 VL 126 IS 2 BP 140 EP 147 DI 10.1016/j.ctim.2007.07.019 PG 8 WC Immunology SC Immunology GA 254SE UT WOS:000252607500003 PM 17889619 ER PT J AU Krause, PJ Gewurz, BE Hill, D Marty, FM Vannier, E Foppa, IM Furman, RR Neuhaus, E Skowron, G Gupta, S McCalla, C Pesanti, EL Young, M Heiman, D Hsue, G Gelfand, JA Wormser, GP Dickason, J Bia, FJ Hartman, B Telford, SR Christianson, D Dardick, K Coleman, M Girotto, JE Spielman, A AF Krause, Peter J. Gewurz, Benjamin E. Hill, David Marty, Francisco M. Vannier, Edouard Foppa, Ivo M. Furman, Richard R. Neuhaus, Ellen Skowron, Gail Gupta, Shaili McCalla, Carlo Pesanti, Edward L. Young, Mary Heiman, Donald Hsue, Gunther Gelfand, Jeffrey A. Wormser, Gary P. Dickason, John Bia, Frank J. Hartman, Barry Telford, Sam R., III Christianson, Diane Dardick, Kenneth Coleman, Morton Girotto, Jennifer E. Spielman, Andrew TI Persistent and relapsing babesiosis in Immunocompromised patients SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID MOLECULAR CHARACTERIZATION; RITUXIMAB THERAPY; BLOOD-TRANSFUSION; INFECTION; MICROTI; ORGANISM; CELL; TRANSMISSION; RESISTANCE; HEPATITIS AB Background. Human babesiosis is a tickborne malaria-like illness that generally resolves without complication after administration of atovaquone and azithromycin or clindamycin and quinine. Although patients experiencing babesiosis that is unresponsive to standard antimicrobial therapy have been described, the pathogenesis, clinical course, and optimal treatment regimen of such cases remain uncertain. Methods. We compared the immunologic status, clinical course, and treatment of 14 case patients who experienced morbidity or death after persistence of Babesia microti infection, despite repeated courses of antibabesial treatment, with those of 46 control subjects whose infection resolved after a single course of standard therapy. This retrospective case-control study was performed in southern New England, New York, and Wisconsin. Results. All case patients were immunosuppressed at the time of acute babesiosis, compared with < 10% of the control subjects. Most case patients experienced B cell lymphoma and were asplenic or had received rituximab before babesial illness. The case patients were more likely than control subjects to experience complications, and 3 died. Resolution of persistent infection occurred in 11 patients after 2-10 courses of therapy, including administration of a final antimicrobial regimen for at least 2 weeks after babesia were no longer seen on blood smear. Conclusions. Immunocompromised people who are infected by B. microti are at risk of persistent relapsing illness. Such patients generally require antibabesial treatment for >= 6 weeks to achieve cure, including 2 weeks after parasites are no longer detected on blood smear. C1 [Krause, Peter J.; Christianson, Diane; Girotto, Jennifer E.] Connecticut Childrens Med Ctr, Div Infect Dis, Hartford, CT 06106 USA. [Pesanti, Edward L.; Dardick, Kenneth] Univ Connecticut, Sch Med, Dept Med, Farmington, CT USA. [Krause, Peter J.; Christianson, Diane; Girotto, Jennifer E.] Univ Connecticut, Sch Med, Dept Pediat, Farmington, CT USA. [Neuhaus, Ellen] Rockville Gen Hosp, Div Infect Dis, Rockville, MD USA. [Gupta, Shaili; Bia, Frank J.] Yale Univ, Sch Med, Yale New Haven Hosp, Div Infect Dis, New Haven, CT USA. [Gewurz, Benjamin E.; Marty, Francisco M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Div Infect Dis, Cambridge, MA 02138 USA. [Gewurz, Benjamin E.; Gelfand, Jeffrey A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Cambridge, MA 02138 USA. [Vannier, Edouard] Tufts Univ New England Med Ctr, Div Geog Med & Infect Dis, Boston, MA 02111 USA. [Vannier, Edouard] Tufts Univ, Sch Med, Medford, MA 02155 USA. [Spielman, Andrew] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Telford, Sam R., III] Tufts Univ, Sch Vet Med, Grafton, MA USA. [Foppa, Ivo M.] Univ S Carolina, Arnold Sch Publ Hlth, Columbia, SC 29208 USA. [Furman, Richard R.; Hartman, Barry; Coleman, Morton] Weill Cornell Med Coll, Div Hematol Oncol, New York, NY USA. [Furman, Richard R.; Hartman, Barry; Coleman, Morton] Weill Cornell Med Coll, Div Infect Dis, New York, NY USA. [McCalla, Carlo; Wormser, Gary P.] New York Med Coll, Div Infect Dis, Valhalla, NY 10595 USA. [Skowron, Gail] Boston Univ, Sch Med, Roger Williams Med Ctr, Div Infect Dis, Providence, RI USA. [Young, Mary] Georgetown Univ, Sch Med, Med Ctr, Div Infect Dis, Washington, DC USA. [Hsue, Gunther] William Beaumont Army Med Ctr, Dept Med, El Paso, TX 79920 USA. [Hill, David] Natl Travel Hlth Network, London, England. [Hill, David] London Sch Hyg & Trop Med, London, England. RP Krause, PJ (reprint author), Connecticut Childrens Med Ctr, Div Infect Dis, 282 Washington St, Hartford, CT 06106 USA. EM PKrause@ccmckids.org FU NCRR NIH HHS [M01 RR06192] NR 37 TC 94 Z9 95 U1 0 U2 8 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD FEB 1 PY 2008 VL 46 IS 3 BP 370 EP 376 DI 10.1086/525852 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 249IJ UT WOS:000252221200004 PM 18181735 ER PT J AU Downes, KJ Metlay, JP Bell, LM McGowan, KL Elliott, MR Shah, SS AF Downes, Kevin J. Metlay, Joshua P. Bell, Louis M. McGowan, Karin L. Elliott, Michael R. Shah, Samir S. TI Polymicrobial bloodstream infections among children and adolescents with central venous catheters evaluated in ambulatory care SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID PEDIATRIC-PATIENTS; RISK-FACTORS; BACTEREMIA; PREVENTION; MORTALITY; COMPLICATIONS; EPIDEMIOLOGY; HOSPITALS AB Background. Bloodstream infections (BSIs) are an ever-present concern for clinicians evaluating ill-appearing pediatric patients with central venous catheters (CVCs) in the ambulatory care setting. Methods. We performed a case-control study of a cohort of 200 pediatric patients who were evaluated in the ambulatory care setting and who were found to have laboratory-confirmed BSI in the context of a CVC. This study sought to compare patients with polymicrobial versus monomicrobial BSIs to identify potential risk factors for polymicrobial BSI. Results. Of the 200 patients enrolled in the study, 73 (37%) had a polymicrobial BSI. Patients with polymicrobial BSI were more likely than those with monomicrobial BSI to be younger (P = .002) and less likely to have been recently discharged from the hospital (P = .01). The odds of a polymicrobial BSI were >4 times greater for patients aged < 3 years than for those aged >= 3 years (odds ratio, 4.54; 95% confidence interval, 1.68-12.29), and the odds were 50% lower for those discharged from the hospital in the prior 7 days than for those without recent hospitalization (odds ratio, 0.46; 95% confidence interval, 0.22-0.95) after controlling for an underlying cancer diagnosis and the time of year during which a patient presented. Recent antibiotic use, recent BSI, duration that the CVC had been in place, and underlying gastrointestinal dysfunction were not associated with a risk of polymicrobial BSI. Conclusions. Younger children and those who had not recently been discharged from the hospital had an increased risk of developing catheter-related polymicrobial BSI. Special consideration should be given to the increased likelihood of polymicrobial BSIs in these pediatric patients when initiating empirical antimicrobial therapy. C1 [Downes, Kevin J.; Bell, Louis M.; Shah, Samir S.] Childrens Hosp Philadelphia, Div Infect Dis, Philadelphia, PA 19104 USA. [McGowan, Karin L.] Childrens Hosp Philadelphia, Clin Microbiol Lab, Philadelphia, PA 19104 USA. [Metlay, Joshua P.; Shah, Samir S.] Univ Penn, Sch Med, Dept Epidemiol, Philadelphia, PA 19104 USA. [Bell, Louis M.; Shah, Samir S.] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. [Metlay, Joshua P.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [McGowan, Karin L.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Metlay, Joshua P.; Shah, Samir S.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Metlay, Joshua P.; Shah, Samir S.] Univ Penn, Sch Med, Ctr Educ & Res Therapeut, Philadelphia, PA 19104 USA. [Metlay, Joshua P.] Vet Affairs Med Ctr, Philadelphia, PA USA. [Elliott, Michael R.] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. [Elliott, Michael R.] Univ Michigan, Inst Social Res, Survey Methodol Program, Ann Arbor, MI USA. RP Shah, SS (reprint author), Childrens Hosp Philadelphia, Div Infect Dis, Rm 1526,N Campus,34th St,Civic Ctr Blvd, Philadelphia, PA 19104 USA. EM shahs@email.chop.edu OI Shah, Samir/0000-0001-7902-7000 NR 26 TC 21 Z9 21 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD FEB 1 PY 2008 VL 46 IS 3 BP 387 EP 394 DI 10.1086/525265 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 249IJ UT WOS:000252221200006 PM 18181737 ER PT J AU Harris, DJ Eilers, J Harriman, A Cashavelly, BJ Maxwell, C AF Harris, Debra J. Eilers, June Harriman, Amber Cashavelly, Barbara J. Maxwell, Cathy TI Putting Evidence Into Practice (R): Evidence-based interventions for the management of oral mucostis SO CLINICAL JOURNAL OF ONCOLOGY NURSING LA English DT Article ID STEM-CELL TRANSPLANTATION; HIGH-DOSE MELPHALAN; COLONY-STIMULATING FACTOR; BONE-MARROW TRANSPLANTATION; PATIENTS RECEIVING RADIOTHERAPY; CHEMOTHERAPY-INDUCED MUCOSITIS; PROSPECTIVE RANDOMIZED-TRIAL; PLACEBO-CONTROLLED TRIAL; NECK-CANCER PATIENTS; DOUBLE-BLIND AB Mucositis, an inflammation of the mucous membranes, is a commonly occurring side effect of chemotherapy and radiation, Oral mucositis can cause significant clinical consequences, such as pain, malnutrition, and local and systemic infections. Nurses have a critical role in all aspects of managing mucositis, including assessing it, teaching oral care, administering pharmacologic interventions, and helping patients cope with symptom distress. Mucositis can have a negative impact on the overall treatment experience, especially when severe pain or infections occur. Many interventions for managing mucositis exist; however, some are based in tradition or expert opinion and have not been studied in large, randomized, controlled trials. In addition, a variety of assessment tools are available, which creates confusion and difficulties when comparing interventions across studies. This article reviews empirical evidence related to interventions for oral mucositis. Oral care and rinses, pharmacologic interventions, and other techniques are evaluated. Gaps in the literature and opportunities for research, education, and practice changes are discussed. C1 [Harris, Debra J.; Harriman, Amber] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Eilers, June] Univ Nebraska Med Ctr, Coll Nursing, Omaha, NE 68198 USA. [Cashavelly, Barbara J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Maxwell, Cathy] Adv Med Specialties, Miami, FL USA. RP Harris, DJ (reprint author), Oregon Hlth & Sci Univ, Portland, OR 97201 USA. EM debrajean_harris@yahoo.com NR 75 TC 40 Z9 44 U1 0 U2 4 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 1092-1095 J9 CLIN J ONCOL NURS JI Clin. J. Oncol. Nurs. PD FEB PY 2008 VL 12 IS 1 BP 141 EP 152 DI 10.1188/08.CJON.141-152 PG 12 WC Oncology; Nursing SC Oncology; Nursing GA 295QO UT WOS:000255489200019 PM 18258584 ER PT J AU Gabeau-Lacet, D Grant, E Stemmer-Rachamimov, A Yock, T Tarbell, NJ AF Gabeau-Lacet, Darlene Grant, Ellen Stemmer-Rachamimov, Anat Yock, Torunn Tarbell, Nancy J. TI Sellar abnormalities in female first-degree relatives SO CLINICAL NEUROLOGY AND NEUROSURGERY LA English DT Article DE Rathke's cleft; germinoma; sella; pituitary; familial; intracranial cyst ID GERM-CELL TUMORS; RATHKES CLEFT CYSTS; DIFFERENTIAL-DIAGNOSIS; PATHOLOGICAL FEATURES; MANAGEMENT; MASSES; MR AB Non-pituitary lesions account for a minority of sellar region abnormalities. We report the unusual occurrence of non-pituitary sellar/suprasellar lesions in a mother and her two daughters. Each of these cases was diagnosed and managed differently, illustrating the relative importance of radiographic imaging, tumor markers and histopathologic examination in the diagnosis and treatment of intracranial disease. The mother had histologically confirmed Rathke's cleft cyst (RCC) with typical radiographic and histologic appearance. One daughter was treated presumptively for germinoma based on characteristic radiographic studies and slightly elevated tumor marker. The other daughter's lesion exhibited radiographic characteristics concerning for pituitary macroadenoma. but with slightly elevated germ cell tumor marker, raising the suspicion for germinoma. Biopsy of the intrasellar mass revealed only proteinaceous material and normal anterior pituitary, consistent with cyst content without evidence of neoplasm. Without a clear unifying diagnosis it is difficult to posit an underlying pathology or genetic mechanisms in this unusual set of cases. At least two of the patients had benign cysts. The diagnosis of the third patient is unclear as there was no tissue biopsy. However, it is highly improbable that three female first-degree relatives would develop such lesions in the same brain region simply by chance. (C) 2007 Elsevier B.V. All rights reserved. C1 [Gabeau-Lacet, Darlene; Yock, Torunn; Tarbell, Nancy J.] Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA 02115 USA. [Gabeau-Lacet, Darlene; Yock, Torunn; Tarbell, Nancy J.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Grant, Ellen] Massachusetts Gen Hosp, Div Pediat Radiol, Dept Radiol, Boston, MA 02114 USA. [Stemmer-Rachamimov, Anat] Massachusetts Gen Hosp, Div Neuropathol, Dept Pathol, Boston, MA 02114 USA. RP Gabeau-Lacet, D (reprint author), Harvard Univ, Sch Med, Harvard Radiat Oncol Program, 75 Francis St,L2, Boston, MA 02115 USA. EM dgabeau@partners.org NR 18 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0303-8467 J9 CLIN NEUROL NEUROSUR JI Clin. Neurol. Neurosurg. PD FEB PY 2008 VL 110 IS 2 BP 202 EP 206 DI 10.1016/j.clineuro.2007.09.021 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 266CE UT WOS:000253408100018 PM 18035480 ER PT J AU Viswanathan, AN AF Viswanathan, A. N. TI The Frank Ellis memorial lecture: the use of three-dimensional Imaging in gynaecological radiation therapy SO CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT United Kingdom Radiation Oncology Conference CY MAR 18-21, 2007 CL Edinburgh, SCOTLAND DE brachytherapy; cervical cancer; radiation ID CERVICAL-CANCER; INTRACAVITARY BRACHYTHERAPY; CARCINOMA; RECOMMENDATIONS; IMPACT AB The use of three-dimensional image guidance in radiation therapy has increased dramatically over the past decade. In gynaecological malignancies, three-dimensional image guidance assists with both external beam and brachytherapy treatment planning, increasing the accuracy of dose delivery. During his lifetime, Frank Ellis made significant contributions to gynaecological brachytherapy. This lecture will focus on novel advances in three-dimensional imageguided radiation therapy for cervical cancer, with the ultimate goal of improving outcomes for our patients. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Viswanathan, AN (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. EM aviswanthan@lroc.harvard.edu NR 16 TC 6 Z9 7 U1 0 U2 2 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0936-6555 J9 CLIN ONCOL-UK JI Clin. Oncol. PD FEB PY 2008 VL 20 IS 1 BP 1 EP 5 DI 10.1016/j.cion.2007.11.002 PG 5 WC Oncology SC Oncology GA 264IT UT WOS:000253281700001 PM 18068960 ER PT J AU Ganz, R Leunig, M Leunig-Ganz, K Harris, WH AF Ganz, Reinhold Leunig, Michael Leunig-Ganz, Katharina Harris, William H. TI The etiology of osteoarthritis of the hip - An integrated mechanical concept SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT Annual Closed Meeting of the International-Hip-Society CY SEP, 2006 CL Paris, FRANCE SP Int Hip Soc ID ANTERIOR FEMOROACETABULAR IMPINGEMENT; FEMORO-ACETABULAR IMPINGEMENT; SURGICAL DISLOCATION; NERVE-ENDINGS; LABRAL REPAIR; YOUNG-ADULTS; NECK; HEAD; CARTILAGE; ARTHROSCOPY AB The etiology of osteoarthritis of the hip has long been considered secondary (eg, to congenital or developmental deformities) or primary (presuming some underlying abnormality of articular cartilage). Recent information supports a hypothesis that so-called primary osteoarthritis is also secondary to subtle developmental abnormalities and the mechanism in these cases is femoroacetabular impingement rather than excessive contact stress. The most frequent location for femoroacetabular impingement is the anterosuperior rim area and the most critical motion is internal rotation of the hip in 90 degrees flexion. Two types of femoroacetabular impingement have been identified. Cam-type femoroacetabular impingement, more prevalent in young male patients, is caused by an offset pathomorphology between head and neck and Produces an outside-in delamination of the acetabulum. Pincer-type femoroacetabular impingement, more prevalent in middle-aged women, is produced by a more linear impact between a local (retroversion of the acetabulum) or general overcoverage (coxa profunda/protrusio) of the acetabulum. The damage pattern is more restricted to the rim and the process of joint degeneration is slower. Most hips, however, show a mixed femoroacetabular impingement pattern with cam predominance. Surgical attempts to restore normal anatomy to avoid femoroacetabular impingement should be performed in the early stage before major cartilage damage is present. C1 [Leunig, Michael] Univ Zurich, Dept Orthopaed, Schulthese Clin, Hip Serv, CH-8008 Zurich, Switzerland. [Ganz, Reinhold; Leunig, Michael] Univ Bern, Bern, Switzerland. [Ganz, Reinhold] Balgrist Univ Hosp, Dept Orthopaed, Zurich, Switzerland. [Leunig-Ganz, Katharina] Triemli City Hosp, Matern Dept, Zurich, Switzerland. [Harris, William H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harris Orthoped Biomech & Biomat Lab, Boston, MA USA. RP Leunig, M (reprint author), Univ Zurich, Dept Orthopaed, Schulthese Clin, Hip Serv, Lengghalde 2, CH-8008 Zurich, Switzerland. EM michael.leunig@kws.ch RI Leunig, Michael/E-7951-2017 OI Leunig, Michael/0000-0002-2036-5416 NR 72 TC 412 Z9 431 U1 13 U2 50 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD FEB PY 2008 VL 466 IS 2 BP 264 EP 272 DI 10.1007/s11999-007-0060-z PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 262QW UT WOS:000253164100003 PM 18196405 ER PT J AU Rightmire, E Zurakowski, D Vrahas, M AF Rightmire, Eric Zurakowski, David Vrahas, Mark TI Acute infections after fracture repair SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID PROSTHETIC JOINT INFECTION; OSTEOMYELITIS; ARTHROPLASTY; DEBRIDEMENT; PREVENTION; RETENTION; TIBIA AB Managing infections in fractures treated with open reduction and internal fixation is an ongoing dilemma. Little published data exist to support the current practice of treating these infections with retained hardware, irrigation, debridement, and antibiotic suppression. We evaluated the effectiveness of this approach. We identified potential subjects from a central trauma database and selected them based on chart review and specific inclusion and exclusion criteria. We divided the patients into two groups. Patients achieving successful union with original hardware in place were considered as having successful results and patients who required hardware removal before healing were considered to have failed results. Data, including age, gender, tobacco use, diabetic status, site of fracture, Orthopaedic Trauma Association class, open grade, type of fixation, joint involvement, and organism, were gathered and compared between the groups by analysis of variance. Sixty-nine cases were available for analysis. Forty-seven (68%) were successful and 22 (32%) were unsuccessful. Average time to healing was 130 days. Most of the failures occurred within 120 days from the time of injury. Smoking was a major risk factor with a 3.7 times greater likelihood of procedures being unsuccessful per month than procedures among nonsmokers. Treating infected fractures with hardware in place is less successful than widely believed. C1 [Vrahas, Mark] Harvard Univ, Massachusetts Gen Hosp, Brigham & Womens Hosp, Partners Chief Orthopaed Trauma Serv, Boston, MA 02114 USA. [Rightmire, Eric] Plymouth Orthoped, Duxbury, MA USA. [Zurakowski, David] Childrens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. RP Vrahas, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Brigham & Womens Hosp, Partners Chief Orthopaed Trauma Serv, 55 Fruit St,YAW 3600, Boston, MA 02114 USA. EM mvrahas@partners.org NR 23 TC 37 Z9 39 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD FEB PY 2008 VL 466 IS 2 BP 466 EP 472 DI 10.1007/s11999-007-0053-y PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 262QW UT WOS:000253164100031 PM 18196433 ER PT J AU Van der Meer, P Veldhuisen, DJN Januzzi, JL AF Van der Meer, Peter Veldhuisen, Dirk J. N. Januzzi, James L. TI Erythropoietin in cardiovascular diseases: exploring new avenues SO CLINICAL SCIENCE LA English DT Editorial Material DE cardiac ischaemia; endothelin; erythropoietin (EPO); ischaemia/reperfusion injury; natriuretic peptide ID HEART-FAILURE; NATRIURETIC PEPTIDE; PROGNOSTIC VALUE; MORTALITY; INJURY; ANEMIA; ALPHA; SAFE AB Cardiovascular disease is an important burden in the Western world, with a prevalence that is increasing exponentially. Indeed, the lifetime risk of coronary artery disease at 40 years of age is I in 2 for men and I in 3 for women, and it is estimated that one-third of the population worldwide will die of cardiovascular disease, with a majority of these deaths related to MI (myocardial infarction) or the complications of MI. Recent research has suggested that EPO (erythropoietin), an endogenous erythropoietic hormone, may have pleiotropic effects well beyond the maintenance of red blood cells, and may have a cardiovascular role as well, including a potentially salutary effect on reperfusion injury. Although findings supportive of a role of EPO as a cardioprotective agent appear promising, the mechanisms behind the observed benefits remain elusive. In the present issue of Clinical Science, Piuhola and co-workers provide an interesting study that may shed light on the effects of EPO (and possibly related compounds) in the context of acute MI. C1 [Van der Meer, Peter; Januzzi, James L.] Massachusetts Gen Hosp, Harvard Med Sch, Div Cardiol, Boston, MA 02114 USA. [Van der Meer, Peter; Veldhuisen, Dirk J. N.] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9700 RB Groningen, Netherlands. RP Van der Meer, P (reprint author), Massachusetts Gen Hosp, Harvard Med Sch, Div Cardiol, Boston, MA 02114 USA. EM pvandermeer@partners.org RI van Veldhuisen, Dirk Jan/E-8967-2014 NR 16 TC 4 Z9 4 U1 0 U2 0 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0143-5221 J9 CLIN SCI JI Clin. Sci. PD FEB PY 2008 VL 114 IS 3-4 BP 289 EP 291 DI 10.1042/CS20070392 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 261PU UT WOS:000253093300012 PM 17999641 ER PT J AU Ye, X Sikirica, V Schein, JR Grant, R Zarotsky, V Doshi, D Benson, CJ Riedel, AA AF Ye, Xin Sikirica, Vanja Schein, Jeffrey R. Grant, Richard Zarotsky, Victoria Doshi, Dilesh Benson, Carmela Janagap Riedel, Aylin A. TI Treatment failure rates and health care utilization and costs among patients with community-acquired pneumonia treated with levofloxacin or Macrolides in an outpatient setting: A retrospective claims database analysis SO CLINICAL THERAPEUTICS LA English DT Article DE community-acquired pneumonia; CAP; levofloxacin; claims analysis; treatment failure; macrolides; costs; resource utilization ID OF-AMERICA GUIDELINES; ANTIMICROBIAL THERAPY; STREPTOCOCCUS-PNEUMONIAE; EMERGENCY-DEPARTMENT; ECONOMIC OUTCOMES; ELDERLY-PATIENTS; SEVERITY INDEX; UNITED-STATES; RESISTANCE; ADULTS AB Background: Macrolide antibiotics and fluoroquinolones are extensively used in the treatment of community-acquired pneumonia (CAP). Objective: This analysis was conducted to compare treatment failure rates and health care utilization and cost outcomes among patients with CAP treated with levofloxacin (500 or 750 mg) or macrolides (azitliromycin, clarithromycin, or erythromycin) in an outpatient setting. Methods: This was a retrospective analysis of claims data from a large US health plan. Patients were aged >= 18 years and had a primary diagnosis of CAP that was treated with oral levofloxacin or a macrolide in an outpatient setting (including physicians' offices, outpatient clinics, urgent care centers, and large ambulatory health centers). Patients were followed for 30 days after the index drug date to measure study outcomes. Multivariate regression analysis and a propensity score technique were used to compare rates of treatment failure and CAP-related health care utilization and costs. Two post hoc subgroup analyses were conducted in patients aged >= 50 and >= 65 years. Results: Of the 7526 patients meeting the inclusion criteria, 2968 (39.4%) were treated with levofloxacin and 4558 (60.6%) with a macrolide. Unadjusted rates of treatment failure were 21.1% and 22.7% in the levofloxacin and macrolide cohorts, respectively. After adjustment for demographic characteristics, baseline comorbidities, and severity of illness, levofloxacin recipients were significantly less likely to experience treatment failure than macrolide recipients (odds ratio [OR] = 0.84; 95% CI, 0.75-0.94, P = 0.003). The likelihood of treatment failure was significantly lower in levofloxacin recipients aged 50 years (OR = 0.79; 95% CI, 0.66-0.94; P = 0.007) and >= 65 years (OR = 0.65; 95% CI, 0.43-1.00; P = 0.049) compared with the corresponding subgroups of macrolide recipients. The magnitude of this difference was greatest in the subgroup aged >= 65 years, which had a 35% reduced risk of treatment failure compared with the corresponding group of macrolide-treated patients. The rate of CAP-related emergency department visits was significantly lower among patients receiving levofloxacin (OR = 0.68; 95% CI, 0.51-0.91; P = 0.009); there were no differences in CAP-related hospitalizations or total CAP-related health care costs between levofloxacin and macrolide recipients. Conclusions: Multivariate-adjusted rates of treatment failure in outpatients with CAP were significantly lower in those treated with levofloxacin relative to those treated with a macrolide. The lower rates of treatment failure with levofloxacin were consistently observed across all patients and in the subgroups aged >= 50 and >= 65 years. Rates of emergency department visits were also significantly lower among levofloxacin-treated patients, whereas overall CAP-related hospitalizations and costs did not differ significantly between the 2 treatment groups. C1 [Ye, Xin; Sikirica, Vanja; Doshi, Dilesh; Benson, Carmela Janagap] Ortho McNeil Janssen Sci Affairs LLC, Raritan, NJ USA. [Grant, Richard] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ye, Xin; Zarotsky, Victoria; Riedel, Aylin A.] i3 Innovus, Eden Prairie, MN 55347 USA. RP Ye, X (reprint author), i3 Innovus, 12125 Technol Dr, Eden Prairie, MN 55347 USA. EM Xin.Ye@i3innovus.com OI Grant, Richard/0000-0002-6164-8025 NR 46 TC 22 Z9 23 U1 0 U2 4 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD FEB PY 2008 VL 30 IS 2 BP 358 EP 371 DI 10.1016/j.clinthera.2008.01.023 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 280ZY UT WOS:000254466900014 PM 18343274 ER PT J AU Garcia, AD AF Garcia, Aimee Dinorah TI The effect of chronic disorders on sleep in the elderly SO CLINICS IN GERIATRIC MEDICINE LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; QUALITY-OF-LIFE; NURSING-HOME RESIDENTS; RESTLESS LEGS SYNDROME; CHRONIC PAIN PATIENTS; PARKINSONS-DISEASE; CHRONIC INSOMNIA; PSYCHIATRIC-DISORDERS; RHEUMATOID-ARTHRITIS; ALZHEIMERS-DISEASE AB Sleep disorders are increasingly common as people age. Along with the numerous physiologic changes that occur with aging, sleep patterns are also altered. Inability to get to sleep, shorter sleep times, and changes in the normal circadian patterns can have an impact on an individual's overall well being. In addition, many common chronic conditions, such as chronic obstructive pulmonary disease, diabetes, dementia, chronic pain, and cancer, that are more common in the elderly, can also have significant effects on sleep and increase the prevalence of insomnia as compared with the general population. This is a result not only of the chronic medical illnesses themselves, but of the psychologic and social factors associated with the disease processes. C1 Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Garcia, AD (reprint author), Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, 2002 Holcombe ECL 110, Houston, TX 77030 USA. EM aimeeg@bcm.tmc.edu NR 98 TC 11 Z9 14 U1 3 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-0690 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD FEB PY 2008 VL 24 IS 1 BP 27 EP + DI 10.1016/j.cger.2007.08.008 PG 13 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 246TB UT WOS:000252028900004 PM 18035229 ER PT J AU Martin, JL Ancoli-Israel, S AF Martin, Jennifer L. Ancoli-Israel, Sonia TI Sleep disturbances in long-term care SO CLINICS IN GERIATRIC MEDICINE LA English DT Article ID NURSING-HOME RESIDENTS; ACTIVITY RHYTHM DISTURBANCES; MINIMUM DATA SET; ENVIRONMENTAL INTERVENTION; ALZHEIMERS-DISEASE; SEDATIVE-HYPNOTICS; CIRCADIAN-RHYTHMS; HIP-FRACTURES; OLDER-PEOPLE; LIGHT AB Nighttime sleep disruption is characteristic of long-term care residents, is typically accompanied by daytime sleepiness, and may be caused by a multitude of factors. Causal factors include medical and psychiatric illness, medications, circadian rhythm abnormalities, sleep disordered breathing and other primary sleep disorders, environmental factors, and lifestyle habits. There is some suggestion that these factors are amenable to treatment; however, further research on the implementation of treatments within the long-term care setting is needed. Additional work is also needed to understand the administrative and policy factors that might lead to systemic changes in how sleep is viewed and sleep problems are addressed in long-term care settings. C1 [Ancoli-Israel, Sonia] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92093 USA. [Ancoli-Israel, Sonia] Vet Affairs San Diego Healthcare Syst, Dept Psychiat, San Diego, CA 92161 USA. [Martin, Jennifer L.] Vet Affairs Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, North Hills, CA 91343 USA. [Martin, Jennifer L.] Univ Calif, Los Angeles Sch Med, Multicampus Program Geriatr Med & Gerontol, North Hills, CA 91343 USA. RP Ancoli-Israel, S (reprint author), Univ Calif San Diego, Dept Psychiat, 9500 Gilman Dr, San Diego, CA 92093 USA. EM sancoliisrael@ucsd.edu FU NCI NIH HHS [R01 CA112035-03, R01 CA112035, CA112035]; NCRR NIH HHS [M01 RR000827, M01 RR000827-301082, M01 RR00827]; NIA NIH HHS [5 P60 AG010415, AG08415, P60 AG010415, R01 AG008415, R01 AG008415-16A2] NR 39 TC 29 Z9 31 U1 1 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-0690 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD FEB PY 2008 VL 24 IS 1 BP 39 EP + DI 10.1016/j.cger.2007.08.001 PG 13 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 246TB UT WOS:000252028900005 PM 18035230 ER PT J AU Soroudi, N Perez, GK Gonzalez, JS Greer, JA Otto, MW Safren, SA Pollack, MH AF Soroudi, Nafisseh Perez, Giselle K. Gonzalez, Jeffrey S. Greer, Joseph A. Otto, Michael W. Safren, Steven A. Pollack, Mark H. TI CBT for medication adherence and depression (CBT-AD) in HIV-Infected patients receiving methadone maintenance therapy SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; VIRAL LOAD; PROTEASE INHIBITORS; DRUG-RESISTANCE; RATING-SCALE; SELF-REPORT; PREDICTORS; DISORDERS; VARIABLES; DISEASE AB For individuals with HIV who are current or former injection drug users, depression is a common, distressing condition that can interfere with a critical self-care behavior-adherence to antiretroviral therapy. The present study describes the feasibility and outcome, in a case series approach, of cognitive behavioral therapy to improve adherence and depression (CBT-AD) among individuals with HI-V and depression undergoing methadone maintenance treatment for heroin dependence. CBT-AD integrates cognitive behavioral therapy for depression with our intervention for improving adherence to antiretroviral therapy for HIV(Life-Steps; [Safren, S. A., Otto, M. W, Worth, J., Salomon, E., Johnson, W., Mayer, K, et al. (2001). Two strategies to increase adherence to HTV antiretroviral medication: Life-Steps and medication monitoring. Behavioral Research and Therapy, 39, 1151-11621]). Specifically, in CBT-AD, patients first receive a cognitive behavioral intervention focusing on improving skills related to medication adherence. Each of the subsequent CBT modules (activity scheduling, cognitive restructuring, problem-solving training, and relaxation training/diaphragmatic breathing) is designed to address both self-care-adherence behaviors as well as depression. The process and outcome with 4 cases suggest that the treatment was feasible and acceptable and was generally associated with improvements. This case series provides an example of how cognitive behavioral therapists can integrate the treatment of depression with the enhancement of critical self-care behaviors in the context of highly complex, medical and psychiatric comorbidity. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Habit Management Inst, Cambridge, MA 02138 USA. [Otto, Michael W.] Boston Univ, Boston, MA 02215 USA. RP Safren, SA (reprint author), Dept Psychiat, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM ssafren@partners.org NR 66 TC 8 Z9 8 U1 3 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD FEB PY 2008 VL 15 IS 1 BP 93 EP 106 PG 14 WC Psychology, Clinical SC Psychology GA 322XB UT WOS:000257407500011 ER PT J AU Zaitchik, D Solomon, GEA AF Zaitchik, Deborah Solomon, Gregg E. A. TI Animist thinking in the elderly and in patients with Alzheimer's disease SO COGNITIVE NEUROPSYCHOLOGY LA English DT Article DE folkbiology; conceptual change; domain-specificity; aging; Alzheimer's disease ID ANIMATE-INANIMATE DISTINCTION; SEMANTIC MEMORY IMPAIRMENT; CATEGORY-SPECIFIC DEFICITS; NONLIVING THINGS; LIVING THINGS; KNOWLEDGE; DEMENTIA; DISSOCIATION; RECOGNITION; OBJECT AB Some patients with Alzheimer's disease (AD) reveal low-level impairment in their concepts of living things (i.e., forgetting that zebras are striped). To test for more profound impairment, we investigated the concept alive-a "higher order" concept spanning every member of the domain. Many elderly controls were animists, attributing life to inanimates capable of self-generated activity (the sun, fire). Most AD patients were animists, with half even attributing life to inanimates whose activity is not self-generated (cars, lamps). Adult animists, like young children who have not yet acquired biological concepts, overattributed life to active inanimates. We believe this reflects an innate disposition to view active entities as agents, and that agency interferes with the biological concept alive. This interference, we suggest, reflects degradation of biological concepts in the face of spared perception of agents. It sheds light on the nature of fundamental questions concerning conceptual organization, innate endowment, and conceptual change. C1 [Zaitchik, Deborah] Massachusetts Gen Hosp East, Gerontol Res Unit, Charlestown, MA 02129 USA. [Zaitchik, Deborah] Harvard Univ, Sch Med, Boston, MA 02129 USA. [Solomon, Gregg E. A.] Natl Sci Fdn, Arlington, VA 22230 USA. RP Zaitchik, D (reprint author), Massachusetts Gen Hosp East, Gerontol Res Unit, 149-2691,149 13th St, Charlestown, MA 02129 USA. EM dzaitchiksamct@partners.com FU NIA NIH HHS [AG020548] NR 43 TC 18 Z9 18 U1 0 U2 1 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0264-3294 J9 COGN NEUROPSYCHOL JI Cogn. Neuropsychol. PD FEB PY 2008 VL 25 IS 1 BP 27 EP 37 DI 10.1080/02643290801904059 PG 11 WC Psychology; Psychology, Experimental SC Psychology GA 289OM UT WOS:000255063800002 PM 18340602 ER PT J AU Feldner, MT Babson, KA Zvolensky, MJ Monson, CM Bonn-Miller, MO Gibson, LE AF Feldner, Matthew T. Babson, Kimberly A. Zvolensky, Michael J. Monson, Candice M. Bonn-Miller, Marcel O. Gibson, Laura E. TI An examination of anxiety sensitivity as a moderator of the relationship between smoking level and posttraumatic stress symptoms among trauma-exposed adults SO COGNITIVE THERAPY AND RESEARCH LA English DT Article DE smoking; posttraumatic stress; anxiety sensitivity; moderator; comorbidity ID RUSSIAN EPIDEMIOLOGIC SAMPLE; CIGARETTE USE; RISK-FACTORS; NEGATIVE AFFECT; PANIC DISORDER; DEPRESSION; SMOKERS; MODEL; SURVIVORS; NICOTINE AB The present investigation tested the prediction that global and lower-order factors of anxiety sensitivity (AS) would moderate the relationship between cigarette smoking level and posttraumatic stress symptom levels among 78 (59 female) traumatic event-exposed adults. Consistent with prediction, global levels of AS and levels of AS mental incapacitation and physical concerns moderated the association between smoking level and posttraumatic stress symptoms; the combination of high levels of AS and greater number of cigarettes smoked per day was associated with higher symptom levels than any other combination of these factors. In a test of specificity, these three aspects of AS did not moderate the relation between smoking level and depressive symptoms. These findings increase our understanding of the association between smoking and posttraumatic symptoms by integrating cognitive factors, such as AS, into current models of this common overlap. Theoretical and treatment implications are discussed. C1 [Feldner, Matthew T.; Babson, Kimberly A.] Univ Arkansas, Dept Psychol, Div Anxiety Res Ctr, Intervent Sci Lab, Fayetteville, AR 72701 USA. [Zvolensky, Michael J.; Bonn-Miller, Marcel O.; Gibson, Laura E.] Univ Vermont, Burlington, VT USA. [Monson, Candice M.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Monson, Candice M.] VA Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. RP Feldner, MT (reprint author), Univ Arkansas, Dept Psychol, Div Anxiety Res Ctr, Intervent Sci Lab, 216 Mem Hall, Fayetteville, AR 72701 USA. EM mfeldne@uark.edu NR 70 TC 6 Z9 6 U1 8 U2 9 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0147-5916 J9 COGNITIVE THER RES JI Cogn. Ther. Res. PD FEB PY 2008 VL 32 IS 1 BP 116 EP 132 DI 10.1007/s10608-007-9138-x PG 17 WC Psychology, Clinical SC Psychology GA 252AY UT WOS:000252418400009 ER PT J AU Harissi-Dagher, M Colby, KA AF Harissi-Dagher, Mona Colby, Kathryn A. TI Cataract extraction after implantation of a type I Boston keratoprosthesis SO CORNEA LA English DT Article DE Boston keratoprosthesis; cataract; extracapsular cataract; extraction; intraocular lens implantation ID INTRAOCULAR-LENS IMPLANTATION; CHAMBER; EYES AB Purpose: To describe cataract extraction and intraocular lens placement in a patient with an existing Type I Boston keratoprosthesis. Methods: Case report to describe the surgical technique used to remove a cataract that developed after Boston keratoprosthesis placement. Results: Extracapsular cataract extraction by using an open-sky technique can be used to remove a cataractous lens in the setting of an existing Boston keratoprosthesis. Conclusions: Although this case shows that it is possible to per-form cataract surgery after Boston keratoprosthesis placement, it is prudent to remove the crystalline lens during the initial surgery, even in the absence of a visually significant cataract, because several factors work together to almost guarantee eventual cataract development if the patient is left phakic. C1 [Harissi-Dagher, Mona; Colby, Kathryn A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. RP Colby, KA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM kacolby@meei.harvard.edu NR 15 TC 2 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD FEB PY 2008 VL 27 IS 2 BP 220 EP 222 PG 3 WC Ophthalmology SC Ophthalmology GA 255BH UT WOS:000252631200017 PM 18216580 ER PT J AU Sorond, FA Schnyer, DM Serrador, JM Milberg, WP Lipsitz, LA AF Sorond, Farzaneh A. Schnyer, Dauid M. Serrador, Jorge M. Milberg, William P. Lipsitz, Lewis A. TI Cerebral blood flow regulation during cognitive tasks: Effects of healthy aging SO CORTEX LA English DT Article DE cerebral blood flow velocity; cognition; aging; transcranial Doppler ultrasound ID TRANSCRANIAL DOPPLER ULTRASONOGRAPHY; AGE-RELATED-CHANGES; WORKING-MEMORY; BRAIN; HEMODYNAMICS; SONOGRAPHY; VELOCITY; CORTEX; FMRI; PET AB Aging is associated with frontal subcortical microangiopathy and executive cognitive dysfunction, suggesting that elderly individuals may have impaired metabolic activation of cerebral blood flow to the frontal lobes. We used transcranial Doppler (TCD) ultrasound to examine the cerebral blood flow response to executive control and visual tasks in the anterior and posterior cerebral circulations and to determine the effects of healthy aging on cerebral blood flow regulation during cognitive tasks. Continuous simultaneous anterior cerebral artery (ACA) and posterior cerebral artery (PCA) blood flow velocities (BFVs) and mean arterial pressure (MAP) were measured in response to word stem completion (WSC) and a visual search (VS) task in 29 healthy subjects (14 young, 30 +/- 1.5 years; 15 old, 74 +/- 1.4 years). We found that: (1) ACA and PCA blood flow velocities are both significantly increased during WSC and VS cognitive tasks, (2) ACA and PCA activations were task specific in our young volunteers, with ACA > PCA BFV during the WSC task and PCA > ACA BFV during the VS task, (3) while healthy elderly subjects also had PCA > ACA BFV during the VS task, they did not have ACA > PCA activation during the WSC task, and (4) healthy elderly subjects tend to have overall greater increases in BFV during both cognitive tasks. We conclude that TCD can be used to monitor cerebrovascular hemodynamics during the performance of cognitive tasks. Our data suggest that there is differential blood flow increase in the ACA and PCA in young versus elderly subjects during cognitive tasks. (C) 2007 Elsevier Masson Srl. All rights reserved. C1 [Sorond, Farzaneh A.] Brigham & Womens Hosp, Dept Neurol, Stroke Div, Boston, MA 02115 USA. [Sorond, Farzaneh A.; Serrador, Jorge M.; Lipsitz, Lewis A.] Hebrew SeniorLife, Inst Aging Res, Boston, MA USA. [Milberg, William P.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Schnyer, Dauid M.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Schnyer, Dauid M.] Boston VA Healthcare Syst, Memory Disorders Res Ctr, Boston, MA USA. [Milberg, William P.] W Roxbury Dept Vet Affairs Med Ctr, Boston, MA USA. [Milberg, William P.] GRECC, Geriatr Neuropsychol Lab, Brockton, MA USA. [Serrador, Jorge M.; Lipsitz, Lewis A.] Beth Israel Deaconess Med Ctr, Dept Med, Div Gerontol, Boston, MA 02215 USA. RP Sorond, FA (reprint author), Brigham & Womens Hosp, Dept Neurol, Stroke Div, 45 Francis St, Boston, MA 02115 USA. EM fsorond@partners.org RI Serrador, Jorge/A-9172-2009 FU NIA NIH HHS [AG00294, AG04390, P60 AG008812, K12 AG000294, P50 AG005134-149004, P01 AG004390-170009, P50 AG005134, R37 AG025037-03, P01 AG004390-24, AG08812, Z01 AG000294, P01 AG004390-16A10009, K12 AG000294-18, P60 AG008812-11A1, R37 AG025037, P01 AG004390-180009, P01 AG004390, P01 AG004390-190009, AG05134] NR 27 TC 29 Z9 29 U1 0 U2 8 PU ELSEVIER MASSON PI MILANO PA VIA PALEOCAPA 7, 20121 MILANO, ITALY SN 0010-9452 J9 CORTEX JI Cortex PD FEB PY 2008 VL 44 IS 2 BP 179 EP 184 DI 10.1016/j.cortex.2006.01.003 PG 6 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 276OK UT WOS:000254151700010 PM 18387547 ER PT J AU Schettino, G Altobelli, N Kacmarek, RM AF Schettino, Guilherme Altobelli, Neila Kacmarek, Robert M. TI Noninvasive positive-pressure ventilation in acute respiratory failure outside clinical trials: Experience at the Massachusetts General Hospital SO CRITICAL CARE MEDICINE LA English DT Article DE noninvasive positive-pressure ventilation; respiratory failure; chronic obstructive pulmonary disease; cardiogenic pulmonary edema; hypoxemic respiratory failure ID OBSTRUCTIVE PULMONARY-DISEASE; RANDOMIZED CONTROLLED-TRIAL; CONVENTIONAL MECHANICAL VENTILATION; AIRWAY PRESSURE; FACE MASK; ACUTE EXACERBATIONS; EDEMA; EXTUBATION; MULTICENTER; RISK AB Background: Noninvasive positive-pressure ventilation (NPPV) has been shown to be effective in select patients enrolled in clinical trials. However, few data are available on the use of NPPV as routine standard medical care for patients with respiratory failure outside of controlled trials. Measurements and Main Results: All patients receiving NPPV for a 1-yr period for acute or acute on chronic respiratory failure who did not select do not intubate/resuscitate status were evaluated. Demographic, physiological, and laboratory data were collected for as long as NPPV was provided. Data were recorded on 449 patients. Intubation rate was 18%, 24%, 38%, 40%, and 60%, respectively, for patients with cardiogenic pulmonary edema (n = 97), acute exacerbation of chronic obstructive pulmonary disease (n = 87), non-chronic obstructive pulmonary disease acute hypercapnic respiratory failure (n = 35), postextubation respiratory failure patients (n = 95), and acute hypoxemic respiratory failure (n = 144). The hospital mortality for patients with acute hypoxemic respiratory failure who failed NPPV was 64%. A logistic regression showed that baseline Simplified Acute Physiology Score II (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.05-1.10; p < .0001), Glasgow Coma Scale (OR, 0.76; 95% CI, 0.66-0.87; p < .0001), Pao(2)/FIo(2) ratio (OR, 0.98; 95% CI, 0.93-0.99; p = .02), and serum albumin (OR, 0.30; 95% CI, 0.16-0.57; p < .001) were the variables associated with NPPV failure. Conclusion: NPPV as routine standard medical care resulted in the intubation of a similar percentage of patients with respiratory failure due to cardiogenic pulmonary edema and chronic obstructive pulmonary disease exacerbation as shown in randomized controlled trials but in a higher percent of patients with hypoxemic respiratory failure than reported in these trials. NPPV failure was associated with high hospital mortality for patients with hypoxemic respiratory failure. C1 [Schettino, Guilherme; Kacmarek, Robert M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Schettino, Guilherme; Altobelli, Neila; Kacmarek, Robert M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Schettino, G (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM rkacmarek@partners.org NR 33 TC 70 Z9 79 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD FEB PY 2008 VL 36 IS 2 BP 441 EP 447 DI 10.1097/01.CCM.0000300084.67277.90 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 257JB UT WOS:000252794000010 PM 18091540 ER PT J AU Conhaim, RL Watson, KE Spiegel, CA Dovi, WF Harms, BA AF Conhaim, Robert L. Watson, Kal E. Spiegel, Carol A. Dovi, William F. Harms, Bruce A. TI Bacteremic sepsis disturbs alveolar perfusion distribution in the lungs of rats SO CRITICAL CARE MEDICINE LA English DT Article DE rheology; bacteremia; pulmonary circulation; pulmonary edema; microcirculation; thromboembolism ID VASCULAR-RESISTANCE; INJURY; TRANSFUSION; CIRCULATION; THROMBOXANE; SHOCK AB Objective: Sepsis often leads to lung injury, although the mechanisms that initiate this are unclear. One preinjury phenomenon that has not been explored previously is the effect of bacterial (nonlipopolysaccharide) sepsis on the distribution of alveolar perfusion. The goals of our studies were to measure this. Design: Randomized, controlled, prospective animal study. Setting: University animal laboratory. Subjects: Male Sprague-Dawley rats (450-550 g). Interventions: We induced sepsis by placing gelatin capsules containing Escherichia coli and Bacteroides fragilis into the abdomens of rats (n = 9). Empty capsules (n = 6) were placed into the abdomens of controls. After 24 hrs, 4-mu m-diameter fluorescent latex particles (2 x 10(8)) were infused into the pulmonary circulation. Sepsis was induced in additional rats and controls to assess lung injury, as follows: Lung histology was performed on eight septic rats and on seven controls; lung lavage was performed on three septic rats and three controls after their plasma albumin had been labeled with Evans blue dye. Measurements and Main Results: Confocal microscopy was used to prepare digital maps of latex particle trapping patterns (eight per lung). Analysis of these patterns revealed statistically more clustering (perfusion inhomogeneity) down to tissue volumes less than that of ten alveoli in septic lungs compared with controls (p <= .05). Bacterial counts and neutrophil counts were significantly higher in the circulation of septic rats (p <= .05). Blood pressures and arterial Po2S were unchanged. Cell counts in histological images were three-fold higher in septic lungs than in controls (p <= .05). Lung lavage revealed 0.41 +/- 0.03 mL of plasma in the lungs of septic rats, and 0.06 +/- 0.05 mL in the lungs of controls (p <= .05). Conclusions: Bacterial sepsis caused significant maldistribution of interalveolar perfusion in the lungs of rats in the absence of significant lung injury. C1 [Conhaim, Robert L.; Watson, Kal E.; Harms, Bruce A.] Univ Wisconsin, Sch Med, Dept Surg, Madison, WI 53706 USA. [Spiegel, Carol A.] Univ Wisconsin, Sch Med, Dept Pathol, Madison, WI USA. [Spiegel, Carol A.] Univ Wisconsin, Sch Med, Lab Med, Madison, WI USA. [Conhaim, Robert L.; Dovi, William F.; Harms, Bruce A.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Conhaim, RL (reprint author), Univ Wisconsin, Sch Med, Dept Surg, Madison, WI 53706 USA. EM conhaim@surgery.wisc.edu NR 31 TC 13 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD FEB PY 2008 VL 36 IS 2 BP 511 EP 517 DI 10.1097/01.CCM.0000300082.75334.48 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 257JB UT WOS:000252794000020 PM 18091533 ER PT J AU Caramez, MP Miyoshi, E Harris, RS Kacmarek, RM Malhotra, A AF Caramez, Maria Paula Miyoshi, Eriko Harris, R. Scoft Kacmarek, Robert M. Malhotra, Atul TI Gas exchange impairment induced by open suctioning in acute respiratory distress syndrome: Impact of permissive hypeycapnia SO CRITICAL CARE MEDICINE LA English DT Article DE airway suctioning; closed suctioning; open suctioning; lung-protective ventilation; intensive care unit ventilators ID ACUTE LUNG INJURY; ENDOTRACHEAL; VENTILATION AB Objective: To determine whether hypercarbia occurs following the use of open suctioning in lung lavage injured sheep and whether the baseline Paco(2) and duration of suctioning affect gas exchange. Design. Prospective laboratory evaluation. Setting, Animal laboratory in a university hospital. Subjects: Seven female Dorset sheep. Interventions. Lung lavage was used to create acute respiratory distress syndrome (ARDS). Mechanical ventilation was provided to produce different baseline Paco(2) levels. Measurements and Main Results. Lung injury was developed by isotonic saline lavage until the Pao(2) decreased to 100-150 mm Hg on an FIO2 of 1.01 positive end-expiratory pressure (PEEP) 5 cm H2O, and tidal volume 10 mL/kg. Then tidal volume was decreased to 6 mL/kg. Open suctioning was performed on each animal. Each animal experienced four experimental conditions in random order (Paco(2) 40 and 80 mm Hg and duration of suctioning 10 and 30 secs). Before each of the four experimental conditions, animals underwent lung recruitment continuous positive airway pressure 40 cm H2O for 40 secs to normalize volume history followed by ventilation for 15 mins where FIO2 and PEEP were set based on the ARDSNet FIO2/PEEP. Mean arterial blood pressure, heart rate, pulmonary artery pressure, pulmonary artery occlusion pressure, cardiac output, and arterial blood gases were measured before, 1 min after, and then every 2 mins after open suctioning for 30 mins. Neither the duration of suctioning nor the baseline level of CO2 had an important influence on the magnitude of the desaturation and the recovery of Po-2 following suctioning (p < .05). Level of PEEP did influence the recovery of Pao(2) following suctioning. Conclusions: While neither baseline CO2 nor duration of suctioning affected the gas exchange alterations induced by endotracheal suction, high levels of PEEP can help to avoid the associated gas exchange abnormalities in ARDS. C1 [Malhotra, Atul] Harvard Univ, Sch Med, Dept Med Pulmonary & Crit Care & Sleep, Boston, MA 02115 USA. [Caramez, Maria Paula; Miyoshi, Eriko; Malhotra, Atul] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Harris, R. Scoft; Kacmarek, Robert M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. [Malhotra, Atul] Brigham & Womens Hosp, Boston, MA 02115 USA. [Malhotra, Atul] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Malhotra, A (reprint author), Harvard Univ, Sch Med, Dept Med Pulmonary & Crit Care & Sleep, Boston, MA 02115 USA. EM amalhotra1@partners.org FU NHLBI NIH HHS [K24 HL093218, P50 HL 060292, R01 HL 73146, R01 HL073146, P50 HL060292]; NIA NIH HHS [K23 AG024837-04, K23 AG024837, AG 024837] NR 8 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD FEB PY 2008 VL 36 IS 2 BP 560 EP 564 DI 10.1097/01.CCM.0B013E3181620977 PG 5 WC Critical Care Medicine SC General & Internal Medicine GA 257JB UT WOS:000252794000026 PM 18091534 ER PT J AU Wright, CD AF Wright, Cameron D. TI Management of thymomas SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY LA English DT Review DE thymoma; surgery; chemotherapy; radiation therapy ID ADJUVANT RADIATION-THERAPY; STAGE-II THYMOMA; MALIGNANT THYMOMA; INVASIVE THYMOMA; MYASTHENIA-GRAVIS; THYMIC TUMORS; MULTIDISCIPLINARY APPROACH; SURGICAL RESECTION; INTERGROUP TRIAL; TITIN ANTIBODIES AB Thymoma is a rare neoplasm usually with an indolent growth pattern, however, local invasion and/or metastases may occur. The association with several paraneoplastic syndromes, especially myasthenia gravis, is noteworthy. Surgery has been the standard of care for early stage disease with high cure rates anticipated. The most important prognostic factors after resection are Masaoka stage, World Health Organization (WHO) histology, complete resection status and size. Multimodality therapy can result in long-term disease-free survival for patients presenting with locally advanced disease. Thymomas are sensitive to both chemotherapy and radiation therapy and are utilized with good effects in unresectable patients. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Div Thorac Surg, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wright, CD (reprint author), Harvard Univ, Sch Med, Div Thorac Surg, Massachusetts Gen Hosp, Blake 1570, Boston, MA 02114 USA. EM wright.cameron@mgh.harvard.edu NR 63 TC 42 Z9 49 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1040-8428 J9 CRIT REV ONCOL HEMAT JI Crit. Rev. Oncol./Hematol. PD FEB PY 2008 VL 65 IS 2 BP 109 EP 120 DI 10.1016/j.critrevonc.2007.04.005 PG 12 WC Oncology; Hematology SC Oncology; Hematology GA 266BU UT WOS:000253407100002 PM 17570676 ER PT J AU Slemmer, JE Shacka, JJ Sweeney, MI Weber, JT AF Slemmer, J. E. Shacka, J. J. Sweeney, M. I. Weber, J. T. TI Antioxidants and free radical scavengers for the treatment of stroke, traumatic brain injury and aging SO CURRENT MEDICINAL CHEMISTRY LA English DT Review DE anthocyanins; natural products; NXY-059; oxidative stress; oxyresveratrol; reactive nitrogen species; reactive oxygen species; superoxide ID ACUTE ISCHEMIC-STROKE; FOCAL CEREBRAL-ISCHEMIA; LONG-TERM POTENTIATION; NEURONAL SIGNAL-TRANSDUCTION; TISSUE-PLASMINOGEN ACTIVATOR; STABLE NITROXIDE TEMPOL; AGE-RELATED DECREASE; SEVERE HEAD-INJURY; OXIDATIVE STRESS; VITAMIN-E AB The overproduction of reactive oxygen species (ROS) and reactive nitrogen species (RNS) is a common underlying mechanism of many neuropathologies, as they have been shown to damage various cellular components, including proteins, lipids and DNA. Free radicals, especially superoxide (O(2)(center dot-)), and non-radicals, such as hydrogen peroxide (H(2)O(2)), can be generated in quantities large enough to overwhelm endogenous protective enzyme systems, such as superoxide dismutase (SOD) and reduced glutathione (GSH). Here we review the mechanisms of ROS and RNS production, and their roles in ischemia, traumatic brain injury and aging. In particular, we discuss several acute and chronic pharmacological therapies that have been extensively studied in order to reduce ROS/RNS loads in cells and the subsequent oxidative stress, so-called "free-radical scavengers." Although the overall aim has been to counteract the detrimental effects of ROS/RNS in these pathologies, success has been limited, especially in human clinical studies. This review highlights some of the recent successes and failures in animal and human studies by attempting to link a compound's chemical structure with its efficacy as a free radical scavenger. In particular, we demonstrate how antioxidants derived from natural products, as well as long-term dietary alterations, may prove to be effective scavengers of ROS and RNS. C1 [Weber, J. T.] Mem Univ Newfoundland, Sch Pharm, Hlth Sci Ctr, St John, NF A1B 3V6, Canada. [Slemmer, J. E.; Sweeney, M. I.] Univ Prince Edward Isl, Dept Biol, Charlottetown, PE C1A 4P3, Canada. [Shacka, J. J.] Univ Alabama, Dept Pathol, Div Neuropathol, Birmingham, AL 35294 USA. [Shacka, J. J.] Birmingham VA Med Ctr, Dept Vet Affairs, Birmingham, AL USA. [Weber, J. T.] Mem Univ Newfoundland, Fac Med, Div Basic Med Sci, St John, NF A1B 3V6, Canada. RP Weber, JT (reprint author), Mem Univ Newfoundland, Sch Pharm, Hlth Sci Ctr, 300 Prince Philip Dr, St John, NF A1B 3V6, Canada. EM jweber@mun.ca NR 224 TC 196 Z9 214 U1 1 U2 38 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8673 J9 CURR MED CHEM JI Curr. Med. Chem. PD FEB PY 2008 VL 15 IS 4 BP 404 EP 414 PG 11 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 274GR UT WOS:000253990300009 PM 18288995 ER PT J AU Hessa, DR Bigatello, LM AF Hessa, Dean R. Bigatello, Luca M. TI The chest wall in acute lung injury/acute respiratory distress syndrome SO CURRENT OPINION IN CRITICAL CARE LA English DT Review DE abdominal compartment syndrome; acute lung injury; chest wall compliance; lung compliance; positive-pressure ventilation; respiratory system compliance ID END-EXPIRATORY PRESSURE; MORBIDLY OBESE-PATIENTS; CRITICALLY-ILL PATIENTS; MECHANICAL VENTILATION; INTRAABDOMINAL HYPERTENSION; TRANSPULMONARY PRESSURES; GAS-EXCHANGE; VOLUME CURVE; ESOPHAGEAL; SYSTEM AB Purpose of review There has recently been renewed interest in the chest wall during mechanical ventilation, related to lung-protective ventilation strategies, as well as in the role of abdominal pressure in many facets of critical illness. The purpose of this review is to address relevant issues related to the chest wall and mechanical ventilation, particularly in patients with acute lung injury/acute respiratory distress syndrome. Recent findings In mechanically ventilated patients with acute lung injury, intra-abdominal pressure is an important determinant of chest wall compliance. With elevated intra-abdominal pressure, the compliance of the chest wall and total respiratory system is decreased, with a relatively normal compliance of the lungs. The lung compression effects of increased intra-abdominal pressure may lead to a loss of lung volume with atelectasis. An appropriate level of positive end-expiratory pressure is necessary to counterbalance this collapsing effect on the lungs. Also, the stiff chest wall results in a lower transpulmonary pressure during positive-pressure ventilation. Summary As chest wall compliance may have important clinical implications during positive-pressure ventilation, the physiology of this effect should be considered, particularly in patients with acute lung injury and increased abdominal pressure. C1 [Hessa, Dean R.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Bigatello, Luca M.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Surg Intens Care Unit, Boston, MA 02114 USA. RP Bigatello, LM (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Surg Intens Care Unit, 55 Fruit St, Boston, MA 02114 USA. EM lbigatello@partners.org NR 37 TC 21 Z9 22 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-5295 J9 CURR OPIN CRIT CARE JI Curr. Opin. Crit. Care PD FEB PY 2008 VL 14 IS 1 BP 94 EP 102 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA 256MI UT WOS:000252732700016 PM 18195633 ER PT J AU Stanley, T Misra, M AF Stanley, Takara Misra, Madhusmita TI Polycystic ovary syndrome in obese adolescents SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY LA English DT Article DE adolescent; hyperandrogenism; hyperinsulinemia; obesity; oligomenorrhea; polycystic ovary syndrome ID BODY-FAT DISTRIBUTION; GROWTH-FACTOR-I; INSULIN-RESISTANCE; PRECOCIOUS PUBARCHE; OVERWEIGHT WOMEN; ANDROGEN EXCESS; YOUNG-WOMEN; ETHINYLESTRADIOL-DROSPIRENONE; FLUTAMIDE-METFORMIN; METABOLIC SYNDROME AB Purpose of review As the prevalence of pediatric obesity escalates, polycystic ovary syndrome is an increasingly common morbidity for adolescent females. This review describes recent insights into the pathophysiology and treatment of polycystic ovary syndrome, with special attention given to the relationship between polycystic ovary syndrome and obesity. Recent findings Recent research has elucidated three key concepts in our understanding of polycystic ovary syndrome. First, patients may enter the hyperandrogenism-hyperinsulinism cycle of polycystic ovary syndrome via several pathways, including genetic polymorphisms that affect androgen synthesis, fetal programming that alters lipid and glucose metabolism, and obesity accompanied by insulin resistance. Second, obesity plays a significant role in the pathophysiology of polycystic ovary syndrome by increasing free androgen concentrations through multiple mechanisms. Finally, just as the etiology of polycystic ovary syndrome is multifactorial, successful treatment will probably require a combination of lifestyle modification and therapeutic interventions. Summary Obesity contributes to the pathophysiology of polycystic ovary syndrome and increases the likelihood of associated metabolic and cardiovascular morbidities. C1 [Stanley, Takara; Misra, Madhusmita] MassGen Hosp Children, Boston, MA 02114 USA. [Stanley, Takara; Misra, Madhusmita] Harvard Univ, Sch Med, Boston, MA USA. [Misra, Madhusmita] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. RP Stanley, T (reprint author), MassGen Hosp Children, 55 Fruit St, Boston, MA 02114 USA. EM tstanley@partners.org NR 58 TC 9 Z9 10 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1752-296X EI 1752-2978 J9 CURR OPIN ENDOCRINOL JI Curr. Opin. Endocrinol. Diabetes Obes. PD FEB PY 2008 VL 15 IS 1 BP 30 EP 36 DI 10.1097/MED.0b013e3282f41d55 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V14SR UT WOS:000207754600004 PM 18185060 ER PT J AU Green, GM Reeve, JR AF Green, Gary M. Reeve, Joseph R., Jr. TI Unique activities of cholecystokinin-58; physiological and pathological relevance SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY LA English DT Article DE acute pancreatitis; cholecystokinin; exocrine pancreatic secretion; gastrointestinal hormones AB Purpose of review Cholecystokinin, a regulatory peptide found in multiple molecular forms in brain and small intestine, is responsible for integration of functions associated with the intake, digestion and absorption of food. Whether the different molecular forms have identical biological activities is controversial. New information suggests that CCK58, the largest form of cholecystokinin detected in blood and tissue, has unique functions compared with other forms, and may be the predominant, perhaps only, circulating form in mammals. Recent findings CCK58 has highly distinctive actions compared with shorter forms, most notably the strong stimulation of water secretion from the pancreas, and the lack of induction of pancreatitis by supramaximal doses of the peptide. Because CCK58 may be the main endogenous form of cholecystokinin, these recent findings have far reaching implications because almost all studies carried out with cholecystokinin have been done with shorter forms, predominately CCK8. Conclusions of studies using CCK8 or other shorter forms of cholecystokinin, therefore, may need to be reevaluated. Summary There is a compelling reason to reevaluate the role of cholecystokinin in health and disease because the predominant form of cholecystokinin, CCK58, has unique biological activities compared with forms of cholecystokinin used in previous basic and clinical studies. C1 [Green, Gary M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Reeve, Joseph R., Jr.] Univ Calif Los Angeles, David Geffen Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst &, CURE Digest Dis Res Ctr, Los Angeles, CA 90095 USA. RP Green, GM (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM greeng@uthscsa.edu NR 37 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1752-296X J9 CURR OPIN ENDOCRINOL JI Curr. Opin. Endocrinol. Diabetes Obes. PD FEB PY 2008 VL 15 IS 1 BP 48 EP 53 DI 10.1097/MED.0b013e3282f3d92b PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V14SR UT WOS:000207754600006 PM 18185062 ER PT J AU Hu, M Polyak, K AF Hu, Min Polyak, Kornelia TI Microenvironmental regulation of cancer development SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Review ID MYOEPITHELIAL CELL-LAYERS; GENE-EXPRESSION PROFILES; BREAST-TUMOR PROGRESSION; PRE-METASTATIC NICHE; CARCINOMA IN-SITU; STROMAL CELLS; MALIGNANT PHENOTYPE; MAMMARY-CARCINOMA; EPITHELIAL-CELLS; FIBROBLASTS AB Numerous studies have demonstrated that the tumor microenvironment not only responds to and supports carcinogenesis, but also actively contributes to tumor initiation, progression, and metastasis. During tumor progression all cells composing the tumor undergo phenotypic and epigenetic changes. Paracrine signaling between epithelial and stromal cells is important for the regulation of the proliferation, invasive, angiogenic, and metastatic behavior of cancer cells. Better understanding the molecular mechanisms by which stromal cells exert these effects may open up new venues for cancer therapeutic and preventative interventions. C1 [Hu, Min; Polyak, Kornelia] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Hu, Min; Polyak, Kornelia] Harvard Univ, Dept Med, Sch Med, Boston, MA 02115 USA. [Hu, Min; Polyak, Kornelia] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Polyak, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM kornelia-polyak@dfci.harvard.edu FU NCI NIH HHS [CA89393, CA116235, CA94074, P50 CA089393, P50 CA089393-010004, P50 CA089393-020004, P50 CA089393-030004, P50 CA089393-040004, P50 CA089393-050004, P50 CA089393-060014, P50 CA089393-070014, P50 CA089393-080014, R01 CA094074, R01 CA116235, R01 CA116235-01A1, R01 CA116235-02, R01 CA116235-03] NR 72 TC 184 Z9 189 U1 2 U2 21 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD FEB PY 2008 VL 18 IS 1 BP 27 EP 34 DI 10.1016/j.gde.2007.12.006 PG 8 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 316MO UT WOS:000256954100005 PM 18282701 ER PT J AU Engelman, JA Settleman, J AF Engelman, Jeffrey A. Settleman, Jeffrey TI Acquired resistance to tyrosine kinase inhibitors during cancer therapy SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Review ID GROWTH-FACTOR-RECEPTOR; CHRONIC MYELOID-LEUKEMIA; CELL LUNG-CANCER; GASTROINTESTINAL STROMAL TUMORS; BCR-ABL; DRUG-RESISTANCE; GENE MUTATION; IMATINIB RESISTANCE; DOMAIN MUTATIONS; EGFR MUTATIONS AB Selective tyrosine kinase inhibitors have emerged as important therapeutic agents in the treatment of a variety of human malignancies. Although several of these inhibitors have marked clinical activity, it is widely recognized that the overall value of these agents is substantially limited by the acquisition of drug resistance, which eventually arises in most, if not all treated patients. Mechanisms of drug resistance are beginning to be elucidated through the molecular analysis of clinical specimens as well as through cell culture modeling. By identifying resistance mechanisms, it should be possible to develop 'second-generation' inhibitors as well as rational drug combinations that can overcome or even prevent acquired resistance to kinase inhibitors, thereby enhancing clinical benefit. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Settleman, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, 149 13th St, Charlestown, MA 02129 USA. EM Settleman@helix.mgh.harvard.edu NR 59 TC 182 Z9 187 U1 2 U2 15 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD FEB PY 2008 VL 18 IS 1 BP 73 EP 79 DI 10.1016/j.gde.2008.01.004 PG 7 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 316MO UT WOS:000256954100012 PM 18325754 ER PT J AU Park, S Schwamm, LH AF Park, Soojin Schwamm, Lee H. TI Organizing regional stroke systems of care SO CURRENT OPINION IN NEUROLOGY LA English DT Review DE health policy; healthcare delivery; stroke ID AMERICAN-HEART-ASSOCIATION; ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN ACTIVATOR; EMERGENCY-DEPARTMENT EVALUATION; TELEMEDIC PILOT PROJECT; ARM SPEECH TEST; CARDIOVASCULAR-DISEASE; COMMUNITY INTERVENTION; TELESTROKE NETWORK; REDUCED MORTALITY AB Purpose of review Stroke is a major public health problem in the US and other developed countries. Stroke units reduce morbidity and mortality, and the efficacy of thrombolytic therapy propelled the development and maturation of a stroke systems of care delivery model. This model addresses the key domains in the chain of stroke survival and recovery, including primordial and primary prevention; community education; notification and response of emergency medical services; acute stroke treatment; subacute stroke treatment and secondary prevention; rehabilitation; and continuous quality improvement activities within each domain and across the system itself. Recent findings To improve care delivery to all, systems must be implemented that link these domains together, and successful examples of these activities are reviewed in detail. Summary Harmonization of efforts by the major healthcare organizations to collect data on hospital-based stroke care and improve care will lead to broader implementation of these programs and better patient outcomes. Health policy changes are needed at the state, regional and federal level to increase funding for stroke education and provider reimbursement, improve provider capabilities and address shortages of acute stroke expertise nationwide. Telemedicine and air medical transport play a key role in creating networks of stroke care that link together hospitals of different capabilities. C1 [Park, Soojin; Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Park, S (reprint author), Massachusetts Gen Hosp, Dept Neurol, ACC 720,55 Fruit St, Boston, MA 02114 USA. EM lschwamm@partners.org OI Schwamm, Lee/0000-0003-0592-9145 NR 121 TC 20 Z9 20 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD FEB PY 2008 VL 21 IS 1 BP 43 EP 55 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 255BB UT WOS:000252630600008 PM 18180651 ER PT J AU Gagnon, A Ye, B AF Gagnon, Audrey Ye, Bin TI Discovery and application of protein biomarkers for ovarian cancer SO CURRENT OPINION IN OBSTETRICS & GYNECOLOGY LA English DT Article DE biomarkers; early detection; ovarian cancer; panel; prognosis and validation ID PROGNOSTIC MARKER; ENDOMETRIAL CARCINOMA; GROWTH-FACTOR; TUMOR-MARKER; EXPRESSION; SERUM; SURVIVAL; VALIDATION; MESOTHELIN; ARRAYS AB Purpose of review To review the protein biomarker research field in ovarian cancer, including the discovered new biomarkers, biomarker panels, their potential clinical applications, and suggested strategies for biomarker discovery and development. Recent findings Ovarian cancer is the fifth leading cause of death from cancer among North American women. Unfortunately, there is currently no reliable circulating biomarker that can detect ovarian cancer in its early stages. The CA125 biomarker is extremely valuable for treatment response monitoring, but its sensitivity is very low for early detection. There is an urgent need to identify new circulating biomarkers/panels of biomarkers that could diagnose ovarian cancer before it becomes clinically detectable and advanced. In the past decade, efforts have accelerated to identify such novel biomarkers/panels of serum and urine biomarkers. A couple of individual biomarkers and biomarker panels have been reported with adaptable sensitivity and specificity range, which might hold great potential to be further validated and developed for diagnosis and prognosis applications and to control ovarian cancer mortality. Summary The present review summarizes the main advances in the past year, with the lists of biomarkers/panels, their potential applications, and new strategies/lessons we learned based on the most important work published during this period. C1 [Ye, Bin] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Obstet & Gynecol, Boston, MA 02115 USA. [Gagnon, Audrey] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol,Lab Gynecol Onc, Boston, MA 02115 USA. RP Ye, B (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Obstet & Gynecol, Boston, MA 02115 USA. EM bye@partners.org FU NCI NIH HHS [R21 CA111949-01, 1U01CA86381, P50-CA105009-02] NR 42 TC 26 Z9 29 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-872X J9 CURR OPIN OBSTET GYN JI Curr. Opin. Obstet. Gynecol. PD FEB PY 2008 VL 20 IS 1 BP 9 EP 13 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 257ZX UT WOS:000252839300003 PM 18196999 ER PT J AU Rosell, A Lo, EH AF Rosell, Anna Lo, Eng H. TI Multiphasic roles for matrix metalloproteinases after stroke SO CURRENT OPINION IN PHARMACOLOGY LA English DT Review ID FOCAL CEREBRAL-ISCHEMIA; BLOOD-BRAIN-BARRIER; SPONTANEOUS INTRACEREBRAL HEMORRHAGE; TISSUE-PLASMINOGEN ACTIVATOR; NEUTROPHIL INFILTRATION; ENDOTHELIAL-CELLS; TEMPORAL PROFILE; MATRIX-METALLOPROTEINASE-9; EXPRESSION; MMP-9 AB Matrix metalloproteinases (MMPs) comprise a family of zinc endopeptidases that play major roles in the physiology and pathology of the mammalian central nervous system (CNS). These proteinases are evolutionarily conserved as modulators of extracellular matrix during CNS development. After acute tissue injury such as that which occurs after stroke, MMPs become dysregulated and subsequently mediate acute neurovascular disruption and parenchymal destruction. Data from gene knockout models and pharmacologic experiments suggest that MMPs may be attractive therapeutic targets for stroke. However, emerging data now also suggest that some aspects of MMP activity during the delayed neuroinflammatory response may contribute to remodelling and stroke recovery. Ultimately, a more nuanced approach to modifying the MMP response after stroke may be needed in order to optimize inhibition during acute stages of injury without interfering with beneficial endogenous mechanisms of neurovascular remodelling. C1 [Rosell, Anna] Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Charlestown, MA 02129 USA. [Lo, Eng H.] Harvard Med Sch, Program Neurosci, Charlestown, MA 02129 USA. RP Rosell, A (reprint author), Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, MGH E 149-2401, Charlestown, MA 02129 USA. EM anna.rosell@gmail.com; Lo@helix.mgh.harvard.edu NR 63 TC 119 Z9 128 U1 1 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4892 J9 CURR OPIN PHARMACOL JI Curr. Opin. Pharmacol. PD FEB PY 2008 VL 8 IS 1 BP 82 EP 89 DI 10.1016/j.coph.2007.12.001 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 266BX UT WOS:000253407400013 PM 18226583 ER PT J AU Marra, DE Fincher, EF Iwasaki, J Moy, RL AF Marra, Diego E. Fincher, Edgar F. Iwasaki, Julie Moy, Ronald L. TI Repair of a large, exposed-cartilage nasal tip defect using nasalis-based subcutaneous pedicle flaps and full-thickness skin grafting SO DERMATOLOGIC SURGERY LA English DT Editorial Material ID RECONSTRUCTION; NOSE C1 [Moy, Ronald L.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Moy, RL (reprint author), 100 UCLA Med Plaza,Suite 590, Los Angeles, CA 90024 USA. EM rmoy@ucla.edu NR 7 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD FEB PY 2008 VL 34 IS 2 BP 249 EP 253 DI 10.1111/j.1524-4725.2007.34046.x PG 5 WC Dermatology; Surgery SC Dermatology; Surgery GA 254LC UT WOS:000252587100018 PM 18093192 ER PT J AU Holzmann, RD Olbricht, SM Thomas, VD Schanbacher, CF AF Holzmann, Ruth Dorothee Olbricht, Suzanne Marie Thomas, Valencia Dorchelle Schanbacher, Carl Frank TI Hemorrhagic foreign body granuloma after cutaneous surgery occurring in the setting of aspirin therapy or thrombocytopenia: A presentation of six cases SO DERMATOLOGIC SURGERY LA English DT Editorial Material ID FIBROBLAST GROWTH-FACTOR; WARFARIN THERAPY; SUTURE MATERIALS; TISSUE REACTION; ANGIOGENESIS; INFLAMMATION; MANAGEMENT; COLLAGEN; MODEL; FLAPS C1 [Holzmann, Ruth Dorothee; Schanbacher, Carl Frank] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Dermatol,Med Sch, Boston, MA 02115 USA. [Holzmann, Ruth Dorothee] Charite Univ Med Berlin, Dept Dermatol, Berlin, Germany. [Olbricht, Suzanne Marie] Harvard Univ, Dept Dermatol, Sch Med, Lahey Clin, Burlington, MA USA. [Thomas, Valencia Dorchelle] Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06510 USA. RP Schanbacher, CF (reprint author), Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Dermatol,Med Sch, 44 Binney St, Boston, MA 02115 USA. EM carl_schanbacher@dfci.harvard.edu NR 34 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD FEB PY 2008 VL 34 IS 2 BP 264 EP 270 DI 10.1111/j.1524-4725.2007.34050.x PG 7 WC Dermatology; Surgery SC Dermatology; Surgery GA 254LC UT WOS:000252587100022 PM 18093188 ER PT J AU Lauritzen, HPMM Galbo, H Brandauer, J Goodyear, LJ Ploug, T AF Lauritzen, Hans P. M. M. Galbo, Henrik Brandauer, Josef Goodyear, Laurie J. Ploug, Thorkil TI Large GLUT4 vesicles are stationary while locally and reversibly depleted during transient insulin stimulation of skeletal muscle of living mice - Imaging analysis of GLUT4-enhanced green fluorescent protein vesicle dynamics SO DIABETES LA English DT Article ID GLUCOSE-TRANSPORT; TRANSVERSE TUBULES; T-TUBULES; IN-VIVO; TRANSLOCATION; CELLS; MEMBRANE; MICROTUBULES; CYTOSKELETON; TRAFFICKING AB OBJECTIVE-Insulin stimulates glucose transport in skeletal muscle by GLUT4 translocation from intracellular compartments to sarcolemma and t-tubules. We studied in living animals the recruitment of GLUT4 vesicles in more detail than previously done and, for the first time, analyzed the steady-state recycling and subsequent re-internalization of GLUT4 on an insulin bolus. RESEARCH DESIGN AND METHODS-A confocal imaging technique was used in GLUT4-enhanced green fluorescent protein-transfected superficial muscle fibers in living mice. RESULTS-During the first 30 min of insulin stimulation, very few superficially or deeply located GLUT4 storage vesicles (> 1 mu m) moved in toto. Rather, big vesicles were stationary in their original position at. sarcolemma or t-tubules and were locally depleted of GLUT4 by budding off of smaller vesicles. Photo-bleaching experiments revealed that during initial translocation and steady-state recycling, GLUT4 inicrovesicles (< 1 mu m) move from perinuclear GLUT4 depots out along the plasma membrane. Furthermore, after photobleaching of t-tubule areas, recovery of GLUT4 was slow or absent, indicating no recycling of GLUT4 from perinuclear or adjacent (1 mu m) or more distant (20 mu m) t-tubule areas. During waning of insulin effect, GLUT4 was re-internalized to basal stores with a delay in t-tubules compared with sarcolemma, probably reflecting delayed disappearance of insulin from t-tubules. CONCLUSIONS-In skeletal muscle, insulin reversibly stimulates local depletion of GLUT4 storage vesicles at sarcolemma and t-tubules rather than inducing movement of intact storage vesicles. During steady-state stimulation, recycling of GLUT4-containing microvesicles over longer distances (10-20 mu m) takes place between perinuclear depots and sarcolemma but not at t-tubules. C1 [Lauritzen, Hans P. M. M.; Brandauer, Josef; Goodyear, Laurie J.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Lauritzen, Hans P. M. M.; Brandauer, Josef; Goodyear, Laurie J.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Galbo, Henrik] Bispebjerg Hosp, Dept Rheumatol, DK-2400 Copenhagen, Denmark. [Ploug, Thorkil] Univ Copenhagen, Panum Inst, Dept Med Physiol, Copenhagen Muscle Res Ctr, DK-2200 Copenhagen N, Denmark. RP Lauritzen, HPMM (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM hans.latiritzen@joslin.harvard.edu FU NIAMS NIH HHS [AR45670]; NIDDK NIH HHS [T32DK07260] NR 32 TC 39 Z9 40 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD FEB PY 2008 VL 57 IS 2 BP 315 EP 324 DI 10.2337/db06-1578 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 259BP UT WOS:000252914400005 PM 17977960 ER PT J AU Brezniceanu, ML Liu, F Wei, CC Chenier, I Godin, N Zhang, SL Filep, JG Ingelfinger, JR Chan, JSD AF Brezniceanu, Marie-Luise Liu, Fang Wei, Chih-Chang Chenier, Isabelle Godin, Nicolas Zhang, Shao-Ling Filep, Janos G. Ingelfinger, Julie R. Chan, John S. D. TI Attenuation of interstitial fibrosis and tubular apoptosis in db/db transgenic mice overexpressing catalase in renal proximal tubular cells SO DIABETES LA English DT Article ID GLOMERULOTUBULAR JUNCTION ABNORMALITIES; ANGIOTENSINOGEN GENE-EXPRESSION; INDUCED OXIDATIVE STRESS; DIABETIC KIDNEY-DISEASE; HIGH GLUCOSE; RAT-KIDNEY; ATUBULAR GLOMERULI; II STIMULATION; NEPHROPATHY; BETA AB OBJECTIVE-The present study investigated the relationships between reactive oxygen species (ROS), interstitial fibrosis, and renal proximal tubular cell (RPTC) apoptosis in type 2 diabetic db/db mice and in db/db transgenic (Tg) mice overexpressing rat catalase (rCAT) in their RPTCs (db/db rCAT-Tg). RESEARCH DESIGN AND METHODS-Blood pressure, blood glucose, and albuminuria were monitored for up to 5 months. Kidneys were processed for histology mid apoptosis studies (terminal transferase-mediated dUTP nick-end labeling or immunostaining for active caspase-3 and Bax). Real-time quantitative PCR assays were used to quantify angiotensinogen (ANG), p53, and Bax mRNA levels. RESULTS-db/db mice developed obesity, hyperglycemia, hypertension, and albuminuria. In contrast, db/db rCAT-Tg mice became obese and hyperglycemic but had normal blood pressure and attenuated albuminuria compared with db/db mice. Kidneys from db/db mice displayed progressive glomerular hypertrophy, glomerulosclerosis, interstitial fibrosis, and tubular apoptosis and increased expression of collagen type TV, Bax, and active caspase-3, as well as increased ROS production. These changes, except glomerular hypertrophy, were markedly attenuated in kidneys of db/db rCAT-Tg mice. Furthermore, ANG, p53, and Bax mRNA expression was increased in renal proximal tubules of db/db mice but not of db/db rCAT-Tg mice. CONCLUSIONS-Our results indicate a crucial role for intrarenal ROS in the progression of hypertension, albuminuria, interstitial fibrosis, and tubular apoptosis in type 2 diabetes and demonstrate the beneficial effects of suppressing ROS formation. C1 [Brezniceanu, Marie-Luise; Liu, Fang; Wei, Chih-Chang; Chenier, Isabelle; Godin, Nicolas; Zhang, Shao-Ling; Chan, John S. D.] Univ Montreal, CHUM, Hotel Dieu, Res Ctr, Montreal, PQ H2W 1T8, Canada. [Filep, Janos G.] Univ Montreal, Maisonneuve Rosemont Hosp, Res Ctr, Montreal, PQ H2W 1T8, Canada. [Ingelfinger, Julie R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Nephrol Lab, Boston, MA USA. RP Chan, JSD (reprint author), Univ Montreal, CHUM, Hotel Dieu, Res Ctr, Pavillon Masson,3850 St Urbain St, Montreal, PQ H2W 1T8, Canada. EM john.chan@umontreal.ca FU NHLBI NIH HHS [HL-48455] NR 49 TC 88 Z9 94 U1 1 U2 12 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD FEB PY 2008 VL 57 IS 2 BP 451 EP 459 DI 10.2337/db07-0013 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 259BP UT WOS:000252914400022 PM 17977949 ER PT J AU Cordovado, SK Zhao, Y Warram, JH Gong, HG Anderson, KL Hendrix, MM Hancock, LN Cleary, PA Mueller, PW AF Cordovado, Suzanne K. Zhao, Yuan Warram, James H. Gong, Hongguang Anderson, Karen L. Hendrix, Miyono M. Hancock, Laura N. Cleary, Patricia A. Mueller, Patricia W. TI Nephropathy in type 1 diabetea is dimnished in carriers of HLA-DRB1*04 - The genetics of kidneys in diabetes (GoKinD) study SO DIABETES LA English DT Article ID TUMOR-NECROSIS-FACTOR; RENAL-FAILURE; SUSCEPTIBILITY; PENTOXIFYLLINE; PATHOGENESIS; RETINOPATHY; INCREASE; HLA-DQA1; DISEASE; URINARY AB OBJECTWE-The purpose of this study was to examine whether known genetic risk factors for type 1 diabetes (HLA-DRB1, -DQA1, and -DQB1 and insulin locus) play a role in the etiology of diabetic nephropathy. RESEARCH DESIGN AND METHODS-Genetic analysis of HLA-DRB1, -DQA1 -DQB1 and the insulin gene (INS) was performed in the Genetics of Kidneys in Diabetes (GoKinD) collection of DNA (European ancestry subset), which includes case patients with type 1 diabetes and nephropathy (n = 829) and control patients With type 1 diabetes but not nephropathy (n = 904). The availability of phenotypic and genotypic data on GoKinD participants allowed a detailed analysis of the association of these genes with diabetic nephropathy. RESULTS-Diabetic probands who were homozygous for HLA-DRB1*04 were 50% less likely to have nephropathy than probands without any DRB1*04 alleles. In heterozygous carriers, a protective effect of this allele was not as clearly evident; the mode of inheritance therefore remains unclear. This association was seen in probands with both short (<28 years, P = 0.02) and long (>= 28 years, P = 0.0001) duration of diabetes. A1C, a marker of sustained hyperglycemia, was increased in control probands With normoalbuminuira, despite long-duration diabetes, from 7.2 to 7.3 to 7.7% with 0, 1, and 2 copies of the DRB1*04 allele, respectively. This result is consistent with a protective effect of DRB1*04 that may allow individuals to tolerate higher levels of hyperglycemia, as measured by A1C, without developing nephropathy. CONCLUSIONS-These data suggest that carriers of DRB1*04 are protected from some of the injurious hyperglycemic effects related to nephropathy. Interestingly, DRB1*04 appears to be both a risk allele for type 1 diabetes and a protective allele for nephropathy. C1 [Cordovado, Suzanne K.; Hendrix, Miyono M.; Hancock, Laura N.; Mueller, Patricia W.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Div Sci Lab, Atlanta, GA 30341 USA. [Zhao, Yuan; Anderson, Karen L.; Cleary, Patricia A.] George Washington Univ, Ctr Biostat, Rockville, MD USA. [Warram, James H.] Joslin Diabet Ctr, Dept Genet & Epidemiol, Boston, MA 02215 USA. RP Cordovado, SK (reprint author), Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Div Sci Lab, 4770,Buford Hwy,MS F-24, Atlanta, GA 30341 USA. EM snc4@cdc.gov FU NIDDK NIH HHS [PL105-33]; None [PL106-554, PL107-360]; PHS HHS [PL-107-360, PL105-33, PL106-554, PL107-360, PL-105-33, PL-106-554] NR 22 TC 11 Z9 11 U1 1 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD FEB PY 2008 VL 57 IS 2 BP 518 EP 522 DI 10.2337/db07-0826 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 259BP UT WOS:000252914400031 PM 18039812 ER PT J AU Weinzimer, SA Ternand, C Howard, C Chang, CT Becker, DJ Laffel, LMB AF Weinzimer, Stuart A. Ternand, Christine Howard, Campbell Chang, Cheng-Tao Becker, Dorothy J. Laffel, Lori M. B. CA Insulin Aspart Pediat Pump Study G TI A Randomized Trial Comparing Continuous Subcutaneous Insulin Infusion of Insulin Aspart Versus Insulin Lispro in Children and Adolescents With Type 1 Diabetes SO DIABETES CARE LA English DT Article ID MULTIPLE DAILY INJECTION; PUMP THERAPY; MELLITUS; HYPOGLYCEMIA; BENEFITS; SAFETY; RISK; CSII; CARE AB OBJECTIVE - The safety and efficacy of insulin aspart continuous subcutaneous insulin infusion (CSII) was compared with that of insulin lispro CSII in children and adolescents With type 1 diabetes. RESEARCH DESIGN AND METHODS - Children and adolescents aged 4-18 years with diagnosed type I diabetes I year previously and treated with insulin analog in a CSII >= 3 months were randomly assigned 2:1 to 16 weeks of insulin aspart CSII (n = 198) or insulin lispro CSII (n = 100) in this open-label, parallel-group, multicenter study. Standard diabetes safety and efficacy parameters were assessed. RESULTS - Baseline demographics, subject characteristics, and diabetes history were similar between treatment groups. After 16 weeks of treatment, insulin aspan CSII was noninferior to insulin lispro CSII as measured by change in AlC from baseline (aspart, -0.15 +/- 0.05%; lispro, -0.05 +/- 0.07% [95% CI of the treatment difference -0.27 to 0.07]; P = 0.241). No significant differences between treatment groups were observed in fasting plasma glucose, hyperglycemia, and rates of hypoglycemic episodes. At week 16, 59.7% of subjects in the aspart group and 43.8% of subjects in the lispro groups achieved age-specific American Diabetes Association AlC goals (<8.5% for subjects aged <6 years; <8% for subjects aged 6-18 years) (P = 0.040, corrected for baseline). Daily insulin dose (units per kilogram) was significantly lower at week 16 for subjects treated with aspan compared with those treated with lispro (0.86 +/- 0.237 vs. 0.94 +/- 0.233, P = 0.018). CONCLUSIONS - insulin aspart was as safe and effective as insulin lispro for use in a CSII in children and adolescents with type I diabetes. C1 [Weinzimer, Stuart A.] Yale Univ, Sch Med, New Haven, CT 06520 USA. [Ternand, Christine] Univ Minnesota Phys, Minneapolis, MN USA. [Becker, Dorothy J.] Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. [Howard, Campbell; Chang, Cheng-Tao] Novo Nordisk AS, Princeton, NJ USA. [Laffel, Lori M. B.] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Weinzimer, SA (reprint author), Yale Univ, Sch Med, POB 208064,333 Cedar St, New Haven, CT 06520 USA. EM stuart.weinzimer@yale.edu FU Novo Nordisk (Princeton, NJ) FX This clinical trial was sponsored by Novo Nordisk (Princeton, NJ). NR 26 TC 30 Z9 37 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD FEB PY 2008 VL 31 IS 2 BP 210 EP 215 DI 10.2337/dc07-1378 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 452TE UT WOS:000266563300004 PM 17989308 ER PT J AU Fleischman, A Shoelson, SE Bernier, R Goldfine, AB AF Fleischman, Amy Shoelson, Steven E. Bernier, Raquel Goldfine, Allison B. TI Salsalate Improves Glycemia and Inflammatory Parameters in Obese Young Adults SO DIABETES CARE LA English DT Article ID INDUCED INSULIN-RESISTANCE; FACTOR-KAPPA-B; DIABETES-MELLITUS; IKK-BETA; SALICYLATE; ASPIRIN; GLUCOSE; PREVENTION; METFORMIN; RISK AB OBJECTIVE - Sedentary lifestyle and a western diet promote subacute-chronic inflammation, obesity, and subsequently dysglycemia. The aim of the current study was to evaluate the efficacy of the anti-inflammatory drug salsalate to improve glycemia by reducing systemic inflammation in obese adults at risk for the development of type 2 diabetes. RESEARCH DESIGN AND METHODS - in a double-masked, placebo controlled trial, we evaluated 20 obese nondiabetic adults at baseline and after 1 month of salsalate or placebo. RESULTS - Compared with placebo, salsalate reduced fasting glucose 13% (P < 0.002), glycemic response after an oral glucose challenge 20% (P < 0.004), and glycated albumin 1.7% (P < 0.0003). Although insulin levels were Unchanged, fasting and oral glucose tolerance test C-peptide levels decreased in the salsalate-treated subjects compared with placebo (P < 0.03), consistent with improved insulin sensitivity and a known effect Of Salicylates to inhibit insulin clearance. Adiponectin increased 57% after salsalate compared With placebo (P < 0.003). Additionally, within the group of salsalate-treated subjects, circulating levels of C-reactive protein were reduced by 34% (P < 0.05). CONCLUSIONS - This proof-of-principle study demonstrates that salsalate reduces glycemia and may improve inflammatory cardiovascular risk indexes in overweight individuals. These data support the hypothesis that subacute-chronic inflammation contributes to the pathogenesis of obesity-related dysglycemia and that targeting inflammation may provide a therapeutic route for diabetes prevention. C1 [Fleischman, Amy; Shoelson, Steven E.; Bernier, Raquel; Goldfine, Allison B.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Fleischman, Amy; Shoelson, Steven E.; Bernier, Raquel; Goldfine, Allison B.] Harvard Univ, Sch Med, Boston, MA USA. [Fleischman, Amy] Childrens Hosp Boston, Boston, MA USA. RP Goldfine, AB (reprint author), Joslin Diabet Ctr, 1 joslin Pl, Boston, MA 02215 USA. EM allison.goldfine@joslin.harvard.edu FU National institutes of Health [K23-DK02795, P50-HL083813, P30-DK36836]; General Clinical Research Center [M01-RR001032]; Lilly Fellowship Grant; Pfizer; Merck FX This work was supported by the National institutes of Health (Grants K23-DK02795 to A.B.G., P50-HL083813 to A.B.G. and S.E.S., P30-DK36836, and General Clinical Research Center Gram M01-RR001032), a Lilly Fellowship Grant, and Clinical Investigator Training Program, Harvard-MIT Division of Health Sciences and Technology-Beth Israel Deaconess Medical Center, with Support from Pfizer and Merck (A.F.). NR 40 TC 187 Z9 193 U1 2 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD FEB PY 2008 VL 31 IS 2 BP 289 EP 294 DI 10.2337/dc07-1338 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 452TE UT WOS:000266563300022 PM 17959861 ER PT J AU Wolpert, HA AF Wolpert, Howard A. TI The Nuts and Bolts of Achieving End Points With Real-Time Continuous Glucose Monitoring SO DIABETES CARE LA English DT Article; Proceedings Paper CT 1st Meeting on Controversies in Obesity, Diabetes and Hypertension CY OCT, 2006 CL Berlin, GERMANY ID INSULIN-INDUCED HYPOGLYCEMIA; THERAPY; BLOOD AB Real-Lime continuous glucose monitoring (RT-CGM) provides detailed information on glucose patterns and trends and promises to be a major advance in diabetes care. To derive full potential benefit from RT-CGM, the patient needs to be skilled in diabetes self-management. In addition, several key concepts and issues need to be addressed in training patients to use RT-CGM. These include 1) the implications of the physiologic lag between interstitial and capillary blood glucose levels and 2) the increased risk among RT-CGM users for hypoglycemia related to blind Postprandial bolusing. Patients need to understand the importance of calibrating during steady-state conditions to improve sensor accuracy. In addition, they need to use fingerstick measurements for treatment decision-making when the glucose level is changing rapidly, i.e., conditions when physiologic lag can lead to a marked discrepancy between blood and interstitial glucose. Consideration of "insulin on board" and the impact of the glycemic index of different foodstuffs on postprandial glucose patterns can help minimize the risk for hypoglycemia from supplemental boluses taken to correct postprandial hyperglycemia. To use continuous glucose data safely and effectively, patients need to be skilled in diabetes self-management, and the widespread adoption of RT-CGM into diabetes care will need to be coupled with comprehensive self-management education. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. RP Wolpert, HA (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM howard.wolpert@joslin.harvard.edu NR 9 TC 16 Z9 16 U1 1 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD FEB PY 2008 VL 31 BP S146 EP S149 DI 10.2337/dc08-s238 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 426IM UT WOS:000264701200008 PM 18227476 ER PT J AU Fonda, SJ Paulsen, CA Perkins, J Kedziora, RJ Rodbard, D Bursell, SE AF Fonda, Stephanie J. Paulsen, Christine A. Perkins, Joan Kedziora, Richard J. Rodbard, David Bursell, Sven-Erik TI Usability test of an Internet-based informatics tool for diabetes care providers: The comprehensive diabetes management program SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Telemedicine-Association CY MAY, 2006 CL San Diego, CA SP Amer Telemed Assoc ID IMPROVEMENT PROJECT; RETINOPATHY; DISEASE; SYSTEM; TRIAL AB Background: Research suggests Internet-based care management tools are associated with improvements in care and patient outcomes. However, although such tools change workflow, rarely is their usability addressed and reported. This article presents a usability study of an Internet-based informatics application called the Comprehensive Diabetes Management Program (CDMP), developed by content experts and technologists. Our aim is to demonstrate a process for conducting a usability study of such a tool and to report results. Methods: We conducted the usability test with six diabetes care providers under controlled conditions. Each provider worked with the CDMP in a single session using a "think aloud" process. Providers performed standardized tasks with fictitious patient data, and we observed how they approached these tasks, documenting verbalizations and subjective ratings. The providers then completed a usability questionnaire and interviews. Results: Overall, the scores on the usability questionnaire were neutral to favorable. For specific subdomains of the questionnaire, the providers' reported problems with the application's ease of use, performance, and support features, but were satisfied with its visual appeal and content. The results from the observational and interview data indicated areas for improvement, particularly in navigation and terminology. Conclusions: The usability study identified several issues for improvement, confirming the need for usability testing of Internet-based informatics applications, even those developed by experts. To our knowledge, there have been no other usability studies of an Internet-based informatics application with the functionality of the CDMP. Such studies can form the foundation for translation of Internet-based medical informatics tools into clinical practice. C1 [Fonda, Stephanie J.; Perkins, Joan; Bursell, Sven-Erik] Joslin Diabet Ctr, Boston, MA 02215 USA. [Fonda, Stephanie J.; Bursell, Sven-Erik] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Paulsen, Christine A.; Rodbard, David] Amer Inst Res, Concord, MA USA. [Paulsen, Christine A.; Rodbard, David] Amer Inst Res, Silver Spring, MD USA. [Kedziora, Richard J.] Estenda Solut Inc, Conshohocken, PA USA. RP Fonda, SJ (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM fondasj@gmail.com NR 23 TC 14 Z9 15 U1 0 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1520-9156 J9 DIABETES TECHNOL THE JI Diabetes Technol. Ther. PD FEB PY 2008 VL 10 IS 1 BP 16 EP 24 DI 10.1089/dia.2007.0252 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 252ZU UT WOS:000252487600003 PM 18275359 ER PT J AU Lorenzi, M Feke, GT Cagliero, E Pitler, L Schaumberg, DA Berisha, F Nathan, DM McMeel, JW AF Lorenzi, M. Feke, G. T. Cagliero, E. Pitler, L. Schaumberg, D. A. Berisha, F. Nathan, D. M. McMeel, J. W. TI Retinal haemodynamics in individuals with well-controlled type 1 diabetes SO DIABETOLOGIA LA English DT Article DE diabetic retinopathy; retinal blood flow; retinal circulation; type 1 diabetes ID BLOOD-FLOW; RETINOPATHY; PROGRESSION; MELLITUS AB Aims/hypothesis Abnormalities in retinal haemodynamics have been reported in patients with type 1 diabetes in advance of clinical retinopathy. These abnormalities could therefore be useful as early markers or surrogate endpoints for studying the microangiopathy. Since the DCCT, the increased focus on good glycaemic control is changing the natural history of diabetic retinopathy. Based on this, the aim of this study was to investigate whether patients with type 1 diabetes treated entirely or mostly in the post-DCCT era and tested in the absence of confounding factors show retinal haemodynamic abnormalities. Methods We measured retinal haemodynamics by laser Doppler flowmetry in 33 type 1 diabetic individuals with no or minimal retinopathy (age 30 +/- 7 years, duration of diabetes 8.8 +/- 4.6 years, 9% showing microaneurysms), and 31 age- and sex-matched non-diabetic controls. The study participants were not taking vasoactive medications, and blood glucose at the time of haemodynamic measurements was required to be between 3.8 and 11.1 mmol/l. Results HbA(1c) was 7.5 +/- 1.2% and blood glucose 7.7 +/- 2.8 mmol/l in these type 1 diabetic individuals, indicating relatively good glycaemic control. Retinal blood speed, arterial diameter and blood flow were not different between the diabetic individuals and the matched controls. Conclusions/interpretation Type 1 diabetic patients with no or minimal retinopathy who maintain relatively good glycaemic control do not show abnormalities of the retinal circulation at steady state, even after several years of diabetes. In such patients it may be necessary to test the vascular response to challenges to uncover any subtle abnormalities of the retinal vessels. C1 [Lorenzi, M.; Pitler, L.] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02115 USA. [Lorenzi, M.; Pitler, L.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. [Feke, G. T.; Berisha, F.; McMeel, J. W.] Harvard Univ, Sch Med, Schepens Retina Assoc Fdn, Boston, MA 02115 USA. [Cagliero, E.; Nathan, D. M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02115 USA. [Cagliero, E.; Nathan, D. M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02115 USA. [Schaumberg, D. A.] Harvard Univ, Sch Med, Div Prevent Med, Boston, MA 02115 USA. [Schaumberg, D. A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Lorenzi, M (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02115 USA. EM mara.lorenzi@schepens.harvard.edu FU NEI NIH HHS [EY014812, R01 EY014812] NR 10 TC 19 Z9 20 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD FEB PY 2008 VL 51 IS 2 BP 361 EP 364 DI 10.1007/s00125-007-0872-0 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 246GJ UT WOS:000251995200019 PM 18026927 ER PT J AU Meyerhardt, JA Zhu, AX Stuart, K Ryan, DP Blaszkowsky, L Lehman, N Earle, CC Kulke, MH Bhargava, P Fuchs, CS AF Meyerhardt, Jeffrey A. Zhu, Andrew X. Stuart, Keith Ryan, David P. Blaszkowsky, Lawrence Lehman, Nicole Earle, Craig C. Kulke, Matthew H. Bhargava, Pankaj Fuchs, Charles S. TI Phase-II study of gemcitabine and cisplatin in patients with metastatic biliary and gallbladder cancer SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE gall bladder cancer; cholangiocarcinoma; biliary cancer; chemotherapy; gemcitabine; cisplatin ID SINGLE-AGENT GEMCITABINE; TRACT CANCER; IN-VITRO; TRIAL; CARCINOMA; CHEMOTHERAPY; CAPECITABINE; 5-FLUOROURACIL; COMBINATION; INFUSION AB There is no standard chemotherapy option for patients with biliary tract cancers. These patients present fairly ill and can have a rapid progression of disease. We conducted a multi-center, phase-II trial for patients with locally unresectable or metastatic bile duct or gallbladder adenocarcinomas using a modified regimen of gemcitabine and cisplatin to potentially improve tolerability. Patients received a 21-day treatment cycle of gemcitabine at 1,000 mg/m(2) and cisplatin at 30 mg/m(2) on days 1 and 8. To participate, 33 patients signed informed consent, and 30 patients received at least one dose of chemotherapy. By intention-to-treat analyses, 7 patients (21%) experienced a partial response and another 12 (36%) had stable disease for at least 12 weeks. The median progression-free survival was 6.3 months and median overall survival was 9.7 months. After 1 year, 39% of patients were alive. Most common grade 3-4 toxicities included neutropenia (33%), thrombocytopenia (23%), anemia (20%), nausea (20%), emesis (13%) and fatigue (10%). Of note, 52% of patients withdrew from study treatment, principally due to treatment-related adverse events. We concluded that this modified regimen appeared to have comparable activity to other gemcitabine and cisplatin regimens against advanced bile duct and gallbladder cancers, but there was still moderate toxicity in this patient population. C1 [Meyerhardt, Jeffrey A.; Lehman, Nicole; Earle, Craig C.; Kulke, Matthew H.; Bhargava, Pankaj; Fuchs, Charles S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Zhu, Andrew X.; Ryan, David P.; Blaszkowsky, Lawrence] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Stuart, Keith] Beth Israel Deaconess Med Ctr, Boston, MA USA. RP Meyerhardt, JA (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM jmeyerhardt@partners.org NR 29 TC 31 Z9 34 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD FEB PY 2008 VL 53 IS 2 BP 564 EP 570 DI 10.1007/s10620-007-9885-2 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 254YK UT WOS:000252623700040 PM 17597402 ER PT J AU Bilimoria, KY Palis, B Stewart, AK Bentrem, DJ Freel, AC Sigurdson, ER Talamonti, MS Ko, CY AF Bilimoria, Karl Y. Palis, Bryan Stewart, Andrew K. Bentrem, David J. Freel, Andrew C. Sigurdson, Elin R. Talamonti, Mark S. Ko, Clifford Y. TI Impact of tumor location on nodal evaluation for colon cancer SO DISEASES OF THE COLON & RECTUM LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Colon-and-Rectal-Surgeons CY JUN 02-06, 2007 CL St Louis, MO SP Amer Soc Colon & Rectal Surg DE colon neoplasms; surgery; colectomy; National Cancer Data Base; lymph nodes; staging ID LYMPH-NODES; COLORECTAL-CANCER; MINIMUM NUMBER; HOSPITAL VOLUME; SURVIVAL; RESECTION; SURGERY; RECOMMENDATIONS; PROGNOSIS; MORTALITY AB PURPOSE: Adequate lymph node evaluation is important to stage colon cancers and make adjuvant treatment decisions. Studies have demonstrated improved survival when >= 12 nodes are examined. Our objective was to assess differences in the adequacy of nodal evaluation for right vs. left colon cancers. METHODS: From the National Cancer Data Base (1998-2004), 142,009 N0M0 colon cancer patients were identified. Logistic regression was used to evaluate the number of nodes examined for right vs. left colectomies. Multivariable modeling was used to determine the impact of examining >= 12 nodes on survival. RESULTS: Of 142,009 patients, 79,444 (56 percent) had right colectomies, and 62,565 (44 percent) patients had left colectomies. More nodes were examined during right colectomies than left (median 12 vs. 8, Pe < 0.0001). When adjusted for patient, tumor, and hospital factors, patients undergoing left colectomy were less likely to have >= 12 nodes identified (P < 0.0001). Patients were more likely to have >= 12 nodes identified for right and left colon cancers at high-volume hospitals. Survival was better with examination of >= 12 nodes for right and left colon cancers (P < 0.0001). CONCLUSIONS: Evaluating >= 12 nodes for right and left colon cancers is a feasible, clinically relevant, and modifiable factor that will likely improve patient outcomes. C1 [Bilimoria, Karl Y.; Palis, Bryan; Stewart, Andrew K.; Freel, Andrew C.; Ko, Clifford Y.] Amer Coll Surg, Natl Ctr Data Base, Canc Programs, Chicago, IL 60611 USA. [Bilimoria, Karl Y.; Bentrem, David J.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Chicago, IL 60611 USA. [Sigurdson, Elin R.] Fox Chase Canc Ctr, Dept Surg, Philadelphia, PA 19111 USA. [Talamonti, Mark S.] Evanston NW Healthcare, Dept Surg, Chicago, IL USA. [Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. RP Bilimoria, KY (reprint author), Amer Coll Surg, Natl Ctr Data Base, Canc Programs, 636 N St Clair St,25th Floor, Chicago, IL 60611 USA. NR 34 TC 59 Z9 60 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-3706 J9 DIS COLON RECTUM JI Dis. Colon Rectum PD FEB PY 2008 VL 51 IS 2 BP 154 EP 161 DI 10.1007/s10350-007-9114-2 PG 8 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 259XW UT WOS:000252975200002 PM 18172729 ER PT J AU Gupta, V Yesilbursa, D Huang, WY Aggarwal, K Gupta, V Gomez, C Patel, V Miller, AP Nanda, NC AF Gupta, Vishal Yesilbursa, Dilek Huang, Wen Ying Aggarwal, Kul Gupta, Vijaya Gomez, Camilo Patel, Vinod Miller, Andrew P. Nanda, Navin C. TI Patent foramen ovale in a large population of ischemic stroke patients: Diagnosis, age distribution, gender, and race SO ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES LA English DT Article DE cerebrovascular disease; patent foramen ovale; atrial septal defect; atrial septal aneurysm; transesophageal echocardiogram; echocardiography ID ATRIAL SEPTAL ANEURYSM; RECURRENT CEREBROVASCULAR EVENTS; NORTHERN MANHATTAN STROKE; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; CONTRAST ECHOCARDIOGRAPHY; RISK-FACTORS; CRYPTOGENIC STROKE; PARADOXICAL EMBOLISM; TRANSMITRAL DOPPLER; ETHNIC DIFFERENCES AB Background: Patent foramen ovale (PFO) is a well-recognized risk factor for ischemic strokes. The true prevalence of PFO among stroke patients is still under debate. Transesophageal echocardiography (TEE) is the "gold standard" in diagnosing PFO but the physiology requires right-to-left atrial shunting. In this report, we evaluate the prevalence of PFO in a diverse group of ischemic stroke patients studied by TEE. Methods: TEE of 1,663 ischemic stroke patients were reviewed for cardiac source of embolism, including PFO and atrial septal aneurysm (ASA). Agitated saline bubble injection was performed to look for right to left atrial shunting. Success of maneuvers to elevate right atrial pressure (RAP) was noted by looking at the atrial septal bulge. Results: Among 1,435 ischemic stroke patients analyzed, the presence or absence of PFO could not be determined in 32.1% because bulging of the septum could not be demonstrated in patients with negative contrast study despite aggressive maneuvers to elevate RAP. Of the remaining 974 patients, 294 patients (30.2%) had a PFO. The mean age was 61.5 years in both groups, with a bimodal distribution of PFO and the highest prevalence occurring in <= 30-year-old group. Prevalence of PFO was similar in men (32.4%) and women (28.15%, P = 0.15); and in Caucasian (32.1%) and African American (27.7%; P = 0.15). ASA was present in 2.02% and hypermobile septum in 2.49% of the 1,435 patients. PFO was seen in 79.3% of the patients with ASA. Conclusion: Successful elevation of RAP cannot be achieved in a significant number of patients undergoing TEE and determination of PFO may be difficult. In our series, the true prevalence of PFO among ischemic stroke patients was 30.2% taking into account only those patients who showed no shunting despite bulging of the atrium septum into the left atrium (PFO absent group) during the contrast study. There was no gender or racial difference in the prevalence of PFO, but there was a bimodal distribution in prevalence with age. C1 [Yesilbursa, Dilek; Huang, Wen Ying; Patel, Vinod; Miller, Andrew P.; Nanda, Navin C.] Univ Alabama, Heart Stn, Echocardiog Lab, Div Cardiovasc Dis, Birmingham, AL 35249 USA. [Gupta, Vishal] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. [Aggarwal, Kul] Univ Missouri, Div Cardiol, Columbia, MO 65212 USA. [Gupta, Vijaya] Western Michigan Univ, Dept Stat, Kalamazoo, MI 49008 USA. [Gomez, Camilo] Alabama Neurol Inst, Birmingham, AL USA. RP Nanda, NC (reprint author), Univ Alabama, Heart Stn, Echocardiog Lab, Div Cardiovasc Dis, Heart Stn SW-S102,620 S 19th St, Birmingham, AL 35249 USA. EM nanda@uab.edu NR 47 TC 19 Z9 22 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0742-2822 J9 ECHOCARDIOGR-J CARD JI Echocardiography-J. Cardiovasc. Ultrasound Allied Tech. PD FEB PY 2008 VL 25 IS 2 BP 217 EP 227 DI 10.1111/j.1540-8175.2007.00583.x PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 258VL UT WOS:000252897500014 PM 18269568 ER PT J AU Papa, A Bonanno, GA AF Papa, Anthony Bonanno, George A. TI Smiling in the face of adversity: The interpersonal and intrapersonal functions of smiling SO EMOTION LA English DT Article DE positive emotion; Duchenne smile; facial expression; social integration ID POSITIVE EMOTIONS; FACIAL EXPRESSIONS; INDIVIDUAL-DIFFERENCES; BRAIN PHYSIOLOGY; SELF-REPORT; EXPERIENCE; BEREAVEMENT; RESILIENCE; SMILES; PSYCHOPATHOLOGY AB This study examined hypothesized interpersonal and intrapersonal functions of smiling in positive and negative affective contexts. Smiles were measured during a lab-based monologue task following either happy or sad emotion-evoking films. Psychological adjustment and social integration were measured longitudinally using data obtained in years prior to and after the experimental task. Duchenne (genuine) smiles predicted better long-term adjustment and this effect was mediated independently by both social integration and undoing of negative emotion during the monologue. These effects were observed only in the negative affective context. Non-Duchenne smiles were not related to psychological adjustment. Neither Duchenne nor non-Duchenne smiles during the monologue task were related to personality variables assessed in this study. C1 [Papa, Anthony] Va Boston Hlth Care Syst, Boston, MA 02130 USA. [Papa, Anthony] Boston Univ, Sch Med, Boston, MA 02215 USA. [Bonanno, George A.] Columbia Univ, Teachers Coll, New York, NY 10027 USA. RP Papa, A (reprint author), Va Boston Hlth Care Syst, 150 S Huntington Ave,116B-5, Boston, MA 02130 USA. EM anthony.papa@va.gov NR 94 TC 37 Z9 37 U1 4 U2 14 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1528-3542 J9 EMOTION JI Emotion PD FEB PY 2008 VL 8 IS 1 BP 1 EP 12 DI 10.1037/1528-3542.8.1.1 PG 12 WC Psychology, Experimental SC Psychology GA 260TZ UT WOS:000253034600001 PM 18266511 ER PT J AU Garcia, JM Cata, JP Dougherty, PM Smith, RG AF Garcia, Jose M. Cata, Juan P. Dougherty, Patrick M. Smith, Roy G. TI Ghrelin prevents cisplatin-induced mechanical hyperalgesia and cachexia SO ENDOCRINOLOGY LA English DT Article ID GROWTH-HORMONE SECRETAGOGUE; TUMOR-NECROSIS-FACTOR; PERIPHERAL NEUROPATHY; CANCER-PATIENTS; FOOD-INTAKE; CELLS; APPETITE; RECEPTOR; PLACEBO; RATS AB Complications induced by the chemotherapeutic agent cisplatin, such as neuropathy and cachexia, occur frequently, are often dose limiting, and have an impact on quality of life and survival in cancer patients. The recently discovered hormone ghrelin is a potent GH secretagogue with orexigenic and neuroprotective properties that may prevent or ameliorate these complications. The objective of this study was to determine the effects of ghrelin administration on mechanical hyperalgesia, anorexia, and cachexia induced by cisplatin. Adult male Sprague-Dawley rats were given cisplatin, ghrelin, ghrelin-cisplatin, or vehicle ip. Food intake and body weight were measured daily. Behavioral tests to assess the development of hyperalgesia were conducted by measuring mechanical and thermal sensitivity. Plasma ghrelin and IGF-I levels were also measured. Our results indicate that ghrelin coadministration inhibited the development of cisplatin-induced mechanical hyperalgesia, anorexia, and cachexia induced by cisplatin. Although ghrelin treatment had no effect on plasma IGF-I levels in control rats, it prevented the decrease in IGF-I levels induced by cisplatin. The attenuation of cisplatin-induced mechanical hyperalgesia induced by ghrelin was correlated with the prevention of cisplatin-induced lowering of IGF-I. In conclusion, ghrelin administration may be useful in the treatment or prevention of chemotherapy induced neuropathy and cachexia. Attenuation of mechanical hyperalgesia in the rat by the hormone ghrelin provides a unique model for elucidating the mechanisms involved, which are essential toward our understanding of these complications. C1 [Garcia, Jose M.] Baylor Coll Med, Div Endocrinol Diabet & Metab, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Garcia, Jose M.; Smith, Roy G.] Baylor Coll Med, Huffington Ctr Aging, Houston, TX 77030 USA. [Cata, Juan P.; Dougherty, Patrick M.] Univ Texas MD Anderson Canc Ctr, Dept Anesthesiol & Pain Med, Houston, TX 77002 USA. RP Garcia, JM (reprint author), Baylor Coll Med, Div Endocrinol Diabet & Metab, Michael E DeBakey Vet Affairs Med Ctr, 2002 Holcombe Blvd,Bldg 100,Room 3B-243, Houston, TX 77030 USA. EM jgarcia1@bcm.edu OI Dougherty, Patrick/0000-0002-2177-2734 FU NINDS NIH HHS [R01 NS039933] NR 31 TC 48 Z9 48 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD FEB PY 2008 VL 149 IS 2 BP 455 EP 460 DI 10.1210/en.2007-0828 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 253GN UT WOS:000252506800003 PM 17962345 ER PT J AU Zhao, CM Martinez, V Piqueras, L Wang, LX Tache, Y Chen, D AF Zhao, Chun-Mei Martinez, Vicente Piqueras, Laura Wang, Lixin Tache, Yvette Chen, Duan TI Control of gastric acid secretion in somatostatin receptor 2 deficient mice: Shift from endocrine/paracrine to neurocrine pathways SO ENDOCRINOLOGY LA English DT Article ID ENTEROCHROMAFFIN-LIKE CELLS; STOMACH ECL CELLS; RAT PARIETAL-CELLS; HISTIDINE-DECARBOXYLASE; KNOCKOUT MICE; CIRCULATING PANCREASTATIN; AMINOPYRINE ACCUMULATION; NEUROHORMONAL REGULATION; GASTROINTESTINAL-TRACT; HISTAMINE-RELEASE AB The gastrin-enterochromaffin-like (ECL) cell-parietal cell axis is known to play an important role in the regulation of gastric acid secretion. Somatostatin, acting on somatostatin receptor type 2 (SSTR2), interferes with this axis by suppressing the activity of the gastrin cells, ECLcells, and parietal cells. Surprisingly, however, freely fed SSTR2 knockout mice seem to display normal circulating gastrin concentration and unchanged acid output. In the present study, we compared the control of acid secretion in these mutant mice with that in wild-type mice. In SSTR2 knockout mice, the number of gastrin cells was unchanged; whereas the numbers of somatostatin cells were reduced in the antrum (-55%) and increased in the oxyntic mucosa (35%). The ECL cells displayed a reduced expression of histidine decarboxylase and vesicle monoamine transport type 2 ( determined by immunohistochemistry), and an impaired transformation of the granules to secretory vesicles ( determined by electron microscopic analysis), suggesting low activity of the ECL cells. These changes were accompanied by an increased expression of galanin receptor type 1 in the oxyntic mucosa. The parietal cells were found to respond to pentagastrin or to vagal stimulation ( evoked by pylorus ligation) with increased acid production. In conclusion, the inhibitory galanin-galanin receptor type 1 pathway is up-regulated in the ECL cells, and the direct stimulatory action of gastrin and vagal excitation is enhanced on the parietal cells in SSTR2 knockout mice. We suggest that there is a remodeling of the neuroendocrine mechanisms that regulate acid secretion in these mutant mice. C1 [Zhao, Chun-Mei; Chen, Duan] Norwegian Univ Sci & Technol, Dept Canc Res & Mol Med, NO-7006 Trondheim, Norway. [Martinez, Vicente] AstraZeneca R&D, Safety Assessment Safety Pharmacol, Alderley Pk SK10 4TF, Cheshire, England. [Martinez, Vicente; Wang, Lixin; Tache, Yvette] Univ Calif Los Angeles, Dept Med, Digest Dis Res Ctr, Ctr Ulcer Res & Educ, Los Angeles, CA 90073 USA. [Martinez, Vicente; Wang, Lixin; Tache, Yvette] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Piqueras, Laura] Univ Valencia, Res Fdn Univ Clin Hosp, Valencia 46022, Spain. RP Zhao, CM (reprint author), Norwegian Univ Sci & Technol, Dept Canc Res & Mol Med, NO-7006 Trondheim, Norway. EM chun-mei.zhao@ntnu.no RI Martinez, Vicente/N-1189-2014 FU NIDDK NIH HHS [P30 DK041301, DK41301, DK30110] NR 58 TC 12 Z9 12 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD FEB PY 2008 VL 149 IS 2 BP 498 EP 505 DI 10.1210/en.2007-0238 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 253GN UT WOS:000252506800010 PM 17974627 ER PT J AU Styer, AK Sullivan, BT Puder, M Arsenault, D Petrozza, JC Serikawa, T Chang, S Hasan, T Gonzalez, RR Rueda, BR AF Styer, Aaron K. Sullivan, Brian T. Puder, Mark Arsenault, Danielle Petrozza, John C. Serikawa, Takehiro Chang, Sung Hasan, Tayyaba Gonzalez, Ruben R. Rueda, Bo R. TI Ablation of leptin signaling disrupts the establishment, development, and maintenance of endometriosis-like lesions in a murine model SO ENDOCRINOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; PERITONEAL-FLUID; MOUSE MODEL; PELVIC ENDOMETRIOSIS; NUDE-MOUSE; EXPRESSION; RECEPTOR; CELLS; WOMEN; ANGIOGENESIS AB Leptin, a 16-kDa cytokine, has been implicated in several reproductive processes and disorders. Notably, elevated leptin levels in the peritoneal fluid of women with mild endometriosis has been demonstrated, suggesting a role for this cytokine in the early stages of disease establishment. To gain insight into the functional significance of leptin during the initial requisite proliferative and neovascularization events involved in endometriosis, we investigated the effect of disruption of in vivo leptin signaling on the establishment and/or maintenance of an endometriosis-like lesion in a syngeneic immunocompetent mouse model of endometriosis. Findings of this study show that the disruption of leptin signaling by ip injection of the pegylated leptin peptide receptor antagonist (LPrA) impairs the establishment of endometriosis-like lesions ( derived from uteri of C57BL/6 female siblings) and results in a reduction of viable organized glandular epithelium, vascular endothelial growth factor-A expression, and mitotic activity. LPrA treatment resulted in a significant reduction of microvascular density in endometriosis-like lesions after continuous and acute courses. Endometriosis-like lesions ( derived from tissue with functional leptin receptor) of Lepr(db) hosts ( nonfunctional leptin receptor) were phenotypically similar to those of LPrA-treated mice. Our results confirm that leptin signaling is a necessary component in lesion proliferation, early vascular recruitment, and maintenance of neoangiogenesis in a murine model of endometriosis. C1 [Styer, Aaron K.; Sullivan, Brian T.; Serikawa, Takehiro; Gonzalez, Ruben R.; Rueda, Bo R.] Harvard Univ, Vincent Ctr Reprod Biol, Dept Obstet & Gynecol, Massachusetts Gen Hosp,Sch Med, Boston, MA 02114 USA. [Styer, Aaron K.; Petrozza, John C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv,Fertil Ctr, Boston, MA 02114 USA. [Styer, Aaron K.; Petrozza, John C.; Rueda, Bo R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Chang, Sung; Hasan, Tayyaba] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Ctr Photomed, Boston, MA 02114 USA. [Puder, Mark; Arsenault, Danielle] Childrens Hosp, Med Ctr, Dept Surg, Boston, MA 02115 USA. [Gonzalez, Ruben R.] Morehouse Sch Med, Atlanta, GA 30310 USA. [Gonzalez, Ruben R.] Boston Biomed Res Inst, Watertown, MA 02472 USA. RP Rueda, BR (reprint author), Harvard Univ, Vincent Ctr Reprod Biol, Dept Obstet & Gynecol, Massachusetts Gen Hosp,Sch Med, THR 901A,55 Fruit St, Boston, MA 02114 USA. EM brueda@partners.org FU NIDDK NIH HHS [DK069621, K08 DK069621] NR 58 TC 30 Z9 30 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD FEB PY 2008 VL 149 IS 2 BP 506 EP 514 DI 10.1210/en.2007-1225 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 253GN UT WOS:000252506800011 PM 17962343 ER PT J AU Pang, SH Leung, WK Graham, DY AF Pang, S. H. Leung, W. K. Graham, D. Y. TI Ulcers and gastritis SO ENDOSCOPY LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; HELICOBACTER-PYLORI ERADICATION; RANDOMIZED-TRIAL; HIGH-RISK; THERAPY; INHIBITORS; INFECTION; CYCLOOXYGENASE-2; COMBINATION; DICLOFENAC C1 [Graham, D. Y.] Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX 77030 USA. [Graham, D. Y.] Baylor Coll Med, Houston, TX 77030 USA. [Pang, S. H.; Leung, W. K.] Chinese Univ Hong Kong, Inst Digest Dis, Shatin, Hong Kong, Peoples R China. RP Graham, DY (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Dept Med, RM 3A-320 111D,2002 Holcombe Blvd, Houston, TX 77030 USA. EM dgraham@bcm.tmc.edu NR 21 TC 4 Z9 4 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X J9 ENDOSCOPY JI Endoscopy PD FEB PY 2008 VL 40 IS 2 BP 136 EP 139 DI 10.1055/s-2007-995318 PG 4 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 269UW UT WOS:000253676800009 PM 18058616 ER PT J AU Brigger, MT McLeod, IK Sorensen, MP AF Brigger, Matthew T. McLeod, Ian K. Sorensen, Martin P. TI Neurosarcoidosis presenting as complicated sinusitis: A case report and review SO ENT-EAR NOSE & THROAT JOURNAL LA English DT Article ID SINONASAL SARCOIDOSIS; MANIFESTATIONS AB Sarcoidosis is a systemic granulomatous disease with widely variable clinical characteristics, including numerous head and neck manifestations. We describe the case of a 49-year-old man who presented to the emergency department with symptoms consistent with complicated sinusitis. He was ultimately found to have an atypical case of neurosarcoidosis. This case illustrates the varied multisystem presentation of sarcoidosis and the diagnostic considerations that are merited. C1 [Brigger, Matthew T.; Sorensen, Martin P.] Natl Naval Med Ctr, Dept Otolaryngol Head & Neck Surg, Bethesda, MD USA. [McLeod, Ian K.] Walter Reed Army Med Ctr, Dept Otolaryngol Head & Neck Surg, Washington, DC USA. RP Brigger, MT (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. EM matt.brigger@alumni.vanderbilt.edu NR 8 TC 1 Z9 1 U1 0 U2 0 PU VENDOME GROUP LLC PI NEW YORK PA 149 FIFTH AVE, 10TH FLOOR, NEW YORK, NY 10010 USA SN 0145-5613 J9 ENT-EAR NOSE THROAT JI ENT-Ear Nose Throat J. PD FEB PY 2008 VL 87 IS 2 BP 93 EP 95 PG 3 WC Otorhinolaryngology SC Otorhinolaryngology GA 266NO UT WOS:000253443200010 PM 18437929 ER PT J AU Mahalingaiah, S Meeker, JD Pearson, KR Calafat, AM Ye, X Petrozza, J Hauser, R AF Mahalingaiah, Shruthi Meeker, John D. Pearson, Kimberly R. Calafat, Antonia M. Ye, Xiaoyun Petrozza, John Hauser, Russ TI Temporal variability and predictors of urinary bisphenol a concentrations in men and women SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE bisphenol A; endocrine disruptors; environment; human; pregnancy ID ENDOCRINE DISRUPTOR; GENDER-DIFFERENCES; EXPOSURE; MIGRATION; POLYCARBONATE; POPULATION; ANDROGEN; REVEALS; PHENOLS; RESIN AB BACKGROUND: Bisphenol A (BPA) is used to manufacture polymeric materials, such as polycarbonate plastics, and is found in a variety of consumer products. Recent data show widespread BPA exposure among the U.S. population. OBJECTIVE: Our goal in the present study was to determine the temporal variability and predictors of BPA exposure. METHODS: We measured urinary concentrations of BPA among male and female patients from the Massachusetts General Hospital Fertility Center. RESULTS: Between 2004 and 2006, 217 urine samples were collected from 82 subjects: 45 women (145 samples) and 37 men (72 samples). Of these, 24 women and men were partners and contributed 42 pairs of samples collected on the same day. Ten women became pregnant during the follow-up period. Among die 217 urine samples, the median BPA concentration was 1.20 mu g/L, ranging from below the limit of detection (0.4 mu g/L) to 42.6 mu g/L. Age, body mass index, and sex were not significant predictors of urinary BPA concentrations. BPA urinary concentrations among pregnant women were 26% higher (-26%, +115%) than those among the same women when no pregnant (p > 0.05). The urinary BPA concentrations of the female and male partner on the same day were correlated (r = 0.36; p = 0.02). The sensitivity of classifying a subject in the highest tertile using a single urine sample was 0.64. CONCLUSION: We found a nonsignificant increase in urinary BPA concentrations in women while pregnant compared with nonpregnant samples from the same women. Samples collected from partners on the same day were correlated, suggesting shared sources of exposure. Finally, a single urine sample showed moderate sensitivity for predicting a subject's tertile categorization. C1 [Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Mahalingaiah, Shruthi] Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. [Meeker, John D.] Univ Michigan, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA. [Pearson, Kimberly R.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Calafat, Antonia M.; Ye, Xiaoyun] Ctr Dis Control & Prevent, Atlanta, GA USA. [Petrozza, John; Hauser, Russ] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Mem Obstet & Gynecol Serv,Fertil Ctr, Boston, MA USA. RP Hauser, R (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave,Bldg 1,Room 1405, Boston, MA 02115 USA. EM rhauser@hohp.harvard.edu OI Mahalingaiah, Shruthi/0000-0002-5527-5787; Meeker, John/0000-0001-8357-5085 FU NIEHS NIH HHS [P30 ES000002, ES 00002, ES 09718, R01 ES009718]; NIOSH CDC HHS [OH 008578, R01 OH008578] NR 33 TC 146 Z9 147 U1 2 U2 20 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD FEB PY 2008 VL 116 IS 2 BP 173 EP 178 DI 10.1289/ehp.10605 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 257XH UT WOS:000252831800026 PM 18288314 ER PT J AU Lee, CL Frost, JD Swann, JW Hrachovy, RA AF Lee, Chong L. Frost, James D., Jr. Swann, John W. Hrachovy, Richard A. TI A new animal model of infantile spasms with unprovoked persistent seizures SO EPILEPSIA LA English DT Article DE epilepsy; infantile spasms; TTX; hypsarrhythmia; animal model ID POSITRON-EMISSION-TOMOGRAPHY; BINOCULAR IMPULSE BLOCKADE; WEST-SYNDROME; BRAIN; EPILEPSY; ACTH; RATS; PATHOGENESIS; AMYGDALA; NEURONS AB Purpose: Infantile spasms is one of the most severe epileptic syndromes of infancy and early childhood. Progress toward understanding the pathophysiology of this disorder and the development of effective therapies has been hindered by the lack of a relevant animal model. We report here the creation of such a model. Methods: The sodium channel blocker, tetrodotoxin (TTX), was chronically infused into the developing neocortex or hippocampus of infant rats by way of an osmotic minipump starting on postnatal day 10-12. Results: After a minimum of 10 days of infusion, approximately one-third of these rats began to display very brief (1-2 s) spasms, which consisted of symmetric or asymmetric flexion or extension of the trunk and sometimes involvement of one or both forelimbs. The typical ictal EEG pattern associated with the behavioral spasms consisted of an initial generalized, high amplitude, slow wave followed by an electrodecrement with superimposed fast activity. The interictal EEG revealed multifocal spikes and sharp waves, and in most animals that had spasms a hypsarrhythmic pattern was seen, at least intermittently, during NREM sleep. Like in humans, the spasms in the rat often occurred in clusters especially during sleep-wake transitions. Comparison of the ictal and interictal EEGs recorded in this model and those from humans with infantile spasms revealed that the patterns and the frequency components of both the ictal events and hypsarrhythmia were very similar. Discussion: The TTX model of infantile spasms should be of value in furthering an understanding of the pathophysiology of this seizure disorder. C1 [Frost, James D., Jr.; Hrachovy, Richard A.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. [Lee, Chong L.; Swann, John W.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Frost, James D., Jr.; Swann, John W.] Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA. [Hrachovy, Richard A.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Lee, Chong L.; Swann, John W.] Baylor Coll Med, Cain Fdn Labs, Houston, TX 77030 USA. RP Hrachovy, RA (reprint author), Baylor Coll Med, Dept Neurol, 1 Baylor Plaza,NB302, Houston, TX 77030 USA. EM hrachovy@bcm.edu FU NINDS NIH HHS [NS 18309, NS 37171] NR 39 TC 46 Z9 48 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD FEB PY 2008 VL 49 IS 2 BP 298 EP 307 DI 10.1111/j.1528-1167.2007.01377.x PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 256FG UT WOS:000252712500011 PM 17941850 ER PT J AU Bratos-Perez, MA Sanchez, PL de Cruz, SG Villacorta, E Palacios, IF Fernandez-Fernandez, JM Di Stefano, S Orduna-Domingo, A Carrascal, Y Mota, P Luengo, CM Bermejo, J Roman, JAS Rodriguez-Torres, A Fernandez-Aviles, F AF Bratos-Perez, Miguel A. Sanchez, Pedro L. de Cruz, Susana Garcia Villacorta, Eduardo Palacios, Igor F. Fernandez-Fernandez, Jose M. Di Stefano, Salvatore Orduna-Domingo, Antonio Carrascal, Yolanda Mota, Pedro Luengo, Candido Martin Bermejo, Javier Roman, Jose A. San Rodriguez-Torres, Antonio Fernandez-Aviles, Francisco CA Grp Aortica TI Association between self-replicating calcifying nanoparticles and aortic stenosis: a possible link to valve calcification SO EUROPEAN HEART JOURNAL LA English DT Article DE nanobacteria; calcifying nanoparticles; aortic stenosis; calcification ID STONE FORMATION; ANIMAL-MODEL; NANOBACTERIA; DISEASE; BIOMINERALIZATION; PROGRESSION; PROTEIN; BLOOD AB Aims Among various hypotheses proposed for pathological tissue calcification, recent evidence supports the possibility that self-replicating calcifying nanoparticles (CNPs) can contribute to such calcification. These CNPs have been detected and isolated from calcified human tissues, including blood vessels and kidney stones, and are referred to as nanobacteria. We evaluated calcific aortic valves for the presence of CNP. Methods and results Calcific aortic valves were obtained from 75 patients undergoing surgical valve replacement. The control group was formed by eight aortic valves corresponding to patients with heart transplants. In the microbiology laboratory, valves were screened for CNP using a 4-6 weeks specific culture method. The culture for CNP was positive in 48 of the 75 valves with aortic stenosis (64.0%) in comparison with zero of eight (0%) for the control group (P = 0.0005). The observation of cultures by way of scanning electron microscopy highlighted the resemblance in size and morphology of CNP. Conclusion Self-replicating calcific nanometer-scale particles, similar to those described as CNP from other calcific human tissues, can be cultured and visualized from calcific human aortic valves. This finding raises the question as to whether CNP contribute to the pathogenesis of the disease or whether they are only innocent bystanders. C1 [Sanchez, Pedro L.; Bermejo, Javier; Fernandez-Aviles, Francisco] Hosp Gen Univ Gregorio Maranon, Serv Cardiol, Madrid 28007, Spain. [Villacorta, Eduardo; Di Stefano, Salvatore; Carrascal, Yolanda; Mota, Pedro; Roman, Jose A. San] Hosp Clin Univ, ICICOR, Valladolid, Spain. [Palacios, Igor F.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Cardiac Unit, Boston, MA 02115 USA. [Luengo, Candido Martin] Hosp Univ Salamanca, Serv Cardiol, Salamanca, Spain. [Bratos-Perez, Miguel A.; de Cruz, Susana Garcia; Fernandez-Fernandez, Jose M.; Orduna-Domingo, Antonio; Rodriguez-Torres, Antonio] Hosp Clin Univ, Fac Med, Microbiol Serv, Valladolid, Spain. RP Sanchez, PL (reprint author), Hosp Gen Univ Gregorio Maranon, Serv Cardiol, Doctor Esquerdo 46, Madrid 28007, Spain. EM pedrolsanchez@secardiologia.es RI 2008, Ibsal/A-1268-2012; Velasco , Berta /D-4325-2014; OI Velasco , Berta /0000-0002-8390-3867; Carrascal, Yolanda/0000-0001-6290-5567; Sanchez, Pedro L/0000-0002-4288-345X NR 36 TC 34 Z9 37 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD FEB PY 2008 VL 29 IS 3 BP 371 EP 376 DI 10.1093/eurheartj/ehm592 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 258YI UT WOS:000252905900019 PM 18192703 ER PT J AU Wang, TJ AF Wang, Thomas J. TI New cardiovascular risk factors exist, but are they clinically useful? SO EUROPEAN HEART JOURNAL LA English DT Article DE biomarkers; risk factors; cardiovascular disease; rrevention; C-reactive protein ID CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; NATRIURETIC PEPTIDE; MULTIPLE BIOMARKERS; PREDICTION; EVENTS; LIMITATIONS; MORTALITY; WOMEN AB There is substantial interest in identifying new risk factors for cardiovascular disease, to improve our understanding of disease biology and to account for the cases of heart disease that cannot be explained by known risk factors. Investigation of putative risk factors frequently involves the study of circulating biomarkers. In recent years, a spirited debate has arisen regarding the validity and usefulness of these new measures. A careful assessment of the evidence suggests that most newer biomarkers are not ready for routine clinical use in the primary prevention setting. The good news is that traditional risk factors perform quite well with regard to the prediction of future cardiovascular risk. Inadequate recognition and control of the 'classic' risk factors continues to account for a large number of avoidable cardiovascular events. At the same time, new insights into disease mechanisms should lead to the development of novel preventive therapies, regardless of how well biomarkers themselves perform in risk stratification. Furthermore, state-of-the-art technologies that allow the profiling of large panels of genes, transcripts, proteins, or small molecules should facilitate the discovery of newer biomarkers capable of providing both mechanistic insight and true prognostic utility. C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Wang, TJ (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St, Boston, MA 02114 USA. EM tjwang@partners.org FU NHLBI NIH HHS [R01-HL-083197, R01-HL-086875] NR 12 TC 36 Z9 36 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD FEB PY 2008 VL 29 IS 4 BP 441 EP 444 DI 10.1093/eurheartj/ehm644 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 267DS UT WOS:000253490300007 PM 18276617 ER PT J AU Nahrendorf, M Aikawa, E Figueiredo, JL Stangenberg, L van den Borne, SW Blankesteijn, WM Sosnovik, DE Jaffer, FA Tung, CH Weissleder, R AF Nahrendorf, Matthias Aikawa, Elena Figueiredo, Jose-Luiz Stangenberg, Lars van den Borne, Susanne W. Blankesteijn, W. Matthijs Sosnovik, David E. Jaffer, Farouc A. Tung, Ching-Hsuan Weissleder, Ralph TI Transglutaminase activity in acute infarcts predicts healing outcome and left ventricular remodelling: implications for FXIII therapy and antithrombin use in myocardial infarction SO EUROPEAN HEART JOURNAL LA English DT Article DE Imaging; inflammation; wound healing; myocardial infarction; factor XIII ID MOLECULAR-WEIGHT HEPARIN; COAGULATION-FACTOR-XIII; CARDIAC RUPTURE; MICE; ANGIOGENESIS; FONDAPARINUX; DYSFUNCTION; INHIBITION; RESPONSES; SELECTIN AB Aims The transglutaminase factor XIII (FXIII) emerges as a key enzyme in healing after myocardial infarction (MI). Here we assess the impact of transglutaminase-modulating therapies on healing and evolution of heart failure using a novel, non-invasive molecular imaging technique. Methods and results Immunoblotting revealed lower FXIII levels in the myocardium of nine patients with infarct rupture when compared to MI patients without rupture (P < 0.0045). In a murine model of MI, we assessed healing while modulating local FXIII activity. Infarct tissue activity was monitored with molecular in vivo single photon emission computed tomography-computed tomography (SPECT-CT) imaging, and activity was found to be increased by 80% in FXIII-treated mice (400 IU FXIII/kg iv.), and decreased by 65% in dalteparin (DP)-treated mice (600 IU/kg DP sc., P < 0.05). DP-treated mice exhibited increased mortality due to infarct rupture (64% by day 7, P < 0.018). Serial Magnetic Resonance Imaging (MRI) showed that left ventricular dilation post-MI was attenuated by FXIII treatment when compared to saline control-treated mice with MI (P = 0.04). Quantitative histological and reverse transcription-polymerase chain reaction analyses revealed that FXIII treatment induced a faster resolution of the neutrophil response, enhanced macrophage recruitment, increased collagen content and augmented angiogenesis in the healing infarct (P < 0.05 vs. control-treated mice with MI). Conclusion FXIII tissue levels are decreased in patients with insufficient healing. Therapeutic strategies that modulate FXIII activity impact murine myocardial healing. Molecular imaging of FXIII activity predicts prognosis in mice with experimental MI. C1 [Nahrendorf, Matthias; Aikawa, Elena; Figueiredo, Jose-Luiz; Stangenberg, Lars; Sosnovik, David E.; Tung, Ching-Hsuan; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. [Nahrendorf, Matthias; Aikawa, Elena; Figueiredo, Jose-Luiz; Stangenberg, Lars; Sosnovik, David E.; Tung, Ching-Hsuan; Weissleder, Ralph] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [van den Borne, Susanne W.; Blankesteijn, W. Matthijs] Maastricht Univ, Dept Pharmacol & Toxicol, Cardiovasc Res Inst Maastricht, Maastricht, Netherlands. [Sosnovik, David E.; Jaffer, Farouc A.] Massachusetts Gen Hosp, Div Cardiol, Dept Med, Boston, MA 02114 USA. RP Nahrendorf, M (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St,Room 5406, Charlestown, MA 02129 USA. EM mnahrendorf@mgh.harvard.edu OI Jaffer, Farouc/0000-0001-7980-384X; Tung, Ching-Hsuan/0000-0001-6648-6195 FU NHLBI NIH HHS [R01-HL078641, U01-HL080731] NR 34 TC 43 Z9 43 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD FEB PY 2008 VL 29 IS 4 BP 445 EP 454 DI 10.1093/eurheartj/ehm558 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 267DS UT WOS:000253490300009 PM 18276618 ER PT J AU Ford, P Seymour, G Beeley, JA Curro, F DePaola, D Ferguson, D Finkelstein, M Gaengler, P Neo, J Niessen, L Oktay, I Park, BK Wolowski, A Claffey, N AF Ford, P. Seymour, G. Beeley, J. A. Curro, F. DePaola, D. Ferguson, D. Finkelstein, M. Gaengler, P. Neo, J. Niessen, L. Oktay, I. Park, B. K. Wolowski, A. Claffey, N. TI Adapting to changes in molecular biosciences and technologies SO EUROPEAN JOURNAL OF DENTAL EDUCATION LA English DT Article; Proceedings Paper CT Global Congress on Dental Education CY SEP 06-08, 2007 CL Dublin, IRELAND SP Int Federat Dent Educators & Assoc, European Union Themat Network Dent Educ, Amer Dent Educ Assoc, Assoc Dent Educ Europe DE biotechnology; dental education; dental research; molecular biosciences; oral health ID FUTURE AB Dental education, like any other educational programme in a research-intensive university environment, must be research led or at least research informed. In this context, as the research and knowledge base of dentistry lies in the biological and physical sciences, dental education must be led by advances in research in both these areas. There is no doubt that biotechnology and nanotechnology have, over the past 25 years, led research in both these areas. It is therefore logical to assume that this has also impacted on dental education. The aim of this paper is twofold; on one hand to examine the effects of biotechnology and nanotechnology and their implications for dental education and on the other to make recommendations for future developments in dental education led by research in biotechnology and nanotechnology. It is now generally accepted that dental education should be socially and culturally relevant and directed to the community it serves. In other words, there can be no universal approach and each dental school or indeed curriculum must apply the outcomes in their own social, cultural and community settings. C1 [Ford, P.] Univ Queensland, Brisbane, Qld, Australia. [Seymour, G.] Univ Otago, Dunedin, New Zealand. [Beeley, J. A.] Univ Glasgow, Glasgow, Lanark, Scotland. [Curro, F.] NYU, New York, NY USA. [DePaola, D.] Forsyth Inst, Boston, MA USA. [Ferguson, D.] Univ Manchester, Manchester, Lancs, England. [Finkelstein, M.] Univ Iowa, Iowa City, IA USA. [Gaengler, P.] Univ Witten Herdecke, Witten, Germany. [Neo, J.] Natl Univ Singapore, Singapore 117548, Singapore. [Oktay, I.] Istanbul Univ, Istanbul, Turkey. [Park, B. K.] Chonbuk Natl Univ, Jeonju, South Korea. [Wolowski, A.] Westfal Univ Muenster, Munster, Germany. [Claffey, N.] Univ Dublin Trinity Coll, Dublin 2, Ireland. RP Ford, P (reprint author), Univ Queensland, St Lucia, Qld 4067, Australia. EM p.ford@uq.edu.au RI Ford, Pauline/F-1232-2010; OI Ford, Pauline/0000-0002-0901-2863; Seymour, Gregory/0000-0001-7595-5651 NR 26 TC 0 Z9 2 U1 0 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1396-5883 J9 EUR J DENT EDUC JI Eur. J. Dent. Educ. PD FEB PY 2008 VL 12 SU 1 BP 40 EP 47 DI 10.1111/j.1600-0579.2007.00479.x PG 8 WC Dentistry, Oral Surgery & Medicine; Education, Scientific Disciplines SC Dentistry, Oral Surgery & Medicine; Education & Educational Research GA 269MO UT WOS:000253653300008 PM 18289267 ER PT J AU Kuter, DJ AF Kuter, David J. TI Meeting the treatment challenges of chronic immune thrombocytopenic purpura SO EUROPEAN JOURNAL OF HAEMATOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Div Hematol, Boston, MA 02114 USA. RP Kuter, DJ (reprint author), Massachusetts Gen Hosp, Div Hematol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0902-4441 J9 EUR J HAEMATOL JI Eur. J. Haematol. PD FEB PY 2008 VL 80 SU 69 BP 1 EP 2 PG 2 WC Hematology SC Hematology GA 253BY UT WOS:000252494900001 ER PT J AU Kuter, DJ AF Kuter, David J. TI New drugs for familiar therapeutic targets: thrombopoietin receptor agonists and immune thrombocytopenic purpura SO EUROPEAN JOURNAL OF HAEMATOLOGY LA English DT Article; Proceedings Paper CT 12th Congress of the European-Hematology-Association CY JUN 07-10, 2007 CL Vienna, AUSTRIA SP European Hematol Assoc DE thrombopoietin; platelet count; megakaryocytes; thrombopoiesis; purpura; thrombocytopenic; idiopathic ID HUMAN MEGAKARYOCYTE GROWTH; RECOMBINANT HUMAN THROMBOPOIETIN; C-MPL LIGAND; PLATELET PRODUCTION; ERYTHROPOIETIN RECEPTOR; ANTIBODY FRAGMENT; BINDING; CHEMOTHERAPY; CANCER; STIMULATION AB Various agents to treat immune thrombocytopenic purpura (ITP) have been developed on the principle that stimulating the thrombopoietin (TPO) receptor would increase platelet production. First-generation agents-recombinant human thrombopoietin (rHuTPO) and pegylated recombinant human megakaryocyte growth and development factor (PEG rHuMGDF)-showed promise, but observations of antibody formation to PEG rHuMGDF led to the discontinuation of development of both agents. Second-generation agents-the TPO peptide mimetics, TPO non-peptide mimetics, and TPO agonist antibodies-have been developed to reduce or eliminate the problem of antigenicity. Clinical studies for some of these agents, such as AMG 531 (romiplosim, Nplate) and eltrombopag (Promacta), are demonstrating their relative safety and efficacy in increasing platelet counts in patients with ITP; AMG 531 and eltrombopag are in late-stage clinical development and are able to stimulate platelet production in patients with ITP. Some differences in safety profiles have been described and are undergoing further study. There are currently seven second-generation TPO receptor agonists that have been reported in the literature, representing the potential advantages-and continuing challenges-with this novel class of platelet-stimulating therapies for ITP and possibly thrombocytopenia in other disease states as well. C1 Massachusetts Gen Hosp, Div Hematol, Boston, MA 02114 USA. RP Kuter, DJ (reprint author), Massachusetts Gen Hosp, Div Hematol, Boston, MA 02114 USA. NR 68 TC 12 Z9 12 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0902-4441 J9 EUR J HAEMATOL JI Eur. J. Haematol. PD FEB PY 2008 VL 80 SU 69 BP 9 EP 18 DI 10.1111/j.1600-0609.2007.00999.x PG 10 WC Hematology SC Hematology GA 253BY UT WOS:000252494900003 PM 18211568 ER PT J AU McMurray, JJV Carson, PE Komajda, M McKelvie, R Zile, MR Ptaszynska, A Staiger, C Donovan, JM Massie, BM AF McMurray, John J. V. Carson, Peter E. Komajda, Michel McKelvie, Robert Zile, Michael R. Ptaszynska, Agata Staiger, Christoph Donovan, J. Mark Massie, Barry M. TI Heart failure with preserved ejection fraction: Clinical characteristics of 4133 patients enrolled in the I-PRESERVE trial SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE heart failure; diastolic heart failure; clinical trial; ejection fraction; epidemiology ID VENTRICULAR SYSTOLIC FUNCTION; NATRIURETIC PEPTIDE; MORTALITY; MORBIDITY; DYSFUNCTION; CANDESARTAN; PROGNOSIS; OUTCOMES; PREVALENCE; MANAGEMENT AB Background: We describe the baseline characteristics of subjects randomised in the largest placebo-controlled, morbidity-mortality trial to date in patients with heart failure and preserved ejection fraction - the irbesartan in heart failure with preserved systolic function trial (I-PRESERVE). Methods and results: 4133 patients with a mean age of 72 years (a third were 75 years or older) were randomised and 60% were women. The mean (SD) LVEF was 59 (9)% and almost 80% of patients were in NYHA Class III or IV Approximately 80% of patients were also overweight or obese. Heart failure was reported by investigators to have a hypertensive aetiology in 64% of patients. Prior myocardial infarction was relatively uncommon (24%), as was coronary revascularisation (13%). Atrial fibrillation and diabetes each occurred in between a quarter and a third of patients. The following treatments were used at baseline: diuretic 83%, beta-blocker 59%, calcium channel blocker 40%, ACE inhibitor 25%, spironolactone 15% and digoxin 14%. Conclusions: Patients in I-PRESERVE are broadly representative of those seen in epidemiological studies and, because of this, the results of this trial should be generally applicable to "real world" patients with heart failure and preserved ejection fraction. (C) 2008 European Society of Cardilogy. Published by Elsevier B.V. All rights reserved. C1 [McMurray, John J. V.] Univ Glasgow, Fac Med, BHF Cardiovasc Res Ctr, Glasgow G12 8TA, Lanark, Scotland. [McMurray, John J. V.] Univ Glasgow, Western Infirm, Dept Cardiol, Glasgow G12 8TA, Lanark, Scotland. [Carson, Peter E.] Washington Vet Affairs Med Ctr, Washington, DC USA. [Carson, Peter E.] Georgetown Univ, Washington, DC USA. [Komajda, Michel] Univ Paris 06, Paris 6, France. [Komajda, Michel] Hop La Pitie Salpetriere, Paris, France. [McKelvie, Robert] McMaster Univ, Hamilton, ON, Canada. [Zile, Michael R.] Med Univ S Carolina, Charleston, SC 29425 USA. [Zile, Michael R.] Vet Affairs Med Ctr, Charleston, SC 29403 USA. [Ptaszynska, Agata] Bristol Myers Squibb Co, Pharmaceut Res Inst, Princeton, NJ 08543 USA. [Staiger, Christoph] Sanofi Aventis, Bridgewater, NJ USA. [Massie, Barry M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Massie, Barry M.] San Francisco VA Med Ctr, San Francisco, CA USA. RP McMurray, JJV (reprint author), Univ Glasgow, Fac Med, BHF Cardiovasc Res Ctr, 126 Univ Pl, Glasgow G12 8TA, Lanark, Scotland. EM j.mcmurray@bio.gla.ac.uk OI mcmurray, john/0000-0002-6317-3975 NR 35 TC 93 Z9 96 U1 3 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1388-9842 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD FEB PY 2008 VL 10 IS 2 BP 149 EP 156 DI 10.1016/j.ejheart.2007.12.010 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 280JS UT WOS:000254423200007 PM 18279770 ER PT J AU Hutter, CM Samii, A Factor, SA Nutt, JG Higgins, DS Bird, TD Griffith, A Roberts, JW Leis, BC Montimurro, JS Kay, DM Edwards, KL Payami, H Zabetian, CP AF Hutter, Carolyn M. Samii, Ali Factor, Stewart A. Nutt, John G. Higgins, Donald S. Bird, Thomas D. Griffith, Alida Roberts, John W. Leis, Berta C. Montimurro, Jennifer S. Kay, Denise M. Edwards, Karen L. Payami, Haydeh Zabetian, Cyrus P. TI Lack of evidence for an association between UCHL1 S18Y and Parkinson's disease SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Article DE case-control study; neuroepidemiology; Parkinson's disease; UCHL1 ID TERMINAL HYDROLASE-L1 GENE; UCH-L1 GENE; SUSCEPTIBILITY GENE; L1 GENE; POLYMORPHISM; RISK AB UCHL1 has been proposed as a candidate gene for Parkinson's disease (PD). A meta-analysis of white and Asian subjects reported an inverse association between the non-synonymous UCHL1 S18Y polymorphism and PD risk. However, this finding was not replicated in a large case-control study and updated meta-analysis restricted to white subjects. We performed a case-control study of 1757 PD patients recruited from movement disorder clinics and 2016 unrelated controls from four regions of the United States. All subjects self-reported as white. We did not observe evidence for an association between S18Y genotypes and PD (overall P-value for association: P = 0.42). After adjustment for age, sex, and recruitment region, the odds ratio for Y/S versus S/S was 0.91 (95% CI: 0.78-1.06) and for Y/Y versus S/S was 0.87 (95% CI: 0.58-1.29). We also did not observe a significant association for recessive or dominant models of inheritance, or after stratification by age at onset, age at blood draw, sex, family history of PD, or recruitment region. Our results suggest that UCHL1 S18Y is not a major susceptibility factor for PD in white populations although we cannot exclude the possibility that the S18Y variant exerts weak effects on risk, particularly in early-onset disease. C1 [Samii, Ali; Zabetian, Cyrus P.] VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin S 1820, Seattle, WA 98108 USA. [Hutter, Carolyn M.; Edwards, Karen L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Samii, Ali; Bird, Thomas D.; Zabetian, Cyrus P.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98195 USA. [Factor, Stewart A.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. [Nutt, John G.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Higgins, Donald S.] Albany Med Ctr, Parkinsons Dis & Movement Disorder Clin, Albany, NY USA. [Griffith, Alida; Leis, Berta C.] Evergreen Hosp Med Ctr, Booth Gardner Parkinsons Care Ctr, Kirkland, WA USA. [Roberts, John W.] Virginia Mason Med Ctr, Seattle, WA 98101 USA. [Montimurro, Jennifer S.; Kay, Denise M.; Payami, Haydeh] New York State Dept Hlth, Genom Inst, Wadsworth Ctr, Albany, NY USA. RP Zabetian, CP (reprint author), VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin S 1820, 1660 S Columbian Way, Seattle, WA 98108 USA. EM zabetian@u.washington.edu OI Zabetian, Cyrus/0000-0002-7739-4306; Kay, Denise/0000-0002-9928-2698 FU NIA NIH HHS [P30 AG008017]; NINDS NIH HHS [K08 NS044138-05, R01 NS036960, K08 NS044138] NR 26 TC 21 Z9 21 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD FEB PY 2008 VL 15 IS 2 BP 134 EP 139 DI 10.1111/j.1468-1331.2007.02012.x PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 253ZX UT WOS:000252557200012 PM 18093156 ER PT J AU Mills, C Makwana, M Wallace, A Benn, S Schmidt, H Tegeder, I Costigan, M Brown, RH Raivich, G Woolf, CJ AF Mills, Charles Makwana, Milan Wallace, Adam Benn, Susanna Schmidt, Helmut Tegeder, Irmgard Costigan, Michael Brown, Robert H., Jr. Raivich, Gennadij Woolf, Clifford J. TI Ro5-4864 promotes neonatal motor neuron survival and nerve regeneration in adult rats SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE apoptosis; axotomy; cell death; peripheral benzodiazepine rece ptor; PK 11195 ID PERIPHERAL BENZODIAZEPINE-RECEPTOR; DORSAL-ROOT GANGLION; DIAZEPAM-BINDING INHIBITOR; PROTEIN 18 KDA; SCIATIC-NERVE; GROWTH-FACTOR; AUTORADIOGRAPHIC LOCALIZATION; DEVELOPMENTAL REGULATION; AXONAL REGENERATION; APOPTOSIS INDUCTION AB The translocator protein (18 kDa; TSPO), formerly known as the peripheral benzodiazepine receptor, is an outer mitochondrial membrane protein that associates with the mitochondrial permeability transition pore to regulate both steroidogenesis and apoptosis. TSPO expression is induced in adult dorsal root ganglion (DRG) sensory neurons after peripheral nerve injury and a TSPO receptor ligand, Ro5-4864, enhances DRG neurite growth in vitro and axonal regeneration in vivo. We have now found that TSPO is induced in neonatal motor neurons after peripheral nerve injury and have evaluated its involvement in neonatal and adult sensory and motor neuron survival, and in adult motor neuron regeneration. The TSPO ligand Ro5-4864 rescued cultured neonatal DRG neurons from nerve growth factor withdrawal-induced apoptosis and protected neonatal spinal cord motor neurons from death due to sciatic nerve axotomy. However, Ro5-4864 had only a small neuroprotective effect on adult facial motor neurons after axotomy, did not delay onset or prolong survival in SOD1 mutant mice, and failed to protect adult DRG neurons from sciatic nerve injury-induced death. In contrast, Ro5-4864 substantially enhanced adult facial motor neuron nerve regeneration and restoration of function after facial nerve axotomy. These data indicate a selective sensitivity of neonatal sensory and motor neurons to survival in response to Ro5-4864, which highlights that survival in injured immature neurons cannot necessarily predict success in adults. Furthermore, although Ro5-4864 is only a very weak promoter of survival in adult neurons, it significantly enhances regeneration and functional recovery in adults. C1 [Mills, Charles; Costigan, Michael; Woolf, Clifford J.] Massachusetts Gen Hosp, Neural Plast Res Grp, Dept Anesthesia & Crit Care, Charlestown, MA 02129 USA. [Mills, Charles; Costigan, Michael; Woolf, Clifford J.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Makwana, Milan; Wallace, Adam; Raivich, Gennadij] UCL, Ctr Perinatal Brain Protect & Repair, Dept Obstet & Gynaecol, London WC1E 6HX, England. [Benn, Susanna; Brown, Robert H., Jr.] Massachusetts Gen Hosp, Cecil B Day Lab Neuromuscular Res, Charlestown, MA 02129 USA. [Schmidt, Helmut; Tegeder, Irmgard] Univ Frankfurt Klinikum, Pharmazentrum Frankfurt, Inst Klin Pharmakol, Zentrum Arzneimittelforsch Entwicklung Sicherheit, D-60590 Frankfurt, Germany. RP Mills, C (reprint author), Neurocrine Biosci, 12790 Camino Real, San Diego, CA 92130 USA. EM cmills@neurocrine.com RI Raivich, Gennadij/A-6770-2011; OI Tegeder, Irmgard/0000-0001-7524-8025 FU NINDS NIH HHS [NS45459] NR 70 TC 26 Z9 29 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD FEB PY 2008 VL 27 IS 4 BP 937 EP 946 DI 10.1111/j.1460-9568.2008.06065.x PG 10 WC Neurosciences SC Neurosciences & Neurology GA 272UP UT WOS:000253886100014 PM 18333964 ER PT J AU Kearney, N Friese, C AF Kearney, Nora Friese, Christopher TI Clinical practice guidelines for the use of colony-stimulating factors in cancer treatment: Implications for oncology nurses SO EUROPEAN JOURNAL OF ONCOLOGY NURSING LA English DT Article DE chemotherapy-induced neutropenia; febrile neutropenia; prophylaxis; colony-stimulating factors; granulocyte colony-stimulating factors; clinical guidelines ID CHEMOTHERAPY-INDUCED NEUTROPENIA; NON-HODGKINS-LYMPHOMA; CELL LUNG-CANCER; SINGLE-ADMINISTRATION PEGFILGRASTIM; INDUCED FEBRILE NEUTROPENIA; EARLY BREAST-CANCER; DOSE-INTENSITY; PHASE-III; ADJUVANT CHEMOTHERAPY; ELDERLY-PATIENTS AB Chemotherapy-induced neutropenia (CIN) is a common and serious toxicity of cancer chemotherapy. It can lead to febrile neutropenia (FN), which often requires patients to be hospitalised for intravenous antibiotic therapy. Chemotherapy dose reductions or delays, which can compromise clinical outcomes, may also result from CIN and FN. Prophylactic use of colony-stimulating factors (CSFs) reduces the incidence, duration, and severity of FIN, and there is evidence that it helps maintain scheduled chemotherapy dose delivery. In 2006, three organisations published new or updated guidelines for the use of CSFs in cancer treatment. Each recommends that FN risk be determined individually for each patient, taking into account patient- and disease-specific risk factors, the chemotherapy regimen, and treatment intent. Particular consideration should be given to patients who are >= 65 years old, receiving chemotherapy regimens associated with >= 20% risk of FN, receiving dose-dense chemotherapy, and receiving treatment that is adjuvant, potentially curative, or intended to prolong survival. Accordingly, oncology nurses can play an important role in assessing and identifying patients at risk for FN before every chemotherapy cycle. There is evidence that, regardless of practice type or size, implementing guidelines for CSF use within a multidisciplinary team improves patient outcomes. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Kearney, Nora] Univ Stirling, Canc Care Res Ctr, Stirling FK9 4NF, Scotland. [Friese, Christopher] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kearney, N (reprint author), Univ Stirling, Canc Care Res Ctr, Unit 1,Scion House, Stirling FK9 4NF, Scotland. EM nora.kearney@stir.ac.uk; christopher_friese@dfci.harvard.edu OI Friese, Christopher/0000-0002-2281-2056 NR 53 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1462-3889 J9 EUR J ONCOL NURS JI Eur. J. Oncol. Nurs. PD FEB PY 2008 VL 12 IS 1 BP 14 EP 25 DI 10.1016/j.ejon.2007.10.001 PG 12 WC Oncology; Nursing SC Oncology; Nursing GA 288GG UT WOS:000254973600003 PM 18291720 ER PT J AU Papakostas, GI Nelson, JC Kasper, S Mooller, HJ AF Papakostas, George I. Nelson, J. Craig Kasper, Siegfried Moeller, Hans-Juergen TI A meta-analysis of clinical trials comparing reboxetine, a norepinephrine reuptake inhibitor, with selective serotonin reuptake inhibitors for the treatment of major depressive disorder SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Article DE reboxetine; SSRI; major; depressive; disorder ID DOUBLE-BLIND; SEXUAL DYSFUNCTION; CITALOPRAM; EFFICACY; FLUOXETINE; ANTIDEPRESSANTS; TOLERABILITY; PREDICTION; SYMPTOMS; PLACEBO AB The goat of the present work was to conduct a meta-analysis comparing reboxetine and the selective serotonin reuptake inhibitors (SSRIs) for major depressive disorder (MDD). Medline/Pubmed was searched for double-blind, randomized trials comparing these two agents for MDD. The makers of reboxetine (Pfizer Inc.) were also contacted to provide missing data and/or unpublished studies. 9 trials (n=2641) were combined using a random effects model. Response rates were comparable between the SSRI (63.9%) and reboxetine (59.2%)-treated groups (p=0.118). There was no significant difference in the degree of improvement in psychosocial functioning, as measured by the social adaptation self-evaluation scale, between the two groups. Overall discontinuation rates (25.1% versus 32.0%; p=0.015), and the rate of discontinuation due to intolerance (8.5% versus 12.6%; p=0.007) favored SSRI treatment. The rate of discontinuation due to lack of efficacy did not differ significantly between the two groups. SSRI-treated patients were more likely to experience nausea, hypersomnia, and fatigue. Reboxetine-treated patients were more likely to experience constipation, difficulty urinating, and insomnia. These results suggest that the NRI reboxetine and the SSRIs differ with respect to their side-effect profile and overall tolerability but not their efficacy in treating MDD. (C) 2007 Elsevier B.V. and ECNP. All rights reserved. C1 [Papakostas, George I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [Nelson, J. Craig] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Kasper, Siegfried] Vienna Med Univ, Dept Gen Psychiat, Vienna, Austria. [Moeller, Hans-Juergen] Univ Munich, Dept Psychiat, D-8000 Munich, Germany. RP Papakostas, GI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, 15 Parkman St,WAC 812, Boston, MA 02114 USA. EM gpapakostas@partners.org RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 FU NIMH NIH HHS [K23 MH069629] NR 34 TC 42 Z9 44 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD FEB PY 2008 VL 18 IS 2 BP 122 EP 127 DI 10.1016/j.euroneuro.2007.07.005 PG 6 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 260VH UT WOS:000253038000006 PM 17719752 ER PT J AU Xie, L Palmsten, K MacDonald, B Kieran, MW Potenta, S Vong, S Kalluri, R AF Xie, Liang Palmsten, Kristin MacDonald, Brian Kieran, Mark W. Potenta, Scott Vong, Sylvia Kalluri, Raghu TI Basement membrane derived fibulin-1 and fibulin-5 function as angiogenesis inhibitors and suppress tumor growth SO EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article DE fibulin; angiogenesis; tumor; neostatin; basement membrane; cancer ID BREAST-CANCER; IN-VIVO; ENDOGENOUS INHIBITORS; EXTRACELLULAR-MATRIX; HUMAN OVARIAN; PROTEIN; EXPRESSION; FIBRONECTIN; DOMAINS; CELLS AB The fibulins are a family of secreted glycoproteins that are characterized by repeated epidermal-growth-factor-like domains and a unique C-terminus structure. Fibulins modulate cell morphology, growth, adhesion, and motility. Our initial basement membrane degradome screen using Cathepsin D, a tumor microenvironment-associated protease, contained fragments of fibulin-1 and full length fibulin-5. In this report, we evaluate the anti-angiogenic activity of fibulin-1 and fibulin-5. Tumor studies demonstrate that both fibulin-1 and fibulin-5 suppress HT1080 tumor growth. CD31 labeling and TUNEL assay further reveal that fibulin-1 suppression of HT1080 tumor growth is associated with diminished angiogenesis and also enhanced apoptosis of endothelial cells and tumor cells. In contrast, fibulin-5 inhibits tumor angiogenesis with a minimal anti-apoptotic affect. Cathepsin D digestion of fibulin-1 produces a fragment with nearly the same molecular weight as fibulin-5, and this fragment (named Neostatin) inhibits endothelial cell proliferation. Additionally, degradation of basement membrane by cathepsin D liberates both fibulin-1 fragments and fibulin-5, which function to inhibit angiogenesis. C1 [Xie, Liang; Palmsten, Kristin; MacDonald, Brian; Potenta, Scott; Vong, Sylvia; Kalluri, Raghu] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Matrix Biol, Boston, MA 02215 USA. [Kieran, Mark W.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Kalluri, Raghu] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Kalluri, Raghu] Harvard Univ, MIT, Div Hlth Sci & Technol, Boston, MA 02215 USA. RP Kalluri, R (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Matrix Biol, 330 Brookline Ave, Boston, MA 02215 USA. EM rkalluri@bidmc.harvard.edu RI Kalluri, Raghu/E-2677-2015; OI Kalluri, Raghu/0000-0002-2190-547X; Kieran, Mark/0000-0003-2184-7692 FU NIAAA NIH HHS [AA 13913]; NIDDK NIH HHS [DK62987, DK 61688, DK55001] NR 26 TC 42 Z9 46 U1 2 U2 8 PU SOC EXPERIMENTAL BIOLOGY MEDICINE PI MAYWOOD PA 195 WEST SPRING VALLEY AVE, MAYWOOD, NJ 07607-1727 USA SN 1535-3702 J9 EXP BIOL MED JI Exp. Biol. Med. PD FEB PY 2008 VL 233 IS 2 BP 155 EP 162 DI 10.3181/0706-RM-167 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 256XZ UT WOS:000252764500007 PM 18222970 ER PT J AU Greenberg, CC Bafford, AC Golshan, M AF Greenberg, Caprice C. Bafford, Andrea C. Golshan, Mehra TI Is axillary dissection needed in node-positive breast cancer.? SO EXPERT REVIEW OF ANTICANCER THERAPY LA English DT Review DE axillary node dissection; breast cancer; sentinel node biopsy ID SENTINEL-NODE; LYMPH-NODES; BIOPSY; METASTASES; CARCINOMA; NOMOGRAM; SURGERY; METAANALYSIS; RADIATION; SURVIVAL AB The standard of care in the management of the axilla for a woman with breast cancer was traditionally a level I and II axillary lymph node dissection (ALND). Since the pivotal studies in the mid-1990s, sentinel lymph node biopsy (SLNB) in breast carcinoma has come to replace ALND in women with clinically negative axillas. With the increased use of SLNB in women who present with breast carcinoma, the role of completion ALND for a positive sentinel lymph node has been challenged. We review the literature available and discuss future directions in identifying a subgroup who may avoid an ALND. C1 [Greenberg, Caprice C.; Bafford, Andrea C.; Golshan, Mehra] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. [Greenberg, Caprice C.; Bafford, Andrea C.; Golshan, Mehra] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Golshan, M (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. EM ccgreenberg@partners.org; acbafford@partners.org; mgolshan@partners.org NR 28 TC 3 Z9 3 U1 0 U2 0 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7140 J9 EXPERT REV ANTICANC JI Expert Rev. Anticancer Ther PD FEB PY 2008 VL 8 IS 2 BP 195 EP 198 DI 10.1586/14737140.8.2.195 PG 4 WC Oncology SC Oncology GA 343EV UT WOS:000258836600015 PM 18279060 ER PT J AU Guerra, CE McDonald, VJ Ravenell, KL Asch, DA Shea, JA AF Guerra, Carmen E. McDonald, Vanessa J. Ravenell, Karima L. Asch, David A. Shea, Judy A. TI Effect of race on patient expectations regarding their primary care physicians SO FAMILY PRACTICE LA English DT Article DE communication; expectations; health literacy; patient; physician relationships; race ID HEALTH LITERACY; AFRICAN-AMERICAN; GENERAL-PRACTICE; OFFICE VISITS; SATISFACTION; COMORBIDITY; INTERVENTIONS; PERCEPTIONS; DIFFERENCE; MORBIDITY AB Background. Fulfilment of patients' expectations has been associated with greater patient satisfaction with care and greater adherence to medical advice. However, little is know about how race influences patient expectations. Objective. To determine the association between patient race and patient expectations of their primary care physician. Methods. The design was a cross-sectional study. Setting and participants were sample of 709 primary care patients from four clinic sites at the Philadelphia Veterans Affairs Medical Center and the University of Pennsylvania Health System. The measures were an expectations instrument asking patients to rate the necessity of the physician performing 13 activities during the index visit, self-reported race, demographics, the Rapid Estimate of Adult Literacy in Medicine, the Charlson Comorbidity Index and SF-12. Results. After adjusting for age, sex, education, clinic site, comorbidity, health literacy and health status, African Americans were more likely to report it was absolutely necessary for the physician to refer them to a specialist [AOR 1.55 (95% confidence interval, CI, 1.09-2.21), P = 0.01], order tests [AOR 1.59 (95% CI 1.11-2.27), P = 0.01] and conduct each of the six physical exam components. Conclusions. African American race is associated with greater expectations of the primary care physicians. More research is needed to confirm the differential expectations by race and determine the reasons for the differential expectations. C1 [Guerra, Carmen E.; McDonald, Vanessa J.; Ravenell, Karima L.; Asch, David A.; Shea, Judy A.] Univ Penn, Philadelphia, PA 19104 USA. [Guerra, Carmen E.; McDonald, Vanessa J.; Ravenell, Karima L.; Asch, David A.; Shea, Judy A.] Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Guerra, Carmen E.; Asch, David A.; Shea, Judy A.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Asch, David A.; Shea, Judy A.] Philadelphia Vet Affairs Med, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Guerra, CE (reprint author), Univ Penn, 1221 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM carmen.guerra@uphs.upenn.edu OI Asch, David/0000-0002-7970-286X FU NCI NIH HHS [K01 CA-097925] NR 47 TC 5 Z9 5 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0263-2136 J9 FAM PRACT JI Fam. Pr. PD FEB PY 2008 VL 25 IS 1 BP 49 EP 55 DI 10.1093/fampra/cmn005 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 278NQ UT WOS:000254294000009 PM 18304974 ER PT J AU Amory, JK Coviello, AD Page, ST Anawalt, BD Matsumoto, AM Bremner, WJ AF Amory, John K. Coviello, Andrea D. Page, Stephanie T. Anawalt, Bradley D. Matsumoto, Alvin M. Bremner, William J. TI Serum 17-hydroxyprogesterone strongly correlates with intratesticular testosterone in gonadotropin-suppressed normal men receiving various dosages of human chorionic gonadotropin SO FERTILITY AND STERILITY LA English DT Article DE intratesticular testosterone; 17-hydroxyprogesterone; male infertility; male contraception ID SPERM PRODUCTION; ESTROGEN-TREATMENT; PROSTATIC-CANCER; HCG STIMULATION; STEROID-LEVELS; HUMAN TESTIS; SPERMATOGENESIS; ANDROGENS; HORMONE; INFERTILITY AB Objective: To determine if serum concentrations of testosterone precursors would correlate with intratesticular testosterone (ITT) concentration measured directly by testicular aspiration and allow for a less invasive means of inferring ITT. Design: Controlled clinical study. Setting: Healthy volunteers in an academic research environment. Patient(s): Twenty-nine normal men. Intervention(s): We determined ITT concentration by testicular aspiration before and after treatment in men receiving exogenous T to block endogenous gonadotropin production and randomly assigned to one of four doses of hCG (0, 125 IU, 250 IU, or 500 IU every other day) for 3 weeks. Main Outcome Measure(s): The association between serum 17-hydroxyprogesterone (17OH-P), androstenedione, and DHEA and ITT. Result(s): With T administration alone, serum 17OH-P decreased significantly and increased significantly when 500 IU hCG was administered. End-of-treatment ITT strongly correlated with serum 17OH-P. Moreover, serum 17OH-P, but not androstenedione or DHEA, was independently associated with end-of-treatment ITT by multivariate linear regression. Conclusion(s): Serum 17OH-P is highly correlated with ITT in gonadotropin-suppressed normal men receiving T and stimulated with hCG. Serum 17OH-P is a surrogate biomarker of ITT and may be useful in research and in men receiving gonadotropin therapy for infertility. (Fertil Steril (R) 2008;89:380-6. (c) 2008 by American Society for Reproductive Medicine.) C1 [Amory, John K.; Anawalt, Bradley D.; Matsumoto, Alvin M.; Bremner, William J.] Univ Washington, Dept Med, Seattle, WA USA. [Coviello, Andrea D.] Boston Univ, Dept Med, Boston, MA 02215 USA. [Page, Stephanie T.; Anawalt, Bradley D.; Matsumoto, Alvin M.] Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. [Matsumoto, Alvin M.] Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. RP Amory, JK (reprint author), Univ Washington, Box 356429, 1959 NE Pacific, Seattle, WA 98195 USA. EM jamory@u.washington.edu FU NCRR NIH HHS [M01 RR000037, M01-RR-00037]; NIA NIH HHS [K23 AG027238-04, K23 AG027238]; NICHD NIH HHS [U54 HD012629, K23 HD45386, U54 HD042454-080001, K23 HD045386, K23 HD045386-04, U54 HD042454, U54 HD-42454, U54-HD-12629] NR 25 TC 5 Z9 5 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD FEB PY 2008 VL 89 IS 2 BP 380 EP 386 DI 10.1016/j.fertnstert.2007.02.059 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 263WB UT WOS:000253246100016 PM 17462643 ER PT J AU Wise, L Correia, A AF Wise, Lori Correia, Angela TI A review of nonpharmacologic and pharmacologic therapies for smoking cessation SO FORMULARY LA English DT Article ID SUSTAINED-RELEASE BUPROPION; RECEPTOR PARTIAL AGONIST; RANDOMIZED CONTROLLED-TRIAL; THEOPHYLLINE DISPOSITION; CIGARETTE-SMOKING; DRUG-INTERACTIONS; FOLLOW-UP; VARENICLINE; PLACEBO; NICOTINE AB Cigarette smoking is one of the leading causes of the development of cardiovascular disease and premature death among men and women in the United States. Smoking is associated with increased morbidity and mortality among both smokers and nonsmokers who are exposed to secondhand smoke. Smoking cessation can improve the health and overall outcomes of smokers almost immediately. Multiple attempts at cessation are often necessary to achieve complete abstinence because of the highly addictive properties of nicotine. Many treatment options, both nonpharmacologic and pharmacologic, are available to assist patients who are attempting to quit smoking. Cognitive behavior therapy has been demonstrated to be efficacious, prolonging abstinence rates when used in combination with pharmacologic therapy. Traditional pharmacologic therapies, including nicotine replacement therapy and bupropion, have been demonstrated to be effective in patients who are attempting smoking cessation. The approval of varenicline, the newest agent for smoking cessation, has provided clinicians with an additional treatment option. Clonidine and nortriptyline, although not approved by FDA for smoking cessation, have also been studied in this patient population; results have been conflicting. C1 [Wise, Lori; Correia, Angela] VA Boston Healthcare Syst, W Roxbury, MA USA. [Wise, Lori; Correia, Angela] Massachusetts Coll Pharm & Hlth Sci, Boston, MA USA. RP Wise, L (reprint author), VA Boston Healthcare Syst, W Roxbury, MA USA. NR 50 TC 1 Z9 1 U1 1 U2 2 PU ADVANSTAR COMMUNICATIONS PI DULUTH PA 131 W FIRST ST, DULUTH, MN 55802 USA SN 1082-801X J9 FORMULARY JI Formulary PD FEB PY 2008 VL 43 IS 2 BP 44 EP + PG 20 GA 265AP UT WOS:000253331800003 ER PT J AU Guo, Z Ran, Q Roberts, LJ Zhou, L Richardson, A Sharan, C Wu, D Yang, H AF Guo, ZhongMao Ran, Qitao Roberts, L. Jackson, II Zhou, Lichun Richardson, Arlan Sharan, Chakradhari Wu, DongFan Yang, Hong TI Suppression of atherogenesis by overexpression of glutathione peroxidase-4 in apolipoprotein E-deficient mice SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE glutathione peroxidase-4; atherosclerosis; lipid peroxidation; monocyte adhesion; necrosis; apoptosis; free radicals ID SMOOTH-MUSCLE-CELLS; OXIDATIVE STRESS; ENDOTHELIAL-CELLS; ANTIOXIDANT ENZYMES; INDUCED APOPTOSIS; MAMMALIAN-CELLS; TRANSGENIC MICE; HYDROPEROXIDE; ATHEROSCLEROSIS; EXPRESSION AB Accmulation of oxidized lipids in the arterial wall contributes to atherosclerosis. Glutathione peroxidase-4 (GPx4) is a hydroperoxide scavenger that removes oxidative modifications from lipids such as free fatty acids, cholesterols, and phospholipids. Here, we set Out to assess the effects of GPx4 overexpression on atherosclerosis in apolipoprotein E-deficient (ApoE(-/-)) mice. The results revealed that atherosclerotic lesions in the aortic tree and aortic sinus of ApoE(-/-) mice overexpressing GPx4 (hGPx4Tg/ApoE(-/-)) were significantly smaller than those of ApoE(-/-)control mice. GPx4 overexpression also diminished signs of advanced lesions in the aortic sinus, as seen by a decreased occurrence of fibrous caps and acellular areas among hGPx4Tg/ApoE(-/-) animals. This delay of atherosclerosis in hGPx4Tg/ApoE(-/-) mice con-elated with reduced aortic F(2)-isoprostane levels (R(2)=0.75, p<0.01). In addition, overexpression of GPx4 lessened atherogenic events induced by the oxidized lipids lysophosphatidylcholine and 7-ketocholesterol, including upregulated expression of adhesion molecules in endothelial cells and adhesion of monocytes to endothelial cells, as well as endothelial necrosis and apoptosis. These results suggest that overexpression of GPx4 inhibits the development of atherosclerosis by decreasing lipid peroxidation and inhibiting the sensitivity of vascular cells to oxidized lipids. Published by Elsevier Inc. C1 [Guo, ZhongMao; Zhou, Lichun; Sharan, Chakradhari; Wu, DongFan; Yang, Hong] Meharry Med Coll, Dept Cardiovasc Biol, Nashville, TN 37208 USA. [Ran, Qitao; Richardson, Arlan] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Ran, Qitao; Richardson, Arlan] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Ran, Qitao; Richardson, Arlan] S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Audie L Murphy Div, San Antonio, TX 78229 USA. [Roberts, L. Jackson, II] Vanderbilt Univ, Dept Pharmacol, Nashville, TN 37232 USA. RP Yang, H (reprint author), Meharry Med Coll, Dept Cardiovasc Biol, Nashville, TN 37208 USA. EM hyaiig@mmc.edu FU NHLBI NIH HHS [HL076623, K01 HL076623, K01 HL076623-04]; NIEHS NIH HHS [ES014471, R01 ES014472]; NIGMS NIH HHS [GM08037, S06 GM008037] NR 42 TC 35 Z9 36 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD FEB 1 PY 2008 VL 44 IS 3 BP 343 EP 352 DI 10.1016/j.frecradbiomed.2007.09.009 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 257WM UT WOS:000252829500012 PM 18215741 ER PT J AU Valente, AJ Zhou, Q Lu, Z He, W Qiang, M Ma, W Li, G Wang, L Banfi, B Steger, K Krause, KH Clark, RA Li, S AF Valente, Anthony J. Zhou, Qing Lu, Zhenhua He, Weijing Qiang, Mei Ma, Wuqiong Li, Guiming Wang, Long Banfi, Botond Steger, Klaus Krause, Karl-Heinz Clark, Robert A. Li, Senlin TI Regulation of NOX1 expression by GATA, HNF-1 alpha, and Cdx transcription factors SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE NOX1; NADPH oxidase; GATA; HNF-1 alpha; Cdx; transcriptional regulation; colon ID COLON EPITHELIAL-CELLS; SEQUENCE-BINDING PROTEIN; NADPH-OXIDASE; HOMEOBOX GENE; INTERFERON-GAMMA; GP91(PHOX) EXPRESSION; INTESTINAL EPITHELIUM; NAD(P)H OXIDASE-1; ISOMALTASE GENE; REACTIVE OXYGEN AB NOX1, a member of the NOX family of NADPH oxidases, is expressed primarily in colon epithelium, where it may function in host defense and growth regulation. We investigated factors responsible for its transcriptional regulation in vitro and its expression in vivo. Analysis of promoter constructs in the CaCo2 cell line identified a complex element between -422 and - 291 critical for promoter activity. This element contained four sites that bound GATA-4, -5, and -6 in vitro with varied affinities. One site also bound the caudal-related homeodomain proteins Cdx1 and Cdx2, whereas another also bound hepatocyte nuclear factor-1 alpha (HNF-1 alpha). GATA-6, HNF-1 alpha, and Cdx2 also bound to this region in the intact chromatin of CaCo2 cells. These factors demonstrated cooperativity when transactivating the NOX1 promoter. NOX1 mRNA was detected in human colon epithelial cells along the crypt-villus axis. A gradient of NOX1 mRNA expression was seen in the colons of normal as well as germ-free mice, with significantly higher levels in distal compared with proximal segments. The expression gradients of NOX1 mRNA in the colon paralleled those of GATA-6, HNF- 1 alpha, and Cdx1. These data indicate that developmental, tissue-restricted transcription factors play a key role in NOX1 regulation in vivo. (c) 2007 Elsevier Inc. All rights reserved. C1 [Valente, Anthony J.; Zhou, Qing; Lu, Zhenhua; He, Weijing; Ma, Wuqiong; Li, Guiming; Clark, Robert A.; Li, Senlin] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Valente, Anthony J.; Zhou, Qing; Lu, Zhenhua; He, Weijing; Ma, Wuqiong; Li, Guiming; Clark, Robert A.; Li, Senlin] S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78229 USA. [Qiang, Mei] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Wang, Long] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Banfi, Botond] Univ Iowa, Inflammat Program, Dept Anat & Cell Biol, Iowa City, IA 52242 USA. [Banfi, Botond] Univ Iowa, Inflammat Program, Dept Med, Iowa City, IA 52242 USA. [Steger, Klaus] Inst Vet Anat, D-35392 Giessen, Germany. [Krause, Karl-Heinz] Univ Geneva, Dept Pathol, CH-1211 Geneva, Switzerland. [Krause, Karl-Heinz] Univ Geneva, Dept Immunol, CH-1211 Geneva, Switzerland. [Krause, Karl-Heinz] Univ Geneva, Dept Clin Pathol, CH-1211 Geneva, Switzerland. RP Valente, AJ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM valente@uthscsa.edu; lisl@uthscsa.edu RI Krause, Karl-Heinz/E-8030-2011 FU NIA NIH HHS [AG019519, AG024579, R01 AG019519]; NIAID NIH HHS [AI020866, R01 AI020866]; NINDS NIH HHS [NS046004] NR 46 TC 17 Z9 18 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD FEB 1 PY 2008 VL 44 IS 3 BP 430 EP 443 DI 10.1016/j.freeradbiomed.2007.10.035 PG 14 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 257WM UT WOS:000252829500020 PM 18005670 ER PT J AU Golshayan, AR Brick, AJ Choueiri, TK AF Golshayan, Ali-Reza Brick, Ashley J. Choueiri, Toni K. TI Predicting outcome to VEGF-targeted therapy in metastatic clear-cell renal cell carcinoma: data from recent studies SO FUTURE ONCOLOGY LA English DT Review DE metastatic clear-cell renal cell carcinoma; molecular markers; prognostic and predictive factors; VEGF; von Hippel-Lindau ID ENDOTHELIAL GROWTH-FACTOR; CARBONIC-ANHYDRASE-IX; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; PROGNOSTIC-FACTORS; INTERFERON-ALPHA; FACTOR-RECEPTOR; SURVIVAL; CANCER; EXPRESSION; INTERLEUKIN-2 AB Attempts to predict outcome in patients with metastatic clear-cell renal cell carcinoma (RCC) have conventionally been based on pretherapy clinical factors such as performance status, disease-free interval, number of metastatic sites and several laboratory variables. These factors were developed before the era of VEGF-targeted therapy. Recent analysis from trials with anti-VEGF agents indicate that these factors continue to be of major importance in patient prognostication. Additionally, several serum and molecular markers, many of which relate to certain alterations of the von Hippel-Lindau pathway, are currently being investigated. Responses to VEGF-targeted agents appear to be related to a greater modulation of serum VEGF and soluble VEGF receptor levels. The impact of von Hippel-Lindau gene status on response to VEGF-targeted therapy was tested in a large study and was not found to predict a higher response rate to these agents. However, a subset of von Hippel-Lindau mutations that predict a 'loss of function' of the von Hippel-Lindau gene seem to have the best response to these agents. Future prognostic models will incorporate molecular markers with clinical variables to refine prognosis and prediction in metastatic clear-cell RCC patients treated with novel VEGF-targeted agents. These models, if externally and prospectively validated, will culminate in the rational selection of patients for specific VEGF-directed therapeutics. C1 [Choueiri, Toni K.] Harvard Univ, Brigham & Womens Hosp, Lank Ctr Genitourinary Oncol, Dana Farber Canc Inst,Med Sch, Boston, MA 02115 USA. [Golshayan, Ali-Reza] Cleveland Clin Taussig Canc Ctr, Cleveland, OH 44195 USA. RP Choueiri, TK (reprint author), Harvard Univ, Brigham & Womens Hosp, Lank Ctr Genitourinary Oncol, Dana Farber Canc Inst,Med Sch, 44 Binney St, Boston, MA 02115 USA. EM golshaa@ccf.org; Ashley_Brick@dfci.harvard.edu; Toni_Choueiri@dfci.harvard.edu NR 58 TC 18 Z9 18 U1 1 U2 2 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1479-6694 J9 FUTURE ONCOL JI Future Oncol. PD FEB PY 2008 VL 4 IS 1 BP 85 EP 92 DI 10.2217/14796694.4.1.85 PG 8 WC Oncology SC Oncology GA 384EM UT WOS:000261727100013 PM 18241003 ER PT J AU Nagahama, K Ogawa, A Shirane, K Shimomura, Y Sugimoto, K Mizoguchi, A AF Nagahama, Kiyotaka Ogawa, Atsuhiro Shirane, Katsunori Shimomura, Yasuko Sugimoto, Ken Mizoguchi, Atsushi TI Protein kinase C theta plays a fundamental role in different types of chronic colitis SO GASTROENTEROLOGY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; T-CELL-RECEPTOR; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CHRONIC INTESTINAL INFLAMMATION; KAPPA-B ACTIVATION; ALPHA MUTANT MICE; PKC-THETA; DEFICIENT MICE; ULCERATIVE-COLITIS; IN-VIVO AB Background & Aims: Dysregulated host/microbial interactions induce the development of colitis by activating deleterious acquired immune responses. Activation of CD4(+) T cells is mainly induced through signaling machinery associated with immunologic synapse (IS). A key molecule associated with the IS is protein kinase C (PKC) theta. However, the role of PKC theta in the pathogenesis of colitis has not fully been defined. Methods: The role of PKC theta for the acquired-immune responses involved in the development of different types of colitis (CD45RB model, T-cell receptor [TCR] alpha knockout [KO] mice and interleukin [IL]-2KO mice) was examined by generating double KO mice and by utilizing cell transfer approaches. Results: Adoptive transfer of PKC theta-deficient naive CD4+ T cells failed to induce T helper cell (Th) 1-mediated colitis in the immune-deficient host (CD45RB model). Development of Th2-mediated colitis in TCR alpha KO mice was also inhibited by the absence of PKC theta. In IL-2KO mice, which develop colitis because of dysregulated T-cell homeostasis, deficiency of PKC theta in CD4(+) T cells failed to induce the development of severe colitis. Interestingly, absence of PKC theta led to a remarkable decrease in the proliferation, but not apoptosis, of colonic memory CD4(+) T cells. This impaired proliferation resulted in a marked decrease in the colonic CD4(+) T cells that are capable of producing IL-17. In addition, deficiency of PKC theta inhibited the production of Th2 cytokines by colonic CD4(+) T cells. Conclusions: PKC theta serves as a common and fundamental signaling molecule in the development of different types of colitis and may represent an attractive target for treating inflammatory bowel disease. C1 [Nagahama, Kiyotaka; Ogawa, Atsuhiro; Shirane, Katsunori; Shimomura, Yasuko; Sugimoto, Ken; Mizoguchi, Atsushi] Massachusetts Gen Hosp, Dept Pathol Expt Pathol, Boston, MA USA. [Nagahama, Kiyotaka; Ogawa, Atsuhiro; Shirane, Katsunori; Shimomura, Yasuko; Sugimoto, Ken; Mizoguchi, Atsushi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Mizoguchi, Atsushi] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA USA. RP Mizoguchi, A (reprint author), Massachusetts Gen Hosp, Expt Pathol Unit, Simches 8234, 185 Cambridge St, Boston, MA 02114 USA. EM amizoguchi@partners.org FU NIDDK NIH HHS [DK64351] NR 44 TC 22 Z9 23 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 2008 VL 134 IS 2 BP 459 EP 469 DI 10.1053/j.gastro.2007.11.005 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 260TI UT WOS:000253032900016 PM 18155708 ER PT J AU Mizoguchi, E Hachiya, Y Kawada, M Nagatani, K Ogawa, A Sugimoto, K Mizoguchi, A Podolsky, DK AF Mizoguchi, Emiko Hachiya, Yuriko Kawada, Mayumi Nagatani, Katsuya Ogawa, Atsuhiro Sugimoto, Ken Mizoguchi, Atsushi Podolsky, Daniel K. TI TNF receptor type I-dependent activation of innate responses to reduce intestinal damage-associated mortality SO GASTROENTEROLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; INFLAMMATORY-BOWEL-DISEASE; ALPHA-MUTANT MICE; EPITHELIAL-CELLS; CHRONIC COLITIS; CROHNS-DISEASE; INFLIXIMAB; APOPTOSIS; MODELS; MECHANISMS AB Background & Aims: Ligation of tumor necrosis factor (TNF) receptors (TNFRs) with TNF plays a critical role in the pathogenesis of human inflammatory bowel disease (IBD). However, it remains unclear which cell types activated through TNFR-associated signaling cascades are involved in the pathogenesis of colitis. Methods: Recombination activating gene-1 (RAG) knockout (KO) (no T or B cells)-based TNFR double and triple KO mice were generated. Bone marrow (BM) chimera mice in which BM-derived myeloid cells, but not colonic epithelial cells (CECs), express TNFRs were also generated. Colitis was induced by administration of dextran sodium sulfate (DSS) in distilled water. Murine lines and chimeras were assessed for disease severity, histopathology, apoptotic cell rate, epithelial proliferation, and bacterial invasion rate. Result: Following DSS administration, mice lacking both RAG and TNFR1 exhibited a high mortality (>80%) rate with an impaired CEC regeneration compared with RAG KO and RAG x TNFR2 double KO (DKO) mice. Transplantation of RAG KO-derived BM cells restored CEC regeneration and rescued the majority of recipient RAG x TNFR1 DKO mice from DSS-induced mortality. After BM transplantation, RAG x TNFR1 DKO mice exhibited an increased rate of apoptosis in the colonic lamina propria macrophages in association with the activation of caspases. In addition, BM reconstitution directly or indirectly enhanced the proliferation of CECs by activating mitogen-activated protein kinase and phosphoinositide-3 kinase/Akt pathways. Conclusions: TNFR1-signaling cascade in colonic myeloid lineage cells contributes to the suppression of acute damage-associated mortality presumably by controlling CEC homeostasis. C1 [Mizoguchi, Emiko; Mizoguchi, Atsushi; Podolsky, Daniel K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Study Inflammatory Bowel Dis, Boston, MA USA. [Mizoguchi, Emiko; Hachiya, Yuriko; Kawada, Mayumi; Nagatani, Katsuya; Podolsky, Daniel K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Gastrointestinal Unit, Boston, MA USA. [Ogawa, Atsuhiro; Sugimoto, Ken; Mizoguchi, Atsushi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,Expt Pathol Unit, Boston, MA USA. RP Mizoguchi, E (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ 702, Boston, MA 02114 USA. EM emizoguchi@partners.org FU NIDDK NIH HHS [DK64289, DK 64351, DK43351, DK60049, DK74454, R01 DK060049] NR 34 TC 37 Z9 39 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 2008 VL 134 IS 2 BP 470 EP 480 DI 10.1053/j.gastro.2007.11.055 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 260TI UT WOS:000253032900017 PM 18242213 ER PT J AU Nanno, M Kanari, Y Naito, T Inoue, N Hisamatsu, T Chinen, H Sugimoto, K Shimomura, Y Yamagishi, H Shiohara, T Ueha, S Matsushima, K Suematsu, M Mizoguchi, A Hibi, T Bhan, AK Ishikawa, H AF Nanno, Masanobu Kanari, Yasuyoshi Naito, Tomoaki Inoue, Nagamu Hisamatsu, Tadakazu Chinen, Hiroshi Sugimoto, Ken Shimomura, Yasuyo Yamagishi, Hideo Shiohara, Tetsuo Ueha, Satoshi Matsushima, Kouji Suematsu, Makoto Mizoguchi, Atsushi Hibi, Toshifumi Bhan, Atul K. Ishikawa, Hiromichi TI Exacerbating role of gamma delta T cells in chronic colitis of T-cell receptor a mutant mice SO GASTROENTEROLOGY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; ALPHA-BETA; INTESTINAL INFLAMMATION; DEFICIENT MICE; ULCERATIVE-COLITIS; ACQUIRED-IMMUNITY; INFECTION; EXPRESSION; LYMPHOCYTES; ABSENCE AB Background & Aim: T-cell receptor (TCR) gamma delta T cells are an important component of the mucosal immune system and regulate intestinal epithelial homeostasis. Interestingly, there is a significant increase in gamma delta T cells in the inflamed mucosa of patients with ulcerative colitis (UC). However, the role of gamma delta T cells in chronic colitis has not been fully identified. Methods: TCR alpha-deficient mice, which spontaneously develop chronic colitis with many features of human UC including an increase in gamma delta T-cell population, represent an excellent model to investigate the role of gamma delta T cells in UC-like colitis. To identify the role of gamma delta T cells in this colitis, we herein have generated TCR gamma-deficient mice through deletion of all TCR C gamma genes (C gamma 1, C gamma 2, C gamma 3, and C gamma 4) using the Cre/loxP site-specific recombination system and subsequently crossing these mice with TCR alpha-deficient mice. Results: An increase in colonic gamma delta T cells was associated with the development of human UC as well as UC-like disease seen in TCR alpha-deficient mice. Interestingly, the newly established TCR alpha(-/-) x TCR gamma(-/-) double mutant mice developed significantly less severe colitis as compared with TCR alpha-deficient mice. The suppression of colitis in TCR alpha(-/-) x TCR gamma(-/-) double mutant mice was associated with a significant reduction of proinflammatory cytokine and chemokine productions and a decrease in neutrophil infiltration. Conclusions: gamma delta T cells are involved in the exacerbation of UC-like chronic disease. Therefore, gamma delta T cells may represent a promising therapeutic target for the treatment of human UC. C1 [Nanno, Masanobu] Yakult Cent Inst Microbiol Res, Tokyo, Japan. [Kanari, Yasuyoshi] Kyoto Univ, Grad Sch Sci, Dept Biophys, Kyoto, Japan. [Naito, Tomoaki; Ishikawa, Hiromichi] Keio Univ, Sch Med, Dept Microbiol & Immunol, Tokyo, Japan. [Naito, Tomoaki; Suematsu, Makoto] Keio Univ, Sch Med, Dept Biochem & Integrat Med Biol, Tokyo, Japan. [Inoue, Nagamu; Hisamatsu, Tadakazu; Chinen, Hiroshi; Hibi, Toshifumi] Keio Univ, Sch Med, Dept Internal Med, Tokyo, Japan. [Sugimoto, Ken; Shimomura, Yasuyo; Mizoguchi, Atsushi; Bhan, Atul K.] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA USA. [Sugimoto, Ken; Shimomura, Yasuyo; Mizoguchi, Atsushi; Bhan, Atul K.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. [Shiohara, Tetsuo] Kyorin Univ, Sch Med, Dept Dermatol, Tokyo, Japan. [Naito, Tomoaki; Ueha, Satoshi; Matsushima, Kouji] Univ Tokyo, Grad Sch Med, Dept Mol Prevent Med, Tokyo, Japan. RP Ishikawa, H (reprint author), Keio Univ, Sch Med, Dept Microbiol & Immunol, Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan. EM h-ishika@sc.itc.keio.ac.jp RI Suematsu, Makoto/I-8135-2013 OI Suematsu, Makoto/0000-0002-7165-6336 FU NIDDK NIH HHS [DK064351, DK47677] NR 51 TC 26 Z9 27 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 2008 VL 134 IS 2 BP 481 EP 490 DI 10.1053/j.gastro.2007.11.056 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 260TI UT WOS:000253032900018 PM 18242214 ER PT J AU Nozaki, K Ogawa, M Williams, JA Lafleur, BJ Ng, V Drapkin, RI Mills, JC Konieczny, SF Nomura, S Goldenring, JR AF Nozaki, Koji Ogawa, Masako Williams, Janice A. Lafleur, Bonnie J. Ng, Vivian Drapkin, Ronny I. Mills, Jason C. Konieczny, Stephen F. Nomura, Sachiyo Goldenring, James R. TI A molecular signature of gastric metaplasia arising in response to acute parietal cell loss SO GASTROENTEROLOGY LA English DT Article ID OXYNTIC ATROPHY; ZYMOGENIC CELLS; DEFICIENT MICE; CANCER; ADENOCARCINOMA; LOCALIZATION; INFECTION; COMPLEX; TISSUES; RISK AB Background & Aims: Loss of gastric parietal cells is a critical precursor to gastric metaplasia and neoplasia. However, the origin of metaplasia remains obscure. Acute parietal cell. loss in gastrin-deficient mice treated with DMP-777 leads to the rapid emergence of spasmolytic polypeptide/trefoil factor family 2 (TFF2)-expressing metaplasia (SPEM) from the bases of fundic glands. We now sought to characterize more definitively the pathway for emergence of SPEM. Methods: Emerging SPEM lineages in gastrin-deficient mice treated with DMP-777 were examined for immunolocalization of TFF2, intrinsic factor, and Mist1, and morphologically with electron microscopy. Emerging SPEM was isolated with laser-capture microdissection and RNA was analyzed using gene microarrays. Immunohistochemistry in mouse and human samples was used to confirm up-regulated transcripts. Results: DMP-777-induced SPEM was immunoreactive for TFF2 and the differentiated chief cell markers, Mist1 and intrinsic factor, suggesting that SPEM derived from transdifferentiation of chief cells. Microarray analysis of microdissected SPEM lineages induced by DMP-777 showed up-regnlation of transcripts associated with G1/S cell-cycle transition including minichromosome maintenance deficient proteins, as well as a number of secreted factors, including human epididymis 4 (HE4). HE4, which was absent in the normal stomach, was expressed in SPEM of human and mouse and in intestinal metaplasia and gastric cancer in human beings. Conclusions: Although traditionally metaplasia was thought to originate from normal mucosal progenitor cells, these studies indicate that SPEM evolves through either transdifferentiation of chief cells or activation of a basal cryptic progenitor. In addition, induction of metaplasia elicits the expression of secreted factors, such as HE4, relevant to gastric preneoplasia. C1 [Nozaki, Koji; Williams, Janice A.; Lafleur, Bonnie J.; Goldenring, James R.] Vanderbilt Univ, Sch Med, Nashville VA Med Ctr, Vanderbilt Ingram Canc Ctr,Dept Surg, Nashville, TN USA. [Nozaki, Koji; Ogawa, Masako; Nomura, Sachiyo] Univ Tokyo, Dept Gastrointestinal Surg, Tokyo, Japan. [Ng, Vivian; Drapkin, Ronny I.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA USA. [Drapkin, Ronny I.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA USA. [Mills, Jason C.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63130 USA. [Konieczny, Stephen F.] Purdue Univ, Ctr Canc, Dept Biol Sci, W Lafayette, IN 47907 USA. RP Goldenring, JR (reprint author), Vanderbilt Univ, Sch Med, Dept Surg, Epithelial Biol Prgram, 465 21st Ave S, Nashville, TN 37232 USA. EM jim.goldenring@vanderbilt.edu RI Drapkin, Ronny/E-9944-2016 OI Drapkin, Ronny/0000-0002-6912-6977 FU NCI NIH HHS [K08 CA108748, 1P 50 CA95103, K08 CA108748-02, P50 CA095103, P50 CA095103-04]; NIDDK NIH HHS [K08 DK066062, K08 DK066062-05, R01 DK055489, R01 DK055489-09, R01 DK079798, R01 DK079798-01A2, R01 DK55489] NR 23 TC 77 Z9 81 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 2008 VL 134 IS 2 BP 511 EP 522 DI 10.1053/j.gastro.2007.11.058 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 260TI UT WOS:000253032900021 PM 18242217 ER PT J AU Leung, FW AF Leung, Felix W. TI Double-EMR-derived full-thickness biopsy and functional GI disorders SO GASTROINTESTINAL ENDOSCOPY LA English DT Editorial Material ID BAND LIGATION; NEUROPATHY; RESECTION C1 Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Hlthcare Syst, Sepulveda Ambulatory Care Ctr, GI Blood Flow Res Lab, Los Angeles, CA 90095 USA. RP Leung, FW (reprint author), Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Hlthcare Syst, Sepulveda Ambulatory Care Ctr, GI Blood Flow Res Lab, Los Angeles, CA 90095 USA. NR 12 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD FEB PY 2008 VL 67 IS 2 BP 304 EP 306 DI 10.1016/j.gie.2007.08.031 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 265OB UT WOS:000253368100021 PM 18226693 ER PT J AU Brugge, WR AF Brugge, William R. TI EUS is an important new tool for accessing the portal vein SO GASTROINTESTINAL ENDOSCOPY LA English DT Editorial Material ID VENOUS-PRESSURE GRADIENT; CIRRHOSIS; FEASIBILITY; THROMBOSIS C1 Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. NR 11 TC 8 Z9 8 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD FEB PY 2008 VL 67 IS 2 BP 343 EP 344 DI 10.1016/j.gie.2007.10.011 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 265OB UT WOS:000253368100028 PM 18226700 ER PT J AU Neale, BM Sham, PC Purcell, S Banaschewski, T Buitelaar, J Franke, B Sonuga-Barke, EJS Ebstein, R Eisenberg, J Mulligan, A Gill, M Manor, I Miranda, A Mulas, F Oades, RD Roeyers, H Rothenberger, A Sergeant, J Steinhausen, HC Taylor, E Thompson, M Zhou, K Asherson, P Faraone, SV AF Neale, Benjamin M. Sham, Pak C. Purcell, Shaun Banaschewski, Tobias Buitelaar, Jan Franke, Barbara Sonuga-Barke, Edmund J. S. Ebstein, Richard Eisenberg, Jacques Mulligan, Aisling Gill, Michael Manor, Iris Miranda, Ana Mulas, Fernando Oades, Robert D. Roeyers, Herbert Rothenberger, Aribert Sergeant, Joseph Steinhausen, Hans-Christoph Taylor, Eric Thompson, Margaret Zhou, Kaixin Asherson, Philip Faraone, Stephen V. TI Population differences in the International Multi-Centre ADHD Gene project SO GENETIC EPIDEMIOLOGY LA English DT Article DE linkage disequilibrium; tagging; HapMap ID LINKAGE-DISEQUILIBRIUM PATTERNS; SINGLE-NUCLEOTIDE POLYMORPHISMS; MULTIPLE POPULATIONS; HAPLOTYPE DIVERSITY; GENOMIC CONTROL; DISEASE GENES; TAG SNPS; ASSOCIATION; TRANSFERABILITY; BLOCKS AB The International Multi-Centre ADHD Gene sample consists of 674 families from eight countries (Belgium, England, Germany, Holland, Ireland, Israel, Spain, and Switzerland) ascertained from clinics for combined-type attention definity hyperactivity disorder in an offspring. 863 SNPs were successfully genotyped across 47 autosomal genes implicated in psychiatric disorders yielding a single nucleotide polymorphism (SNP) density of approximately one SNP per 2.5kb. A global test of heterogeneity showed 269 SNPs nominally significant (expected 43). Inclusion of the Israeli population accounted for approximately 70% of these nominally significant tests. Hardy-Weinberg equilibrium tests suggest that combining all these populations would induce stratification, but that the Northern European populations (Belgium, England, Germany, Holland, and Ireland) could be appropriate. Tag SNPs were generated using pair-wise and aggressive tagging from Carlson et al. [20041 and de Bakker et al. [2005], respectively, in each population and applied to the other populations. Cross-population performance across Northern Europe was consistent with within population comparisons. Smaller sample size for each population tended to yield more problems for the generation of aggressive tags and the application of pair-wise tags. Any case-control sample employing an Israeli sample with Northern Europeans must consider stratification. A Northern European tag set, however, appears to be appropriate for capturing the variation across populations. C1 [Neale, Benjamin M.; Zhou, Kaixin; Asherson, Philip] Kings Coll London, Inst Psychiat, MRC Social Genet Dev & Psychiat Ctr, London WC2R 2LS, England. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. [Oades, Robert D.; Taylor, Eric] Univ Clin Child & Adolescent Psychiat, Essen, Germany. [Banaschewski, Tobias] Univ Gottingen, D-3400 Gottingen, Germany. [Buitelaar, Jan; Franke, Barbara] Radboud Univ Nijmegen, Med Ctr, Dept Psychiat, Nijmegen, Netherlands. [Franke, Barbara] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, Nijmegen, Netherlands. [Miranda, Ana] Univ Valencia, Dept Dev & Educ Psychol, E-46003 Valencia, Spain. [Sonuga-Barke, Edmund J. S.] Univ Southampton, Univ London Kings Coll, Dept Psychol, Southampton, Hants, England. [Sergeant, Joseph] Vrije Univ Amsterdam, Dept Neuropsychol, Amsterdam, Netherlands. [Ebstein, Richard] Geha Mental Hlth Ctr, ADHD Clin, Petak, Tikvah, Israel. [Eisenberg, Jacques] S Herzog Mem Hosp, Jerusalem, Israel. [Mulligan, Aisling; Gill, Michael] St James Hosp, Trinity Ctr Hlth Sci, Dept Psychiat, Dublin 8, Ireland. [Roeyers, Herbert] Univ Ghent, Dept Expt & Clin Psychol, Ghent, Belgium. [Steinhausen, Hans-Christoph] Univ Zurich, Dept Child & Adolescent Psychiat, CH-8006 Zurich, Switzerland. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY 13210 USA. [Sham, Pak C.] Univ Hong Kong, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China. [Sham, Pak C.] Univ Hong Kong, Ctr Gene Res, Hong Kong, Hong Kong, Peoples R China. [Purcell, Shaun] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Purcell, Shaun] Broad Inst Harverd, Program Med & Populat Genet, Boston, MA USA. [Purcell, Shaun] MIT, Cambridge, MA 02139 USA. RP Neale, BM (reprint author), Kings Coll London, Inst Psychiat, MRC Social Genet Dev & Psychiat Ctr, London WC2R 2LS, England. EM b.neale@iop.kcl.ac.uk RI Sham, Pak Chung/C-4388-2009; Franke, Barbara/D-4836-2009; Sonuga-Barke, Edmund/D-9137-2011; Buitelaar, Jan/E-4584-2012; Miranda, Ana/G-8619-2015; OI Franke, Barbara/0000-0003-4375-6572; Mulligan, Aisling/0000-0001-7708-1177; Buitelaar, Jan/0000-0001-8288-7757; Miranda, Ana/0000-0001-6998-5686; Gill, Michael/0000-0003-0206-5337; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH 62873] NR 28 TC 14 Z9 14 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 EI 1098-2272 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD FEB PY 2008 VL 32 IS 2 BP 98 EP 107 DI 10.1002/gepi.20265 PG 10 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 264RK UT WOS:000253306500002 PM 17868146 ER PT J AU Miyata, S Begun, J Troemel, ER Ausubel, FM AF Miyata, Sachiko Begun, Jakob Troemel, Emily R. Ausubel, Frederick M. TI DAF-16-dependent suppression of immunity during reproduction in Caenorhabditis elegans SO GENETICS LA English DT Article ID SEX-DETERMINATION GENE; C-ELEGANS; LIFE-SPAN; INNATE IMMUNITY; GERM-LINE; PATHOGEN RECOGNITION; TRANSCRIPTION FACTOR; PROTEIN DAF-16; FAMILY-MEMBER; RNAI SCREEN AB To further understand how the nematode Caenorhabditis elegans defends itself against pathogen attack, we analyzed enhanced pathogen resistance (epr) mutants obtained from a forward genetic screen. We also examined several well-characterized sterile mutants that exhibit an Epr phenotype. We found that sterility and pathogen resistance are highly correlated and that resistance in both epr and sterile mutants is dependent on DAF-16 activity. Our data indicate that a DAF-16-dependent signaling pathway distinct from previously described pathways is involved in the activation of genes that confer resistance to bacterial pathogens. The timing of DAF-16-dependent gene activation in sterile mutants coincides with the onset of embryonic development in wild-type animals, suggesting that signals from developing embryos normally downregulate the immune response. C1 [Miyata, Sachiko; Begun, Jakob; Troemel, Emily R.; Ausubel, Frederick M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Begun, Jakob; Troemel, Emily R.; Ausubel, Frederick M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Ausubel, FM (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, 185 Cambridge St, Boston, MA 02114 USA. EM ausubel@molbio.mgh.harvard.edu RI Begun, Jakob/J-6793-2014 OI Begun, Jakob/0000-0001-5256-7672 FU NIAID NIH HHS [R01-AI064332, R01 AI064332] NR 76 TC 51 Z9 66 U1 1 U2 9 PU GENETICS SOC AM PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 J9 GENETICS JI Genetics PD FEB PY 2008 VL 178 IS 2 BP 903 EP 918 DI 10.1534/genetics.107.083923 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA 268JW UT WOS:000253577100024 PM 18245330 ER PT J AU Farber, K Markworth, S Pannasch, U Nolte, C Prinz, V Kronenberg, G Gertz, K Endres, M Bechmann, I Enjyoji, K Robson, SC Kettenmann, H AF Faerber, Katrin Markworth, Soeren Pannasch, Ulrike Nolte, Christiane Prinz, Vincent Kronenberg, Golo Gertz, Karen Endres, Matthias Bechmann, Ingo Enjyoji, Keiichi Robson, Simon C. Kettenmann, Helmut TI The ectonucleotidase cd39/ENTPDase1 modulates purinergic-mediated microglial migration SO GLIA LA English DT Article DE microglia; purinergic receptors type 2; migration; ATP; cd39; ENTPDase; brain ID FOCAL CEREBRAL-ISCHEMIA; ACTIVATED MICROGLIA; ATP-DIPHOSPHOHYDROLASE; CULTURED MICROGLIA; EXTRACELLULAR ATP; BRAIN-INJURY; IN-VITRO; CELLS; EXPRESSION; RECEPTOR AB Microglia is activated by brain injury. They migrate in response to ATP and although adenosine alone has no effect on wild type microglial migration, we show that inhibition of adenosine receptors impedes ATP triggered migration. CD39 is the dominant cellular ectonucleotidase that degrades nucleotides to nucleosides, including adenosine. Importantly, ATP fails to stimulate P2 receptor mediated migration in cd39(-/-) microglia. However, the effects of ATP on migration in cd39(-/-) microglia can be restored by co-stimulation with adenosine or by addition of a soluble ectonucleotidase. We also tested the impact of cd39-deletion in a model of ischemia, in an entorhinal cortex lesion and in the facial nucleus after facial nerve lesion. The accumulation of microglia at the pathological sites was markedly decreased in cd39(-/-) animals. We conclude that the co-stimulation of purinergic and adenosine receptors is a requirement for microglial migration and that the expression of cd39 controls the ATP/adenosine balance. (C) 2007 Wiley-Liss, Inc. C1 [Faerber, Katrin; Markworth, Soeren; Pannasch, Ulrike; Nolte, Christiane; Kettenmann, Helmut] Max Delbruck Ctr Mol Med, D-13092 Berlin, Germany. [Prinz, Vincent; Kronenberg, Golo; Gertz, Karen; Endres, Matthias] Charite Univ Med Berlin, Neurol Klin & Poliklin, Berlin, Germany. [Kronenberg, Golo] Free Univ Berlin, Dept Psychiat, D-1000 Berlin, Germany. [Bechmann, Ingo] Univ Frankfurt, Inst Clin Neuroanat, Frankfurt, Germany. [Enjyoji, Keiichi; Robson, Simon C.] BIDMC, Transplantat Ctr, Boston, MA USA. RP Kettenmann, H (reprint author), Max Delbruck Ctr Mol Med, Robert Rossle Str 10, D-13092 Berlin, Germany. EM kettenmann@mdc-berlin.de RI Kronenberg, Golo/F-8772-2010; Gertz, Karen/J-1603-2015 FU NHLBI NIH HHS [R01 HL063972, R01 HL063972-08] NR 51 TC 51 Z9 52 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0894-1491 J9 GLIA JI Glia PD FEB PY 2008 VL 56 IS 3 BP 331 EP 341 DI 10.1002/glia.20606 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 254KQ UT WOS:000252585900008 PM 18098126 ER PT J AU Rouvas, AA Papakostas, TD Ladas, ID Vergados, I AF Rouvas, Alexandros A. Papakostas, Thanos D. Ladas, Ioannis D. Vergados, Ioannis TI Enlargement of the hypofluorescent post photodynamic therapy treatment spot after a combination of photodynamic therapy with an intravitreal injection of bevacizumab for retinal angiomatous proliferation SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Article DE retinal angiomatous proliferation; age-related macular degeneration; photodynamic therapy; bevacizumab; hypofluorescence ID CHOROIDAL NEOVASCULARIZATION; MACULAR DEGENERATION; PIGMENT-EPITHELIUM; VERTEPORFIN; EXPRESSION; ACTIVATION; RECEPTOR; VEGF AB Background To report a case of enlargement of the post photodynamic therapy treatment (PDT) spot in a patient with retinal angiomatous proliferation (RAP) that was treated with PDT combined with an intravitreal injection of bevacizumab. Methods 74-year-old woman with RAP due to age-related macular degeneration was treated with one verteporfin PDT session, sequenced by a single intravitreal injection of bevacizumab (1.25 mg) after 30 minutes. Results The patient's visual acuity (VA) at baseline was 20/200 and is now at the 10-month follow-up visit 20/400, while the RAP has disappeared according to the indocyanine angiography (ICG) findings. The post PDT hypofluorescent treatment spot has enlarged from 1,450 mu m at the day of the treatment, to 5,360 mu m at the 6-week visit. The patient is now at the 10-month follow-up visit and the hypofluorescence is still persisting. Conclusions The simultaneous combination of PDT with bevacizumab in patients with RAP may enhance the photochemical stress in normal choroid with prolonged and magnified hypofluorescence in ICG, due to ischemia in normal choriocapillaries. C1 [Rouvas, Alexandros A.; Vergados, Ioannis] Univ Athens, Sch Med, Dept Ophthalmol 2, GR-11527 Athens, Greece. [Papakostas, Thanos D.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Ladas, Ioannis D.] Univ Athens, Sch Med, Dept Ophthalmol 1, GR-11527 Athens, Greece. RP Rouvas, AA (reprint author), Univ Athens, Sch Med, Dept Ophthalmol 2, Ag Meletiou 85-87 Str, GR-11527 Athens, Greece. EM rallex@hol.gr NR 14 TC 18 Z9 19 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0721-832X J9 GRAEF ARCH CLIN EXP JI Graefes Arch. Clin. Exp. Ophthalmol. PD FEB PY 2008 VL 246 IS 2 BP 315 EP 318 DI 10.1007/s00417-007-0669-3 PG 4 WC Ophthalmology SC Ophthalmology GA 252SU UT WOS:000252467700022 PM 17957379 ER PT J AU Moore, RG Brown, AK Miller, MC Skates, S Allard, WJ Verch, T Steinhoff, M Messerlian, G DiSilvestro, P Granai, CO Bast, RC AF Moore, Richard G. Brown, Amy K. Miller, M. Craig Skates, Steven Allard, W. Jeffrey Verch, Thorsten Steinhoff, Margaret Messerlian, Geralyn DiSilvestro, Paul Granai, C. O. Bast, Robert C., Jr. TI The use of multiple novel tumor biomarkers for the detection of ovarian carcinoma in patients with a pelvic mass SO GYNECOLOGIC ONCOLOGY LA English DT Article DE CA125; HE4; tumor markers; ovarian cancer; pelvic mass ID SERUM CA-125 LEVELS; CANCER-PATIENTS; POSTMENOPAUSAL WOMEN; CA 125; DIAGNOSIS; MARKERS; ULTRASONOGRAPHY; MANAGEMENT; SURVIVAL; CA72-4 AB Objectives. The CA125 tumor marker is used to help predict the presence of ovarian cancer in patients with an adnexal mass. Because elevated CA125 levels occur in many benign gynecologic conditions, we set out to identify other novel biomarkers that would increase the sensitivity and specificity of CA125. Methods. Serum and urine samples were obtained preoperatively from women undergoing surgery for an adnexal mass. The samples were analyzed for levels of CA125, SMRP, HE4, CA72-4, activin, inhibin, osteopontin, epidermal growth factor (EGFR), and ERBB2 (Her2) and were compared to final pathology results. Logistic regression models were estimated for all markers and combinations, with cross-validation analysis performed to obtain the sensitivities at set specificities of 90%, 95%, and 98%. Results. Two hundred and fifty-nine patients with adnexal masses were enrolled. Of these, 233 patients were eligible for analysis with 67 invasive epithelial ovarian cancers and 166 benign ovarian neoplasms. Mean values for all marker levels except Her2 differed significantly between patients with benign masses and cancer. As a single marker, HE4 had the highest sensitivity at 72.9% (specificity 95%). Comparatively, combined CA 125 and HE4 yielded the highest sensitivity at 76.4% (specificity 95%), with additional markers adding minimally to the sensitivity of this combination. HE4 was the best single marker for Stage I disease, with no increase in sensitivity when combined with CA125 or any other marker. Conclusions. As a single tumor marker, HE4 had the highest sensitivity for detecting ovarian cancer, especially Stage I disease. Combined CA125 and HE4 is a more accurate predictor of malignancy than either alone. (C) 2007 Elsevier Inc. All rights reserved. C1 [Moore, Richard G.; Steinhoff, Margaret; Messerlian, Geralyn; DiSilvestro, Paul; Granai, C. O.] Brown Univ, Women & Infants Hosp, Providence, RI 02925 USA. [Brown, Amy K.] Hartford Hosp, Hartford, CT 06115 USA. [Miller, M. Craig; Allard, W. Jeffrey; Verch, Thorsten] Fujirebio Diagnost Inc, Malvern, PA USA. [Skates, Steven] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. [Bast, Robert C., Jr.] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX USA. RP Moore, RG (reprint author), Brown Univ, Program Womens Oncol Women & Infants Hosp, Providence, RI 02925 USA. EM rmoore@wihri.org RI Bast, Robert/E-6585-2011; OI Bast, Robert/0000-0003-4621-8462; Messerlian, Geralyn/0000-0002-9440-3411 FU NCI NIH HHS [CA086381, P50 CA083639, CA105009] NR 34 TC 291 Z9 341 U1 6 U2 29 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD FEB PY 2008 VL 108 IS 2 BP 402 EP 408 DI 10.1016/j.ygyno.2007.10.017 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 263XB UT WOS:000253248700024 PM 18061248 ER PT J AU Ring, D AF Ring, David TI Instability after total elbow arthroplasty SO HAND CLINICS LA English DT Article ID POSTEROLATERAL ROTATORY INSTABILITY; ULNAR COLLATERAL LIGAMENT; RHEUMATOID-ARTHRITIS; TOTAL REPLACEMENT; DISLOCATION; PROSTHESIS; JOINT; RECONSTRUCTION; STABILITY AB Instability has limited the indications and appeal of unlinked (unconstrained, surfacing replacing) total elbow arthroplasties. True dislocation occurs in fewer than 5% of patients and may be less common when careful operative technique ensures appropriate tensioning of the medial collateral ligament, secure repair of the lateral collateral ligament, and preservation of the anterior capsule and triceps. Conversion of an unstable unlinked total elbow arthroplasty to a linked total elbow arthroplasty can be a complex and difficult procedure, but usually salvages a functional elbow. C1 [Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. [Ring, David] Harvard Univ, Sch Med, Boston, MA USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 47 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-0712 J9 HAND CLIN JI Hand Clin. PD FEB PY 2008 VL 24 IS 1 BP 105 EP + DI 10.1016/j.hcl.2007.11.002 PG 9 WC Orthopedics SC Orthopedics GA 277NV UT WOS:000254221200010 PM 18299024 ER PT J AU Resto, VA Chan, AW Deschler, DG Lin, DT AF Resto, Vicente A. Chan, Annie W. Deschler, Daniel G. Lin, Derrick T. TI Extent of surgery in the management of locally advanced sinonasal malignancies SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article; Proceedings Paper CT 17th Annual Meeting of the North-America-Skull-Base-Society CY FEB 16-19, 2006 CL Phoenix, AZ SP N Amer Skull Base Soc DE surgery; proton beam radiation; skull base; sinonasal tumors; outcomes ID PARANASAL SINUS TUMORS; SKULL-BASE TUMORS; RADIATION-THERAPY; CRANIOFACIAL RESECTION; ENDOSCOPIC TECHNIQUES; NASAL CAVITY; NECK-CANCER; RADIOTHERAPY; CARCINOMA; HEAD AB Background. The relative importance of surgery within multimodality regimens commonly used to treat advanced sinonasal malignancies remains unknown. Methods. One hundred two patients with locally advanced sinonasal cancers treated with proton beam radiation therapy with or without surgery were retrospectively reviewed. Extent of surgery and outcome variables of local control, disease-free survival, and overall survival were evaluated. Patterns of failure were also assessed. Results. Extent of surgery correlated with disease-free survival and overall survival rates. Local control rate, however, was independent of the degree of surgical resection achieved. Overall, treatment failure most commonly resulted from distant metastases, which occurred in 30% of patients and also correlated with extent of surgical resection. Tumor type-specific outcomes reveal differences associated with the extent of surgery achieved. Conclusion. High-dose radiotherapy with proton beam resulted in excellent local control rates in patients with locally advanced sinonasal cancer, irrespective of the extent of surgery. Complete resection, however, was predictive of improved disease-free survival and decreased rate of distant metastasis. (C)2007 Wiley Periodicals, Inc. C1 [Resto, Vicente A.; Deschler, Daniel G.; Lin, Derrick T.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Chan, Annie W.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Resto, VA (reprint author), Univ Texas Galveston, Med Branch, Dept Otolaryngol Head & Neck Surg, Galveston, TX 77550 USA. EM derrick-lin@meei.harvard.edu RI Resto, Vicente/D-9891-2014 FU NCI NIH HHS [P01-CA-21239] NR 19 TC 29 Z9 32 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD FEB PY 2008 VL 30 IS 2 BP 222 EP 229 DI 10.1002/hed.20681 PG 8 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 259NK UT WOS:000252945800011 PM 17902164 ER PT J AU Dunn, GP Lewis, JS Sunwoo, JB Uppaluri, R AF Dunn, Gavin P. Lewis, James S., Jr. Sunwoo, John B. Uppaluri, Ravindra TI Spontaneous regression of cutaneous head and neck melanoma: Implications for the immunologic control of neoplasia SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article DE melanoma; tumor; TIL; immunoediting; immunotherapy ID TUMOR-INFILTRATING LYMPHOCYTES; T-CELLS; MALIGNANT-MELANOMA; COLORECTAL-CANCER; PROGNOSTIC-FACTOR; OVARIAN-CANCER; SURVIVAL; MACROPHAGE; IMMUNOSURVEILLANCE; PROGRESSION AB Background. Spontaneous regression of cancer in the head and neck is a rare event. Moreover, there are rare reported cases of spontaneous regression of primary head and neck melanoma with accompanying immunohistochemical analysis of the tumor. Methods. We used detailed preoperative and postoperative pathologic examination of a lesion in the right supraclavicular region. Results. Pathologic examination of the initial specimen identified a melanoma of superficial spreading type with vertical growth and a thickness of 1.8 mm. The excised specimen demonstrated a complete regression of the melanoma with a florid host inflammatory response predominantly composed of a histiocytic reaction. Conclusion. The case presented illustrates histopathologic findings occurring in a head and neck melanoma as it is undergoing spontaneous regression. These findings point to a potentially critical role for histiocytes in effecting tumor elimination. Pathologic analysis of spontaneous head and neck melanoma regression will ultimately facilitate an improved understanding of naturally-occurring tumor elimination. (C) 2007 Wiley Periodicals, Inc. C1 [Sunwoo, John B.; Uppaluri, Ravindra] Washington Univ, Sch Med, Dept Otolaryngol, St Louis, MO 63110 USA. [Dunn, Gavin P.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Lewis, James S., Jr.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. RP Uppaluri, R (reprint author), Washington Univ, Sch Med, Dept Otolaryngol, Box 8115,600 S Euclid Ave, St Louis, MO 63110 USA. EM uppalurir@ent.wustl.edu NR 32 TC 9 Z9 10 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD FEB PY 2008 VL 30 IS 2 BP 267 EP 272 DI 10.1002/hed.20701 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 259NK UT WOS:000252945800017 PM 17657794 ER PT J AU Shen, YJ Hendricks, A Wang, FH Gardner, J Kazis, LE AF Shen, Yujing Hendricks, Ann Wang, Fenghua Gardner, John Kazis, Lewis E. TI The impact of private insurance coverage on Veterans' use of VA care: Insurance and selection effects SO HEALTH SERVICES RESEARCH LA English DT Article DE VA health care system; insurance effect; selection effect; access/demand/utilization of services; instrumental variables ID ADVERSE SELECTION; MEDIGAP INSURANCE; HEALTH-INSURANCE; MEDICARE; INSTRUMENTS; HOSPITALS; WEAK AB Objective. To examine private insurance coverage and its impact on use of Veterans Health Administration (VA) care among VA enrollees without Medicare coverage. Data Sources. The 1999 National Health Survey of Veteran Enrollees merged with VA administrative data, with other information drawn from American Hospital Association data and the Area Resource File. Study Design. We modeled VA enrollees' decision of having private insurance coverage and its impact on use of VA care controlling for sociodemographic information, patients' health status, VA priority status and access to VA and non-VA alternatives. We estimated the true impact of insurance on the use of VA care by teasing out potential selection bias. Bias came from two sources: a security selection effect (sicker enrollees purchase private insurance for extra security and use more VA and non-VA care) and a preference selection effect (VA enrollees who prefer non-VA care may purchase private insurance and use less VA care). Principal Findings. VA enrollees with private insurance coverage were less likely to use VA care. Security selection dominated preference selection and naive models that did not control for selection effects consistently underestimated the insurance effect. Conclusions. Our results indicate that prior research, which has not controlled for insurance selection effects, may have underestimated the potential impact of any private insurance policy change, which may in turn affect VA enrollees' private insurance coverage and consequently their use of VA care. From the decline in private insurance coverage from 1999 to 2002, we projected an increase of 29,400 patients and 158 million dollars for VA health care services. C1 [Shen, Yujing] E Orange VA Med Ctr, VA New Jersey Healthcare Syst Ctr Healthcare Know, E Orange, NJ 07018 USA. [Hendricks, Ann; Gardner, John] VA Boston Healthcare Syst, Boston, MA USA. [Wang, Fenghua] Shanghai Stock Exchange, Res Ctr, Shanghai, Peoples R China. [Kazis, Lewis E.] CHQOER, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. RP Shen, YJ (reprint author), E Orange VA Med Ctr, VA New Jersey Healthcare Syst Ctr Healthcare Know, 385 Tremont Ave,Mailstop 129, E Orange, NJ 07018 USA. OI Kazis, Lewis/0000-0003-1800-5849 NR 23 TC 11 Z9 11 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD FEB PY 2008 VL 43 IS 1 BP 267 EP 286 DI 10.1111/j.1475-6773.2007.00743.x PN 1 PG 20 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 252FX UT WOS:000252433500015 PM 18211529 ER PT J AU Schelbert, EB Rumsfeld, JS Krumholz, HM Canto, JG Magid, DJ Masoudi, FA Reid, KJ Spertus, JA AF Schelbert, E. B. Rumsfeld, J. S. Krumholz, H. M. Canto, J. G. Magid, D. J. Masoudi, F. A. Reid, K. J. Spertus, J. A. TI Ischaemic symptoms, quality of care and mortality during myocardial infarction SO HEART LA English DT Editorial Material CT 6th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY MAY 14-16, 2005 CL Washington, DC SP Amer Heart Assoc, Qual Care & Outcomes Res Interdisciplinary Working Grp, Councils Cardiovasc Nursing, Councils Cardiovasc Surg & Anesthesia, Councils Clin Cardiol, Councils Epidemiol & Prevent & Stroke, Amer Coll Cardiol Fdn, Ctr Dis Control & Prevent, Dept Vet Affairs ID ACUTE CORONARY SYNDROMES; HEART-ASSOCIATION; CHEST-PAIN; GUIDELINES; TROPONIN; COMMITTEE; REGISTRY; COLLEGE; DISEASE; EVENTS AB Objective: To study in myocardial infarction (MI) whether documentation of ischaemic symptoms is associated with quality of care and outcomes, and to compare patient reports of ischaemic symptoms during interviews with chart documentation. Design: Observational acute MI study from 2003 to 2004 (Prospective Registry Evaluating Myocardial Infarction: Event and Recovery). Setting: 19 diverse US hospitals. Patients: 2094 consecutive patients with MI (10 911 patients screened; 3953 patients were eligible and enrolled) with both positive cardiac enzymes and other evidence of infarction (eg, symptoms, electrocardiographic changes). Transferred patients and those with confounding non-cardiac comorbidity were not included (n=1859). Main outcome measures: Quality of care indicators and adjusted in-hospital survival. Results: The records of 10% of all patients with MI (217/2094) contained no documented ischaemic symptoms at presentation. Patients without documented symptoms were less likely (p<0.05) to receive aspirin (89% vs 96%) or beta-blockers (77% vs 90%) within 24 hours, reperfusion therapy for ST-elevation MI (7% vs 58%) or to survive their hospitalisation (adjusted odds ratio= 3.2, 95% CI 1.8 to 5.8). Survivors without documented symptoms were also less likely (p< 0.05) to be discharged with aspirin (87% vs 93%), beta-blockers (81% vs 91%), ACE/ARB (67% vs 80%), or smoking cessation counselling (46% vs 66%). In the subset of 1356 (65%) interviewed patients, most of those without documented ischaemic symptoms (75%) reported presenting symptoms consistent with ischaemia. Conclusions: Failure to document patients' presenting MI symptoms is associated with poorer quality of care from admission to discharge, and higher in-hospital mortality. Symptom recognition may represent an important opportunity to improve the quality of MI care. C1 [Schelbert, E. B.] Univ Iowa, Iowa City, IA USA. [Rumsfeld, J. S.] Denver VA Med Ctr, Denver, CO USA. [Krumholz, H. M.] Yale Univ, New Haven, CT USA. [Canto, J. G.] Watson Clin, Ctr Cardiovasc Prevent Res & Educ, Lakeland, FL USA. [Canto, J. G.] Univ Alabama, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Magid, D. J.] Colorado Permanente Med Grp, Denver, CO USA. [Masoudi, F. A.] Denver Hlth Med Ctr, Denver, CO USA. [Reid, K. J.; Spertus, J. A.] St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. [Reid, K. J.; Spertus, J. A.] Univ Missouri, Kansas City, MO 64110 USA. RP Schelbert, EB (reprint author), NHLBI, NIH, 10 Ctr Dr,Room B1D416,MSC 1061, Bethesda, MD 20892 USA. EM schelberteb@nhlbi.nih.gov FU NHLBI NIH HHS [K30 HL004117, HL 07121, K30HL04117-01A1, P50 HL077113, T32 HL007121] NR 24 TC 7 Z9 8 U1 0 U2 3 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 J9 HEART JI Heart PD FEB PY 2008 VL 94 IS 2 AR e2 DI 10.1136/hrt.2006.111674 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 256QX UT WOS:000252745800045 PM 17639097 ER PT J AU Seeff, LB Curto, TM Szabo, G Everson, GT Bonkovsky, HL Dienstag, JL Shifftnan, ML Lindsay, KL Lok, ASF Bisceglie, AM Lee, WM Ghany, MG AF Seeff, Leonard B. Curto, Teresa M. Szabo, Gyongyi Everson, Gregory T. Bonkovsky, Herbert L. Dienstag, Jules L. Shifftnan, Mitchell L. Lindsay, Karen L. Lok, Anna S. F. Di Bisceglie, Adrian M. Lee, William M. Ghany, Marc G. CA HALT-C Trial Grp TI Herbal product use by persons enrolled in the hepatitis C antiviral long-term treatment against cirrhosis (HALT-C) trial SO HEPATOLOGY LA English DT Article ID ALTERNATIVE MEDICINE USE; CHRONIC LIVER-DISEASE; SILYMARIN TREATMENT; PLUS RIBAVIRIN; SUPPLEMENT USE; UNITED-STATES; MILK THISTLE; COMPLEMENTARY; ANTIOXIDANT; POPULATION AB Herbal products, used for centuries in Far Eastern countries, are gaining popularity in western countries. Surveys indicate that persons with chronic hepatitis C (CHC) often use herbals, especially silymarin (milk thistle extract), hoping to improve the modest response to antiviral therapy and reduce side effects. The Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial, involving persons with advanced CHC, nonresponders to prior antiviral therapy but still willing to participate in long-term pegylated interferon treatment, offered the opportunity to examine the use and potential effects of silymarin. Among 1145 study participants, 56% had never taken herbals, 21% admitted past use, and 23% were using them at enrollment. Silymarin constituted 72% of 60 herbals used at enrollment. Among all participants, 67% had never used silymarin, 16% used it in the past, and 17% used it at baseline. Silymarin use varied widely among the 10 participating study centers; men were more frequent users than women, as were non-Hispanic whites than African Americans and Hispanics. Silymarin use correlated strongly with higher education. No beneficial effect of silymarin was found on serum alanine aminotransferase or hepatitis C virus (HCV) RNA levels. Univariate analysis showed significantly fewer liver-related symptoms and better quality-of-life parameters in users than nonusers, but after reanalysis adjusted for covariates of age, race, education, alcohol consumption, exercise, body mass index, and smoking, only fatigue, nausea, liver pain, anorexia, muscle and joint pain, and general health remained significantly better in silymarin users. Conclusion: Silymarin users had similar alanine aminotransferase and HCV levels to those of nonusers but fewer symptoms and somewhat better quality-of-life indices. Because its use among these HALT-C participants was self-motivated and uncontrolled, however, only a well-designed prospective study can determine whether silymarin provides benefit to persons with chronic hepatitis C. C1 [Seeff, Leonard B.] NIDDK, NIH, Dept Hlth & Human Serv, Div Digest Dis & Nutr, Bethesda, MD 20892 USA. [Curto, Teresa M.] New England Res Inst, Watertown, MA 02172 USA. [Szabo, Gyongyi] Univ Massachusetts, Sch Med, Dept Med, Div Gastroenterol,Hepatol & Liver Ctr, Worcester, MA 01605 USA. [Everson, Gregory T.] Univ Colorado, Sch Med, Div Gastroenterol & Hepatol, Sect Hepatol, Denver, CO 80202 USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Mol & Struct Biol, Farmington, CT USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Liver Biliary Pancreat Canc, Farmington, CT USA. [Dienstag, Jules L.] Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. [Dienstag, Jules L.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Shifftnan, Mitchell L.] Virginia Commonwealth Univ, Med Ctr, Sect Hepatol, Richmond, VA USA. [Lindsay, Karen L.] Univ So Calif, Keck Sch Med, Div Gastrointestinal & Liver Dis, Los Angeles, CA USA. [Lok, Anna S. F.] Univ Michigan, Ctr Med, Div Gastroenterol, Ann Arbor, MI 48109 USA. [Di Bisceglie, Adrian M.] St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO 63103 USA. [Lee, William M.] Univ Texas SW Med Ctr Dallas, Div Digest & Kidney Dis, Dallas, TX 75390 USA. [Ghany, Marc G.] NIDDKD, NIH, Dept Hlth & Human Serv, Liver Dis Branch, Bethesda, MD 20892 USA. RP Seeff, LB (reprint author), NIDDK, NIH, Dept Hlth & Human Serv, Div Digest Dis & Nutr, 31A Ctr Dr,Room 9A27, Bethesda, MD 20892 USA. EM seeffl@extra.niddk.nih.gov RI Lok, Anna /B-8292-2009; OI Yang, Shuman/0000-0002-9638-0890 FU NCRR NIH HHS [M01RR-00042, M01RR-00043, M01RR-00051, M01RR-00065, M01RR-00633, M01RR-00827, M01RR-01066, M01RR-06192]; NIAAA NIH HHS [K24 AA13736]; NIDDK NIH HHS [N01-DK-9-2327, N01-DK-9-2318, N01-DK-9-2319, N01-DK-9-2320, N01-DK-9-2321, N01-DK-9-2322, N01-DK-9-2323, N01-DK-9-2324, N01-DK-9-2325, N01-DK-9-2326, N01-DK-9-2328] NR 55 TC 73 Z9 74 U1 6 U2 15 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD FEB PY 2008 VL 47 IS 2 BP 605 EP 612 DI 10.1002/hep.22044 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 259KZ UT WOS:000252939500030 PM 18157835 ER PT J AU Lonyai, A Kodama, S Burger, D Davis, M Faustman, DL AF Lonyai, A. Kodama, S. Burger, D. Davis, M. Faustman, D. L. TI The promise of Hox11+stem cells of the spleen for treating autoimmune diseases SO HORMONE AND METABOLIC RESEARCH LA English DT Review DE spleen; regeneration; Hox11; Sjogren's syndrome; type 1 diabetes; hearing loss ID TYPE-1 DIABETES-MELLITUS; ACUTE LYMPHOBLASTIC-LEUKEMIA; EMBRYONIC STEM-CELLS; NF-KAPPA-B; DEVELOPMENTAL EXPRESSION; SJOGRENS-SYNDROME; HOMEOBOX GENE; BETA-CELLS; NOD MICE; REVERSAL AB The spleen of human adults uniquely possesses a reservoir of multilineage adult stem cells that express the developmental transcription factor Hox11. In contrast to hematopoietic stem cells, Hox11+ stem cells hold potentially broader therapeutic applications because they are less lineage restricted. Hox11/Tlx1 is part of a homeodomain gene family essential for organogenesis of the spleen and for contributions to development of hindbrain, cochlea, pancreas, salivary glands, among other organs and tissues. While Hox11/Tlx1 displays widespread patterns of expression during embryogenesis, its expression was thought to cease after birth. Recent findings in human post-mortem tissue have shattered this dogma, finding that Hox11/Tlx1 stem cells are uniquely and abundantly expressed throughout adulthood in the human spleen. While their role in humans is not yet understood, Hox11/Tlx1 stem cells from the spleen of normal mice have been harvested to assist in both the treatment and cure at least two autoimmune diseases: type 1 diabetes, Sjogren's syndrome, and possibly their comorbid hearing loss. The splenic stem cells are infused, with an immune therapy, into diseased NOD mice, where they can home to the diseased organ, differentiate into the appropriate cell type, and assume normal functioning with the endogenous regeneration of the animal due to disease removal. This review covers Hox11/Tlx1+ stem cells' success in an animal model and their potential for treating autoimmune diseases in organs that mirror their extensive expression patterns during embryogenesis. C1 [Lonyai, A.; Burger, D.; Davis, M.; Faustman, D. L.] Massachusetts Gen Hosp, Boston, MA 02129 USA. [Lonyai, A.; Burger, D.; Davis, M.; Faustman, D. L.] Harvard Univ, Sch Med, Boston, MA 02129 USA. [Kodama, S.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Faustman, DL (reprint author), Massachusetts Gen Hosp, Bldg 149,13th St,Room 3602, Boston, MA 02129 USA. EM faustman@helix.mgh.harvard.edu NR 55 TC 15 Z9 16 U1 1 U2 1 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD FEB PY 2008 VL 40 IS 2 BP 137 EP 146 DI 10.1055/s-2007-1022560 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 272CY UT WOS:000253837800010 PM 18283632 ER PT J AU Dutta, A Kobetic, R Triolo, RJ AF Dutta, Anirban Kobetic, Rudi Triolo, Ronald J. TI Ambulation after incomplete spinal cord injury with EMG-triggered functional electrical stimulation SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE functional electrical stimulation (FES); spinal cord injury (SCI); electromyogram (EMG); gait event detector AB Individuals with incomplete spinal cord injury (iSCI) retain some control of the partially paralyzed muscles, necessitating careful integration of functional electrical stimulation (FES) with intact motor function. In this communication, the volitional surface electromyogram (sEMG) from partially paralyzed muscle was used to detect the intent to step in an iSCI volunteer. The classifier was able to trigger the FES-assisted swing phase with a false positive rate less than 1% and true positive rate of 82% for left foot-off (FO) and 83% for right FO over 110 steps taken during three testing sessions spread over a week. C1 [Dutta, Anirban; Triolo, Ronald J.] Case Western Reserve Univ, Dept Biomed Engn, Cleveland, OH 44106 USA. [Dutta, Anirban; Kobetic, Rudi; Triolo, Ronald J.] Cleveland VA Med Ctr, Cleveland, OH 44106 USA. [Dutta, Anirban; Kobetic, Rudi; Triolo, Ronald J.] Cleveland FES Ctr, Cleveland, OH 44106 USA. [Triolo, Ronald J.] US Dept Vet Affairs, Adv Platform Technol Ctr Excellence, Cleveland, OH USA. RP Dutta, A (reprint author), Case Western Reserve Univ, Dept Biomed Engn, 319 Wickenden Bldg, Cleveland, OH 44106 USA. EM adutta@case.edu; rkobetic@fes.case.edu; rxt24@case.edu NR 11 TC 21 Z9 22 U1 0 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD FEB PY 2008 VL 55 IS 2 BP 791 EP 794 DI 10.1109/TBME.2007.902225 PN 1 PG 4 WC Engineering, Biomedical SC Engineering GA 254XV UT WOS:000252622200045 PM 18270018 ER PT J AU Lasser, T Soubret, A Ripoll, J Ntziachristos, V AF Lasser, Tobias Soubret, Antoine Ripoll, Jorge Ntziachristos, Vasilis TI Surface reconstruction for free-space 360 degrees fluorescence molecular tomography and the effects of animal motion SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE fluorescence molecular tomography (FMT); optical tomography; surface reconstruction from silhouettes ID NONCONTACT OPTICAL TOMOGRAPHY; MEDIA; SILHOUETTES AB Complete projection (360 degrees) free-space fluorescence tomography of opaque media is poised to enable 3-D imaging through entire small animals in vivo with improved depth resolution compared to 360 degrees-projection fiber-based systems or limited-view angle systems. This approach can lead to a new generation of Fluorescence Molecular Tomography (FMT) performance since it allows high spatial sampling of photon fields propagating through tissue at any projection, employing nonconstricted animal surfaces. Herein, we employ a volume carving method to capture 3-D surfaces of diffusive objects and register the captured surface in the geometry of an FMT 360 degrees-projection acquisition system to obtain 3-D fluorescence image reconstructions. Using experimental measurements we evaluate the accuracy of the surface capture procedure by reconstructing the surfaces of phantoms of known dimensions. We then employ this methodology to characterize the animal movement of anaesthetized animals. We find that the effects of animal movement on the FMT reconstructed image were within system resolution limits (similar to 0.07 cm). C1 [Lasser, Tobias] Tech Univ Munich, Dept Informat, Chair Comp Aided Med Procedures & Augmented Real, D-85748 Garching, Germany. [Lasser, Tobias; Soubret, Antoine; Ntziachristos, Vasilis] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Lab Bioopt & Mol Imaging, Charlestown, MA 02129 USA. [Lasser, Tobias; Soubret, Antoine; Ntziachristos, Vasilis] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Ripoll, Jorge] FORTH, Inst Struct & Lasers, Iraklion 71110, Greece. RP Lasser, T (reprint author), Tech Univ Munich, Dept Informat, Chair Comp Aided Med Procedures & Augmented Real, D-85748 Garching, Germany. EM lasser@in.tum.de; vasilis@helix.mgh.harvard.edu RI Ripoll, Jorge/J-8134-2012 OI Ripoll, Jorge/0000-0001-8856-7738 FU NIEHS NIH HHS [R43ES012360]; PHS HHS [R01 000750] NR 20 TC 21 Z9 23 U1 0 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD FEB PY 2008 VL 27 IS 2 BP 188 EP 194 DI 10.1109/TMI.2007.904662 PG 7 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 257RC UT WOS:000252815200004 PM 18334440 ER PT J AU Khanicheh, A Mintzopoulos, D Weinberg, B Tzika, AA Mavroidis, C AF Khanicheh, Azadeh Mintzopoulos, Dionyssios Weinberg, Brian Tzika, A. Aria Mavroidis, Constantinos TI MR_CHIROD v.2: Magnetic resonance compatible smart hand rehabilitation device for brain imaging SO IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING LA English DT Article DE electrorheological fluids; functional magnetic resonance imaging (fMRI); motor control; magnetic resonance (MR)-compatible devices ID FORCE; FMRI; INTERVENTIONS; ACTIVATION; FEEDBACK; SYSTEM AB This paper presents the design, fabrication, and testing of a novel, one degree-of-freedom, magnetic resonance compatible smart hand interfaced rehabilitation device (MR_CHIROD v.2), which may be used in brain magnetic resonance (MR) imaging during handgrip rehabilitation. A key feature of the device is the use of electrorheological fluids (ERFs) to achieve computer controlled, variable, and tunable resistive force generation. The device consists of three major subsystems: 1) an ERF based resistive element, 2) handles, and c) two sensors, one optical encoder and one force sensor, to measure the patient induced motion and force. MR-CHIROD v.2 is designed to resist up to 50% of the maximum level of gripping force of a human hand and be controlled in real time. Our results demonstrate that the MR environment does not interfere with the performance of the MR_CHIROD v.2, and, reciprocally, its use does not cause fMR image artifacts. The results are encouraging in jointly using MR_CHIROD v.2 and brain MR imaging to study motor performance and assess rehabilitation after neurological injuries such as stroke. C1 [Khanicheh, Azadeh; Weinberg, Brian; Mavroidis, Constantinos] Northeastern Univ, Dept Mech & Ind Engn, Boston, MA 02115 USA. [Mintzopoulos, Dionyssios; Tzika, A. Aria] Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Sch Med, Boston, MA 02114 USA. [Mintzopoulos, Dionyssios; Tzika, A. Aria] Harvard Univ, Sch Med, Shriners Burns Inst, Boston, MA 02114 USA. RP Khanicheh, A (reprint author), Northeastern Univ, Dept Mech & Ind Engn, Boston, MA 02115 USA. EM azadeh@coe.neu.edu; dionyssi@nmr.mgh.harvard.edu; weinberg@coe.neu.edu; aaria-tzika@hms.harvard.edu; mavro@coe.neu.edu FU NIBIB NIH HHS [5R21EB004665-02] NR 20 TC 21 Z9 21 U1 0 U2 3 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1534-4320 EI 1558-0210 J9 IEEE T NEUR SYS REH JI IEEE Trans. Neural Syst. Rehabil. Eng. PD FEB PY 2008 VL 16 IS 1 BP 91 EP 98 DI 10.1109/TNSRE.2007.910286 PG 8 WC Engineering, Biomedical; Rehabilitation SC Engineering; Rehabilitation GA 266NH UT WOS:000253442400012 PM 18303810 ER PT J AU Wang, JH Mallis, RJ Reinherzl, EL AF Wang, Jia-Huai Mallis, Robert J. Reinherzl, Ellis L. TI Lmmunodominant-peptide recognition: Beta testing TCR alpha beta SO IMMUNITY LA English DT Editorial Material ID INFLUENZA-A VIRUS; COMPLEX; REPERTOIRE; SELECTION AB In this issue, Ishizuka et al. (2008) define human T cell-receptor recognition of an immunodominant influenza A matrix peptide bound to human leukocyte antigen HLA-A*0201 in atomic detail, raising provocative questions about beta chain function. C1 [Wang, Jia-Huai; Mallis, Robert J.; Reinherzl, Ellis L.] Dana Farber Canc Inst, Dept Med Oncol, Immunobiol Lab, Medford, MA 02155 USA. [Wang, Jia-Huai] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Wang, Jia-Huai; Mallis, Robert J.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Reinherzl, Ellis L.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Reinherzl, EL (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Immunobiol Lab, 44 Binney St, Medford, MA 02155 USA. EM ellis_reinherz@dfci.harvard.edu RI Mallis, Robert/A-2270-2015 NR 10 TC 5 Z9 5 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD FEB PY 2008 VL 28 IS 2 BP 139 EP 141 DI 10.1016/j.immuni.2008.01.007 PG 3 WC Immunology SC Immunology GA 264GH UT WOS:000253275000002 PM 18275824 ER PT J AU Pittet, MJ Mempel, TR AF Pittet, Mikael J. Mempel, Thorsten R. TI Regulation of T-cell migration and effector functions: insights from in vivo imaging studies SO IMMUNOLOGICAL REVIEWS LA English DT Review DE T cells; cell activation; cell trafficking; cytotoxicity; tolerance/suppression/anergy; in vivo imaging ID HIGH ENDOTHELIAL VENULES; AFFERENT LYMPHATIC VESSELS; SUPRAMOLECULAR ACTIVATION CLUSTER; FIBROBLASTIC RETICULAR CELLS; SECONDARY LYMPHOID ORGANS; ANTIGEN-PRESENTING CELLS; CHEMOTACTIC AGENT 4; SPLENIC B-CELLS; DENDRITIC CELLS; IMMUNOLOGICAL SYNAPSE AB Studies of the immune system are providing us with ever more detailed information on the cellular and molecular mechanisms that underlie our evolutionarily conserved ability to fend off infectious pathogens. Progress has probably been fastest at two levels: the various basic biological functions of isolated cells on one side and the significance of individual molecules or cells to the organism as a whole on the other. In both cases, direct phenomenological observation has been an invaluable methodological approach. Where we know least is the middle ground, i.e. how immune functions are integrated through the dynamic interplay of immune cell subsets within the organism. Most of our knowledge in this area has been obtained through inference from static snapshots of dynamic processes, such as histological sections, or from surrogate cell co-culture models. The latter are employed under the assumption that an in vivo equivalent exists for each type of cellular contact artificially enforced in absence of anatomical compartmentalization. In this review, we summarize recent insights on migration and effector functions of T cells, focusing on observations gained from their dynamic microscopic visualization in physiological tissue environments. C1 [Mempel, Thorsten R.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Charlestown, MA 02129 USA. [Pittet, Mikael J.; Mempel, Thorsten R.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Pittet, Mikael J.; Mempel, Thorsten R.] Massachusetts Gen Hosp, Ctr Syst Biol, Charlestown, MA 02129 USA. RP Mempel, TR (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Bldg 149,13th St, Charlestown, MA 02129 USA. EM tmempel@mgh.harvard.edu FU NCI NIH HHS [P50 CA86355]; NIAID NIH HHS [AI073457-01] NR 230 TC 34 Z9 36 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD FEB PY 2008 VL 221 BP 107 EP 129 DI 10.1111/j.1600-065X.2008.00584.x PG 23 WC Immunology SC Immunology GA 260WZ UT WOS:000253042400008 PM 18275478 ER PT J AU Sonnenberg, A Chang, J AF Sonnenberg, Amnon Chang, Joanne TI Time trends of physician visits for Crohn's disease and ulcerative colitis in the United States, 1960-2006 SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE epidemiology; environmental influences; incidence; prevalence; physician visits; time trends ID INFLAMMATORY-BOWEL-DISEASE; MANAGED CARE; HOSPITALIZATION; PREVALENCE; RATES AB Background: The purpose of this study was to analyze physician visits associated with inflammatory bowel disease in the United States in order to shed light on the underlying disease time trends in the United States. Methods: The National Diseases and Therapeutic Index of IMS America from 1960 until 2006 was used as the data source. Survey data had been obtained from a representative sample of U.S. physicians 4 times per year during a 48-hour period and extrapolated to a national level. All physician visits for Crohn's disease and ulcerative colitis were expressed as rates per 100,000 people living in the United States. Results: Physician visits for Crohn's disease increased almost 5-fold between 1960-1964 and 1990-1994 and have leveled off since then. Except for a slight decrease between 1960-1964 and 1980-1984, physician visits for ulcerative colitis have remained largely unchanged, especially during the most recent 15 years. Similar trends were observed for both men and women. Conclusions: U.S. time trends of physician visits are similar to other previously published time trends of inflammatory bowel disease. It appears that the overall incidence of inflammatory bowel disease has remained stable in the past 15 years. C1 [Sonnenberg, Amnon] Portland VA Med Ctr, Portland, OR 97239 USA. [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Chang, Joanne] Bayer Healthcare Pharmaceut, Portland, OR USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, P3 GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 17 TC 14 Z9 14 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD FEB PY 2008 VL 14 IS 2 BP 249 EP 252 DI 10.1002/ibd.20273 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 259ML UT WOS:000252943300012 PM 17879275 ER PT J AU Mora, JR AF Mora, J. Rodrigo TI Homing imprinting and immunomodulation in the gut: Role of dendritic cells and retinoids SO INFLAMMATORY BOWEL DISEASES LA English DT Review DE adhesion molecules; dendritic cells in IBD ID CD8(+) T-CELLS; ANTIBODY-SECRETING CELLS; THYMUS-EXPRESSED CHEMOKINE; MUCOSAL IGA RESPONSES; GROWTH-FACTOR-BETA; LYMPHOCYTE-ASSOCIATED ANTIGEN; INFLAMMATORY-BOWEL-DISEASE; HIGH ENDOTHELIAL VENULES; A-DEFICIENT RATS; CHRONIC MURINE ILEITIS AB Lymphocyte migration is at the heart of chronic inflammatory ailments, including inflammatory bowel disease (IBD). Whereas naive lymphocytes migrate to all secondary lymphoid organs, they are mostly excluded from nonlymphoid peripheral tissues. Upon activation, lymphocytes change their pattern of adhesion receptors and acquire the capacity to migrate to extralymphoid tissues. Antigen-experienced T cells are subdivided into different subsets based on their expression of homing receptors that favor their accumulation in specific tissues, such as the skin and the gut mucosa. B cells and antibody-secreting cells (ASC) also show tissue-tropism, which is somewhat correlated with the class of immunoglobulin that they produce. In fact, IgA-ASC are located in mucosal tissues, where they produce IgA, the main class of antibodies found in secretions. Although IgA-ASC are usually considered as a homogeneous pool of cells, those located in the small bowel have some unique migratory characteristics, suggesting that they are generated under different conditions as compared to IgA-ASC in other mucosal compartments. Foxp3(+) regulatory T cells (T-REG) can also exhibit tissue-specific migratory potential and recent evidence suggests that T-REG can be imprinted with gut-specific homing. Moreover, foxp3(+) TREG are enriched in the small bowel lamina propria, where they can be generated locally. The present review addresses our current understanding of how tissue-specific homing is acquired and modulated on T cells, B cells, and ASC, with a special emphasis on the intestinal mucosa. Harnessing these mechanisms could offer novel, effective, and more specific therapeutic strategies in IBD. C1 [Mora, J. Rodrigo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. RP Mora, JR (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St,GRJ 815, Boston, MA 02114 USA. EM j_rodrigo_mora@hms.harvard.edu NR 237 TC 53 Z9 59 U1 2 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD FEB PY 2008 VL 14 IS 2 BP 275 EP 289 DI 10.1002/ibd.20280 PG 15 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 259ML UT WOS:000252943300016 PM 17924560 ER PT J AU Kellum, JA Cerda, J Kaplan, LJ Nadim, MK Palevsky, PM AF Kellum, J. A. Cerda, J. Kaplan, L. J. Nadim, M. K. Palevsky, P. M. TI Fluids for prevention and management of acute kidney injury SO INTERNATIONAL JOURNAL OF ARTIFICIAL ORGANS LA English DT Article; Proceedings Paper CT 5th International Acute Dialysis Quality Initiative Conference CY JAN, 2007 CL Tambor, COSTA RICA DE acute kidney injury; fluids; colloids; crystalloids; starch; renal replacement therapy; dialysis; hemofiltration ID ACUTE-RENAL-FAILURE; CRITICALLY-ILL PATIENTS; CONTINUOUS VENOVENOUS HEMOFILTRATION; LACTATED RINGERS SOLUTION; LARGE-VOLUME PARACENTESIS; ACID-BASE-BALANCE; SPONTANEOUS BACTERIAL PERITONITIS; HYPERTONIC SALINE RESUSCITATION; RANDOMIZED CONTROLLED-TRIAL; ABDOMINAL AORTIC-ANEURYSM AB Fluids are the only known method of attenuating renal injury. Furthermore, whether for hydration, resuscitation or renal replacement therapy, fluid prescriptions must be tailored to the fluid and electrolyte, cardiovascular status and residual renal function of the patient. Different fluids have significantly different effects both on volume expansion as well as on the electrolyte and acid-base balance; while controversial, different fluids may even influence renal function differently. This systematic review focuses on fluids for prevention and management of acute kidney injury. We have reviewed the available evidence and have made recommendations for clinical practice and future studies. C1 [Kellum, J. A.] Univ Pittsburgh, Dept Crit Care Med, Sch Med, Pittsburgh, PA 15261 USA. [Cerda, J.] Albany Med Coll & Capital Dist Renal Physicians, Div Nephrol, Albany, NY USA. [Kaplan, L. J.] Yale Univ, Sch Med, Dept Surg, Sect Trauma Surg Crit Care & Surg Emergencies, New Haven, CT 06510 USA. [Nadim, M. K.] Univ So Calif, Keck Sch Med, Dept Med, Div Nephrol, Los Angeles, CA 90033 USA. [Palevsky, P. M.] VA Pittsburgh Healthcare Syst, Univ Dr Div, Pittsburgh, PA USA. RP Kellum, JA (reprint author), Univ Pittsburgh, Dept Crit Care Med, Sch Med, 608 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA. EM kellumja@ccm.upmc.edu NR 118 TC 17 Z9 19 U1 2 U2 5 PU WICHTIG EDITORE PI MILAN PA 72/74 VIA FRIULI, 20135 MILAN, ITALY SN 0391-3988 J9 INT J ARTIF ORGANS JI Int. J. Artif. Organs PD FEB PY 2008 VL 31 IS 2 BP 96 EP 110 PG 15 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 268DS UT WOS:000253559200004 PM 18311727 ER PT J AU Steinberg, M Shao, H Zandi, P Lyketsos, CG Welsh-Bohmer, KA Norton, MC Breitner, JCS Steffens, DC Tschanz, JT AF Steinberg, Martin Shao, Huibo Zandi, Peter Lyketsos, Constantine G. Welsh-Bohmer, Kathleen A. Norton, Maria C. Breitner, John C. S. Steffens, David C. Tschanz, JoAnn T. CA Investigators, CC TI Point and 5-year period prevalence of neuropsychiatric symptoms in dementia: the Cache County Study SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE dementia; neuropsychiatric; prevalence ID ALZHEIMERS-DISEASE; BEHAVIORAL DISTURBANCES; DIAGNOSTIC-CRITERIA; CONSORTIUM; CAREGIVERS; INVENTORY AB Background Neuropsychiatric symptoms are nearly universal in dementia, yet little is known about their longitudinal course in the community. Objective To estimate point and 5-year period prevalence of neuropsychiatric symptoms in an incident sample of 408 dementia participants from the Cache County Study. Methods The Neuropsychiatric Inventory assessed symptoms at baseline and at 1.5 years, 3.0 years, 4.1 years, and 5.3 years. Point prevalence, period prevalence and mean symptom severity at each time point were estimated. Results Point prevalence for delusions was 18% at baseline and 34 - 38% during the last three visits; hallucinations, 10% at baseline and 19 - 24% subsequently; agitation/aggression fluctuated between 13% and 24%; depression 29% at baseline and 41 - 47% subsequently; apathy increased from 20% at baseline to 51% at 5.3 years; elation never rose above 1%; anxiety 14% at baseline and 24 - 32% subsequently; disinhibition fluctuated between 2% and 15%; irritability between 17% and 27%; aberrant motor behavior gradually increased from 7% at baseline to 29% at 5.3 years. Point prevalence for any symptom was 56% at baseline and 76 - 87% subsequently. Five-year period prevalence was greatest for depression (77%), apathy (71%), and anxiety (62%); lowest for elation (6%), and disinhibition (31 %). Ninety-seven percent experienced at least one symptom. Symptom severity was consistently highest for apathy. Conclusions Participants were most likely to develop depression, apathy, or anxiety, and least likely to develop elation or disinhibition. Give converging evidence that syndromal definitions may more accurately capture neuropsychiatric co-morbidity in dementia, future efforts to validate such syndromes are warranted. Copyright ((c) 2007 John Wiley & Sons, Ltd. C1 [Steinberg, Martin; Lyketsos, Constantine G.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Shao, Huibo; Zandi, Peter] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Welsh-Bohmer, Kathleen A.; Steffens, David C.] Duke Univ, Sch Med, Dept Psychiat & Behav Sci, Durham, NC USA. [Norton, Maria C.; Tschanz, JoAnn T.] Utah State Univ, Ctr Epidemiol Studies, Logan, UT 84322 USA. [Norton, Maria C.; Tschanz, JoAnn T.] Utah State Univ, Dept Psychol, Logan, UT 84322 USA. [Norton, Maria C.] Utah State Univ, Dept Family & Human Dev, Logan, UT 84322 USA. [Breitner, John C. S.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Steinberg, M (reprint author), 550 N Broadway,Suite 308, Baltimore, MD 21205 USA. EM martins@jhmi.edu RI Tschanz, JoAnn/E-5986-2010; Norton, Maria/E-6994-2013; Hayden, Kathleen/B-6442-2012 OI Hayden, Kathleen/0000-0002-7745-3513 FU NIA NIH HHS [AG-11380, AG-21136, R01 AG011380, R01 AG011380-06, R01 AG021136, R01 AG021136-01] NR 24 TC 177 Z9 181 U1 2 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0885-6230 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD FEB PY 2008 VL 23 IS 2 BP 170 EP 177 DI 10.1002/gps.1858 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 266XV UT WOS:000253472100008 PM 17607801 ER PT J AU Tzika, AA Mintzopoulos, D Padfield, K Wilhelmy, J Mindrinos, MN Yu, HG Cao, HH Zhang, QH Astrakasi, LG Zhang, JW Yu, YM Rahme, LG Tompkins, RG AF Tzika, A. Aria Mintzopoulos, Dionyssios Padfield, Katie Wilhelmy, Julie Mindrinos, Michael N. Yu, Hongue Cao, Haihui Zhang, Qunhao Astrakasi, Loukas G. Zhang, Jiangwen Yu, Yong-Ming Rahme, Laurence G. Tompkins, Ronald G. TI Reduced rate of adenosine triphosphate synthesis by in vivo (31)P nuclear magnetic resonance spectroscopy and downregulation of PGG-1 beta in distal skeletal muscle following burn SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Article DE nuclear magnetic resonance; skeletal muscle; burn trauma; adenosine triphosphate; PGC-1 beta; mitochondria ID RANDOMIZED CONTROLLED-TRIAL; PPAR-GAMMA; ENERGY-EXPENDITURE; MITOCHONDRIAL-FUNCTION; NMR; PGC-1-BETA; INJURY; COACTIVATORS; METABOLISM; ACTIVATION AB Using a mouse model of burn trauma, we tested the hypothesis that severe burn trauma corresponding to 30% of total body surface area (TBSA) causes reduction in adenosine triphosphate (ATP) synthesis in distal skeletal muscle. We employed in Vivo (31)P nuclear magnetic resonance (NMR) in intact mice to assess the rate of ATP synthesis, and characterized the concomitant gene expression patterns in skeletal muscle in burned (30% TBSA) versus control mice. Our NMR results showed a significantly reduced rate of ATP synthesis and were complemented by genomic results showing downregulation of the ATP synthase mitochondrial F(1)F(0) complex and PGC-1 beta gene expression. Our findings suggest that inflammation and muscle atrophy in burns are due to a reduced ATP synthesis rate that may be regulated upstream by PGC-1 beta. These findings implicate mitochondrial dysfunction in distal skeletal muscle following burn injury. That PGC-1 beta is a highly inducible factor in most tissues and responds to common calcium and cyclic adenosine monophosphate (cAMP) signaling pathways strongly suggests that it may be possible to develop drugs that can induce PGC-1 beta. C1 [Tzika, A. Aria; Mintzopoulos, Dionyssios; Padfield, Katie; Yu, Hongue; Cao, Haihui; Zhang, Qunhao; Astrakasi, Loukas G.; Yu, Yong-Ming; Rahme, Laurence G.; Tompkins, Ronald G.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,NMR Surg Lab, Boston, MA 02114 USA. [Tzika, A. Aria; Mintzopoulos, Dionyssios; Yu, Hongue; Cao, Haihui; Astrakasi, Loukas G.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Wilhelmy, Julie; Mindrinos, Michael N.] Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA. [Zhang, Jiangwen] Harvard Univ, Bauer Ctr Genom Res, Cambridge, MA 02138 USA. RP Tzika, AA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,NMR Surg Lab, 51 Blossom St,Room 261, Boston, MA 02114 USA. EM atzika@partners.org RI Zhang, Jiangwen/A-7654-2013 FU NIDDK NIH HHS [P30 DK040561, P30 DK040561-12]; NIGMS NIH HHS [P50GM021700] NR 36 TC 10 Z9 10 U1 0 U2 1 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PD FEB PY 2008 VL 21 IS 2 BP 201 EP 208 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 254XM UT WOS:000252621300008 PM 18204786 ER PT J AU Postemak, M Novak, S Stem, R Hennessey, J Joffe, R Prange, A Zimmerman, M AF Postemak, Michael Novak, Scott Stem, Robert Hennessey, James Joffe, Russell Prange, Arthur, Jr. Zimmerman, Mark TI A pilot effectiveness study: placebo-controlled trial of adjunctive L-triiodothyronine (T(3)) used to accelerate and potentiate the antidepressant response SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE acceleration; antidepressant; depression; effectiveness; thyroid hormone ID DEPRESSION RATING-SCALE; CLINICAL-TRIALS; RESISTANT DEPRESSION; HAMILTON DEPRESSION; TREATMENT HISTORY; MAJOR DEPRESSION; METAANALYSIS; DISORDER; PSYCHIATRISTS; AUGMENTATION AB The aim was to evaluate whether adjunctive T3 can help accelerate the antidepressant response and improve overall outcomes when used under naturalistic conditions. Fifty consecutive psychiatric outpatients diagnosed with major depressive disorder who were initiated on antidepressant therapy were randomized to receive adjunctive T3 or placebo in a double-blind manner over the course of 6 wk. There were no restrictions placed on the selection of antidepressant agent, dosing, ancillary medications, or psychotherapy, and there were few exclusion criteria. A positive response was defined as a >= 50% reduction in Montgomery-Asberg Depression Rating Scale scores. Response rates were higher for the adjunctive T3 cohort compared to the adjunctive placebo cohort after 1 wk (45% vs. 24%) and 2 wk (57% vs. 33%) of treatment. The likelihood of experiencing a positive response at any point over the 6-wk trial was 4.5 times greater in the adjunctive T3 cohort (95% CI 1.3-15.7). The study provides preliminary evidence that T3 can successfully be used in clinical practice to accelerate the antidepressant response and improve overall outcomes. The effectiveness model may be an untapped mechanism for evaluating the value of psychopharmacological agents. C1 [Postemak, Michael] Massachusetts Gen Hosp, Dept Clin & Res Program, Boston, MA 02114 USA. [Novak, Scott] Triangle Inst Int, Div Hlth Social & Econ Res, Res Triangle Pk, NC USA. [Stem, Robert] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Hennessey, James] Brown Univ, Sch Med, Dept Endocrinol, Providence, RI 02912 USA. [Joffe, Russell] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Psychiat, Newark, NJ 07103 USA. [Prange, Arthur, Jr.] Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC USA. [Zimmerman, Mark] Brown Univ, Sch Med, Dept Psychiat, Providence, RI 02912 USA. RP Postemak, M (reprint author), 50 Staniford St,Suite 401, Boston, MA 02114 USA. EM mposternak@partners.org OI Stern, Robert/0000-0002-5008-077X NR 49 TC 13 Z9 13 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD FEB PY 2008 VL 11 IS 1 BP 15 EP 25 DI 10.1017/S1461145707007663 PG 11 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 262SH UT WOS:000253167800002 PM 17352847 ER PT J AU Engelsen, IB Stefansson, IM Beroukhim, R Sellers, WR Meyerson, M Akslen, LA Salvesen, HB AF Engelsen, Ingeborg B. Stefansson, Ingunn M. Beroukhim, Rameen Sellers, William R. Meyerson, Matthew Akslen, Lars A. Salvesen, Helga B. TI HER-2/neu expression is associated with high tumor cell proliferation and aggressive phenotype in a population based patient series of endometrial carcinomas SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE endometrial carcinoma; curettage; tumor markers; HER-2/neu; proliferation ID EPIDERMAL-GROWTH-FACTOR; FACTOR RECEPTOR; PROGNOSTIC-SIGNIFICANCE; CANCER; OVEREXPRESSION; P53; KI-67; TRASTUZUMAB; CURETTAGE; PATHWAYS AB Gene alterations and overexpression of various oncogenes and cell-cycle regulators are important in tumor development. In a population based series of 3 16 endometrial carcinomas with long and complete follow-up we investigated the distribution of HER-2/neu and EGFR expression and copy number alteration in endometrial cancers. HER-2/neu, EGFR and Ki-67 expression in curettage and hysterectomy specimens were studied immunohistochemically for expression in relation to molecular markers and clinical phenotype. Fresh tumor samples (n=76) were studied by global characterization of genetic alterations by single nucleotide polymorphism (SNP) array for detection of high level amplification for HER-2/neu and EGFR. Pathological expression of HER-2/neu in curettage was detected in 23% which significantly correlated to high FIGO stage, non-endometrioid subtype, high grade and aneuploidy. In hysterectomy specimens, pathological HER-2/neu staining was seen in 13% which correlated significantly with high FIGO stage, non-endometrioid subtype, high proliferation and poor survival (p=0.009). Expression of EGFR was examined with three different antibodies, but none showed significant correlation with molecular markers or clinical phenotype. High level amplification of HER-2/neu or EGFR was seen in only one out of 76 samples, respectively. High proliferation estimated in tumors from hysterectomy specimens showed independent prognostic impact and was superior to estimation in curettage specimens as a prognostic marker. In conclusion, high level amplification of HER-2/neu or EGFR is infrequent in endometrial cancer. Pathological HER-2/neu staining identifies endometrial carcinomas with an aggressive phenotype, high proliferation and patients with poor,survival in a population based setting. These results motivate further clinical trials with trastuzumab based on HER-2/neu status in endometrial carcinomas. C1 [Stefansson, Ingunn M.; Akslen, Lars A.] Haukeland Univ Hosp 2, Dept Pathol, NO-5021 Bergen, Norway. [Beroukhim, Rameen; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Beroukhim, Rameen; Meyerson, Matthew] Broad Inst Harvard, Boston, MA 02115 USA. [Beroukhim, Rameen; Meyerson, Matthew] MIT, Boston, MA 02115 USA. [Sellers, William R.] Novartis Inst BioMed Res, Cambridge, MA USA. [Engelsen, Ingeborg B.; Salvesen, Helga B.] Univ Bergen, Inst Clin Med, N-5020 Bergen, Norway. [Engelsen, Ingeborg B.; Salvesen, Helga B.] Haukeland Univ Hosp 2, Dept Obstet & Gynecol, NO-5021 Bergen, Norway. RP Engelsen, IB (reprint author), Haukeland Hosp, Dept Obstet & Gynecol, NO-5021 Bergen, Norway. EM iben@helse-bergen.no RI Meyerson, Matthew/E-7123-2012; Akslen, Lars /C-1202-2017; salvesen, Helga/C-1187-2017 OI Akslen, Lars /0000-0003-2710-9543; salvesen, Helga/0000-0002-4438-8831 FU NCI NIH HHS [K08 CA122833-01A1, K08 CA122833] NR 28 TC 19 Z9 23 U1 0 U2 3 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD FEB PY 2008 VL 32 IS 2 BP 307 EP 316 PG 10 WC Oncology SC Oncology GA 254XI UT WOS:000252620900003 PM 18202752 ER PT J AU Sartippour, MR Seeram, NP Rao, JY Moro, A Harris, DM Henning, SM Firouzi, A Rettig, MB Aronson, WJ Pantuck, AJ Heber, D AF Sartippour, Maryam R. Seeram, Navindra P. Rao, Jian Yu Moro, Aune Harris, Diane M. Henning, Susanne M. Firouzi, Amita Rettig, Matthew B. Aronson, William J. Pantuck, Allan J. Heber, David TI Ellagitannin-rich pomegranate extract inhibits angiogenesis in prostate cancer in vitro and in vivo SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE hypoxia inducible factor-1 alpha; pomegranate; angiogenesis; vascular endothelial growth factor; prostate cancer ID HYPOXIA-INDUCIBLE FACTOR-1; BREAST-CANCER; FACTOR 1-ALPHA; GREEN TEA; TUMOR-GROWTH; HIF-ALPHA; KAPPA-B; ACTIVATION; JUICE; TRANSCRIPTION AB Angiogenesis is critical to tumor growth and is stimulated by tissue hypoxia due to poor oxygen delivery. In turn, cellular hypoxia leads to angiogenesis via the induction of hypoxia-inducible factor-1 alpha (HIF-alpha) and vascular endothelial growth factor (VEGF) at a cellular level. Pomegranate juice and extracts, which are rich sources of ellagitannins, have been shown to have chemopreventive potential against prostate cancer, but there have been no studies on the effects of an ellagitannin-rich pomegranate extract on angiogenesis. Human prostate cancer cells (LNCaP) and human umbilical vein endothelial cells (HUVEC) were incubated with a pomegranate extract standardized to ellagitannin content (POMx), under normoxic and hypoxic conditions in vitro. Human prostate cancer cells (LAPC4) were injected subcutaneously into severe combined immunodeficient (SCID) mice and the effects of oral administration of POMx on tumor growth, microvessel density, and HIF-1 alpha and VEGF expression were determined after 4 weeks of treatment. POMx inhibited the proliferation of LNCaP and HUVEC cells significantly under both normoxic and hypoxic conditions. HIF-1 alpha and VEGF protein levels were also reduced by POMx under hypoxic conditions. POMx decreased prostate cancer xenograft size, tumor vessel density, VEGF peptide levels and HIF-1 alpha expression after 4 weeks of treatment in SCID mice. These results demonstrate that an ellagitannin-rich pomegranate extract can inhibit tumor-associated angiogenesis as one of several potential mechanisms for slowing the growth of prostate cancer in chemopreventive applications. Further studies in humans are needed to confirm that angiogenesis can be inhibited by an ellagitannin-rich pomegranate extract administered orally as a dietary supplement. C1 [Sartippour, Maryam R.; Seeram, Navindra P.; Moro, Aune; Harris, Diane M.; Henning, Susanne M.; Firouzi, Amita; Heber, David] Univ Calif Los Angeles, Ctr Human Nutr, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Rao, Jian Yu] Univ Calif Los Angeles, Dept Pathol, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Rettig, Matthew B.] Univ Calif Los Angeles, Div Hematol Oncol, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Rettig, Matthew B.; Aronson, William J.; Pantuck, Allan J.] Univ Calif Los Angeles, Dept Urol, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Rettig, Matthew B.] Univ Calif Los Angeles, Greater Los Angeles VA Healthcare Syst, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Heber, D (reprint author), Univ Calif Los Angeles, Ctr Human Nutr, David Geffen Sch Med, Box 951742, Los Angeles, CA 90095 USA. EM dheber@mednet.ucla.edu FU NCI NIH HHS [P50 CA 92131, CA 42710]; NIDDK NIH HHS [T32 DK 07688] NR 37 TC 56 Z9 58 U1 0 U2 9 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD FEB PY 2008 VL 32 IS 2 BP 475 EP 480 PG 6 WC Oncology SC Oncology GA 254XI UT WOS:000252620900022 PM 18202771 ER PT J AU Glowacki, J Schulten, AJM Perrott, D Kaban, LB AF Glowacki, J. Schulten, A. J. M. Perrott, D. Kaban, L. B. TI Nicotine impairs distraction osteogenesis in the rat mandible SO INTERNATIONAL JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article DE distraction osteogenesis; nicotine; rat; mandible ID PROMOTES TUMOR-GROWTH; BONE-GRAFT; RABBITS; ANGIOGENESIS; REGENERATION; SMOKE; MODEL AB Distraction osteogenesis (DO) has gained clinical acceptance as a surgical technique for treatment of congenital craniomaxillofacial deficiencies requiring skeletal expansion. The use of this technique elsewhere requires more information on overcoming difficult clinical settings, for which new animal models will be needed. The aim of this study was to develop and validate a model of impaired DO of the rat mandible with nicotine. Twenty rats underwent a right vertical mandibular body osteotomy, after which distraction began with custom-made percutaneous devices and a 3-day latency period, 6-day distraction (0.25 mm twice daily) and 30 days of neutral fixation. Rats received either nicotine or placebo slow-release pellets. Specimens were analysed after removal of the devices for quantitative radiographic bone fill, amount of bone advancement and histological features. The mean radiographic bone-fill score with nicotine treatment was 75% of that with placebo (P = 0.0036). The nicotine-treated rats had less (49%) elongation than the placebo-treated controls (P = 0.0008). Histological analysis demonstrated less bone, vascularity and cellular activity in nicotine-treated rats. This study shows that nicotine reproducibly inhibits osteogenesis, vascularity and bone lengthening in mandibular DO. C1 [Glowacki, J.; Schulten, A. J. M.; Perrott, D.; Kaban, L. B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Glowacki, J (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM jglowacki@rics.bwh.harvard.edu NR 25 TC 12 Z9 13 U1 1 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0901-5027 J9 INT J ORAL MAX SURG JI Int. J. Oral Maxillofac. Surg. PD FEB PY 2008 VL 37 IS 2 BP 156 EP 161 DI 10.1016/j.ijom.2007.08.001 PG 6 WC Dentistry, Oral Surgery & Medicine; Surgery SC Dentistry, Oral Surgery & Medicine; Surgery GA 267YC UT WOS:000253544100009 PM 17983728 ER PT J AU Lawton, CA Bae, K Pilepich, M Hanks, G Shipley, W AF Lawton, Colleen A. Bae, Kyoungwha Pilepich, Miljenko Hanks, Gerald Shipley, William TI Long-term treatment sequelae after external beam irradiation with or without hormonal manipulation for adenocarcinoma of the prostate: Analysis of radiation therapy oncology group studies 85-31, 86-10, and 92-02 SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE prostate cancer; toxicity; hormone therapy ID ADJUVANT ANDROGEN DEPRIVATION; LOCALLY ADVANCED-CARCINOMA; DEFINITIVE RADIOTHERAPY; GROUP RTOG; TOXICITY AB Purpose: Late gastrointestinal (GI) and genitourinary (GU) morbidity from external beam irradiation used to treat adenocarcinoma of the prostate continue to be a concern of physicians and patients alike. In addition, for locally advanced/high- risk cancer, the appropriate use of hormonal manipulation in addition to radiation therapy (RT) may increase toxicity. We analyzed three large Radiation Therapy Oncology Group (RTOG) studies (85-31, 86-10, and 92-02) to try to address these issues. Methods and Materials: A total of 2,922 patients were accrued with a median follow-up of 10.3 years for surviving patients. The RTOG scoring scheme was used to assess GI, GU, and other toxicities. Toxicity reported was Grade 3 or higher late toxicity. Patient toxicity level was assessed by study and by treatment type combining RT only vs. RT + short-course hormone therapy (STH) vs. RT + long-term hormone therapy (LTH). Results: Multivariate analysis reveals that age >70 was statistically significantly associated with a decrease in late any Grade 3+ toxicity (hazard ratio [HR] = 0.78, p = 0.0476) adjusted for treatment type. Comparing treatment type, patients treated with RT+STH had a statistically significant lower probability of Grade 3+ GI, GU, and other toxicity compared with RT alone (p = .00006; p = 0.0037; p = 0.0127, respectively). Patients treated with RT+LTH had a statistically significant lower probability of Grade 3+ GU toxicity compared with RT alone (p = 0.023). Conclusions: These data show that external beam radiation therapy remains a safe option for locally advanced/ high-risk prostate cancer, and the use of hormonal manipulation does appear to be protective for GU and GI toxicity depending upon length of treatment. (C) 2008 Elsevier Inc. C1 [Lawton, Colleen A.] Med Coll Wisconsin, Dept Radiat Oncol, Milwaukee, WI 53226 USA. [Bae, Kyoungwha] Amer Coll Radiol, Radiat Therapy Oncol Grp, Philadelphia, PA USA. [Shipley, William] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Lawton, CA (reprint author), Med Coll Wisconsin, Dept Radiat Oncol, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM clawton@radonc.mcw.edu FU NCI NIH HHS [U10 CA037422-12] NR 9 TC 37 Z9 37 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD FEB 1 PY 2008 VL 70 IS 2 BP 437 EP 441 DI 10.1016/j.ijrobp.2007.06.050 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 253MG UT WOS:000252521700018 PM 17881145 ER PT J AU Sher, DJ Wittenberg, E Taghian, AG Bellon, JR Punglia, RS AF Sher, David J. Wittenberg, Eve Taghian, Alphonse G. Bellon, Jennifer R. Punglia, Rinaa S. TI Partial breast irradiation versus whole breast radiotherapy for early-stage breast cancer: A decision analysis SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE decision analysis; partial breast irradiation; breast cancer ID CONSERVING SURGERY; RADIATION-THERAPY; RANDOMIZED-TRIAL; TOTAL MASTECTOMY; CONSERVATIVE SURGERY; LOCAL RECURRENCES; FOLLOW-UP; CARCINOMA; RISK; ADJUVANT AB Purpose: To compare the quality-adjusted life expectancy between women treated with partial breast irradiation (PBI) vs. whole breast radiotherapy (WBRT) for estrogen receptor-positive early-stage breast cancer. Methods and Materials: We developed a Markov model to describe health states in the 15 years after radiotherapy for estrogen receptor-positive early-stage breast cancer. Breast cancer recurrences were separated into local recurrences and elsewhere failures. Ipsilateral breast tumor recurrence (IBTR) risk was extracted from the Oxford overview, and rates and utilities were adapted from the literature. We studied two cohorts of women (aged 40 and 55 years), both of whom received adjuvant tamoxifen. Results: Assuming a no evidence of disease (NED)-PBI utility of 0.93, quality-adusted life expectancy after PBI (and WBRT) was 12.61 (12.57) and 12.10 (12.06) years for 40-year-old and 55-year-old women, respectively. The NED-PBI utility thresholds for preferring PBI over WBRT were 0.923 and 0.921 for 40-year-old and 55-year-old women, respectively, both slightly greater than the NED-WBRT utility. Outcomes were sensitive to the utility of NED-PBI, the PBI hazard ratio for local recurrence, the baseline IBTR risk, and the percentage of IBTRs that were local. Overall the degree of superiority of PBI over WBRT was greater for 55-year-old women than for 40-year-old women. Conclusions: For most utility values of the NED-PBI health state, PBI was the preferred treatment modality. This result was highly sensitive to patient preferences and was also dependent on patient age, PBI efficacy, IBTR risk, and the fraction of IBTRs that were local. (C) 2008 Elsevier Inc. C1 [Sher, David J.; Bellon, Jennifer R.; Punglia, Rinaa S.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Sher, David J.; Bellon, Jennifer R.; Punglia, Rinaa S.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Wittenberg, Eve; Taghian, Alphonse G.] Massachusetts Gen Hosp, Inst Technol Assessment, Dept Radiat Oncol, Boston, MA 02114 USA. RP Punglia, RS (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM rpunglia@lroc.harvard.edu FU NCI NIH HHS [1K07 CA 11 8629, K07 CA118269-01, K07 CA118269] NR 28 TC 11 Z9 13 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD FEB 1 PY 2008 VL 70 IS 2 BP 469 EP 476 DI 10.1016/j.ijrobp.2007.08.054 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 253MG UT WOS:000252521700023 PM 17967514 ER PT J AU Skondra, D Noda, K Almulki, L Tayyari, F Frimmel, S Nakazawa, T Kim, IK Zandi, S Thomas, KL Miller, JW Gragoudas, ES Hafezi-Moghadam, A AF Skondra, Dimitra Noda, Kousuke Almulki, Lama Tayyari, Faryan Frimmel, Sonja Nakazawa, Toru Kim, Ivana K. Zandi, Souska Thomas, Kennard L. Miller, Joan W. Gragoudas, Evangelos S. Hafezi-Moghadam, Ali TI Characterization of azurocidin as a permeability factor in the retina: Involvement in VEGF-induced and early diabetic blood-retinal barrier breakdown SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; INTERCELLULAR-ADHESION MOLECULE-1; SERINE PROTEINASE HOMOLOG; GLYCATION END-PRODUCTS; VASCULAR-PERMEABILITY; LEUKOCYTE ADHESION; BRAIN-BARRIER; IN-VIVO; CARDIAC-SURGERY; CELLS AB PURPOSE. Azurocidin, released by neutrophils during leukocyte-endothelial interaction, is a main cause of neutrophil-evoked vascular leakage. Its role in the retina, however, is unknown. METHODS. Brown Norway rats received intravitreal injections of azurocidin and vehicle control. Blood-retinal barrier (BRB) breakdown was quantified using the Evans blue (EB) dye technique 1, 3, and 24 hours after intravitreal injection. To block azurocidin, aprotinin was injected intravenously before the intravitreal injections. To investigate whether azurocidin plays a role in vascular endothelial growth factor (VEGF)-induced BRB breakdown, rats were treated intravenously with aprotinin, followed by intravitreal injection of VEGF 164. BRB breakdown was quantified 24 hours later. To investigate whether azurocidin may mediate BRB breakdown in early diabetes, aprotinin or vehicle was injected intravenously each day for 2 weeks to streptozotocin-induced diabetic rats, and BRB breakdown was quantified. RESULTS. Intravitreal injection of azurocidin (20 mu g) induced a 6.8-fold increase in vascular permeability compared with control at 1-3 hours (P < 0.05), a 2.7-fold increase at 3 to 5 hours (P < 0.01), and a 1.7-fold increase at 24 hours (P < 0.05). Aprotinin inhibited azurocidin-induced BRB breakdown by more than 95% (P < 0.05). Furthermore, treatment with aprotinin significantly suppressed VEGF-induced BRB breakdown by 93% (P < 0.05) and BRB breakdown in early experimental diabetes by 40.6% (P < 0.05). CONCLUSIONS. Azurocidin increases retinal vascular permeability and is effectively blocked by aprotinin. The inhibition of VEGF-induced and early diabetic BRB breakdown with aprotinin indicates that azurocidin may be an important mediator of leukocyte-dependent BRB breakdown secondary to VEGF. Azurocidin may become a new therapeutic target in the treatment of retinal vascular leakage, such as during diabetic retinopathy. C1 [Skondra, Dimitra; Noda, Kousuke; Almulki, Lama; Tayyari, Faryan; Frimmel, Sonja; Nakazawa, Toru; Kim, Ivana K.; Zandi, Souska; Thomas, Kennard L.; Miller, Joan W.; Gragoudas, Evangelos S.; Hafezi-Moghadam, Ali] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm,Angiogenesis Lab, Boston, MA 02114 USA. RP Hafezi-Moghadam, A (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm,Angiogenesis Lab, 325 Cambridge St, Boston, MA 02114 USA. EM ahm@meei.harvard.edu OI Hafezi-Moghadam, Ali/0000-0002-5336-0697 FU NEI NIH HHS [EY 14104]; NIAID NIH HHS [AI 050775] NR 34 TC 21 Z9 26 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB PY 2008 VL 49 IS 2 BP 726 EP 731 DI 10.1167/iovs.07-0405 PG 6 WC Ophthalmology SC Ophthalmology GA 256RK UT WOS:000252747100034 PM 18235021 ER PT J AU Joy, T Keogh, HM Hadigan, C Dolan, SE Fitch, K Liebau, J Johnsen, S Lo, J Grinspoon, SK AF Joy, Tisha Keogh, Hester M. Hadigan, Colleen Dolan, Sara E. Fitch, Kathleen Liebau, James Johnsen, Stine Lo, Janet Grinspoon, Steven K. TI Relation of body composition to body mass index in HIV-infected patients with metabolic abnormalities SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE body composition; body mass index; HIV; visceral adiposity ID HUMAN-IMMUNODEFICIENCY-VIRUS; ANTIRETROVIRAL THERAPY; PROTEASE INHIBITORS; FAT DISTRIBUTION; ABDOMINAL ADIPOSITY; GLUCOSE-TOLERANCE; RANDOMIZED-TRIAL; LIPODYSTROPHY; WOMEN; MEN AB Objective: To determine visceral adiposity (VAT), subcutaneous adiposity (SAT), and regional body adipose differences between HIV-infected and non-HIV-infected subjects in relation to body mass index (BMI) and World Health Organization BMI categories. Design, Setting, and Participants: Analyses were conducted of 306 HIV-infected and 107 community-derived HIV-negative subjects evaluated for metabolic studies between 1999 and 2006. Analyses were stratified by gender. Additional analyses were performed stratifying subjects by metabolic syndrome status. Results: HIV-infected men and women demonstrated decreased total extremity fat by 1.1 kg and 0.85 kg, respectively, relative to non-HIV-infected control subjects. VAT was increased among HIV-infected men and women in the normal (18.5 to 24.9 kg/m(2)) and overweight (25.0 to 29.9 kg/m(2)) categories relative to control subjects but not among those in the obese category ( >= 30.0 kg/m(2)). In contrast, abdominal SAT was reduced among HIV-infected men in the normal and overweight categories but was similar among HIV-infected women and control subjects in these categories. Abdominal SAT was increased among HIV-infected women in the obese category relative to control subjects. Similar results were obtained limiting the analysis to HIV-infected (n = 204) and control subjects (n = 89) without the metabolic syndrome. Conclusions: Peripheral lipoatrophy is a consistent finding among HIV-infected men and women with metabolic abnormalities. Relative increases in VAT are most pronounced among male and female HIV-infected subjects in the normal weight and overweight categories. Gender differences in abdominal SAT accumulation are observed, with preservation of SAT among HIV-infected women relative to control subjects. C1 [Joy, Tisha; Keogh, Hester M.; Hadigan, Colleen; Dolan, Sara E.; Fitch, Kathleen; Liebau, James; Johnsen, Stine; Lo, Janet; Grinspoon, Steven K.] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. [Joy, Tisha; Keogh, Hester M.; Hadigan, Colleen; Dolan, Sara E.; Fitch, Kathleen; Liebau, James; Johnsen, Stine; Lo, Janet; Grinspoon, Steven K.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hadigan, Colleen] NIH, Bethesda, MD USA. RP Grinspoon, SK (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU NCRR NIH HHS [M01-RR01066, M01 RR001066]; NICHD NIH HHS [T32 HD052961, T32HD-052961]; NIDDK NIH HHS [DK-02844, R01 DK049302, K23 DK002844, P30 DK040561-12, P30 DK040561]; PHS HHS [DKR01-49302] NR 40 TC 18 Z9 18 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD FEB 1 PY 2008 VL 47 IS 2 BP 174 EP 184 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 255VA UT WOS:000252684600006 PM 17971710 ER PT J AU Brigham, KS Goldstein, MA AF Brigham, Kathryn S. Goldstein, Mark A. TI An assessment of adolescents' knowledge of confidentiality in health care SO JOURNAL OF ADOLESCENT HEALTH LA English DT Meeting Abstract C1 [Brigham, Kathryn S.; Goldstein, Mark A.] Harvard Univ, Sch Med, MassGen Hosp Children, Div Adolescent & Young Adult Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD FEB PY 2008 VL 42 IS 2 SU S BP S16 EP S16 PG 1 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 258QO UT WOS:000252882900033 ER PT J AU Kahn, JA Huang, B Ding, L Frazier, AL AF Kahn, Jessica A. Huang, Bin Ding, Lili Frazier, A. Lindsay TI Impact of maternal communication about skin, cervical and lung cancer prevention on adolescent prevention behaviors SO JOURNAL OF ADOLESCENT HEALTH LA English DT Meeting Abstract C1 [Kahn, Jessica A.; Huang, Bin; Ding, Lili; Frazier, A. Lindsay] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. [Kahn, Jessica A.; Huang, Bin; Ding, Lili; Frazier, A. Lindsay] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kahn, Jessica A.; Huang, Bin; Ding, Lili; Frazier, A. Lindsay] Childrens Hosp, Boston, MA 02115 USA. RI Ding, Lili/E-8018-2012; Huang, bin/G-2468-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD FEB PY 2008 VL 42 IS 2 SU S BP S29 EP S29 PG 1 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 258QO UT WOS:000252882900063 ER PT J AU Miller, E Decker, M Silverman, J Reed, EA Marable, D Raj, A AF Miller, Elizabeth Decker, Michele Silverman, Jay Reed, Elizabeth A. Marable, Danelle Raj, Anita TI Adolescent intimate partner violence and contraceptive nonuse among adolescent females utilizing teen clinics SO JOURNAL OF ADOLESCENT HEALTH LA English DT Meeting Abstract C1 [Miller, Elizabeth; Decker, Michele; Silverman, Jay; Reed, Elizabeth A.; Marable, Danelle; Raj, Anita] Univ Calif Davis, Sch Med, Sacramento, CA 95817 USA. [Miller, Elizabeth; Decker, Michele; Silverman, Jay; Reed, Elizabeth A.; Marable, Danelle; Raj, Anita] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Miller, Elizabeth; Decker, Michele; Silverman, Jay; Reed, Elizabeth A.; Marable, Danelle; Raj, Anita] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Miller, Elizabeth/E-7939-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD FEB PY 2008 VL 42 IS 2 SU S BP S8 EP S8 PG 1 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 258QO UT WOS:000252882900017 ER PT J AU Cardenas, J Frye, MA Marusak, SL Levander, EM Chirichigno, JW Lewis, S Nakelsky, S Hwang, S Mintz, J Altshuler, LL AF Cardenas, Jeffrey Frye, Mark A. Marusak, Susan L. Levander, Eric M. Chirichigno, Jason W. Lewis, Stryder Nakelsky, Shoshanna Hwang, Sun Mintz, Jim Altshuler, Lori L. TI Modal subcomponents of metabolic syndrome in patients with bipolar disorder SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article; Proceedings Paper CT 159th Annual Meeting of the American-Psychiatric-Association CY MAY 20-25, 2006 CL Toronto, CANADA SP Amer Psychiat Assoc DE bipolar disorder; metabolic syndrome; psychotropic ID CORONARY-HEART-DISEASE; MIDDLE-AGED MEN; CARDIOVASCULAR-DISEASE; LIPID-LEVELS; LIFE-STYLE; RISK; INTERVENTION; ADULTS; CARBAMAZEPINE; APPROPRIATE AB Background: The metabolic syndrome is a growing global public health problem. Objective: To evaluate the prevalence rate and modal subcomponents of the metabolic syndrome in subjects treated at the West Los Angeles Veterans Administration Medical Center Bipolar Clinic. Methods: In this cross-sectional design study, using the National Cholesterol Education Program definition, metabolic syndrome prevalence rates were calculated. Results: 48/98 (49%) of subjects met criteria for metabolic syndrome. There was no difference in prevalence rate by gender or race. Almost 70% of the cohort met criteria for metabolic syndrome by the components of reduced HDL and increased waist circumference. Treatment with carbamazepine at study entry was associated with a lower prevalence rate of metabolic syndrome. Limitations and conclusions: This study is limited by its small size and non-structured assessment of Axis I diagnosis. Nonetheless, bipolar patients in this select cohort have high rates of metabolic syndrome; given this cardiovascular risk, close clinical monitoring for these parameters is recommended. While not controlling for genetics, environmental influences, and/or medical factors such as additional comorbidity and treatment duration, psychotropic drug use may confer differential risk for developing the metabolic syndrome. (c) 2007 Published by Elsevier B.V. C1 [Frye, Mark A.] Mayo Coll Med, Mayo Clin, Dept Psychiat & Psychol, Rochester, MN 55905 USA. [Cardenas, Jeffrey; Marusak, Susan L.; Levander, Eric M.; Chirichigno, Jason W.; Lewis, Stryder; Nakelsky, Shoshanna; Hwang, Sun; Mintz, Jim; Altshuler, Lori L.] Univ Calif Los Angeles, David Geffen Sch Med, UCLA Mood Disorders Res Program, Dept Psychiat, Los Angeles, CA USA. [Cardenas, Jeffrey; Marusak, Susan L.; Levander, Eric M.; Chirichigno, Jason W.; Lewis, Stryder; Nakelsky, Shoshanna; Hwang, Sun; Mintz, Jim; Altshuler, Lori L.] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Frye, MA (reprint author), Mayo Coll Med, Mayo Clin, Dept Psychiat & Psychol, 200 1st St SW, Rochester, MN 55905 USA. EM mfrye@mayo.edu NR 26 TC 52 Z9 55 U1 2 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD FEB PY 2008 VL 106 IS 1-2 BP 91 EP 97 DI 10.1016/j.jad.2007.05.030 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 258YC UT WOS:000252905300008 PM 17628693 ER PT J AU Khalsa, HMK Salvatore, P Hennen, J Baethge, C Tohen, M Baldessarini, RJ AF Khalsa, Hari Mandir Kaur Salvatore, Paola Hennen, John Baethge, Christopher Tohen, Mauricio Baldessarini, Ross J. TI Suicidal events and accidents in 216 first-episode bipolar I disorder patients: Predictive factors SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE bipolar disorder; first-episode; risk factors; suicide; accidents ID LITHIUM TREATMENT; EXCESS MORTALITY; RISK; BEHAVIOR; PREVENTION; DEPRESSION; RECOVERY AB Background: Risks of life-threatening behaviors are high among bipolar disorder (BPD) patients, but early rates and associated risk factors for suicides and accidents remain ill-defined. Methods: We assessed 216 DSM-IV BP-I patients prospectively for 4.2 years from first-lifetime hospitalization, using ordinal logistic-regression to estimate risks and associated demographic and clinical factors among risk-groups with: [1] no suicidal ideation, acts, or accidents, [2] suicidal ideation only, [3] suicides and attempts, [4] accidents, and [5] both suicidal acts and accidents. Results: Suicidal thoughts or acts were identified in 127/216 subjects/4.2 years (14%/year), including suicidal ideation in 88 (9.7%/year), and acts in 39 (4.3%/year: 38 attempts [I 7.6%/year], I suicide [0. 11 %/year]); 87% of acts occurred within a year of a first-episode. Life-threatening accidents occurred in 20 cases (2.2%/year) with a mean latency of 3.8 years, including 12 with suicidal ideation or attempts (60% co-occurrence of accidents and suicidality); alcohol was implicated in 25% of accidents. The 53 cases of violent behaviors (5.84%/year) included a fatal car-wreck and a suicide, for a mortality risk of 0.22%/year (2/216/4.2 years). Suicidality was associated with initial mixed-state, proportion of follow-up weeks in mixed-states or depression, and prior suicide attempts; accidents were associated selectively with initial mania or psychosis, later mania or hypomania, and alcohol abuse. Violent acts also were associated with use of more psychotropic medicines/person, and with use of antipsychotics or sedative-anxiolytics. Limitations: Treatment was clinical and uncontrolled, illness relatively severe, and statistical power limited. Conclusions: Early in BP-I disorder, risks of suicidal acts and accidents were high, inter-related, and associated with particular types of initial and later morbidity, suggesting some predictability and potential for preventive intervention. (c) 2007 Elsevier B.V. All rights reserved. C1 [Khalsa, Hari Mandir Kaur; Salvatore, Paola; Hennen, John; Baethge, Christopher; Tohen, Mauricio; Baldessarini, Ross J.] Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Int Consortium Bipolar Disorder Res, Belmont, MA 02478 USA. [Khalsa, Hari Mandir Kaur; Salvatore, Paola; Hennen, John; Baethge, Christopher; Tohen, Mauricio; Baldessarini, Ross J.] Harvard Univ, Sch Med, Dept Psychiat, Belmont, MA 02478 USA. [Salvatore, Paola] Univ Parma, Dept Neurosci, Sect Psychiat, I-43100 Parma, Italy. [Baethge, Christopher] Univ Cologne, Sch Med, Dept Psychiat, Cologne, Germany. [Tohen, Mauricio] Lilly Res Labs, Indianapolis, IN USA. RP Baldessarini, RJ (reprint author), McLean Hosp, Mailman Res Ctr 312, 115 Mill St, Belmont, MA 02478 USA. EM rjb@mclean.org FU NIMH NIH HHS [MH-073049] NR 22 TC 45 Z9 46 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD FEB PY 2008 VL 106 IS 1-2 BP 179 EP 184 DI 10.1016/j.jad.2007.05.027 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 258YC UT WOS:000252905300019 PM 17614135 ER PT J AU Love, TM Moffett, HF Novina, CD AF Love, Tara M. Moffett, Howell F. Novina, Carl D. TI Not miR-ly small RNAs: Big potential for microRNAs in therapy SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE RNA interference; small interfering RNA; microRNA; antagomiR ID SHORT INTERFERING RNA; CELL-PENETRATING PEPTIDES; IN-VIVO; OVARIAN-CARCINOMA; BURKITT-LYMPHOMA; CATIONIC LIPIDS; SYNTHETIC SIRNA; GENE-EXPRESSION; DOWN-REGULATION; PROTECTS MICE AB RNA interference (RNAi) describes a set of natural processes in which genes are silenced by small RNAs. RNAi has been widely used as an experimental tool that has recently become the focus of drug development efforts to treat a variety of diseases and disorders. Like all molecular therapies, in vivo delivery is the major hurdle to realizing therapeutic RNAi. Several strategies have been developed that increase small RNA half-life in the blood, facilitate transduction across biological membranes, and mediate cell-specific delivery. Importantly, these strategies permit targeting of mRNAs as well as microRNAs (miRNAs), a class of small RNAs encoded in the genome. miRNAs are required for multiple developmental and cellular processes. Dysfunction of miRNAs can result in a host of pathologies, suggesting that miRNAs are potential targets of therapy. Recent studies of miRNA function in immune-specific pathways indicate that specific miRNAs might be exploited as therapeutic targets to treat immune disorders, including autoimmunity, allergy, and hematopoietic cancers. C1 [Love, Tara M.; Moffett, Howell F.; Novina, Carl D.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Love, Tara M.; Moffett, Howell F.; Novina, Carl D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Novina, Carl D.] Harvard & Massachusetts Inst Technol, Broad Inst, Cambridge, MA USA. RP Love, TM (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM carl_novina@dfci.harvard.edu NR 86 TC 45 Z9 48 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2008 VL 121 IS 2 BP 309 EP 319 DI 10.1016/j.jaci.2007.12.1167 PG 11 WC Allergy; Immunology SC Allergy; Immunology GA 265CX UT WOS:000253337800003 PM 18269923 ER PT J AU Esch, RE Bush, RK Skoner, D Gentile, D McLaughlin, A Fasano, MB AF Esch, R. E. Bush, R. K. Skoner, D. Gentile, D. McLaughlin, A. Fasano, M. B. TI Parallel, randomized, double-blind, placebo-controlled, dose-response phase IIb trial in adults for short ragweed sublingual-oral immunotherapy (SLIT) SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 14-18, 2008 CL Philadelphia, PA SP Amer Acad Allergy, Asthma & Immunol C1 [Esch, R. E.] Greer Labs, Lenoir, NC USA. [Bush, R. K.] Univ Wisconsin, William S Middleton Mem Vet Hosp, Madison, WI USA. [Skoner, D.; Gentile, D.] Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. [McLaughlin, A.] Welborn Clin Res Ctr, Evansville, IL USA. [Fasano, M. B.] Univ Iowa, Dept Internal Med, Iowa City, IA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2008 VL 121 IS 2 SU 1 MA 492 BP S127 EP S127 DI 10.1016/j.jaci.2007.12.505 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 266HZ UT WOS:000253426400491 ER PT J AU Lee, CH Corren, J AF Lee, C. H. Corren, J. TI Effects of nasal allergen challenge upon airway responsiveness to exercise SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 14-18, 2008 CL Philadelphia, PA SP Amer Acad Allergy, Asthma & Immunol C1 [Lee, C. H.] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. [Corren, J.] Allergy Res Fdn, Los Angeles, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2008 VL 121 IS 2 SU 1 MA 1008 BP S260 EP S260 DI 10.1016/j.jaci.2007.12.1034 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 266HZ UT WOS:000253426401471 ER PT J AU McEldowney, SJ Bush, RK AF McEldowney, S. J. Bush, R. K. TI House dust mite-specific IgA and exhaled nitric oxide are elevated in allergic asthma and rhinitis patients with positive: Methacholine challenges SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 14-18, 2008 CL Philadelphia, PA SP Amer Acad Allergy, Asthma & Immunol C1 [McEldowney, S. J.; Bush, R. K.] Univ Wisconsin Hosp & Clins, Madison, WI USA. [McEldowney, S. J.; Bush, R. K.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2008 VL 121 IS 2 SU 1 MA 761 BP S198 EP S198 DI 10.1016/j.jaci.2007.12.737 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 266HZ UT WOS:000253426401225 ER PT J AU Sheinkopf, LE Rafi, AW Do, LT Klaustermeyer, WB Katz, RM AF Sheinkopf, L. E. Rafi, A. W. Do, L. T. Klaustermeyer, W. B. Katz, R. M. TI Reasons for discontinuation of Omalizumab therapy in the treatment of patients with moderate to severe persistent asthma SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 14-18, 2008 CL Philadelphia, PA SP Amer Acad Allergy, Asthma & Immunol C1 [Sheinkopf, L. E.; Klaustermeyer, W. B.] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. [Rafi, A. W.; Do, L. T.; Katz, R. M.] Allergy Asthma Care Ctr Inc, Santa Monica, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2008 VL 121 IS 2 SU 1 MA 537 BP S139 EP S139 DI 10.1016/j.jaci.2007.12.552 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 266HZ UT WOS:000253426401001 ER PT J AU Watson, C Rafi, A Do, L Sheinkopt, L Katz, R AF Watson, C. Rafi, A. Do, L. Sheinkopt, L. Katz, R. TI Efficacy of Omalizumab for the treatment of food allergy SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 14-18, 2008 CL Philadelphia, PA SP Amer Acad Allergy, Asthma & Immunol C1 [Watson, C.; Sheinkopt, L.] Univ Calif Los Angeles, Greater Los Angeles VA Med Ctr, Los Angeles, CA USA. [Rafi, A.; Do, L.; Katz, R.] Allergy Asthma Care Ctr, Santa Monica, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2008 VL 121 IS 2 SU 1 MA 975 BP S252 EP S252 DI 10.1016/j.jaci.2007.12.1000 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 266HZ UT WOS:000253426401438 ER PT J AU Pietrement, C Da Silva, N Silberstein, C James, M Marsolais, M Van Hoek, A Brown, D Pastor-Soler, N Ameen, N Laprade, R Ramesh, V Breton, S AF Pietrement, Christine Da Silva, Nicolas Silberstein, Claudia James, Marianne Marsolais, Mireille Van Hoek, Alfred Brown, Dennis Pastor-Soler, Nuria Ameen, Nadia Laprade, Raynald Ramesh, Vijaya Breton, Sylvie TI Role of NHERF1, cystic fibrosis transmembrane conductance regulator, and cAMP in the regulation of aquaporin 9 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CONGENITAL BILATERAL ABSENCE; RAT CAUDA-EPIDIDYMIDIS; NEUTRAL SOLUTE CHANNEL; VAS-DEFERENS; MOLECULAR CHARACTERIZATION; WATER REABSORPTION; EPITHELIAL-CELLS; PROXIMAL TUBULE; INITIAL SEGMENT; EFFERENT DUCTS AB Water and solute transport across the plasma membrane of cells is a crucial biological function that is mediated mainly by aquaporins and aquaglyceroporins. The regulation of these membrane proteins is still incompletely understood. Using the male reproductive tract as a model system in which water and glycerol transport are critical for the establishment of fertility, we now report a novel pathway for the regulation of aquaporin 9 (AQP9) permeability. AQP9 is the major aquaglyceroporin of the epididymis, liver, and peripheral leukocytes, and its COOH-terminal portion contains a putative PDZ binding motif (SVIM). Here we show that NHERF1, cystic fibrosis transmembrane conductance regulator (CFTR), and AQP9 co-localize in the apical membrane of principal cells of the epididymis and the vas deferens, and that both NHERF1 and CFTR co-immunoprecipitate with AQP9. Overlay assays revealed that AQP9 binds to both the PDZ1 and PDZ2 domains of NHERF1, with an apparently higher affinity for PDZ1 versus PDZ2. Pull-down assays showed that the AQP9 COOH-terminal SVIM motif is essential for interaction with NHERF1. Functional assays on isolated tubules perfused in vitro showed a high permeability of the apical membrane to glycerol, which is inhibited by the AQP9 inhibitor, phloretin, and is markedly activated by cAMP. The CFTR inhibitors DPC, GlyH-101 and CFTRinh-172 all significantly reduced the cAMP-activated glycerol-induced cell swelling. We propose that CFTR is an important regulator of AQP9 and that the interaction between AQP9, NHERF1, and CFTR may facilitate the activation of AQP9 by cAMP. C1 [Pietrement, Christine; Da Silva, Nicolas; Silberstein, Claudia; Van Hoek, Alfred; Brown, Dennis; Breton, Sylvie] Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Div Nephrol, Boston, MA 02114 USA. [James, Marianne; Ramesh, Vijaya] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Van Hoek, Alfred; Brown, Dennis; Ramesh, Vijaya; Breton, Sylvie] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. [Marsolais, Mireille; Laprade, Raynald] Univ Montreal, Grp Proteins Membranaires, Montreal, PQ, Canada. [Ameen, Nadia] Univ Pittsburgh, Sch Med, Dept Pediat, Pittsburgh, PA 15261 USA. RP Breton, S (reprint author), Massachusetts Gen Hosp, Simches Res Ctr, Program Membrane Biol, 185 Cambridge St,Suite 8204, Boston, MA 02114 USA. EM sbreton@partners.org FU NICHD NIH HHS [HD 045821]; NIDDK NIH HHS [DK 43351, DK 57521] NR 67 TC 40 Z9 44 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 1 PY 2008 VL 283 IS 5 BP 2986 EP 2996 DI 10.1074/jbc.M704678200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 254XW UT WOS:000252622300054 PM 18055461 ER PT J AU Kaufman, AM Alabre, CI Rubash, HE Shanbhag, AS AF Kaufman, Adam M. Alabre, Claude I. Rubash, Harry E. Shanbhag, Arun S. TI Human macrophage response to UHMWPE, TiAlV, CoCr, and alumina particles: Analysis of multiple cytokines using protein arrays SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A LA English DT Review DE macrophages; wear debris; cytokines; protein chips; UHMWPE; debris ID TOTAL HIP-ARTHROPLASTY; DEBRIS-INDUCED OSTEOLYSIS; VOLUMETRIC COMPUTERIZED-TOMOGRAPHY; WEIGHT POLYETHYLENE PARTICLES; BLOOD MONONUCLEAR PHAGOCYTES; TITANIUM-ALLOY PARTICLES; PARTICULATE WEAR DEBRIS; HUMAN MONOCYTE RESPONSE; VIL-10 GENE-TRANSFER; MURINE AIR POUCH AB Aseptic loosening of total joint replacements is believed to be initiated by a macrophage response to prosthetic wear debris. To better characterize the early response to clinically relevant wear debris, we challenged primary human macrophages from four donors with ultra high molecular weight polyethylene (UHMWPE), TiAlV, CoCr, and alumina particles. After a 24-h culture, protein arrays were used to quantify the secretion of 30 different cytokines and chemokines. Macrophages secreted detectable levels of nine mediators in culture: Interleukin-1 alpha (IL-1 alpha) tumor necrosis factor-alpha (TNF-alpha), IL-1 beta, MCP-1, IL-8, IL-6, GM-CSF, IL-10, and IL-12p40. TiAIV particles were the most stimulatory, causing 5- to 900-fold higher cytokine expression compared with nonstimulated cells and uniquely eliciting high levels of IL-1 alpha, IL-6, IL-10, and GM-CSF. CoCr and alumina were mildly stimulatory and typically elicited two- to fivefold greater levels than nonstimulated cells. Surprisingly, UHMWPE did not elicit a significant increase in cytokine release. Our data suggests that IL-1 alpha, TNF-alpha, IL-1 beta, and MCP-1 are the primary initiators of osteolysis and implicates metallic debris as an important trigger for their release. (c) 2007 Wiley Periodicals, Inc. C1 [Kaufman, Adam M.; Alabre, Claude I.; Rubash, Harry E.; Shanbhag, Arun S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Biomat Lab, Boston, MA 02474 USA. RP Shanbhag, AS (reprint author), Biomat Lab, GRJ 1115,55 Fruit St, Boston, MA 02114 USA. EM shanbhau@helix.mgh.harvard.edu NR 112 TC 55 Z9 59 U1 3 U2 21 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1549-3296 J9 J BIOMED MATER RES A JI J. Biomed. Mater. Res. Part A PD FEB PY 2008 VL 84A IS 2 BP 464 EP 474 DI 10.1002/jbm.a.31467 PG 11 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 247ZU UT WOS:000252121900020 PM 17618502 ER PT J AU Bhattacharyya, T Wadgaonkar, AD AF Bhattacharyya, Timothy Wadgaonkar, Ajay D. TI Inadvertent retention of angled drill guides after volar locking plate fixation of distal radial fractures SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID COMPRESSION PLATES; COMPLICATIONS; SYSTEM AB Advances in locking plate technology have proven especially valuable for fixation of distal radial fractures, and preliminary results have been excellent(1-6). However, new technology can sometimes lead to new complications. In some systems, the locking plates are preloaded with angled drill guides to allow for easy placement of locking screws in the proper direction (Fig. 1). The drill guides are designed to be removed prior to closure. We report the cases of three patients in whom the angled drill guides were retained after surgery. Institutional review board approval was obtained for this study, and the patients were informed that data concerning the case would be submitted for publication, and they consented. C1 [Bhattacharyya, Timothy; Wadgaonkar, Ajay D.] Massachusetts Gen Hosp, Orthopaed Traumat Surg, Boston, MA 02118 USA. [Bhattacharyya, Timothy; Wadgaonkar, Ajay D.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Bhattacharyya, T (reprint author), Massachusetts Gen Hosp, Orthopaed Traumat Surg, 55 Fruit St,Yawkey 3600, Boston, MA 02118 USA. NR 16 TC 11 Z9 12 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD FEB PY 2008 VL 90A IS 2 BP 401 EP 403 DI 10.2106/JBJS.G.00939 PG 3 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 258XX UT WOS:000252904800027 PM 18245602 ER PT J AU Moran, A Katz, R Smith, NL Fried, LF Sarnak, MJ Seliger, SL Psaty, B Siscovick, DS Gottdiener, JS Shlipak, MG AF Moran, Andrew Katz, Ronit Smith, Nicolas L. Fried, Linda F. Sarnak, Mark J. Seliger, Stephen L. Psaty, Bruce Siscovick, David S. Gottdiener, John S. Shlipak, Michael G. TI Cystatin C concentration as a predictor of systolic and diastolic heart failure SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE cystatin C; diastolic heart failure; ejection fraction; elderly; estimated glomerular filtration rate; heart failure; systolic heart failure ID LEFT-VENTRICULAR HYPERTROPHY; CHRONIC KIDNEY-DISEASE; GLOMERULAR-FILTRATION-RATE; BLOOD-PRESSURE CONTROL; CHRONIC RENAL-DISEASE; CARDIOVASCULAR MORTALITY; COMPETING RISKS; INSUFFICIENCY; PROGRESSION; DYSFUNCTION AB Background: Risk factors for heart failure (HF) may differ according to ejection fraction (EF). Higher cystatin C, a marker of kidney dysfunction, is associated with incident HF, but previous studies did not determine EF at diagnosis. We hypothesized that kidney dysfunction would predict diastolic HF (DHF) better than systolic HF (SHF) in the Cardiovascular Health Study. Methods and Results: Cystatin C was measured in 4453 participants without HF at baseline. Incident HF was categorized as DHF (EF >= 50%) or SHF (EF < 50%). We compared the association of cystatin C with the risk for DHF and SHE after adjustment for age, sex, race, medications, and HF risk factors. During 8 years of follow-up, 167 participants developed DHF and 206 participants developed SHE After adjustment, sequentially higher quartiles of cystatin C were associated with risk for SHF (competing risks hazard ratios 1.0 [reference], 1.99 [95% confidence interval 1.14-3.48], 2.32 [1.32-4.07], 3.17 [1.82-5.50], P for trend < .001). The risk for DHF was apparent only at the highest cystatin C quartile (hazard ratios 1.0 [reference], 1.09 [0.62-1.89], 1.08 [0.61-1.93], and 1.83 [1.07-3.11]). Conclusions: Cystatin C levels are linearly associated with the incidence of systolic HF, whereas only the highest concentrations of cystatin C predict diastolic HF. C1 [Moran, Andrew; Shlipak, Michael G.] Vet Adm Med Ctr, Gen Internal Med Sect, San Francisco, CA 94121 USA. [Moran, Andrew; Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Smith, Nicolas L.; Psaty, Bruce; Siscovick, David S.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Fried, Linda F.] Vet Affairs Pittsburgh Healthcare Syst, Renal Sect, Med Serv, Pittsburgh, PA USA. [Sarnak, Mark J.] Tufts Univ New England Med Ctr, Boston, MA USA. [Seliger, Stephen L.] Univ Maryland, Baltimore, MD 21201 USA. [Gottdiener, John S.] Univ Maryland, Sch Med, Div Cardiol, Baltimore, MD 21201 USA. RP Shlipak, MG (reprint author), Vet Adm Med Ctr, Gen Internal Med Sect, 111A1,4150 Clement St, San Francisco, CA 94121 USA. FU NHLBI NIH HHS [N01-HC-85086, N01 HC035129, N01 HC015103, N01HC75150, N01-HC-85079, N01HC85086, N01HC85079, N01 HC045133, N01-HC-75150]; NIDDK NIH HHS [R01 DK066488-04, R01 DK066488] NR 39 TC 29 Z9 34 U1 0 U2 5 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD FEB PY 2008 VL 14 IS 1 BP 19 EP 26 DI 10.1016/j.cardfail.2007.09.002 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 261HW UT WOS:000253070700004 PM 18226769 ER PT J AU Ong, KC Hilgenberg, AD Alston, TA AF Ong, Kah Chuan Hilgenberg, Alan D. Alston, Theodore A. TI An echogenic mass after composite aortic root replacement SO JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA LA English DT Article DE hemostasis; hydrogel; polyethylene glycol; sealant ID CARDIAC-SURGERY; SEALANTS C1 [Ong, Kah Chuan; Alston, Theodore A.] Harvard Univ, Dept Anesthesia & Crit Care, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hilgenberg, Alan D.] Harvard Univ, Dept Surg, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Alston, TA (reprint author), Harvard Univ, Dept Anesthesia & Crit Care, Sch Med, Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM talston@partners.org NR 6 TC 1 Z9 1 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1053-0770 J9 J CARDIOTHOR VASC AN JI J. Cardiothorac. Vasc. Anesth. PD FEB PY 2008 VL 22 IS 1 BP 160 EP 161 DI 10.1053/j.jvca.2007.04.017 PG 2 WC Anesthesiology; Cardiac & Cardiovascular Systems; Respiratory System; Peripheral Vascular Disease SC Anesthesiology; Cardiovascular System & Cardiology; Respiratory System GA 265VH UT WOS:000253389200034 PM 18249354 ER PT J AU Aryana, A Ellinor, PT Aleong, RG Donaldson, DM Mamuya, WS Ruskin, JN Mansour, MC AF Aryana, Arash Ellinor, Patrick T. Aleong, Ryan G. Donaldson, David M. Mamuya, Wilfred S. Ruskin, Jeremy N. Mansour, Moussa C. TI Ablation of atrial flutter in a patient with situs inversus totalis using integration of real-time three-dimensional electroanatomical mapping SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Editorial Material C1 [Aryana, Arash; Ellinor, Patrick T.; Aleong, Ryan G.; Donaldson, David M.; Ruskin, Jeremy N.; Mansour, Moussa C.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Mamuya, Wilfred S.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Mamuya, Wilfred S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Mansour, MC (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, GRB-109,55 Fruit St, Boston, MA 02114 USA. EM mmansour@partners.org NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD FEB PY 2008 VL 19 IS 2 BP 221 EP 222 DI 10.1111/j.1540-8167.2007.00987.x PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 257PM UT WOS:000252811000023 PM 17916136 ER PT J AU Sarwar, A Nasir, K Shapiro, MD Abbara, S AF Sarwar, Ammar Nasir, Khurram Shapiro, Michael D. Abbara, Suhny TI Anomalous left inferior pulmonary vein crossing midline and draining via common ostium with right inferior pulmonary vein SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Editorial Material C1 [Sarwar, Ammar; Nasir, Khurram; Shapiro, Michael D.; Abbara, Suhny] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Cardiac MR PET CT Program, Boston, MA 02114 USA. RP Abbara, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Cardiac MR PET CT Program, 55 Fruit Str,GRB-290, Boston, MA 02114 USA. EM sabbara@partners.org FU NHLBI NIH HHS [1T32 HL076136-02] NR 2 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD FEB PY 2008 VL 19 IS 2 BP 223 EP 223 DI 10.1111/j.1540-8167.2007.00988.x PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 257PM UT WOS:000252811000024 PM 17916135 ER PT J AU Prystowsky, EN Jais, P Kowey, P Nattel, S Ruskin, JN AF Prystowsky, Eric N. Jais, Pierre Kowey, Peter Nattel, Stanley Ruskin, Jeremy N. TI Case studies with the experts: Management decisions in atrial fibrillation SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE atrial fibrillation; catheter ablation; cardioversion; anticoagulation; antiarrhythmic drugs ID ASSOCIATION TASK-FORCE; HEART-FAILURE; SINUS RHYTHM; CARDIOLOGY COMMITTEE; PRACTICE GUIDELINES; AMERICAN-COLLEGE; EUROPEAN-SOCIETY; PREVENTION; DRONEDARONE; PREVALENCE AB Case Studies with the Experts. Atrial fibrillation (AF) is the most common outpatient arrhythmia. The recent ACC/AHA/ESC guidelines outline a variety of approaches to the management of AF, but their implementation into clinical practice requires multi-faceted patient evaluations and assessments for optimizing patient care. Using a case-based approach, issues such as rate versus rhythm control, anticoagulation, cardioversion, pharmacological and catheter ablation for maintenance of sinus rhythm, and the pathophysiology of AF are discussed. These data were originally presented at a satellite symposium titled Case Studies with the Experts: Management Decisions in AF, held on May 10, 2007, during the annual Heart Rhythm Society meeting. C1 [Prystowsky, Eric N.] LLC, Care Grp, Indianapolis, IN 46260 USA. [Jais, Pierre] Hop Haut Leveque, Pessac, France. [Kowey, Peter] Div Cardiovasc Dis, Wynnewood, PA USA. [Nattel, Stanley] Univ Montreal, Paul David Chair Cardiovasc Electrophysiol, Montreal, PQ H3C 3J7, Canada. [Nattel, Stanley] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Ruskin, Jeremy N.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Kowey, Peter] Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. RP Prystowsky, EN (reprint author), LLC, Care Grp, 8333 Naab Rd,Suite 400, Indianapolis, IN 46260 USA. EM eprystow@thecaregroup.com NR 24 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD FEB PY 2008 VL 19 SU 1 BP S1 EP S12 DI 10.1111/j.1540-8167.2007.01053.x PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 254PZ UT WOS:000252601100001 PM 18226097 ER PT J AU Das, F Ghosh-Choudhury, N Venkatesan, B Li, XN Mahimainathan, L Choudhury, GG AF Das, Falguni Ghosh-Choudhury, Nandini Venkatesan, Balachandar Li, Xiaonan Mahimainathan, Lenin Choudhury, Goutam Ghosh TI Akt kinase targets association of CBP with SMAD 3 to regulate TGF beta-induced expression of plasminogen activator inhibitor-1 SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; GLOMERULAR MESANGIAL CELLS; PAI-1 GENE-EXPRESSION; TUMOR-SUPPRESSOR PTEN; COLLAGEN-I EXPRESSION; PHOSPHATIDYLINOSITOL 3-KINASE; EXTRACELLULAR-MATRIX; BINDING PROTEIN; TRANSCRIPTIONAL ACTIVATION; SERINE PHOSPHORYLATION AB Transforming growth factor-P (TGF beta) controls expression of plasminogen activator inhibitor type 1 (PAI-1), which regulates degradation of extracellular matrix proteins in fibrotic diseases. The TGF beta receptor-specific Smad 3 has been implicated in the PAI-1 expression. The mechanism by which non-Smad signaling contributes to this process is not known. We studied the cross-talk between Smad 3 and PI 3 kinase/Akt signaling in TGF beta-induced PAI-1 expression in renal mesangial cells. Inhibition of PI 3 kinase and Akt kinase blocked TGF beta- and Smad 3-mediated expression of PAI-1. In contrast, constitutively active PI 3 kinase and Akt kinase increased PAI-1 expression, similar to TGF beta. Inhibition of PI 3 kinase and Akt kinase had no effect on TGF beta-induced Smad 3 phosphorylation and its translocation to the nucleus. Notably, inhibition of PI 3 kinase-dependent Akt kinase abrogated TGF beta-induced PAI-1 transcription, without affecting binding of Smad 3 to the PAI-1 Smad binding DNA element. However, PI 3 kinase inhibition and dominant negative Akt kinase antagonized the association of the transcriptional coactivator CBP with Smad 3 in response to TGF beta, resulting in inhibition of Smad 3 acetylation. Together our findings identify TGF beta-induced PI 3 kinase/Akt signaling as a critical regulator of Smad 3-CBP interaction and Smad 3 acetylation, which cause increased PAI-1 expression. C1 [Das, Falguni; Venkatesan, Balachandar; Li, Xiaonan; Mahimainathan, Lenin; Choudhury, Goutam Ghosh] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Ghosh-Choudhury, Nandini; Choudhury, Goutam Ghosh] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Ghosh-Choudhury, Nandini; Choudhury, Goutam Ghosh] S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX USA. RP Choudhury, GG (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Mail Code 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM choudhuryg@uthscsa.edu FU NIAMS NIH HHS [R01 AR52425]; NIDDK NIH HHS [R01 DK50190] NR 91 TC 42 Z9 42 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD FEB PY 2008 VL 214 IS 2 BP 513 EP 527 DI 10.1002/jcp.21236 PG 15 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 248OM UT WOS:000252163400026 PM 17671970 ER PT J AU Alston, TA AF Alston, Theodore A. TI Lipmann and Anfinsen: Nobel biochemists of Beecher's anesthesia laboratory SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Article DE anesthesiologists; arterial blood gas analysis; Henry K. Beecher, MD, PhD; Fritz Lipmann, MD, PhD; Christian B. Anfinsen, MD, PhD ID VENOUS-PRESSURE; WALKING AB Henry K. Beecher performed blood pH and gas analysis on patients in the 1940s, though the biochemical technology was not widely available until the 1950s. Two of Beecher's biochemist coworkers, Fritz Lipmann and Christian B. Anfinsen, went on to earn Nobel Prizes. (C) 2008 Elsevier Inc. All rights reserved. C1 [Alston, Theodore A.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Alston, Theodore A.] Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA. RP Alston, TA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. EM talston@partners.org NR 14 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD FEB PY 2008 VL 20 IS 1 BP 61 EP 63 DI 10.1016/j.jclinane.2007.08.001 PG 3 WC Anesthesiology SC Anesthesiology GA 280ST UT WOS:000254447200014 PM 18346614 ER PT J AU Petit, JH Biller, BMK Yock, TI Swearingen, B Coen, JJ Chapman, P Ancukiewicz, M Bussiere, M Klibanski, A Loeffler, JS AF Petit, Joshua H. Biller, Beverly M. K. Yock, Torunn I. Swearingen, Brooke Coen, John J. Chapman, Paul Ancukiewicz, Marek Bussiere, Marc Klibanski, Anne Loeffler, Jay S. TI Proton stereotactic radiotherapy for persistent adrenocorticotropin-producing adenomas SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article; Proceedings Paper CT 88th Annual Meeting of the Endocrine-Society CY JUN 24-27, 2006 CL Boston, MA SP Endocrine Soc ID GAMMA-KNIFE RADIOSURGERY; TERM FOLLOW-UP; CUSHINGS-DISEASE; RADIATION-THERAPY; PITUITARY-ADENOMAS; TRANSSPHENOIDAL SURGERY; IRRADIATION; TUMORS; MICROSURGERY; GLIOMA AB Context: Radiation therapy is a potentially curative treatment for corticotroph adenomas refractory to surgery. Protons have an advantage over photons(x-rays) by depositing energy at the target with no exit dose, providing a lower dose to adjacent normal tissues. Until recently, proton stereotactic radiotherapy (PSR) was available at only two U.S. centers; use will increase as proton facilities are under development. Objective: Our objective was to evaluate the efficacy and safety of PSR for persistent Cushing's disease (CD) and Nelson's syndrome (NS). Design: This was a retrospective review of 38 patients (33 with CD and five with NS) treated between 1992 and 2005. Participants: All patients had transsphenoidal surgery without biochemical cure. Four had previous irradiation with photons. The patients with INS underwent bilateral adrenalectomy 29-228 months (median 40) before PSR. Intervention: Single-fraction PSR was delivered at a median dose of 20 Cobalt Gray Equivalents (range 15-20) on 1 treatment day. Main Outcome Measures: Complete response (CR) was defined as sustained ( >= 3 months) normalization of urinary free cortisol off medical therapy. CR in NS was based on normalization of plasma corticotropin. Results: At a median follow-up of 62 months (range 20-136), CR was achieved in five patients (100%) with NS and 17 (52%) patients with CD. Among all patients with CR, median time to CR was 18 months (range 5-49). No secondary tumors were noted on follow-up magnetic resonance imaging scans, and there was no clinical evidence of optic nerve damage, seizure, or brain injury. There were 17 patients (52%) who developed new pituitary deficits. Conclusions: PSR is effective for patients with persistent corticotroph adenomas with low morbidity after a median follow-up of 62 months; longer follow-up is warranted for late radiation related sequelae. C1 [Petit, Joshua H.; Yock, Torunn I.; Coen, John J.; Ancukiewicz, Marek; Bussiere, Marc; Loeffler, Jay S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Swearingen, Brooke; Chapman, Paul] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Biller, Beverly M. K.; Klibanski, Anne] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med Neuroendocrinol, Boston, MA 02114 USA. RP Loeffler, JS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 347, Boston, MA 02114 USA. EM jloeffler@partners.org NR 34 TC 50 Z9 53 U1 1 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD FEB PY 2008 VL 93 IS 2 BP 393 EP 399 DI 10.1210/jc.2007-1220 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 262RN UT WOS:000253165800012 PM 18029460 ER PT J AU Yachimski, P Pratt, DS AF Yachimski, Patrick Pratt, Daniel S. TI Cholangiocarcinoma - Natural history, treatment, and strategies for surveillance in high-risk patients SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Review DE primary sclerosing cholangitis; cholangiocarcinoma ID PRIMARY SCLEROSING CHOLANGITIS; BILE-DUCT STRICTURES; POSITRON-EMISSION-TOMOGRAPHY; FINE-NEEDLE-ASPIRATION; MALIGNANT BILIARY OBSTRUCTION; DONOR LIVER-TRANSPLANTATION; SERUM TUMOR-MARKERS; K-RAS MUTATIONS; BRUSH CYTOLOGY; HILAR CHOLANGIOCARCINOMA AB Cholangiocarcinoma is a primary malignancy of biliary epithelium. Risk factors for cholangiocarcinoma include primary sclerosing cholangitis and other conditions that produce chronic inflammation of the biliary tree. The diagnosis of cholangiocarcinoma can be elusive; it is often not made until advanced disease is present and at a stage when a curative surgical resection is not feasible. Currently used diagnostic modalities include serum and bile tumor markers, radiologic and endoscopic imaging, and pathologic analysis. Surveillance strategies to increase the chance of early diagnosis should be strongly considered in individuals at high risk for cholangiocarcinoma. Patients with long-standing primary sclerosing cholangitis would be the ideal candidates for a screening program. C1 [Yachimski, Patrick; Pratt, Daniel S.] Massachusetts Gen Hosp, Liver Biliary Pancreas Ctr, GI Unit, Boston, MA 02114 USA. RP Pratt, DS (reprint author), Massachusetts Gen Hosp, Liver Biliary Pancreas Ctr, GI Unit, Blake 4,55 Fruit St, Boston, MA 02114 USA. EM DSPRATT@PARTNERS.ORG NR 140 TC 45 Z9 46 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD FEB PY 2008 VL 42 IS 2 BP 178 EP 190 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 258IU UT WOS:000252862400013 PM 18209589 ER PT J AU Mukherjee, S Raje, N Schoonmaker, JA Liu, JC Hideshima, T Wein, MN Jones, DC Vallet, S Bouxsein, ML Pozzi, S Chhetri, S Seo, YD Aronson, JP Patel, C Fulciniti, M Purton, LE Glimcher, LH Lian, JB Stein, G Anderson, KC Scadden, DT AF Mukherjee, Siddhartha Raje, Noopur Schoonmaker, Jesse A. Liu, Julie C. Hideshima, Teru Wein, Marc N. Jones, Dallas C. Vallet, Sonia Bouxsein, Mary L. Pozzi, Samantha Chhetri, Shweta Seo, Y. David Aronson, Joshua P. Patel, Chirayu Fulciniti, Mariateresa Purton, Louise E. Glimcher, Laurie H. Lian, Jane B. Stein, Gary Anderson, Kenneth C. Scadden, David T. TI Pharmacologic targeting of a stem/progenitor population in vivo is associated with enhanced bone regeneration in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID MESENCHYMAL STEM-CELLS; TRANSCRIPTION FACTOR CBFA1; MULTIPLE-MYELOMA CELLS; OSTEOBLAST DIFFERENTIATION; STROMAL CELLS; MORPHOGENETIC PROTEIN-2; CLEIDOCRANIAL DYSPLASIA; MARROW; VITRO; OSTEOGENESIS AB Drug targeting of adult stem cells has been proposed as a strategy for regenerative medicine, but very few drugs are known to target stem cell populations in vivo. Mesenchymal stem/progenitor cells (MSCs) are a multipotent population of cells that can differentiate into muscle, bone, fat, and other cell types in context-specific manners. Bortezomib (Bzb) is a clinically available proteasome inhibitor used in the treatment of multiple myeloma. Here, we show that Bzb induces MSCs to preferentially undergo osteoblastic differentiation, in part by modulation of the bone-specifying transcription factor runt-related transcription factor 2 (Runx-2) in mice. Mice implanted with MSCs showed increased ectopic ossicle and bone formation when recipients received low doses of Bzb. Furthermore, this treatment increased bone formation and rescued bone loss in a mouse model of osteoporosis. Thus, we show that a tissue-resident adult stem cell population in vivo can be pharmacologically modified to promote a regenerative function in adult animals. C1 [Mukherjee, Siddhartha; Schoonmaker, Jesse A.; Seo, Y. David; Aronson, Joshua P.; Purton, Louise E.; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02115 USA. [Mukherjee, Siddhartha; Schoonmaker, Jesse A.; Bouxsein, Mary L.; Seo, Y. David; Aronson, Joshua P.; Purton, Louise E.; Scadden, David T.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Mukherjee, Siddhartha; Scadden, David T.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Mukherjee, Siddhartha; Raje, Noopur; Scadden, David T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Mukherjee, Siddhartha; Schoonmaker, Jesse A.; Seo, Y. David; Aronson, Joshua P.; Patel, Chirayu; Purton, Louise E.; Scadden, David T.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Raje, Noopur; Hideshima, Teru; Vallet, Sonia; Pozzi, Samantha; Chhetri, Shweta; Fulciniti, Mariateresa; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Liu, Julie C.; Lian, Jane B.; Stein, Gary] Univ Massachusetts, Dept Cell Biol, Worcester, MA 01605 USA. [Wein, Marc N.; Jones, Dallas C.; Glimcher, Laurie H.] Harvard Univ, Harvard Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Bouxsein, Mary L.] Beth Israel Deaconess Med Ctr, Dept Orthopaed Surg, Boston, MA 02215 USA. RP Scadden, DT (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, 185 Cambridge St, Boston, MA 02115 USA. EM dscadden@mgh.harvard.edu RI Liu, Julie/H-7496-2013; Pozzi, Samantha/A-7617-2012 OI Liu, Julie/0000-0003-0784-2529; Pozzi, Samantha/0000-0001-7917-1774 FU NCI NIH HHS [P01 CA082834]; NHLBI NIH HHS [U54 HL081030, HL044851, HL081030, K08 HL085872, K08HL085872, R01 HL044851]; NIDDK NIH HHS [DK050234, R01 DK050234] NR 43 TC 140 Z9 145 U1 0 U2 6 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB PY 2008 VL 118 IS 2 BP 491 EP 504 DI 10.1172/JC133102 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 257CS UT WOS:000252777400018 PM 18219387 ER PT J AU Sugimoto, K Ogawa, A Mizoguchi, E Shimomura, Y Andoh, A Bhan, AK Blumberg, RS Xavier, RJ Mizoguchi, A AF Sugimoto, Ken Ogawa, Atsuhiro Mizoguchi, Emiko Shimomura, Yasuyo Andoh, Akira Bhan, Atul K. Blumberg, Richard S. Xavier, Ramnik J. Mizoguchi, Atsushi TI IL-22 ameliorates intestinal inflammation in a mouse model of ulcerative colitis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID BOWEL-DISEASE; CROHNS-DISEASE; GENE-EXPRESSION; INNATE IMMUNITY; CELL-MIGRATION; POTENTIAL ROLE; MUTANT MICE; IN-VIVO; STAT3; INTERLEUKIN-22 AB Expression of IL-22 is induced in several human inflammatory conditions, including inflammatory bowel disease (IBD). Expression of the IL-22 receptor is restricted to innate immune cells; however, the role of IL-22 in colitis has not yet been defined. We developed what we believe to be a novel microinjection-based local gene-delivery system that is capable of targeting the inflamed intestine. Using this approach, we demonstrated a therapeutic potency for IL-22-mediated activation of the innate immune pathway in a mouse model of Th2-mediated colitis that induces disease with characteristics similar to that of IBD ulcerative colitis (UC). IL-22 gene delivery enhanced STAT3 activation specifically within colonic epithelial cells and induced both STAT3-dependent expression of mucus-associated molecules and restitution of mucus-producing goblet cells. Importantly, IL-22 gene delivery led to rapid amelioration of local intestinal inflammation. The amelioration of disease by IL-22 was mediated by enhanced mucus production. In addition, local gene delivery was used to inhibit IL-22 activity through overexpression of IL-22-binding protein. Treatment with IL-22-binding protein suppressed goblet cell restitution during the recovery phase of a dextran sulfate sodium-induced model of acute colitis. These data demonstrate what we believe to be a novel function for IL-22 in the intestine and suggest the potency of a local IL-22 gene-delivery system for treating UC. C1 [Sugimoto, Ken; Ogawa, Atsuhiro; Shimomura, Yasuyo; Bhan, Atul K.; Mizoguchi, Atsushi] Massachusetts Gen Hosp, Expt Pathol Unit, Boston, MA 02114 USA. [Sugimoto, Ken; Ogawa, Atsuhiro; Mizoguchi, Emiko; Bhan, Atul K.; Blumberg, Richard S.; Xavier, Ramnik J.; Mizoguchi, Atsushi] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Ogawa, Atsuhiro; Andoh, Akira] Shiga Univ Med Sci, Dept Internal Med, Otsu, Shiga 52021, Japan. [Mizoguchi, Emiko; Bhan, Atul K.; Xavier, Ramnik J.; Mizoguchi, Atsushi] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Mizoguchi, Emiko; Xavier, Ramnik J.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Blumberg, Richard S.] Brigham & Womens Hosp, Div Gastroenterol Hepatol & Endoscopy, Boston, MA 02115 USA. [Blumberg, Richard S.] Harvard Digest Dis Ctr, Boston, MA 02115 USA. [Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP Mizoguchi, A (reprint author), Massachusetts Gen Hosp, Expt Pathol Unit, Simches 8234,185 Cambridge St, Boston, MA 02114 USA. EM amizoguchi@partners.org FU NIDDK NIH HHS [DK43351, DK44319, DK47677, DK64351, P30 DK043351, R01 DK044319, R01 DK047677, R01 DK064351, R37 DK044319] NR 52 TC 440 Z9 462 U1 2 U2 30 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB PY 2008 VL 118 IS 2 BP 534 EP 544 DI 10.1172/JC133194 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 257CS UT WOS:000252777400022 PM 18172556 ER PT J AU Hou, JH Renigunta, A Konrad, M Gornes, AS Schneeberger, EE Paul, DL Waldegger, S Goodenough, DA AF Hou, Jianghui Renigunta, Aparna Konrad, Martin Gornes, Antonio S. Schneeberger, Eveline E. Paul, David L. Waldegger, Siegfried Goodenough, Daniel A. TI Claudin-16 and claudin-19 interact and form a cation-selective tight junction complex SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID BIOCHEMICAL-CHARACTERIZATION; MEMBRANE-PROTEINS; PARACELLIN-1; EXPRESSION; IDENTIFICATION; LOCALIZATION; POLYPEPTIDE; MUTATIONS; MAGNESIUM; NEPHRON AB Tight junctions (TJs) play a key role in mediating paracellular ion reabsorption in the kidney. Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is an inherited disorder caused by mutations in the genes encoding the TJ proteins claudin-16 (CLDN16) and CLDN19; however, the mechanisms underlying the roles of these claudins in mediating paracellular ion reabsorption in the kidney are not understood. Here we showed that in pig kidney epithelial cells, CLDN19 functioned as a Cl- blocker, whereas CLDN16 functioned as a Ne channel. Mutant forms of CLDN19 that are associated with FHHNC were unable to block Cl- permeation. Coexpression of CLDN16 and CLDN19 generated cation selectivity of the TJ in a synergistic manner, and CLDN16 and CLDN19 were observed to interact using several criteria. In addition, disruption of this interaction by introduction of FHHNC-causing mutant forms of either CLDN16 or CLDN19 abolished their synergistic effect. Our data show that CLDN16 interacts with CLDN19 and that their association confers a TJ with cation selectivity, suggesting a mechanism for the role of mutant forms of CLDN16 and CLDN19 in the development of FHHNC. C1 [Hou, Jianghui; Gornes, Antonio S.; Goodenough, Daniel A.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Renigunta, Aparna; Waldegger, Siegfried] Univ Marburg, Univ Childrens Hosp, Marburg, Germany. [Konrad, Martin] Univ Munster, Dept Pediat, Munster, Germany. [Schneeberger, Eveline E.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA. [Paul, David L.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. RP Goodenough, DA (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA. EM daniel_goodenough@hms.harvard.edu FU NEI NIH HHS [EY014127, EY02430, R01 EY002430, R01 EY014127]; NHLBI NIH HHS [R01 HL025822, HL25822, HL36781, R01 HL036781]; NIGMS NIH HHS [GM37751, R01 GM037751] NR 25 TC 164 Z9 166 U1 6 U2 8 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB PY 2008 VL 118 IS 2 BP 619 EP 628 DI 10.1172/JCI33970 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 257CS UT WOS:000252777400029 PM 18188451 ER PT J AU Depreux, FFS Darrow, K Conner, DA Eavey, RD Liberman, MC Seidman, CE Seidman, JG AF Depreux, Frederic F. S. Darrow, Keith Conner, David A. Eavey, Roland D. Liberman, M. Charles Seidman, Christine E. Seidman, J. G. TI Eya4-deficient mice are a model for heritable otitis media SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID SENSORINEURAL HEARING-LOSS; EYES-ABSENT; MIDDLE-EAR; CBA/CAJ MICE; MOUSE; GENE; EYA4; DFNA10; MANIFESTATIONS; PHOSPHATASE AB Otitis media is an extremely common pediatric inflammation of the middle ear that often causes pain and diminishes hearing. Vulnerability to otitis media is due to eustachian tube dysfunction as well as other poorly understood factors, including genetic susceptibility. As EYA4 mutations cause sensorineural hearing loss in humans, we produced and characterized Eya4-deficient (Eya4(-/-)) mice, which had severe hearing deficits. In addition, all Eya4(-/-) mice developed otitis media with effusion. Anatomic studies revealed abnormal middle ear cavity and eustachian tube dysmorphology; thus, Eya4 regulation is critical for the development and function of these structures. We suggest that some human otitis media susceptibility reflects underlying genetic predisposition in genes like EYA4 that regulate middle ear and eustachian tube anatomy. C1 [Depreux, Frederic F. S.; Conner, David A.; Seidman, Christine E.; Seidman, J. G.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Darrow, Keith; Liberman, M. Charles] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Eavey, Roland D.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Pediat Otolaryngol Serv, Boston, MA 02114 USA. [Eavey, Roland D.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Seidman, Christine E.] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Seidman, JG (reprint author), Harvard Univ, Sch Med, Dept Genet, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM seidman@genetics.med.harvard.edu FU NIDCD NIH HHS [R01 DC000188, R01 DC000188-27, R01 DC0188, P30 DC005209, P30 DC 05209] NR 47 TC 48 Z9 51 U1 0 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB PY 2008 VL 118 IS 2 BP 651 EP 658 DI 10.1172/JCI32899 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 257CS UT WOS:000252777400032 PM 18219393 ER PT J AU Offit, K Garber, JE AF Offit, Kenneth Garber, Judy Ellen TI Time to check CHEK2 in families with breast cancer? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID SUSCEPTIBILITY; CHEK2-ASTERISK-1100DELC; POPULATION; PENETRANCE; MUTATION; ALLELE; FREQUENCY; VARIANTS; 1100DELC; WOMEN C1 [Offit, Kenneth] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Garber, Judy Ellen] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Offit, K (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. NR 24 TC 28 Z9 28 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2008 VL 26 IS 4 BP 519 EP 520 DI 10.1200/JCO.2007.13.8503 PG 2 WC Oncology SC Oncology GA 276XQ UT WOS:000254177400003 PM 18172189 ER PT J AU Partridge, AH LaFountain, A Mayer, E Taylor, BS Winer, E Asnis-Alibozek, A AF Partridge, Ann H. LaFountain, Andrea Mayer, Erica Taylor, Brooke S. Winer, Eric Asnis-Alibozek, Aviva TI Adherence to initial adjuvant anastrozole therapy among women with early-stage breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy & Res Ctr, Univ Texas, Hlth Sci Ctr ID RANDOMIZED-TRIAL; POSTMENOPAUSAL WOMEN; TAMOXIFEN THERAPY; ANTIHYPERTENSIVE THERAPY; PHARMACY RECORDS; CLINICAL-TRIALS; PILL COUNTS; OLDER WOMEN; MEDICATION; DISCONTINUATION AB Purpose Previous research evaluating adherence to tamoxifen therapy among women with early-stage breast cancer has revealed adherence estimates ranging from 25% to 96%. No previous studies have focused on adherence to adjuvant aromatase inhibitors. Methods We used longitudinal claims data from three large commercial health programs to estimate adherence with anastrozole therapy among women with early-stage breast cancer. Adherence was defined as the proportion of days that patients had medication available over the observation period ( ie, days covered); women with fewer than 80% of days covered were defined as nonadherent. Results More than 12,000 women in the databases were found to have new anastrozole prescription claims during the period of study: 1,498 women were classified as having early-stage disease in one commercial health program ( Plan A) data set, 1,899 women in another program ( Plan B) data set, and 8,994 women in MarketScan, a commercial data set made up of several health programs. Mean adherence over the first 12 months of therapy ranged from 82% to 88% in the three data sets. Between 19% and 28% of women had fewer than 80% of days covered. For women with 36 months of continuous eligibility, the mean adherence decreased each year, ranging from 78% to 86% in year 1 to 62% to 79% in year 3 within the three data sets. Conclusion A substantial proportion of women with early-stage breast cancer may be suboptimally adherent to adjuvant anastrozole therapy. Future research should focus on the identification of patients at risk for nonadherence with oral hormonal therapy for breast cancer and the development of interventions to improve adherence. C1 [Partridge, Ann H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. AstraZeneca, Wilmington, DE USA. RP Partridge, AH (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM ahpartridge@partners.org NR 36 TC 251 Z9 253 U1 0 U2 10 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2008 VL 26 IS 4 BP 556 EP 562 DI 10.1200/JCO.2007.11.5451 PG 7 WC Oncology SC Oncology GA 276XQ UT WOS:000254177400010 PM 18180462 ER PT J AU Elting, LS Lu, C Escalante, CP Giordano, SH Trent, JC Cooksley, C Avritscher, EBC Shih, YCT Ensor, J Bekele, BN Gralla, RJ Talcott, JA Rolston, K AF Elting, Linda S. Lu, Charles Escalante, Carmelita P. Giordano, Sharon H. Trent, Jonathan C. Cooksley, Catherine Avritscher, Elenir B. C. Shih, Ya-Chen Tina Ensor, Joe Bekele, B. Nebiyou Gralla, Richard J. Talcott, James A. Rolston, Kenneth TI Outcomes and cost of outpatient or inpatient management of 712 patients with febrile neutropenia SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol ID EARLY HOSPITAL DISCHARGE; RISK CANCER-PATIENTS; ANTIBIOTIC-THERAPY; ORAL ANTIBIOTICS; SUPPORTIVE-CARE; ACUTE-LEUKEMIA; MULTINATIONAL-ASSOCIATION; RANDOMIZED TRIAL; PREDICTION RULE; CLINICAL-TRIALS AB Purpose We retrospectively compared the outcomes and costs of outpatient and inpatient management of low-risk outpatients who presented to an emergency department with febrile neutropenia ( FN). Patients and Methods A single episode of FN was randomly chosen from each of 712 consecutive, low-risk solid tumor outpatients who had been treated prospectively on a clinical pathway ( 1997-2003). Their medical records were reviewed retrospectively for overall success ( resolution of all signs and symptoms of infection without modification of antibiotics, major medical complications, or intensive care unit admission) and nine secondary outcomes. Outcomes were assessed by physician investigators who were blinded to management strategy. Outcomes and costs ( payer's perspective) in 529 low- risk outpatients were compared with 123 low- risk patients who were psychosocially ineligible for outpatient management ( no access to caregiver,telephone, or transportation; residence > 30 minutes from treating center; poor compliance with previous outpatient therapy) using univariate statistical tests. Results Overall success was 80% among low- risk outpatients and 79% among low- risk inpatients. Response to initial antibiotics was 81% among outpatients and 80% among inpatients ( P =.94); 21% of those initially treated as outpatients subsequently required hospitalization. All patients ultimately responded to antibiotics; there were no deaths. Serious complications were rare ( 1%) and equally frequent between the groups. The mean cost of therapy among inpatients was double that of outpatients ($ 15,231 v $ 7,772; P <.001). Conclusion Outpatient management of low- risk patients with FN is as safe and effective as inpatient management of low- risk patients and is significantly less costly. C1 [Elting, Linda S.] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Sect Hlth Serv Res, Houston, TX 77030 USA. Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. Univ Texas MD Anderson Canc Ctr, Dept Gen Internal Med, Houston, TX 77030 USA. Univ Texas MD Anderson Canc Ctr, Dept Ambulatory Treatment & Emergency Care, Houston, TX 77030 USA. Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA. Univ Texas MD Anderson Canc Ctr, Dept Sarcoma Med Oncol, Houston, TX 77030 USA. Univ Texas MD Anderson Canc Ctr, Dept Infect Dis & Infect Control, Quantitat Sci Div, Houston, TX 77030 USA. New York Lung Canc Alliance, New York, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Elting, LS (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Biostat, Sect Hlth Serv Res, 1515 Holcombe Blvd,Unit 447, Houston, TX 77030 USA. EM lelting@mdanderson.org OI Ensor, Joe/0000-0003-3533-4388 NR 45 TC 71 Z9 73 U1 0 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2008 VL 26 IS 4 BP 606 EP 611 DI 10.1200/JCO.2007.13.8222 PG 6 WC Oncology SC Oncology GA 276XQ UT WOS:000254177400017 PM 18235119 ER PT J AU Blanke, CD Demetri, GD von Mehren, M Heinrich, MC Eisenberg, B Fletcher, JA Corless, CL Fletcher, CDM Roberts, PJ Heinz, D Wehre, E Nikolova, Z Joensuu, H AF Blanke, Charles D. Demetri, George D. von Mehren, Margaret Heinrich, Michael C. Eisenberg, Burton Fletcher, Jonathan A. Corless, Christopher L. Fletcher, Christopher D. M. Roberts, Peter J. Heinz, Daniela Wehre, Elisabeth Nikolova, Zariana Joensuu, Heikki TI Long-term results from a randomized phase II trial of standard- versus higher-dose imatinib mesylate for patients with unresectable or metastatic gastrointestinal stromal tumors expressing KIT SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT Annual Symposium of the American-Society-of-Clinical-Oncology-Gastrointestinal CY JAN 19-21, 2007 CL Orlando, FL SP Amer Soc Clin Oncol Gastrointestinal ID TYROSINE KINASE INHIBITOR; C-KIT; GIST; MUTATIONS; STI571 AB Purpose The outcome of patients diagnosed with advanced gastrointestinal stromal tumor ( GIST) and treated long-term with imatinib mesylate is unknown. A previous report of a randomized phase II trial of imatinib mesylate in patients with incurable GIST detailed high response rates at both the 400 and the 600 mg/d dose levels. We conducted a long-term analysis of patients treated on the trial, including patients followed during an extension phase, to evaluate survival, patterns of failure, and potential prognostic factors, including tumor mutational status. Patients and Methods Patients with advanced GIST were enrolled onto an open-label, multicenter trial and were randomly assigned ( 1: 1) to receive imatinib 400 versus 600 mg/d. Data were prospectively collected on KIT mutational status, total tumor area, and other potential prognostic factors. Patients were followed for a median of 63 months. Results One hundred forty-seven patients were enrolled: 73 were in arm A ( imatinib 400 mg/d), and 74 were in arm B ( imatinib 600 mg/d). Response rates, median progression-free survival, and median overall survival were essentially identical on both arms, and median survival was 57 months for all patients. Forty-one patients overall ( 28%) remained on the drug long-term. Female sex, the presence of an exon 11 mutation, and normal albumin and neutrophil levels were independently associated with better survival. Conclusion Nearly 50% of patients with advanced GIST who were treated with imatinib mesylate survived for more than 5 years, regardless of a 400 or 600 mg/d starting dose. C1 Oregon Hlth & Sci Univ, Ctr Canc, Portland, OR 97201 USA. Portland Vet Affairs Hosp, Portland, OR USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Dartmouth Hitchcock Med Ctr, Labanon, NH USA. Novartis Corp, Basel, Switzerland. Turku Univ Hosp, FIN-20520 Turku, Finland. Univ Helsinki, Cent Hosp, Helsinki, Finland. RP Blanke, CD (reprint author), 3181 SW Sam Jackson Pk Rd,MC-L-586, Portland, OR 97239 USA. EM blankec@ohsu.edu OI Joensuu, Heikki/0000-0003-0281-2507 NR 21 TC 433 Z9 469 U1 0 U2 18 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2008 VL 26 IS 4 BP 620 EP 625 DI 10.1200/JCO.2007.13.4403 PG 6 WC Oncology SC Oncology GA 276XQ UT WOS:000254177400019 PM 18235121 ER PT J AU Blanke, CD Rankin, C Demetri, GD Ryan, CW von Mehren, M Benjamin, RS Raymond, AK Bramwell, VHC Baker, LH Maki, RG Tanaka, M Hecht, JR Heinrich, MC Fletcher, CDM Crowley, JJ Borden, EC AF Blanke, Charles D. Rankin, Cathryn Demetri, George D. Ryan, Christopher W. von Mehren, Margaret Benjamin, Robert S. Raymond, A. Kevin Bramwell, Vivien H. C. Baker, Laurence H. Maki, Robert G. Tanaka, Michael Hecht, J. Randolph Heinrich, Michael C. Fletcher, Christopher D. M. Crowley, John J. Borden, Ernest C. TI Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol ID C-KIT; PROGNOSTIC-FACTORS; SARCOMA-GROUP; MUTATIONS; SURVIVAL; ST1571; PROGRESSION; INHIBITOR; EFFICACY; SAFETY AB Purpose To assess potential differences in progression-free or overall survival when imatinib mesylate is administered to patients with incurable gastrointestinal stromal tumors ( GIST) at a standard dose ( 400 mg daily) versus a high dose ( 400 mg twice daily). Patients and Methods Patients with metastatic or surgically unresectable GIST were eligible for this phase III open-label clinical trial. At registration, patients were randomly assigned to either standard or high-dose imatinib, with close interval follow-up. If objective progression occurred by Response Evaluation Criteria in Solid Tumors, patients on the standard-dose arm could reregister to the trial and receive the high-dose imatinib regimen. Results Seven hundred forty-six patients with advanced GIST from 148 centers across the United States and Canada were enrolled onto this trial in 9 months. With a median follow-up of 4.5 years, median progression-free survival was 18 months for patients on the standard-dose arm, and 20 months for those receiving high-dose imatinib. Median overall survival was 55 and 51 months, respectively. There were no statistically significant differences in objective response rates, progression-free survival, or overall survival. After progression on standard-dose imatinib, 33% of patients who crossed over to the high-dose imatinib regimen achieved either an objective response or stable disease. There were more grade 3, 4, and 5 toxicities noted on the high-dose imatinib arm. Conclusion This trial confirms the effectiveness of imatinib as primary systemic therapy for patients with incurable GIST but did not show any advantage to higher dose treatment. It appears reasonable to initiate therapy with 400 mg daily and to consider dose escalation on progression of disease. C1 [Blanke, Charles D.] Oregon Hlth & Sci Univ, Inst Canc, Portland, OR 97239 USA. SW Oncol Grp, Ctr Stat, Seattle, WA USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Dana Farber Harvard Canc Inst, Boston, MA USA. Univ Texas MD Anderson Canc Ctr, Houston, TX USA. London Reg Canc Ctr, Calgary, AB, Canada. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Mem Hosp, New York, NY USA. Univ Calif Davis, Sacramento, CA 95817 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. RP Blanke, CD (reprint author), Oregon Hlth & Sci Univ, Inst Canc, 3181 SW Sam Jackson Pk Rd,L-586, Portland, OR 97239 USA. EM blankec@ohsu.edu FU NCI NIH HHS [CA86780, CA02599, CA03927, CA04326, CA04457, CA04919, CA08025, CA11028, CA114558-02, CA11789, CA12449, CA12644, CA13612, CA14028, CA16385, CA16450, CA20319, CA21115, CA22433, CA27057, CA27525, CA31946, CA32102, CA32291, CA33601, CA35090, CA35091, CA35113, CA35119, CA35176, CA35192, CA35261, CA35262, CA35281, CA37981, CA38926, CA41287, CA42777, CA45377, CA45450, CA45560, CA45807, CA46113, CA46282, CA46368, CA46441, CA47559, CA47577, CA58348, CA58416, CA58666, CA58861, CA58882, CA60138, CA63844, CA63845, CA63850, CA68183, CA71323, CA76447, CA77440, CA77651, CA77658, N01-CM-17003, U01-CA70172-01]; PHS HHS [A35178] NR 22 TC 490 Z9 527 U1 0 U2 10 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2008 VL 26 IS 4 BP 626 EP 632 DI 10.1200/JCO.2007.13.4452 PG 7 WC Oncology SC Oncology GA 276XQ UT WOS:000254177400020 PM 18235122 ER PT J AU Bogren, A Teles, RP Torresyap, G Haffajee, AD Socransky, SS Jonsson, K Wennstrom, JL AF Bogren, Anna Teles, Ricardo P. Torresyap, Gay Haffajee, Anne D. Socransky, Sigmund S. Jonsson, Kerstin Wennstrom, Jan L. TI Long-term effect of the combined use of powered toothbrush and triclosan dentifrice in periodontal maintenance patients SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE clinical trial; longitudinal; periodontal maintenance; prevention; randomized controlled trial; toothbrushing; triclosan ID ROTARY ELECTRIC TOOTHBRUSHES; DNA-DNA HYBRIDIZATION; TRICLOSAN/COPOLYMER DENTIFRICE; MANUAL TOOTHBRUSHES; PROGRESSION; THERAPY; DISEASE; ADULTS; HEALTH; PARAMETERS/ AB Aim: To test the hypothesis of a superior clinical and microbiological effect of the combined use of powered toothbrush + triclosan-containing dentifrice compared with manual toothbrush + regular fluoride-containing dentifrice in periodontal maintenance patients. Material and Methods: A total of 128 periodontitis subjects involved in recall programmes were randomized to use either powered toothbrush with triclosan-dentifrice (test) or manual toothbrush and standard dentifrice (control). Supportive periodontal treatment was provided at baseline and every 6 months. Plaque, bleeding on probing (BoP), probing pocket depth (PPD) and relative attachment level (RAL) were scored at baseline, 1, 2 and 3 years. Subgingival plaque samples were taken and analysed for their content of 40 bacterial species at each examination interval. All analyses were performed by "intention-to-treat" protocol. Results: Both groups showed significant reduction in BoP, PPD and in mean total counts of the 40 bacterial species between baseline and 3 years, while plaque score and RAL remained almost unchanged. No significant differences between the two prevention programmes were found for any of the clinical outcome variables or in mean counts of the various bacterial species. Conclusions: The study failed to demonstrate superior clinical and microbiological effects of powered toothbrush + triclosan dentifrice compared with manual toothbrush + standard fluoride-dentifrice in periodontitis-susceptible patients on regular maintenance therapy. C1 [Bogren, Anna; Wennstrom, Jan L.] Gothenburg Univ, Sahlgrenska Acad, Inst Odontol, Dept Periodontol, SE-40530 Gothenburg, Sweden. [Teles, Ricardo P.; Torresyap, Gay; Haffajee, Anne D.; Socransky, Sigmund S.] Forsyth Inst, Boston, MA USA. [Jonsson, Kerstin] Karnsjukhuset, Clin Periodont, Skovde, Sweden. RP Bogren, A (reprint author), Gothenburg Univ, Sahlgrenska Acad, Inst Odontol, Dept Periodontol, Box 450, SE-40530 Gothenburg, Sweden. EM Anna.Bogren@odontologi.gu.se FU NIDCR NIH HHS [DE012861] NR 26 TC 8 Z9 10 U1 1 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD FEB PY 2008 VL 35 IS 2 BP 157 EP 164 DI 10.1111/j.1600-051X.2007.01180.x PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 250SF UT WOS:000252320100009 PM 18199149 ER PT J AU Arpino, PA Kalafatas, K Thompson, BT AF Arpino, P. A. Kalafatas, K. Thompson, B. T. TI Feasibility of dexmedetomidine in facilitating extubation in the intensive care unit SO JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS LA English DT Article DE agitation; dexmedetomidine; extubation; intensive care unit ID CRITICALLY-ILL PATIENTS; MECHANICAL VENTILATION; SEDATION; SCALE AB Background: Spontaneous breathing trials (SBT) and intermittent mandatory ventilation (IMV) are common techniques utilized to expedite the ventilator weaning process. These techniques often require the reduction and/or discontinuation of sedatives and analgesics. Reducing these medications can lead to agitation and the inability to conduct SBTs or weaning by IMV. Adding dexmedetomidine (dex), a potent alpha-2-adrenergic receptor agonist that possesses sedative, anxiolytic and analgesic effects without causing significant respiratory depression, may facilitate extubation in these patients. Objective: To assess the feasibility of adding dex to facilitate extubation in a group of difficult-to-extubate patients secondary to agitation. Methods: Mechanically ventilated patients who were deemed difficult to wean and extubate secondary to agitation were evaluated for dex therapy. Inclusion criteria were location in an intensive care unit, intubated and mechanically ventilated, required IV sedation, deemed suitable by unit criteria for weaning and extubation within 24 h of dex initiation, previous attempts at weaning sedation and/or analgesia resulted in agitation causing either severe patient ventilator dyssynchrony, prolong need for intubation, or an inability to conduct a successful SBT. Additional inclusion criteria were unsuccessful use of traditional intravenous agents to control agitation. Recommended dex dosing was a bolus of 1 mu g/kg followed by an infusion of 0.2-0.7 mu g/kg/h. Results: Twenty-five patients were evaluated for dex therapy with 20 meeting the criteria to treat. All had failed prior attempts at weaning. Fourteen of the 20 patients were successfully weaned and extubated and one patient was reintubated within 48 h, giving a 65% success rate. Heart rate trended down after dex initiation in most patients but did not result in the discontinuation of dex in any patient. The addition of dex was associated with minimal changes in mean arterial pressure. Conclusions: Dexmedetomidine was initiated in a group of mechanically ventilated patients who failed previous attempts at weaning and extubation secondary to agitation. After dex initiation, 65% of the patients was successfully extubated. Dexmedetomidine was associated with a reduction in concomitant sedative and analgesic use with minimal adverse effect. C1 [Arpino, P. A.; Kalafatas, K.] Massachusetts Gen Hosp, Dept Pharm, Boston, MA 02114 USA. [Thompson, B. T.] Massachusetts Gen Hosp, Dept Med, Med Intens Care Unit, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Arpino, PA (reprint author), Massachusetts Gen Hosp, Dept Pharm, 55 Fruit St, Boston, MA 02114 USA. EM parpino@partners.org NR 13 TC 20 Z9 29 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0269-4727 J9 J CLIN PHARM THER JI J. Clin. Pharm. Ther. PD FEB PY 2008 VL 33 IS 1 BP 25 EP 30 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 252KJ UT WOS:000252445100004 PM 18211613 ER PT J AU Thase, ME Jonas, A Khan, A Bowden, CL Wu, XL McQuade, RD Carson, WH Marcus, RN Owen, R AF Thase, Michael E. Jonas, Alan Khan, Arif Bowden, Charles L. Wu, Xiaoling McQuade, Robert D. Carson, William H. Marcus, Ronald N. Owen, Randall TI Aripiprazole monotherapy in non-psychotic bipolar I depression SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID SEROTONIN REUPTAKE INHIBITORS; DOUBLE-BLIND; PARTIAL AGONIST; SCHIZOAFFECTIVE DISORDER; PLACEBO; EFFICACY; SCHIZOPHRENIA; AUGMENTATION; SAFETY; TRIAL AB Although most treatment research on bipolar disorder has focused on mania, depressive episodes occur more frequently among patients with bipolar disorder. Here, we report the results of 2 identically designed, 8-week, multicenter, randomized, double-blind, placebo-controlled studies (CN138-096 and CN138-146) to evaluate the efficacy and safety of aripiprazole monotherapy in outpatients with bipolar I disorder experiencing a major depressive episode without psychotic features. Patients were randomized to placebo or aripiprazole (initiated at 10 mg/d, then flexibly dosed at 5-30 mg/d based on clinical effect and tolerability). The primary end point was mean change from baseline to Week 8 (last observation carried forward) in the Montgomery-Asberg Depression Rating Scale total score. In Studies 1 and 2, respectively, 186 and 187 patients were randomized to aripiprazole, and 188 and 188 to placebo. Although statistically significant differences were observed during Weeks 1 to 6, aripiprazole did not achieve statistical significance versus placebo at Week 8 in either study in the change in Montgomery-Asberg Depression Rating Scale total (primary end point). In addition, despite early statistical separation on the Clinical Global Impressions Bipolar Version Severity of Illness-Depression score (key secondary end point), aripiprazole was not superior to placebo at end point. Aripiprazole was associated with a higher incidence of akathisia, insomnia, nausea, fatigue, restlessness, and dry mouth versus placebo. More patients discontinued with aripiprazole versus placebo in Study 1 (46.8% vs 35.1%) and Study 2 (41.2% vs 29.8%). Aripiprazole monotherapy - as dosed in this study design was - not significantly more effective than placebo in the treatment of bipolar depression at end point (Week 8). C1 [Thase, Michael E.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Thase, Michael E.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Jonas, Alan] PharmaSite Res Inc, Baltimore, MD USA. [Khan, Arif] NW Clin Res Ctr, Bellevue, WA USA. [Khan, Arif] Duke Univ, Med Ctr, Durham, NC USA. [Bowden, Charles L.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Wu, Xiaoling; Marcus, Ronald N.; Owen, Randall] Bristol Myers Squibb Co, Wallingford, CT 06492 USA. [McQuade, Robert D.; Carson, William H.] Otsuka Pharmaceut Dev & Commercializat Inc, Princeton, NJ USA. RP Thase, ME (reprint author), Univ Penn, Sch Med, 3535 Market St,Room 689, Philadelphia, PA 19104 USA. EM thase@mail.med.upenn.edu NR 28 TC 147 Z9 150 U1 3 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD FEB PY 2008 VL 28 IS 1 BP 13 EP 20 DI 10.1097/jcp.0b013e3181618eb4 PG 8 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 252XN UT WOS:000252481100003 PM 18204335 ER PT J AU Kilzieh, N Todd-Stenberg, JA Kennedy, A Wood, AE Tapp, AM AF Kilzieh, Nael Todd-Stenberg, Jeffrey A. Kennedy, Annette Wood, Amanda E. Tapp, Andre M. TI Time to discontinuation and self-discontinuation of olanzapine and risperidone in patients with schizophrenia in a naturalistic outpatient setting SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID SCHIZOAFFECTIVE DISORDER; 2ND-GENERATION ANTIPSYCHOTICS; FOLLOW-UP; MEDICATION; NONADHERENCE; EFFICACY AB Background: Although efficacy of antipsychotic medications is well documented, their effectiveness in real-world practice is less robust. We examined the effectiveness of olanzapine and risperidone in schizophrenia in a naturalistic setting. Methods: We used an electronic medical records database at a Veterans Affairs Medical Center to conduct a retrospective study of all new outpatient medication trials of olanzapine (n = 221) and risperidone (n = 274) over a 2-year period beginning January 1999 in patients diagnosed with schizophrenia or schizoaffective disorder. We defined medication discontinuation as a switch between the 2 agents (most switches) or self-discontinuation when a patient is without medication supply for longer than 1 month. Results: Sample mean age (+/- SD) was 48.4 (+/- 11.6) years; 91% were men. Discontinuation rates were high (73%), trending lower in olanzapine (70%) than risperidone (76%) (P = 0.12). Median time to discontinuation was 120 days (95% confidence interval [CI], 105-135), longer for olanzapine (150 days, 95% CI, 120-180) than risperidone (90 days; 95% CI, 71-109) (P = 0.04). Self-discontinuation was high (48%), with no significant difference between olanzapine (50%) and risperidone (46%). Switching rate was 25% and more likely to occur in risperidone (30%) than olanzapine (20%) (odds ratio, 1.72; 95% CI, 1.13-2.61). Conclusions: Effectiveness of antipsychotic medications in schizophrenia may be hampered by high rates of medication self-discontinuation in outpatient practice settings. Time to discontinuation C1 [Kilzieh, Nael; Todd-Stenberg, Jeffrey A.; Kennedy, Annette; Wood, Amanda E.; Tapp, Andre M.] Univ Washington, Dept Psychiat & Behav Sci, VA Puget Sound Hlth Care Syst,Vet Integrated Serv, Amer Lake Div,Mental Illness Res Educ & Clin Ctr, Tacoma, WA 98493 USA. [Kennedy, Annette] Seattle Inst Biomed & Clin Res, Seattle, WA USA. RP Kilzieh, N (reprint author), Univ Washington, Dept Psychiat & Behav Sci, VA Puget Sound Hlth Care Syst,Vet Integrated Serv, Amer Lake Div,Mental Illness Res Educ & Clin Ctr, 116-A, Tacoma, WA 98493 USA. EM nael.kilzieh@va.gov NR 16 TC 12 Z9 12 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD FEB PY 2008 VL 28 IS 1 BP 74 EP 77 DI 10.1097/jcp.0b013e3181602cf3 PG 4 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 252XN UT WOS:000252481100013 PM 18204345 ER PT J AU Schroy, PC Glick, JT Robinson, PA Lydotes, MA Evans, SR Emmons, KM AF Schroy, Paul C., III Glick, Julie T. Robinson, Patricia A. Lydotes, Maria A. Evans, Stephen R. Emmons, Karen M. TI Has the surge in media attention increased public awareness about colorectal cancer and screening? SO JOURNAL OF COMMUNITY HEALTH LA English DT Article DE colorectal cancer; screening; public awareness; patient education; media campaigns ID SERVICES TASK-FORCE; AFRICAN-AMERICANS; CLINICAL GUIDELINES; COST-EFFECTIVENESS; AVERAGE-RISK; KNOWLEDGE; BARRIERS; PERCEPTIONS; POPULATION; RATIONALE AB The Centers for Disease Control and Prevention's Screen for Life campaign in March 1999 followed by the creation of National Colorectal Cancer Awareness Month in March 2000 heralded a surge in media attention to promote awareness about CRC and stimulate interest in screening. Our objective was to assess whether these campaigns have achieved their goal of educating the public about CRC and screening. The study sample was comprised of mostly unscreened, average-risk, English-speaking patients aged 50-75 years seen in an urban primary care setting. Knowledge was assessed using a 12-item true/false questionnaire based primarily on the content of key messages endorsed by the National Colorectal Cancer Roundtable (Cancer 95: 1618-1628, 2002) and adopted in many of the media campaigns. Multiple linear regression was performed to identify demographic correlates of knowledge. A total of 356 subjects (83% < age 65, 58% female, 60% Black, 7% Hispanic, 60% <= high school degree, 31% prior FOBT) were surveyed. Most respondents (>= 67%) were aware of who gets CRC, age to initiate screening, the goals of screening and potential benefits. Fewer were aware that removing polyps can prevent CRC and that both polyps and CRC may be asymptomatic. Knowledge scores were lower among Blacks and those with a high school degree or less. Race and education were independent correlates of knowledge. These data suggest that recent media campaigns have been effective in increasing public awareness about CRC risk and screening but important gaps in knowledge remain. C1 [Schroy, Paul C., III] Boston Univ, Sch Med, Dept Med, Gastroenterol Sect, Boston, MA 02118 USA. [Glick, Julie T.; Robinson, Patricia A.; Lydotes, Maria A.] Boston Univ, Med Ctr, Gastroenterol Sect, Boston, MA 02118 USA. [Evans, Stephen R.] Boston Univ, Sch Publ Hlth, Data Coordinating Ctr, Boston, MA 02118 USA. [Emmons, Karen M.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. RP Schroy, PC (reprint author), Boston Univ, Sch Med, Dept Med, Gastroenterol Sect, 85 E Concord St,Suite 7715, Boston, MA 02118 USA. EM paul.schroy@bmc.org FU AHRQ HHS [R01HS013912] NR 27 TC 19 Z9 19 U1 1 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0094-5145 J9 J COMMUN HEALTH JI J. Community Health PD FEB PY 2008 VL 33 IS 1 BP 1 EP 9 DI 10.1007/s10900-007-9065-5 PG 9 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 241GA UT WOS:000251643700001 PM 18080203 ER PT J AU Weierich, MR Nock, MK AF Weierich, Mariann R. Nock, Matthew K. TI Posttraumatic stress symptoms mediate the relation between childhood sexual abuse and nonsuicidal self-injury SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE self-injury; child abuse; trauma; posttraumatic stress disorder; self-harm ID SUICIDE ATTEMPTS; VALIDITY; ADOLESCENTS; MUTILATION; RELIABILITY; POPULATION; PREVALENCE; BEHAVIORS; THOUGHTS; DISORDER AB Prior research consistently has shown a strong relation between childhood abuse and nonsuicidal self-injury (NSSI), yet it is unclear why this relation exists. The authors examined 2 specific posttraumatic stress disorder (PTSD) symptom clusters as potential mechanisms through which childhood abuse may be related to NSSI. Participants were 86 adolescents (78% female, 22% male; 73% Caucasian, 27% other races/ethnicities; mean age = 17.03 years, range = 12-19 years) who completed measures of childhood abuse, Diagnostic and Statistical Manual of Mental Disorders (4th ed.) PTSD symptoms, and NSSI. Analyses revealed a significant relation between childhood sexual abuse in particular and the presence and frequency of NSSI. Moreover, data supported a theoretical model in which PTSD reexperiencing and avoidance/numbing symptoms independently mediate this relation. Future research must test the temporal relation between childhood sexual abuse, PTSD symptoms, and NSSI and identify additional pathways to engagement in NSSI. C1 [Weierich, Mariann R.] Vet Affairs Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Boston, MA USA. [Weierich, Mariann R.] Boston Univ, Sch Med, Boston, MA 02215 USA. [Nock, Matthew K.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. RP Weierich, MR (reprint author), Massachusetts Gen Hosp East, Dept Psychiat, Massachusetts Gen Hosp, Psychiat Neuroimaging Program, Bldg 149,13th St,Room 2681, Charlestown, MA 02129 USA. EM weierich@nmr.mgh.harvard.edu FU NIMH NIH HHS [MH076047] NR 19 TC 82 Z9 83 U1 0 U2 17 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD FEB PY 2008 VL 76 IS 1 BP 39 EP 44 DI 10.1037/0022-006X.76.1.39 PG 6 WC Psychology, Clinical SC Psychology GA 257UJ UT WOS:000252823900006 PM 18229981 ER PT J AU Bolton, LE Reed, A Volpp, KG Armstrong, K AF Bolton, Lisa E. Reed, Americus, II Volpp, Kevin G. Armstrong, Katrina TI How does drug and supplement marketing affect a healthy lifestyle? SO JOURNAL OF CONSUMER RESEARCH LA English DT Article ID DIETARY-SUPPLEMENTS; SELF-EFFICACY; CONSEQUENCES; PERCEPTION; BEHAVIOR; REMEDIES; WEIGHT; MODEL AB This research investigates consumer reactions to the marketing of drugs and supplements and the consequences for a healthy lifestyle. A series of experiments provides evidence that drug marketing undermines intentions to engage in health-protective behaviors (i.e., a boomerang effect). The boomerang arises from two psychological mechanisms: (1) drugs reduce risk perceptions and perceived importance of, and motivation to engage in, complementary health-protective behaviors, and (2) drugs are associated with poor health that reduces self-efficacy and perceived ability to engage in complementary health-protective behaviors. A combined intervention accompanying a drug remedy that targets both motivation and ability mitigates the drug boomerang on a healthy lifestyle. C1 [Bolton, Lisa E.; Reed, Americus, II] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. [Volpp, Kevin G.] Univ Penn, Sch Med, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Armstrong, Katrina] Univ Penn, Leonard Davis Inst, Philadelphia, PA 19104 USA. [Armstrong, Katrina] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. RP Bolton, LE (reprint author), Univ Penn, Wharton Sch, 3730 Walnut St,700 Jon M Huntsman Hall, Philadelphia, PA 19104 USA. EM boltonl@wharton.upenn.edu NR 33 TC 23 Z9 23 U1 4 U2 20 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0093-5301 J9 J CONSUM RES JI J. Consum. Res. PD FEB PY 2008 VL 34 IS 5 BP 713 EP 726 DI 10.1086/521906 PG 14 WC Business SC Business & Economics GA 249QP UT WOS:000252244300012 ER PT J AU DePaola, DP AF DePaola, Dominick P. TI The revitalization of US dental education SO JOURNAL OF DENTAL EDUCATION LA English DT Article ID MEDICINE C1 [DePaola, Dominick P.] Forsyth Inst, Boston, MA USA. [DePaola, Dominick P.] Tufts Univ, Sch Dent Med, Medford, MA 02155 USA. [DePaola, Dominick P.] Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23284 USA. [DePaola, Dominick P.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX USA. [DePaola, Dominick P.] Univ Med & Dent New Jersey, Sch Dent, Newark, NJ 07103 USA. [DePaola, Dominick P.] Baylor Coll Dent, Dallas, TX 75246 USA. [DePaola, Dominick P.] Harvard Univ, Sch Dent Med, Cambridge, MA 02138 USA. [DePaola, Dominick P.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP DePaola, DP (reprint author), 144 Coventry Pl, Palm Beach Gardens, FL 33418 USA. EM ddepaola@forsyth.org NR 26 TC 34 Z9 38 U1 1 U2 5 PU AMER DENTAL EDUCATION ASSOC PI WASHINGTON PA 1400 K STREET, NW, STE 1100, WASHINGTON, DC 20005 USA SN 0022-0337 J9 J DENT EDUC JI J. Dent. Educ. PD FEB PY 2008 VL 72 IS 2 SU S BP 28 EP 42 PG 15 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 281NU UT WOS:000254505200007 PM 18250375 ER PT J AU Garcez, AS Nunez, SC Hamblin, MR Ribeiro, MS AF Garcez, Aguinaldo Silva Nunez, Silvia Cristina Hamblin, Michael R. Ribeiro, Martha Simoes TI Antimicrobial effects of photodynamic therapy on patients with necrotic pulps and periapical lesion SO JOURNAL OF ENDODONTICS LA English DT Article DE endodontics; polyethylenimine and chlorin(e6) conjugate; red laser; root canal ID ENDODONTIC TREATMENT; LETHAL PHOTOSENSITIZATION; ORAL INFECTIONS; BACTERIA; TEETH; DISINFECTION; CANALS; DOGS AB This study analyzed the antimicrobial effect of photodynamic therapy (PDT) in association with endodontic treatment. Twenty patients were selected. Microbiological samples were taken after accessing the canal, endodontic therapy, and PDT. At the end of the first session, the root canal was filled with Ca(OH)(2), and after 1 week, a second session of the therapies was performed. Endodontic therapy gave a mean reduction of 1.08 log. The combination with PDT significantly enhanced the reduction (1.83 log, p = 0.00002). The second endodontic session gave a similar diminution to the first (1.14 log), and the second PDT was significantly more effective than the first (p = 0.002). The second total reduction was significantly higher than the second endodontic therapy (p = 0.0000005). The total first + second reduction (3.19 log) was significantly different from the first combination (p = 0.00006). Results suggest that the use of PDT added to endodontic treatment leads to an enhanced decrease of bacterial load and may be an appropriate approach for the treatment of oral infections. C1 [Garcez, Aguinaldo Silva; Nunez, Silvia Cristina; Ribeiro, Martha Simoes] Ctr Laser & Aplicacoes IPEN CNEN SP, BR-05508000 Sao Paulo, Brazil. [Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Ribeiro, MS (reprint author), Ctr Laser & Aplicacoes IPEN CNEN SP, Av Lineu Prestes 2242,Cidade Univ, BR-05508000 Sao Paulo, Brazil. EM marthasr@usp.br RI Garcez, Aguinaldo/B-3556-2013; Ribeiro, Martha/G-3517-2012; Nunez, Silvia/C-7241-2017; OI Garcez, Aguinaldo/0000-0003-2037-7211; Ribeiro, Martha/0000-0002-4203-1134; Nunez, Silvia/0000-0003-2101-8333; Hamblin, Michael/0000-0001-6431-4605 FU NIAID NIH HHS [R01 AI050875-03, R01-AI050875, R01 AI050875, R01-CA/AI838801] NR 33 TC 73 Z9 78 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0099-2399 J9 J ENDODONT JI J. Endod. PD FEB PY 2008 VL 34 IS 2 BP 138 EP 142 DI 10.1016/j.joen.2007.10.020 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 259PP UT WOS:000252951500004 PM 18215668 ER PT J AU Driss, N Selim, A Khachemoune, A AF Driss, Nayla Selim, Abdulhafez Khachemoune, Amor TI Dusky plaque on the knee SO JOURNAL OF FAMILY PRACTICE LA English DT Editorial Material ID CUTANEOUS SARCOIDOSIS; SCAR SARCOIDOSIS C1 [Driss, Nayla] Tulane Univ, New Orleans, LA 70118 USA. [Selim, Abdulhafez] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Internal Med,Endocrine Unit, Boston, MA USA. [Khachemoune, Amor] SUNY Downstate, Brooklyn, NY USA. RP Driss, N (reprint author), Tulane Univ, New Orleans, LA 70118 USA. EM amorkh@pol.net NR 13 TC 0 Z9 0 U1 0 U2 0 PU DOWDEN HEALTH MEDIA PI MONTVALE PA 110 SUMMIT AVE, MONTVALE, NJ 07645-1712 USA SN 0094-3509 J9 J FAM PRACTICE JI J. Fam. Pract. PD FEB PY 2008 VL 57 IS 2 BP 97 EP 99 PG 3 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 266HD UT WOS:000253424200009 ER PT J AU Fredman, SJ Baucom, DH Miklowitz, DJ Stanton, SE AF Fredman, Steffany J. Baucom, Donald H. Miklowitz, David J. Stanton, Susan E. TI Observed emotional involvement and overinvolvement in families of patients with bipolar disorder SO JOURNAL OF FAMILY PSYCHOLOGY LA English DT Article DE expressed emotion (EE); emotional overinvolvement (EOI); emotional involvement; bipolar disorder; behavioral observations ID EXPRESSED EMOTION; SCHIZOPHRENIA; VALIDATION; PREDICTORS; PSYCHOSIS; BEHAVIOR; THERAPY; HEALTH; CARE AB Many studies have examined the construct validity of the criticism component of expressed emotion, but little work has been done on clarifying the emotional overinvolvement (EOI) construct. In a sample of 115 recently episodic patients with bipolar disorder, the authors of the present study examined the construct validity of an observational coding system for both appropriate and inappropriate emotional involvement that permitted separate ratings for relatives' intrusiveness, self-sacrificing behaviors, and distress related to the patient's wellbeing. Findings support the measure's reliability and convergent validity and are moderately supportive of the measure's discriminant validity. Results also suggest that Camberwell Family Interview (C. E. Vaughn & J. P. Leff, 1976) EOI ratings do not discriminate among the different dimensions of the emotional involvement construct (or their appropriateness or inappropriateness) as revealed in laboratory-based interactions. The findings suggest that clinicians working with such families might consider differentiating among the various ways in which family members are involved with the patient and helping them learn to judge under what circumstances such involvement is appropriate and inappropriate. C1 [Fredman, Steffany J.; Baucom, Donald H.; Stanton, Susan E.] Univ N Carolina, Dept Psychol, Chapel Hill, NC USA. [Miklowitz, David J.] Univ Colorado, Dept Psychol, Boulder, CO 80309 USA. RP Fredman, SJ (reprint author), Vet Affairs Boston Healthcare Syst, Womens Hlth Sci Div 116B 3, Natl Ctr Posttraumat Stress Disorder, 150 S Huntington Ave, Boston, MA 02130 USA. EM fredman@email.unc.edu; dbaucom@email.unc.edu FU NIMH NIH HHS [MH62555, MH72124, MH43931, MH55101] NR 33 TC 6 Z9 6 U1 2 U2 5 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0893-3200 J9 J FAM PSYCHOL JI J. Fam. Psychol. PD FEB PY 2008 VL 22 IS 1 BP 71 EP 79 DI 10.1037/0893-3200.22.1.71 PG 9 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 262EJ UT WOS:000253131500008 PM 18266534 ER PT J AU Bell, ME Cattaneo, LB Goodman, LA Dutton, MA AF Bell, Margret E. Cattaneo, Lauren Bennett Goodman, Lisa A. Dutton, Mary Ann TI Assessing the risk of future psychological abuse: Predicting the accuracy of battered women's predictions SO JOURNAL OF FAMILY VIOLENCE LA English DT Article DE intimate partner violence; battered women; psychological abuse; risk assessment; victim accuracy ID ASSAULT; DECISIONS; VIOLENCE AB Building on a handful of studies demonstrating battered women's accuracy in assessing their risk of being physically reabused, this study examined how accurately victims assess their risk of future psychological abuse. Participants' ratings of the likelihood that their partner would engage in controlling/dominance behaviors or efforts to humiliate/degrade them in the coming year and their reports 18 months later of whether this had actually occurred were used to create a four category version of accuracy (true positive, false positive, true negative, false negative). Victims were more likely to be right than wrong in their assessments of risk; PTSD symptoms, the recency of physical violence, and the degree of stalking and psychological abuse in the relationship predicted membership in the four accuracy categories. These findings overlap considerably with those examining victim accuracy in predicting physical abuse and inform ongoing debates about the value of incorporating victims' insights into risk assessment efforts. C1 [Cattaneo, Lauren Bennett] George Mason Univ, Dept Psychol, Fairfax, VA 22030 USA. [Goodman, Lisa A.] Boston Coll, Lynch Sch Educ, Dept Counseling Dev & Educ Psychol, Chestnut Hill, MA 02167 USA. [Dutton, Mary Ann] Georgetown Univ, Dept Psychiat, Washington, DC USA. [Bell, Margret E.] Off Mental Hlth Serv, Mil Sexual Trauma Support Team, Dept Vet Affairs, Boston, MA 02130 USA. [Bell, Margret E.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. RP Bell, ME (reprint author), Off Mental Hlth Serv, Mil Sexual Trauma Support Team, Dept Vet Affairs, 150 S Huntington Ave 116B-3, Boston, MA 02130 USA. EM mebell@aya.yale.edu NR 42 TC 27 Z9 27 U1 1 U2 5 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7482 J9 J FAM VIOLENCE JI J. Fam. Violence PD FEB PY 2008 VL 23 IS 2 BP 69 EP 80 DI 10.1007/s10896-007-9128-5 PG 12 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 247UC UT WOS:000252107100001 ER PT J AU Rose, AJ Shimada, SL Rothendler, JA Reisman, JI Glassman, PA Berlowitz, DR Kressin, NR AF Rose, Adam J. Shimada, Stephanie L. Rothendler, James A. Reisman, Joel I. Glassman, Peter A. Berlowitz, Dan R. Kressin, Nancy R. TI The accuracy of clinician perceptions of "Usual" blood pressure control SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE hypertension; ambulatory care; informatics; quality of care; chronic disease ID PRIMARY-CARE; AFRICAN-AMERICANS; CORONARY-DISEASE; MANAGEMENT; HYPERTENSION; INERTIA; INTERVENTION; GUIDELINES; PHYSICIANS; ADHERENCE AB BACKGROUND: The term "clinical inertia" is used to describe the failure to manage a chronic condition aggressively enough to bring it under control. The underlying mechanisms for clinical inertia remain poorly understood. OBJECTIVE: To describe one potential mechanism for clinical inertia, seen through the lens of clinician responses to a computerized hypertension reminder. DESIGN: Cohort study. PARTICIPANTS: A total of 509 hypertensive patients from 2 primary care clinics in urban Veterans Health Administration (VA) Medical Centers. All patients had elevated blood pressure (BP) values that triggered a computerized reminder. Given a set of possible responses to the reminder, clinicians asserted at least once for each patient that medication adjustments were unnecessary because the BP was "usually well controlled". MEASUREMENTS: Using recent BP values from the electronic medical record, we assessed the accuracy of this assertion. RESULTS: In most instances (57%), recent BP values were not well controlled, with the systolic BP (56%) much more likely to be elevated than the diastolic BP (13%). Eighteen percent of recent systolic BP values were 160 mmHg or greater. CONCLUSIONS: When clinicians asserted that the BP was "usually well controlled", objective evidence frequently suggested otherwise. This observation provides insight into one potential mechanism underlying clinical inertia. C1 [Rose, Adam J.; Shimada, Stephanie L.; Rothendler, James A.; Reisman, Joel I.; Berlowitz, Dan R.; Kressin, Nancy R.] Bedford VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA. [Rose, Adam J.; Berlowitz, Dan R.; Kressin, Nancy R.] Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02215 USA. [Shimada, Stephanie L.; Rothendler, James A.; Berlowitz, Dan R.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02215 USA. [Glassman, Peter A.] VA Greater Los Angeles, Ctr Study Healthcare Provider Behav, Los Angeles, CA USA. [Glassman, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. RP Rose, AJ (reprint author), Bedford VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, 200 Springs Rd,Bldg 70, Bedford, MA 01730 USA. EM adamrose@bu.edu OI Kressin, Nancy/0000-0003-2767-4286 NR 18 TC 24 Z9 24 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD FEB PY 2008 VL 23 IS 2 BP 180 EP 183 DI 10.1007/s11606-007-0464-1 PG 4 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 259MY UT WOS:000252944600012 PM 18043980 ER PT J AU Souer, JS Lozano-Calderon, SA Ring, D AF Souer, John-Sebastiaan Lozano-Calderon, Santiago A. Ring, David TI Predictors of wrist function and health status after operative treatment of fractures of the distal radius SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE distal radius fracture; health status; operative treatment; outcome; wrist function. ID CHRONIC PAIN; SOMATOFORM DISORDERS; PHYSICAL IMPAIRMENT; UNSTABLE FRACTURES; INTERNAL-FIXATION; ADULT ATTACHMENT; MUSCLE STRENGTH; OPEN REDUCTION; BODY-MASS; DISABILITY AB Purpose To identify the most important determinants of physician-based and patient-based scoring systems for the wrist and upper extremity after operative treatment of a fracture of the distal radius, with the hypothesis that pain is the strongest determinant of both types of scores. Methods Eighty-four patients were evaluated a minimum of 6 months after operative fixation of an unstable distal radius fracture using 2 physician-based evaluation instruments (the Mayo Wrist Score and the Gartland and Werley Score) and an upper extremity-specific health status questionnaire (Disabilities of the Arm, Shoulder, and Hand; DASH). Multivariate analysis of variance and multiple linear regression modeling were used to identify the degree to which various factors affect variability in the scores derived with these measures. Results The physician-based scoring systems showed moderate correlation with each other and with DASH scores. The results of multiple linear regression modeling were as follows (percent variability accounted for by the best fit model/model with top factor alone): Mayo: 54% grip and flexion arc/47% grip alone; Gartland and Werley: 70% pain, flexion arc, radiocarpal arthritis, and duration of follow-up/53% pain alone; DASH: 71% pain, forearm arc, and type of fracture/65% pain alone. Conclusions At early follow-up, pain dominates the patient's perception of function after recovery from an operatively treated distal radius fracture as measured by the DASH score and the physician-based rating according to the system of Gartland and Werley. The Mayo Wrist Score is determined primarily by grip strength rather than pain. Because perception of pain and strength of grip have been shown to be influenced by psychosocial factors in some individuals, both patient-based and physician-based measures of wrist function may be vulnerable to illness behavior. C1 [Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Hand & Upper Extrem Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 39 TC 27 Z9 29 U1 2 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD FEB PY 2008 VL 33A IS 2 BP 157 EP 163 DI 10.1016/j.jhsa.2007.10.003 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 269ZL UT WOS:000253689400003 PM 18294534 ER PT J AU Weissman, JS Zaslavsky, AM Wolf, RE Ayanian, JZ AF Weissman, Joel S. Zaslavsky, Alan M. Wolf, Robert E. Ayanian, John Z. TI State medicaid coverage and access to care for low-income adults SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE medicaid; access to care; BRFSS; preventive services ID PREVENTIVE SERVICES; UNITED-STATES; HEALTH; INSURANCE AB Objective. Budgetary pressures have led some states to limit Medicaid eligibility. We evaluated access to care for all low-income adults by the extent of state Medicaid coverage. Methods. Current Population Survey data compiled by the Kaiser Commission on Medicaid and the Uninsured were used to rank the 48 continental states by the extent of Medicaid coverage for low-income non-elderly adults during 2000-2003. Data from the Behavioral Risk Factor Surveillance System for 2000-2003 were used to assess indicators of access to care, including being unable to see a physician due to cost, not obtaining routine checkups, and four preventive services for appropriate age groups by state. Access gaps were calculated between low-income (under $25,000/year) and high-income ($50,000 or more/year) adults within each state to control for unmeasured economic and health system differences between states. Results. Access gaps between high and low-income people who could not see physicians due to cost were significantly smaller in states with the broadest Medicaid coverage compared with states with the narrowest coverage (19.2% vs. 23.7%, p=.003). Significantly smaller access gaps also occurred in states with broader Medicaid coverage for cholesterol testing (16.0% vs. 18.7%, p=.01), and Pap testing (6.0% vs. 10.8%, p=.002), but not colorectal cancer screening (13.3% vs. 12.5%, p=.28), mammography (14.3% vs. 19.7%, p=.07), and routine checkup within two years (8.0% vs. 9.3%, p=.10). Conclusions. A state's level of Medicaid coverage was associated with access to physicians' services, cholesterol testing, and cervical cancer screening for low-income adults. Broad Medicaid coverage may be an effective strategy for states to improve access to care and preventive services for low-income adults. C1 [Weissman, Joel S.; Zaslavsky, Alan M.; Wolf, Robert E.; Ayanian, John Z.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Weissman, Joel S.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. [Ayanian, John Z.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Weissman, Joel S.; Ayanian, John Z.] Harvard Univ, Sch Publ Hlth, Boston, MA 02114 USA. RP Weissman, JS (reprint author), Harvard Univ, Sch Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM jweissman@partners.org NR 27 TC 17 Z9 17 U1 1 U2 3 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1049-2089 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD FEB PY 2008 VL 19 IS 1 BP 307 EP 319 DI 10.1353/hpu.2008.0021 PG 13 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 262LC UT WOS:000253149000025 PM 18264004 ER PT J AU Stempfle, HU Alt, A Stief, J Siebert, U AF Stempfle, Hans-Ulrich Alt, Andrea Stief, Jutta Siebert, Uwe TI The Munich score: A clinical index to predict survival in ambulatory patients with chronic heart failure in the era of new medical therapies SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article ID BETA-BLOCKER THERAPY; PROGNOSTIC VALUE; CARDIAC TRANSPLANTATION; EXERCISE CAPACITY; SERIAL CHANGES; IMPACT; SIZE AB Background: Risk stratification in patients with congestive heart failure (CHF) is an obligatory part of the heart transplantation (HTx) selection process. New medical therapies and the predictive value of hemodynamic changes over time have not been adequately taken into account in previous stratification models. In this study we assessed the prognostic value of 55 variables at baseline and 9 variables representing changes of hemodynamic parameters over time. Methods: A total of 178 patients with CHF were examined on 3.4 +/- 2.6 occasions (mean follow-up 19 19 months). Using the Cox proportional hazards model, univariate and multivariate relative risks (RRs) with 95% confidence intervals (CI) were determined for predicting event-free survival. A prognostic score (Munich score) was derived from the multivariate Cox model and three risk groups were derived. Results: During follow-up, 23 patients (13%) died and 63 (35%) underwent HTx. The univariate analysis yielded 21 statistically significant (p < 0.05) predictors of event-free survival. However, only four baseline variables (etiology of ischemic cardiomyopathy, systolic blood pressure, left ventricular [IV] end-diastolic diameter, maximal workload) and the change over 12 months in fractional shortening remained statistically significant (p < 0.05) in the multivariate Cox model and were used for the prognostic score. Within 12 months, no event occurred in the low-risk group, 8.1% in the intermediate, and 30.1% in the high-risk group. Conclusions: The incorporation of changes over time in hemodynamic parameters allowed for an improved baseline risk stratification model for the HTx selection process, especially in the era of new medical therapies such as beta-blocker therapy. All significant variables of the Munich score can be obtained in routinely performed non-invasive tests. C1 [Stempfle, Hans-Ulrich; Alt, Andrea; Stief, Jutta] Univ Munich, Med Poliklin Innenstadt, Dept Cardiol, D-80336 Munich, Germany. [Stempfle, Hans-Ulrich] Asklepios Stadtklin Bad Tolz, Dept Internal Med, Bad Tolz, Germany. [Siebert, Uwe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA USA. [Siebert, Uwe] Univ Hlth Sci Med Informat & Technol, UMIT, Dept Publ Hlth Med Decis Making & Hlth Technol As, Tyrol, Austria. RP Stempfle, HU (reprint author), Univ Munich, Med Poliklin Innenstadt, Dept Cardiol, Ziemssenstr 1, D-80336 Munich, Germany. EM u.stempfle@asklepios.com NR 28 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2008 VL 27 IS 2 BP 222 EP 228 DI 10.1016/j.healun.2007.10.016 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 264AY UT WOS:000253258800013 PM 18267231 ER PT J AU Ennis, SC Moukarbel, GV MacGillivray, TE AF Ennis, S. C. Moukarbel, G. V. MacGillivray, T. E. TI Left ventricular assist devices provide renal protection in patients awaiting heart transplantation SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 28th Annual Meeting of the International-Society-for-Heart-and-Lung-Transplantation CY APR 09-12, 2008 CL Boston, MA SP Int Soc Heart & Lung Transplantat C1 [Ennis, S. C.; Moukarbel, G. V.; MacGillivray, T. E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2008 VL 27 IS 2 SU S MA 6 BP S62 EP S62 DI 10.1016/j.healun.2007.11.010 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 265EQ UT WOS:000253342300007 ER PT J AU John, R Boyle, AJ MacGillivray, TE Rogers, JG Chen, L Goldstein, DJ Dembitsky, WP Farrar, DJ Pagani, FD AF John, R. Boyle, A. J. MacGillivray, T. E. Rogers, J. G. Chen, L. Goldstein, D. J. Dembitsky, W. P. Farrar, D. J. Pagani, F. D. TI Can continuous flow LVADs provide a similar level of circulatory support as Pulsatile LVADs for large patients? SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 28th Annual Meeting of the International-Society-for-Heart-and-Lung-Transplantation CY APR 09-12, 2008 CL Boston, MA SP Int Soc Heart & Lung Transplantat C1 [John, R.; Boyle, A. J.] Univ Minnesota, Dept Surg, Minneapolis, MN USA. [MacGillivray, T. E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rogers, J. G.] Duke Univ, Med Ctr, Durham, NC USA. [Chen, L.] Univ Rochester, Rochester, NY USA. [Goldstein, D. J.] Montefiore Med Ctr, Bronxville, NY USA. [Dembitsky, W. P.] Sharp Mem Hosp & Rehabil Ctr, San Diego, CA USA. [Farrar, D. J.] Thoratec Corp, Pleasanton, CA USA. [Pagani, F. D.] Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2008 VL 27 IS 2 SU S MA 8 BP S62 EP S63 DI 10.1016/j.healun.2007.11.012 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 265EQ UT WOS:000253342300009 ER PT J AU Khurana, HS Chaux, G Kole, A Falk, J Simsir, S Cheng, W Kass, RM Khurana, J Soohoo, G AF Khurana, H. S. Chaux, G. Kole, A. Falk, J. Simsir, S. Cheng, W. Kass, R. M. Khurana, J. Soohoo, G. TI Low dose valganciclovir for CMV prophylaxis after lung transplantation SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 28th Annual Meeting of the International-Society-for-Heart-and-Lung-Transplantation CY APR 09-12, 2008 CL Boston, MA SP Int Soc Heart & Lung Transplantat C1 [Khurana, H. S.; Chaux, G.; Kole, A.; Falk, J.; Simsir, S.; Cheng, W.; Kass, R. M.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Khurana, J.; Soohoo, G.] W Los Angeles VA Healthcare Ctr, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2008 VL 27 IS 2 SU S MA 35 BP S72 EP S72 DI 10.1016/j.healun.2007.11.039 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 265EQ UT WOS:000253342300036 ER PT J AU Lam, KM Ennis, S MacGillivray, TE Crisalli, K Cumuso, J Picard, MH AF Lam, K. M. Ennis, S. MacGillivray, T. E. Crisalli, K. Cumuso, J. Picard, M. H. TI Non invasive measures of right heart hemodynamics associated with clinical improvement post heartmate II SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 28th Annual Meeting of the International-Society-for-Heart-and-Lung-Transplantation CY APR 09-12, 2008 CL Boston, MA SP Int Soc Heart & Lung Transplantat C1 [Lam, K. M.; Picard, M. H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ennis, S.; MacGillivray, T. E.; Crisalli, K.; Cumuso, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2008 VL 27 IS 2 SU S MA 276 BP S160 EP S160 DI 10.1016/j.healun.2007.11.285 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 265EQ UT WOS:000253342300277 ER PT J AU Martins, PNA Germana, SK LeGuern, C AF Martins, P. N. A. Germana, S. K. LeGuern, C. TI Influence of MHC class II matching on regulatory tolerance to heart transplants SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 28th Annual Meeting of the International-Society-for-Heart-and-Lung-Transplantation CY APR 09-12, 2008 CL Boston, MA SP Int Soc Heart & Lung Transplantat C1 [Martins, P. N. A.; Germana, S. K.; LeGuern, C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr,Dept Surg, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2008 VL 27 IS 2 SU S MA 128 BP S105 EP S106 DI 10.1016/j.healun.2007.11.134 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 265EQ UT WOS:000253342300129 ER PT J AU Meltzer, AJ Veillette, GR Aoyama, A Cochrane, ME Houser, SL Wain, JC Madsen, JC Sachs, DH Allan, JS Rosengard, BR AF Meltzer, A. J. Veillette, G. R. Aoyama, A. Cochrane, M. E. Houser, S. L. Wain, J. C. Madsen, J. C. Sachs, D. H. Allan, J. S. Rosengard, B. R. TI Donor brain death prevents tolerance induction in miniature swine recipients of MHC-disparate lung allografts SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 28th Annual Meeting of the International-Society-for-Heart-and-Lung-Transplantation CY APR 09-12, 2008 CL Boston, MA SP Int Soc Heart & Lung Transplantat C1 [Meltzer, A. J.; Veillette, G. R.; Aoyama, A.; Cochrane, M. E.; Houser, S. L.; Wain, J. C.; Madsen, J. C.; Sachs, D. H.; Allan, J. S.; Rosengard, B. R.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2008 VL 27 IS 2 SU S MA 548 BP S257 EP S258 DI 10.1016/j.healun.2007.11.562 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 265EQ UT WOS:000253342300548 ER PT J AU Meltzer, AJ Houser, SL Madsen, JC Chien, KR Cochrane, ME Allan, JS Rosengard, BR AF Meltzer, A. J. Houser, S. L. Madsen, J. C. Chien, K. R. Cochrane, M. E. Allan, J. S. Rosengard, B. R. TI Identification of cells expressing the IsI1 cardiac progenitor marker in miniature swine SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 28th Annual Meeting of the International-Society-for-Heart-and-Lung-Transplantation CY APR 09-12, 2008 CL Boston, MA SP Int Soc Heart & Lung Transplantat C1 [Meltzer, A. J.; Houser, S. L.; Madsen, J. C.; Cochrane, M. E.; Rosengard, B. R.] Massachusetts Gen Hosp, Boston, MA USA. [Chien, K. R.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2008 VL 27 IS 2 SU S MA 474 BP S230 EP S231 DI 10.1016/j.healun.2007.11.487 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 265EQ UT WOS:000253342300475 ER PT J AU Meltzer, AJ Weiss, MJ Sahara, H Cochrane, ME Sayre, JK Houser, SL Madsen, JC Sachs, DH Rosengard, BR Wain, JC Allan, JS AF Meltzer, A. J. Weiss, M. J. Sahara, H. Cochrane, M. E. Sayre, J. K. Houser, S. L. Madsen, J. C. Sachs, D. H. Rosengard, B. R. Wain, J. C. Allan, J. S. TI Gastric aspiration leads to the development of an immune response to collagen V and donor-derived class I peptides following lung transplantation in miniature swine SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 28th Annual Meeting of the International-Society-for-Heart-and-Lung-Transplantation CY APR 09-12, 2008 CL Boston, MA SP Int Soc Heart & Lung Transplantat C1 [Meltzer, A. J.; Weiss, M. J.; Sahara, H.; Cochrane, M. E.; Sayre, J. K.; Houser, S. L.; Madsen, J. C.; Sachs, D. H.; Rosengard, B. R.; Wain, J. C.; Allan, J. S.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2008 VL 27 IS 2 SU S MA 31 BP S71 EP S71 DI 10.1016/j.healun.2007.11.035 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 265EQ UT WOS:000253342300032 ER PT J AU Moukarhel, GV Lee, S Jneid, H Gonczarek, KM Hoyer, FF Keck, SA Haggan, CD Yurchak, PM Semigran, MJ AF Moukarhel, G. V. Lee, S. Jneid, H. Gonczarek, K. M. Hoyer, F. F. Keck, S. A. Haggan, C. D. Yurchak, P. M. Semigran, M. J. TI Electrocardiographic infarct pattern early following cardiac transplantation: Prevalence and prognostic implication SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 28th Annual Meeting of the International-Society-for-Heart-and-Lung-Transplantation CY APR 09-12, 2008 CL Boston, MA SP Int Soc Heart & Lung Transplantat C1 [Moukarhel, G. V.; Lee, S.; Jneid, H.; Gonczarek, K. M.; Hoyer, F. F.; Keck, S. A.; Haggan, C. D.; Yurchak, P. M.; Semigran, M. J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2008 VL 27 IS 2 SU S MA 254 BP S152 EP S152 DI 10.1016/j.healun.2007.11.263 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 265EQ UT WOS:000253342300255 ER PT J AU Ng, CY Weiss, MJ Boskovic, S Kawai, T Millington, TM Benichou, G Madsen, JC Wain, J Allan, JS AF Ng, C. Y. Weiss, M. J. Boskovic, S. Kawai, T. Millington, T. M. Benichou, G. Madsen, J. C. Wain, J. Allan, J. S. TI Induction of mixed chimerism and transplantation tolerance in a non-human primate lung allograft model: Early results SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 28th Annual Meeting of the International-Society-for-Heart-and-Lung-Transplantation CY APR 09-12, 2008 CL Boston, MA SP Int Soc Heart & Lung Transplantat C1 [Ng, C. Y.] Papworth Hosp NHS Trust, Cambridge, England. [Boskovic, S.; Kawai, T.; Millington, T. M.; Benichou, G.; Madsen, J. C.; Wain, J.; Allan, J. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Weiss, M. J.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2008 VL 27 IS 2 SU S MA 364 BP S192 EP S192 DI 10.1016/j.healun.2007.11.375 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 265EQ UT WOS:000253342300365 ER PT J AU Weiss, MJ Meltzer, AJ Sahara, H Rosengard, BR Cochrane, ME Sayre, JK Allan, JS Houser, SL Sachs, DH Benicbou, G Madsen, JC AF Weiss, M. J. Meltzer, A. J. Sahara, H. Rosengard, B. R. Cochrane, M. E. Sayre, J. K. Allan, J. S. Houser, S. L. Sachs, D. H. Benicbou, G. Madsen, J. C. TI Sensitization to cardiac myosin induces rejection of cardiac allografts in miniature swine SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 28th Annual Meeting of the International-Society-for-Heart-and-Lung-Transplantation CY APR 09-12, 2008 CL Boston, MA SP Int Soc Heart & Lung Transplantat C1 [Weiss, M. J.; Meltzer, A. J.; Sahara, H.; Rosengard, B. R.; Cochrane, M. E.; Sayre, J. K.; Allan, J. S.; Houser, S. L.; Sachs, D. H.; Benicbou, G.; Madsen, J. C.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2008 VL 27 IS 2 SU S MA 547 BP S257 EP S257 DI 10.1016/j.healun.2007.11.561 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 265EQ UT WOS:000253342300547 ER PT J AU Lieber, CS DeCarli, LM Leo, MA Mak, KM Ponomarenko, A Ren, C Wang, XL AF Lieber, Charles S. DeCarli, Leonore M. Leo, Maria A. Mak, Ki M. Ponomarenko, Anatoly Ren, Chaoling Wang, Xiaolei TI Beneficial effects versus toxicity of medium-chain triacylglycerols in rats with NASH SO JOURNAL OF HEPATOLOGY LA English DT Article DE long-chain triacylglycerols; medium-chain triacylglycerols; non-alcoholic steatohepatitis; TNF-alpha ID HEPATIC CYTOCHROME-P450 2E1; NONALCOHOLIC STEATOHEPATITIS; DIMINISHED DEPOSITION; OXIDATIVE STRESS; LIVER-INJURY; IN-VIVO; TRIGLYCERIDES; FAT; ETHANOL; THERMOGENESIS AB Background/Aims: Replacing long-chain triacylglycerols (LCT) with medium-chain triacylglycerols (MCT) reduces alcohol-induced liver injury. Because of the similarity of the pathogenesis of alcohol-induced liver damage and non-alcoholic steatohepatitis (NASH), our aim was to assess whether MCT is also beneficial in NASH. Methods: We used a rat NASH model in which corn oil (35% of total calories) was isocalorically replaced with MCT. Results: Partial replacement of LCT did not ameliorate hepatic fat accumulation, 4-hydroxynonenal, collagen type I and its mRNA but it increased TNF-alpha( and its mRNA (p < 0.001). However, in rats given the high-fat diet restricted to 2/3 of the amount they were consuming, these adverse effects decreased, with and without MCT including less liver steatosis and lower triacylglycerols, but without beneficial effects of MCT. When 70% of the fat calories were replaced with MCT with no LCT remaining in the diet, no steatosis developed and hepatic TNF-alpha was low. When all MCT were given with carbohydrates (instead of LCT) hepatic TNF-alpha also decreased (p < 0.001). Conclusions: MCT are not hepatotoxic, provided the diet contains no significant amount of LCT. Total replacement of dietary LCT with MCT fed ad libitum is beneficial whereas partial replacement becomes hepatotoxic, unless the dietary intake is restricted. (c) 2007 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. C1 [Lieber, Charles S.; DeCarli, Leonore M.; Leo, Maria A.; Ponomarenko, Anatoly] James J Peters VA Med Ctr, Alcohol Res Ctr, Bronx, NY 10468 USA. [Lieber, Charles S.; Leo, Maria A.; Mak, Ki M.; Ren, Chaoling; Wang, Xiaolei] Mt Sinai Sch Med, New York, NY USA. RP Lieber, CS (reprint author), James J Peters VA Med Ctr, Alcohol Res Ctr, 130 W Kingsbridege Rd 151-2, Bronx, NY 10468 USA. EM liebercs@aol.com FU NCCIH NIH HHS [AT001583] NR 32 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD FEB PY 2008 VL 48 IS 2 BP 318 EP 326 DI 10.1016/j.jhep.2007.09.016 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 264XS UT WOS:000253324300017 PM 18093684 ER PT J AU Corry, DB Eslami, P Yamamoto, K Nyby, MD Makino, H Tuck, ML AF Corry, Dalila B. Eslami, Pirooz Yamamoto, Kei Nyby, Michael D. Makino, Hirofumi Tuck, Michael L. TI Uric acid stimulates vascular smooth muscle cell proliferation and oxidative stress via the vascular renin-angiotensin system SO JOURNAL OF HYPERTENSION LA English DT Article DE oxidative stress; renin-angiotensin system; uric acid; vascular smooth muscle cells ID ACTIVATED PROTEIN-KINASE; ESSENTIAL-HYPERTENSION; INSULIN; HYPERURICEMIA; SUPEROXIDE; GROWTH; HUMANS AB Background Plasma uric acid has been associated with hypertension in a variety of disorders, and has been shown to be predictive of hypertension. The mechanistic role of uric acid in the development of hypertension is not known however. Method We tested the hypothesis that uric acid stimulates vascular smooth muscle cell (VSMC) proliferation and oxidative stress by stimulating the vascular renin angiotensin system (RAS). Rat VSMC were exposed to 0-300 mu mol uric acid for 48 h. Results Uric acid (200 and 300 mu mol) stimulated the proliferation of VSMC as measured by thymidine uptake. This effect was prevented by 10(-6) mol losartan or by 10(-6) mol captopril. Incubation of VSMC with uric acid for 48 h also increased angiotensinogen messenger RNA expression and intracellular concentrations of angiotensin II. These responses were also inhibited by losartan and captopril. Increased expression of angiotensinogen mRNA was also inhibited by co-incubation with PD 98059, a mitogen-activated protein (MAP) kinase inhibitor. Uric acid stimulated the production of hydrogen peroxide and 8-isoprostane in VSMC. These increases in oxidative stress indicators were significantly reduced by co-incubating the cells with captopril or losartan. Uric acid also decreased nitrite and nitrate concentrations in the culture medium, an effect that was prevented by losartan and captopril. Conclusion These results demonstrate that uric acid stimulates proliferation, angiotensin II production, and oxidative stress in VSMC through tissue RAS. This suggests that uric acid causes cardiovascular disorders by stimulating the vascular RAS, and this stimulation may be mediated by the MAP kinase pathway. C1 [Eslami, Pirooz; Yamamoto, Kei; Nyby, Michael D.; Makino, Hirofumi; Tuck, Michael L.] VA Greater Los Angeles Healthcare Syst, Sepulveda, CA 91343 USA. [Corry, Dalila B.] Olive View UCLA Med Ctr, Sylmar, CA 91342 USA. [Eslami, Pirooz; Yamamoto, Kei; Nyby, Michael D.; Makino, Hirofumi; Tuck, Michael L.] Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, Los Angeles, CA 90024 USA. RP Nyby, MD (reprint author), VA Greater Los Angeles Healthcare Syst, 16111 Plummer St, Sepulveda, CA 91343 USA. EM mnyby@ucla.edu NR 28 TC 226 Z9 254 U1 5 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD FEB PY 2008 VL 26 IS 2 BP 269 EP 275 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 257CZ UT WOS:000252778100019 PM 18192841 ER PT J AU Gupta, V Alonso, JL Sugimori, T Issafi, M Xiong, JP Arnaout, MA AF Gupta, Vineet Alonso, Jose Luis Sugimori, Takashi Issafi, Makram Xiong, Jiang-Ping Arnaout, M. Amin TI Role of the beta-subunit arginine/lysine finger in integrin heterodimer formation and function SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LEU-CAM DEFICIENCY; CD11B A-DOMAIN; GLANZMANN THROMBASTHENIA; CRYSTAL-STRUCTURE; EXTRACELLULAR SEGMENT; MONOCLONAL-ANTIBODY; POINT MUTATIONS; HIGH-AFFINITY; COMPLEX; ALPHA-V-BETA-3 AB Formation of the integrin alpha beta heterodimer is essential for cell surface expression and function. At the core of the alpha beta interface is a conserved Arg/Lys "finger" from the beta-subunit that inserts into a cup-like "cage" formed of two layers of aromatic residues in the alpha-subunit. We evaluated the role of this residue in heterodimer formation in an alpha A-lacking and an alpha A-containing integrin alpha V beta 3 and alpha M beta 2 (CD11b/CD18), respectively. Arg261 of beta 3 was mutated to Ala or Glu; the corresponding Lys252 of beta 2 was mutated to Ala, Arg, Glu, Asp, or Phe; and the effects on heterodimer formation in each integrin examined by ELISA and. immunoprecipitation in HEK 293 cells cotransfected with plasmids encoding the alpha- and beta-subunits. The Arg261Glu (but not Arg261Ala) substitution significantly impaired cell surface expression and heterodimer formation of alpha V beta 3. Although Lys252Arg, and to a lesser extent Lys252Ala, were well tolerated, each of the remaining substitutions markedly reduced cell surface expression and heterodimer formation of CD11b/CD18. Lys252Arg and Lys252Ala integrin heterodimers displayed a significant increase in binding to the physiologic ligand iC3b. These data demonstrate an important role of the Arg/Lys finger in formation of a stable integrin heterodimer, and suggest that subtle changes at this residue affect the activation state of the integrin. C1 [Gupta, Vineet; Alonso, Jose Luis; Sugimori, Takashi; Issafi, Makram; Xiong, Jiang-Ping; Arnaout, M. Amin] Massachusetts Gen Hosp, Div Nephrol, Leukocyte Biol & Inflammat Program, Struct Biol Program, Charlestown, MA 02129 USA. [Gupta, Vineet; Alonso, Jose Luis; Sugimori, Takashi; Issafi, Makram; Xiong, Jiang-Ping; Arnaout, M. Amin] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Arnaout, MA (reprint author), Massachusetts Gen Hosp, Div Nephrol, Leukocyte Biol & Inflammat Program, Struct Biol Program, 149 13th St, Charlestown, MA 02129 USA. EM arnaout@receptor.mgh.harvard.edu RI Gupta, Vineet/B-1134-2009; Alonso, Jose Luis/G-7961-2012; OI Gupta, Vineet/0000-0001-6987-2550 FU NIDDK NIH HHS [DK 068253, DK 48549, K01 DK068253-04, DK 50305, R01 DK048549, K01 DK068253, P01 DK050305] NR 34 TC 8 Z9 8 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2008 VL 180 IS 3 BP 1713 EP 1718 PG 6 WC Immunology SC Immunology GA 255BY UT WOS:000252632900047 PM 18209068 ER PT J AU Oyoshi, MK Bryce, P Goya, S Pichavant, M Umetsu, DT Oettgen, HC Tsitsikov, EN AF Oyoshi, Michiko K. Bryce, Paul Goya, Sho Pichavant, Muriel Umetsu, Dale T. Oettgen, Hans C. Tsitsikov, Erdyni N. TI TNF receptor-associated factor 1 expressed in resident lung cells is required for the development of allergic lung inflammation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; KAPPA-B ACTIVATION; BRONCHIAL EPITHELIAL-CELLS; DENDRITIC CELLS; T-CELLS; AIRWAY HYPERRESPONSIVENESS; MEDIATED APOPTOSIS; NEGATIVE REGULATOR; LYMPH-NODES; TRAF1 AB TNF is a major therapeutic target in a range of chronic inflammatory disorders, including asthma. TNFR-associated factor (TRAF)l is an intracellular adaptor molecule important for signaling by TNFR. In this study, we investigated the role of TRAF1 in an adoptive transfer model of allergic lung inflammation. Mice deficient in TRAF1 (TRAFI(-/-)) and wild-type (WT) control animals were adoptively transferred with WT OVA-immune CD(4+) T cells, exposed to an aerosol of LPS-free OVA, and analyzed for the development of allergic lung inflammation. In contrast to WT mice, TRAF1(-/-) recipients failed to display goblet cell hyperplasia, eosinophilic inflammation, and airway hyperresponsiveness in this model of asthma. Neither T cell recruitment nor expression of the proinflammatory cytokines IL-4, IL-5, IL-13, or TNF occurred in the lungs of TRAF1(-/-) mice. Although purified myeloid TRAF1(-/-) dendritic cells (DCs) exhibited normal Ag-presenting function and transmigratory capacity in vitro and were able to induce OVA-specific immune responses in the lung draining lymph nodes (LNs) following adoptive transfer in vivo, CD11c(+)CD11b(+) DCs from airways of TRAF1(-/-) recipients were not activated, and purified draining LN cells did not proliferate in vitro. Moreover, transfer of WT or TRAF1(-/-) DCs failed to restore T cell recruitment and DC activation in the airways of TRAF1(-/-) mice, suggesting that the expression of TRAF1 in resident lung cells is required for the development of asthma. Finally, we demonstrate that T cell-transfused TRAF1(-/-) recipient mice demonstrated impaired up-regulation of ICAM-1 expression on lung cells in response to OVA exposure. C1 [Oyoshi, Michiko K.; Tsitsikov, Erdyni N.] Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. [Oyoshi, Michiko K.; Goya, Sho; Pichavant, Muriel; Umetsu, Dale T.; Oettgen, Hans C.] Harvard Univ, Sch Med, Childrens Hosp, Div Immunol, Boston, MA 02115 USA. [Oyoshi, Michiko K.; Goya, Sho; Pichavant, Muriel; Umetsu, Dale T.; Oettgen, Hans C.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Bryce, Paul] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. RP Tsitsikov, EN (reprint author), CBR Inst Biomed Res, 800 Huntington Ave, Boston, MA 02215 USA. EM tsitsikov@cbrinstitute.org FU NCI NIH HHS [CA095127]; NIAID NIH HHS [AI054471] NR 57 TC 9 Z9 9 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2008 VL 180 IS 3 BP 1878 EP 1885 PG 8 WC Immunology SC Immunology GA 255BY UT WOS:000252632900064 PM 18209085 ER PT J AU Baudino, L Nimmerjahn, F da Silveira, SA Martinez-Soria, E Saito, T Carroll, M Ravetch, JV Verbeek, JS Izui, S AF Baudino, Lucie Nimmerjahn, Falk da Silveira, Samareh Azeredo Martinez-Soria, Eduardo Saito, Takashi Carroll, Michael Ravetch, Jeffrey V. Verbeek, J. Sjef Izui, Shozo TI Differential contribution of three activating IgG Fc receptors (Fc gamma RI, FcyRIII, and Fc gamma RIV) to IgG2a- and IgG2b-induced autoimmune hemolytic anemia in mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID DEFICIENT MICE; IN-VIVO; COMPLEMENT; AUTOANTIBODIES; PROTECTION; GLOMERULONEPHRITIS; ENGAGEMENT; INFECTION; ARTHRITIS; RESPONSES AB Murine phagocytes express three different activating IgG Fc gamma R: Fc gamma RI is specific for IgG2a; Fc gamma RIII for IgG1, IgG2a, and IgG2b; and Fc gamma RIV for IgG2a and IgG2b. Although the role of Fc gamma RIII in IgG1 and IgG2a anti-RBC-induced autoimmune hemolytic anemia (AIHA) is well documented, the contribution of Fc gamma RI and Fc gamma RIV to the development of IgG2a- and IgG2b-induced anemia has not yet been defined. In the present study, using mice deficient in Fc gamma RI, Fc gamma RIII, and C3, in combination with an Fc gamma RIV-blocking mAb, we assessed the respective roles of these three Fc gamma R in the development of mild and severe AIHA induced by two different doses (50 and 200 mu g) of the IgG2a and IgG2b subclasses of the 34-3C anti-RBC monoclonal autoantibody. We observed that the development of mild anemia induced by a low dose of 34-3C IgG2a autoantibody was highly dependent, on Fc gamma RIII, while Fc gamma RI and Fc gamma RIV additionally contributed to the development of severe anemia induced by a high dose of this subclass. In contrast, the development of both mild and severe anemia induced by 34-3C IgG2b was dependent on Fc gamma RIII and Fc gamma RIV. Our results indicate differential roles of the three activating Fc gamma R in IgG2a- and IgG2b-mediated AIHA. C1 [Baudino, Lucie; da Silveira, Samareh Azeredo; Martinez-Soria, Eduardo; Izui, Shozo] Univ Geneva, Dept Pathol & Immunol, Geneva, Switzerland. [Nimmerjahn, Falk] Univ Erlangen Nurnberg, Nikolaus Fiebiger Ctr Mol Med, Lab Expt Immunol & Immunotherapy, Erlangen, Germany. [Saito, Takashi] Inst Phys & Chem Res Ctr Allergy & Immunol, Lab Cell Signaling, Yokohama, Kanagawa, Japan. [Carroll, Michael] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Carroll, Michael] Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. [Ravetch, Jeffrey V.] Rockefeller Univ, New York, NY 10065 USA. [Verbeek, J. Sjef] Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands. RP Izui, S (reprint author), Ctr Med Univ Geneva, Dept Pathol & Immunol, CH-1211 Geneva, Switzerland. EM Shozo.Izui@medecine.unige.ch RI Nimmerjahn, Falk/J-4986-2013 NR 31 TC 44 Z9 46 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2008 VL 180 IS 3 BP 1948 EP 1953 PG 6 WC Immunology SC Immunology GA 255BY UT WOS:000252632900072 PM 18209093 ER PT J AU Young, MRL AF Young, M. Rita L. TI Use of carcinogen-induced premalignant oral lesions in a dendritic cell-based vaccine to stimulate immune reactivity against both premalignant oral lesions and oral cancer SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE oral cancer; OSCC; oral lesions; premalignant; vaccine ID CD34(+) PROGENITOR CELLS; NECK-CANCER; PROSTATE-CANCER; PRECANCEROUS LESIONS; CLINICAL-RESPONSES; GROWTH-FACTOR; T-CELL; HEAD; IMMUNOTHERAPY; EXPRESSION AB Select groups of premalignant oral lesions carry a high risk of development of secondary premalignant lesions and oral squamous cell carcinoma (OSCC). The goal of the present study was to determine the feasibility of using premalignant lesion-pulsed dendritic cells as a treatment option to prevent development of secondary lesions and development of OSCC. Mice that were treated with the carcinogen 4-nitroquinoline-l-oxide (4NQO) developed premalignant oral lesions and, subsequently, OSCC. Immunohistochemical analyses showed that these 4NQO-induced lesions and OSCC both overexpressed the tumor antigens epidermal growth factor receptor, RAGE and, to a lesser extent, MUC1. Because there was shared overexpression of tumor antigens on premalignant oral lesions and OSCC, dendritic cells pulsed with lysates of 4NQO-induced premalignant lesion cells were tested in vitro and in vivo for their capacity to stimulate T-cell reactivity to premalignant lesion cells and to OSCC. Spleen cells that were sensitized during coculture or in vivo with premalignant lesion-pulsed dendritic cells were cytolytic toward both premalignant lesion cells and OSCC, and secreted increased levels of interferon -gamma in response to challenge with premalignant lesion cells or OSCC as compared with spleen cells that were sensitized with keratinocyte-pulsed dendritic cells. Levels of CD8(+) Tcells and interferon-gamma release were also increased in lesions of mice that were vaccinated with premalignant lesion-pulsed dendritic cells. The mice that were vaccinated against premalignant lesions were also more resistant to OSCC challenge. These studies show the feasibility of using premalignant oral lesions to stimulate immune reactivity against both premalignant oral lesions and OSCC. C1 [Young, M. Rita L.] Ralph H Johnson Vet Affairs Hosp, Res Serv, Charleston, SC 29401 USA. [Young, M. Rita L.] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. [Young, M. Rita L.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. RP Young, MRL (reprint author), Ralph H Johnson Vet Affairs Hosp, Res Serv, 151,109 Bee St, Charleston, SC 29401 USA. EM rita.young@med.va.gov FU NCI NIH HHS [CA85266, CA97813] NR 33 TC 6 Z9 6 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD FEB-MAR PY 2008 VL 31 IS 2 BP 148 EP 156 PG 9 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 266KE UT WOS:000253433300004 PM 18481384 ER PT J AU D'Souza, MP Altfeld, M AF D'Souza, M. Patricia Altfeld, Marcus TI Measuring HIV-1-specific T cell immunity: How valid are current assays? SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; VACCINE EFFICACY; HIV-1 INFECTION; TYPE-1; LYMPHOCYTES; RESPONSES; VIREMIA; ESCAPE C1 [Altfeld, Marcus] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. [Altfeld, Marcus] Harvard Univ, Sch Med, Div Aids, Boston, MA 02115 USA. [D'Souza, M. Patricia] NIAID, Vaccine Clin Res Branch, Div Aids, NIH, Bethesda, MD 20892 USA. RP Altfeld, M (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM maltfeld@partners.org NR 21 TC 19 Z9 19 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD FEB 1 PY 2008 VL 197 IS 3 BP 337 EP 339 DI 10.1086/525288 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 262EK UT WOS:000253131600003 PM 18184092 ER PT J AU Lombard, DB Schwer, B Alt, FW Mostoslavsky, R AF Lombard, D. B. Schwer, B. Alt, F. W. Mostoslavsky, R. TI SIRT6 in DNA repair, metabolism and ageing SO JOURNAL OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT Symposium on the Biology of Aging CY SEP, 2007 CL Stockholm, SWEDEN SP Biotechnol Biolog Sci Res Council, Med Res Council, Wellcome Trust, Unilever plc, Ellison Med Fdn, Nat Inst Hlth, Swedish Res Council, Swedish Heart Lunch Fdn DE ageing; DNA damage; metabolism ID PANCREATIC BETA-CELLS; BASE EXCISION-REPAIR; LIFE-SPAN EXTENSION; DOUBLE-STRAND BREAKS; FACTOR-I RECEPTOR; OXIDATIVE STRESS; CALORIE RESTRICTION; SACCHAROMYCES-CEREVISIAE; ADP-RIBOSYLTRANSFERASE; CAENORHABDITIS-ELEGANS AB Ageing, or increased mortality with time, coupled with physiologic decline, is a nearly universal yet poorly understood biological phenomenon. Studies in model organisms suggest that two conserved pathways modulate longevity: DNA damage repair and Insulin/Igf1-like signalling. In addition, homologs of yeast Sir2 - the sirtuins - regulate lifespan in diverse organisms. Here, we focus on one particular sirtuin, SIRT6. Mice lacking SIRT6 develop a degenerative disorder that in some respects mimics models of accelerated ageing [Cell (2006) 124:315]. We discuss how sirtuins in general and SIRT6 specifically relate to other evolutionarily conserved pathways affecting ageing, and how SIRT6 might function to ensure organismal homeostasis and normal lifespan. C1 [Lombard, D. B.; Schwer, B.; Alt, F. W.; Mostoslavsky, R.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Childrens Hosp,CBR Inst Biomed Res, Boston, MA 02115 USA. [Lombard, D. B.; Schwer, B.; Alt, F. W.; Mostoslavsky, R.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Lombard, D. B.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Alt, FW (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Childrens Hosp,CBR Inst Biomed Res, Boston, MA 02115 USA. EM alt@enders.tch.harvard.edu FU Howard Hughes Medical Institute NR 133 TC 68 Z9 70 U1 0 U2 9 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0954-6820 J9 J INTERN MED JI J. Intern. Med. PD FEB PY 2008 VL 263 IS 2 BP 128 EP 141 DI 10.1111/j.1365-2796.2007.01902.x PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 254AE UT WOS:000252557900003 PM 18226091 ER PT J AU Sun, W Xu, RJ Hu, W Jin, JF Crellin, HA Bielawski, J Szulc, ZM Thiers, BH Obeid, LM Mao, CG AF Sun, Wei Xu, Ruijuan Hu, Wei Jin, Junfei Crellin, Heather A. Bielawski, Jacek Szulc, Zdzislaw M. Thiers, Bruce H. Obeid, Lina M. Mao, Cungui TI Upregulation of the human alkaline ceramidase 1 and acid ceramidase mediates calcium-induced differentiation of epidermal keratinocytes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID CULTURED HUMAN KERATINOCYTES; STEM-CELLS; SPHINGOMYELIN HYDROLYSIS; PROLIFERATION; SPHINGOSINE; APOPTOSIS; CLONING; SPHINGOLIPIDS; EXPRESSION; ENZYME AB Extracellular calcium (Ca-o(2+)) potently induces the growth arrest and differentiation of human epidermal keratinocytes (HEKs). We report that Ca-o(2+) markedly upregulates the human alkaline ceramidase 1 (haCER1) in HEKs; and its upregulation mediates the Cao2_-induced growth arrest and differentiation of HEKs. haCER1 is the human ortholog of mouse alkaline ceramidase 1 that we previously identified. haCER1 catalyzed the hydrolysis of very long-chain ceramides to generate sphingosine (SPH). This in vitro activity required Ca2+. Ectopic expression of haCER1 in HEKs decreased the levels of D-e-C-24:1-ceramide and D-e-C-24:0-ceramide but elevated the levels of both SPH and its phosphate (S1P), whereas RNA interference-mediated knockdown of haCER1 caused the opposite effects on the levels of these sphingolipids in HEKs. Similar to haCER1 overexpression, Ca-o(2+) increased the levels of SPH and S1P, and this was attenuated by haCER1 knockdown. haCER1 knockdown also inhibited the Ca-o(2+)-induced growth arrest of HEKs and the Ca-o(2+)-induced expression of keratin 1 and involucrin in HEKs. In addition, the acid ceramidase (AC) was also upregulated by Ca-o(2+); and its knockdown attenuated the Ca-o(2+)-induced expression of keratin 1 and involucrin in HEKs. These results strongly suggest that upregulation of haCER1 and AC mediates the Ca-o(2+)-induced growth arrest and differentiation of HEKs by generating SPH and S1P. C1 [Sun, Wei; Xu, Ruijuan; Hu, Wei; Jin, Junfei; Crellin, Heather A.; Obeid, Lina M.; Mao, Cungui] Med Univ S Carolina, Div Gen Internal Med, Dept Med, Charleston, SC 29425 USA. [Bielawski, Jacek; Szulc, Zdzislaw M.; Obeid, Lina M.; Mao, Cungui] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Thiers, Bruce H.; Mao, Cungui] Med Univ S Carolina, Dept Dermatol, Charleston, SC 29425 USA. [Obeid, Lina M.] Med Univ S Carolina, Ralph H Johnson Vet Adm Hosp, Charleston, SC 29425 USA. RP Mao, CG (reprint author), Med Univ S Carolina, Div Gen Internal Med, Dept Med, 114 Doughty St,Room 646,STD,POB 250779, Charleston, SC 29425 USA. EM maoc@musc.edu OI obeid, lina/0000-0002-0734-0847 FU NCI NIH HHS [R01CA104834]; NCRR NIH HHS [P20RR017677] NR 28 TC 38 Z9 38 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD FEB PY 2008 VL 128 IS 2 BP 389 EP 397 DI 10.1038/sj.jid.5701025 PG 9 WC Dermatology SC Dermatology GA 252NH UT WOS:000252452700019 PM 17713573 ER PT J AU Yonetani, S Moriyama, M Nishigori, C Osawa, M Nishikawa, SI AF Yonetani, Saori Moriyama, Mariko Nishigori, Chikako Osawa, Masatake Nishikawa, Shin-Ichi TI In vitro expansion of immature melanoblasts and their ability to repopulate melanocyte stem cells in the hair follicle SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID MOUSE EPIDERMAL MELANOCYTES; C-KIT ANTIBODY; HEMATOPOIETIC STEM; TYROSINE KINASE; GROWTH-FACTOR; DIFFERENTIATION; PROLIFERATION; CULTURE; KERATINOCYTES; PIGMENTATION AB Elucidation of the molecular mechanisms underlying stem cell regulation is of great importance both for basic biology and for clinical applications. Melanocyte stem cells (MSCs) are an excellent model in which to study the molecular basis of stem cell regulation, as the genetic alterations involved in the maintenance of the stem cells are readily identifiable by a premature hair graying phenotype. Research on MSCs has been hampered by the lack of a reliable system to assay their function. Here, by co-culturing highly purified melanoblasts (MBs) with XB2 keratinocytes, we describe an efficient culture method that allows the expansion of immature MBs in vitro. These MBs are also capable of undergoing terminal differentiation into mature melanocytes (MCs) when differentiation is induced. Furthermore, by performing a hair-follicle reconstitution assay in which expanded MBs in a mixture of epidermal and dermal cells were grafted to reconstitute a hair follicle, we demonstrate that the expanded MBs retain their capacity to become incorporated into newly developed hair follicles and repopulate the MC stem cell population there. Thus, by integrating genetic manipulations in cultured MBs in vitro, this method provides a powerful tool with which to study the molecular basis of stem cell regulation. C1 [Moriyama, Mariko; Osawa, Masatake] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Yonetani, Saori; Moriyama, Mariko; Osawa, Masatake; Nishikawa, Shin-Ichi] RIKEN Ctr Dev Biol, Lab Stem Cell Biol, Kobe, Hyogo, Japan. [Yonetani, Saori; Nishigori, Chikako] Kobe Univ, Grad Sch Med, Div Dermatol, Dept Clin Mol Med, Kobe, Hyogo 657, Japan. RP Osawa, M (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, MGH E,Bldg 149,13th St, Charlestown, MA 02129 USA. EM masatake.osawa@cbrc2.mgh.harvard.edu NR 51 TC 19 Z9 25 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD FEB PY 2008 VL 128 IS 2 BP 408 EP 420 DI 10.1038/sj.jid.5700997 PG 13 WC Dermatology SC Dermatology GA 252NH UT WOS:000252452700022 PM 17657242 ER PT J AU Duan, XB Yarmush, D Leeder, A Yarmush, ML Mitchell, RN AF Duan, Xunbao Yarmush, David Leeder, Avrum Yarmush, Martin L. Mitchell, Richard N. TI Burn-induced immunosuppression: attenuated T cell signaling independent of IFN-gamma- and nitric oxide-mediated pathways SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE immune suppression; T lymphocytes; antigen-presenting cells; costimulation ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; INJURY-INDUCED IMMUNOSUPPRESSION; THERMAL-INJURY; LYMPHOPROLIFERATIVE RESPONSES; MURINE MODEL; SUPPRESSION; INHIBITION; INTERLEUKIN-10; MACROPHAGES; ACTIVATION AB Burn injury results in immunosuppression; previous work implicated a combination of altered T lymphocyte subpopulations and the elaboration of macrophage-derived mediators. However, the conclusions were based on T cell stimulations in the setting of high-dose polyclonal mitogenic stimuli and a single kinetic time-point. In this study, splenocytes from burned animals were used to examine lymphocyte responses over a multi-day time course following saturating and subsaturating anti-CD3, as well as mixed lymphocyte response ( MLR) stimulation. Burn injury resulted in suppressed splenocyte-proliferative responses to high-dose anti-CD3 ( 2 mu g/ml) at all culture time-points ( Days 2-5); this inhibition was eliminated by removing macrophages from the splenocyte cultures, by blocking NO production, or by using splenocytes from burned animals congenitally deficient in IFN-gamma (IFN-gamma-/-). The results are consistent with immunosuppression attributable to burn-induced IFN-gamma production, which in turn, drives macrophage NO synthesis ( NOS). In MLR cultures, lymphocyte proliferation and IFN-gamma production were depressed at later time-points (Days 3-5). APC from burned animals showed no defects as MLR stimulators; T cells from burned animals showed defective, proliferative responses, regardless of the stimulator population. Removing macrophages, adding a NOS inhibitor, or using IFN-gamma(-/-) splenocytes did not restore the MLR response of burned splenocytes. T cells from burned IFN-gamma(-/-) animals also showed depressed proliferation with subsaturating levels of antiCD3 (0.1 mu g/ml); anti-CD-28 augmented the proliferative response. We conclude that burn-induced immunosuppression to authentic antigenic stimulation is related at least in part to defective CD3 signaling pathways and not simply to increased IFN-gamma or NO production. C1 [Mitchell, Richard N.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Duan, Xunbao; Yarmush, David; Leeder, Avrum; Yarmush, Martin L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med,Surg Serv, Boston, MA 02115 USA. [Duan, Xunbao; Yarmush, David; Leeder, Avrum; Yarmush, Martin L.] Shriners Hosp Children, Boston, MA USA. RP Mitchell, RN (reprint author), Brigham & Womens Hosp, Dept Pathol, 77 Ave Louis Pasteur NRB 730D, Boston, MA 02115 USA. EM rmitchell@rics.bwh.harvard.edu NR 27 TC 7 Z9 8 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD FEB 1 PY 2008 VL 83 IS 2 BP 305 EP 313 DI 10.1189/jlb.0407228 PG 9 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 257AR UT WOS:000252772100011 PM 18024716 ER PT J AU Stahl, JE Tramontano, AC Swan, JS Cohen, BJ AF Stahl, J. E. Tramontano, A. C. Swan, J. S. Cohen, B. J. TI Balancing urgency, age and quality of life in organ allocation decisions - what would you do? a survey SO JOURNAL OF MEDICAL ETHICS LA English DT Article ID COST-UTILITY ANALYSIS AB Purpose: Explore public attitudes towards the trade-offs between justice and medical outcome inherent in organ allocation decisions. Background: The US Task Force on Organ Transplantation recommended that considerations of justice, autonomy and medical outcome be part of all organ allocation decisions. Justice in this context may be modeled as a function of three types of need, related to age, clinical urgency, and quality of life. Methods: A web-based survey was conducted in which respondents were asked to choose between two hypothetical patients who differed in clinical urgency (time to death <1 year), age, pretransplant and post-transplant quality of life, and life expectancy. Results: A pool of 1600 people were notified via email about the survey; 623 (39%) responded. Respondents preferred giving organs to younger people up to an age difference of <15.4 years (SD 18) and more clinically urgent people up to a difference in urgency of <2.54 months (SD 3). Priority varied with the quality of life of the worst-off patient and the relative status of the patients. If both had worse than average quality of life, respondents preferred the better-off patient. When both had better than average quality of life, they preferred the worse-off patient. In analysis according to age versus clinical urgency, the older the patient, the more urgency needed to receive priority. In quality of life versus clinical urgency, the better the control's quality of life, the more urgency the competing patient required. The worse the patient's post-transplant outcome, the more urgency needed to receive priority. Conclusions: It appears that clinical urgency is only one of many factors influencing attitudes about allocation decisions and that respondents may invoke different principles of fairness depending the relative clinical status of patients. C1 [Stahl, J. E.; Tramontano, A. C.; Swan, J. S.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Stahl, J. E.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Swan, J. S.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Cohen, B. J.] Tufts Univ New England Med Ctr, Dept Med, Boston, MA USA. [Cohen, B. J.] Massachusetts Gen Hosp, Div Clin Decis Making Informat & Telemed, Boston, MA 02114 USA. RP Stahl, JE (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 101 Mermac St,10th Floor, Boston, MA 02114 USA. EM James@mgh-ita.org NR 15 TC 6 Z9 6 U1 0 U2 4 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-6800 J9 J MED ETHICS JI J. Med. Ethics PD FEB 1 PY 2008 VL 34 IS 2 BP 109 EP 115 DI 10.1136/jme.2006.018291 PG 7 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 257CJ UT WOS:000252776500016 PM 18234950 ER PT J AU Harley, R Sprich, S Safren, S Jacobo, M Fava, M AF Harley, Rebecca Sprich, Susan Safren, Steven Jacobo, Michelle Fava, Maurizio TI Adaptation of dialectical behavior therapy skills training group for treatment-resistant depression SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE depression; dialectical behavior therapy; group theory ID SOCIAL ADJUSTMENT; SYMPTOMS; PSYCHOTHERAPY; DISORDER; COMBINATION; REMISSION; RELAPSE AB Treatment resistant depression is common, persistent, and results in substantial functional and social impairment. This study describes the development and preliminary outcome evaluation of a dialectical behavior therapy-based skills training group to treat depressive symptoms in adult outpatients for whom antidepressant medication had not produced remission. The 16-session, once-weekly group covered the 4 dialectical behavior therapy skill sets: mindfulness, interpersonal effectiveness, emotion regulation, and distress tolerance. Twenty-four patients with ongoing depressive symptoms despite stable, adequate medication treatment for major depressive disorder were randomly assigned to either the skills group or a wait-list condition. The depressive symptoms of participants who completed the study (9 wait-list participants, 10 skills group participants) were compared using a clinician-rated Hamilton rating scale for depression and then replicated using a self-report measure Beck depression inventory. Clinician raters were blind to each participant's assigned study condition. Skills group participants showed significantly greater improvements in depressive symptoms compared with the control condition. Effect sizes were large for both measures of depression (Cohen's d=1.45 for Hamilton rating scale for depression and 1.31 for Beck depression inventory), suggesting that larger scale trials are warranted. C1 [Harley, Rebecca; Sprich, Susan; Safren, Steven; Jacobo, Michelle; Fava, Maurizio] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Harley, R (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,WAC 812, Boston, MA 02114 USA. EM rharley@partners.org NR 26 TC 48 Z9 49 U1 6 U2 21 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD FEB PY 2008 VL 196 IS 2 BP 136 EP 143 DI 10.1097/NMD.0b013e318162aa3f PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 264FO UT WOS:000253272500008 PM 18277222 ER PT J AU Grubaugh, AL Cain, GD Elhai, JD Patrick, SL Frueh, BC AF Grubaugh, Anouk L. Cain, Gregory D. Elhai, Jon D. Patrick, Sarah L. Frueh, B. Christopher TI Attitudes toward medical and mental health care delivered via Telehealth applications among rural and urban primary care patients SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE Telehealth; primary care; telepsychiatry; telepsychology; rural health; access to care; patient attitudes; posttraumatic stress disorder (PTSD). ID POSTTRAUMATIC-STRESS-DISORDER; TELEPSYCHIATRY; OUTCOMES; ISSUES AB Adequate health care services are often not available in rural and remote areas, and this problem is expected to grow worse in the near future. "Telehealth" interventions represent a strategy for addressing access to care problems. We examined and compared attitudes toward medical and mental health care delivered via telehealth applications among adult rural (n=112) and urban (n=78) primary care patients. We also examined attitudes toward telehealth applications among a subset of patients with posttraumatic stress disorder (PTSD) - a group likely in need of specialized services. Both urban and rural patients were receptive to receiving medical and psychiatric services via telehealth. There were few meaningful differences across variables between urban and rural patients, and there were no meaningful differences by PTSD status. These findings support the feasibility of telehealth applications, particularly for rural patients who may not otherwise receive needed services. C1 [Grubaugh, Anouk L.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Grubaugh, Anouk L.; Cain, Gregory D.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Elhai, Jon D.] Univ S Dakota, Disaster Mental Hlth Inst, Vermillion, SD 57069 USA. [Patrick, Sarah L.] Univ S Dakota, Ctr Rural Hlth Improvement, Sch Med, Sioux Falls, SD USA. [Patrick, Sarah L.] Univ S Dakota, Dept Family Med, Sch Med, Sioux Falls, SD USA. [Frueh, B. Christopher] Univ Hawaii, Hilo, HI 96720 USA. RP Grubaugh, AL (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, POB 250861,67 President St, Charleston, SC 29425 USA. EM grubaugh@musc.edu NR 18 TC 31 Z9 31 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD FEB PY 2008 VL 196 IS 2 BP 166 EP 170 DI 10.1097/NMD.0b013e318162aa2d PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 264FO UT WOS:000253272500013 PM 18277227 ER PT J AU Lacan, G De Salles, AAF Gorgulho, AA Krahl, SE Frighetto, L Behnke, EJ Melega, WP AF Lacan, Goran De Salles, Antonio A. F. Gorgulho, Alessandra A. Krahl, Scott E. Frighetto, Leonardo Behnke, Eric J. Melega, William P. TI Modulation of food intake following deep brain stimulation of the ventromedial hypothalamus in the vervet monkey SO JOURNAL OF NEUROSURGERY LA English DT Article DE anorexia nervosa; feeding behavior; nonhuman primate; obesity ID GLOBUS-PALLIDUS INTERNUS; PARKINSONS-DISEASE; ELECTRICAL-STIMULATION; CLUSTER HEADACHE; POSTERIOR HYPOTHALAMUS; SUBSTANTIA-NIGRA; SEXUAL-BEHAVIOR; PEDUNCULOPONTINE NUCLEUS; DOPAMINERGIC DEFICITS; LATERAL HYPOTHALAMUS AB Object. Deep brain stimulation (DBS) has become an effective therapy for an increasing number of brain disorders. Recently demonstrated DBS of the posterior hypothalamus as a safe treatment for chronic intractable cluster headaches has drawn attention to this target, which is involved in the regulation of diverse autonomic functions and feeding behavior through complex integrative mechanisms. In this study, the authors assessed the feasibility of ventromedial hypothalamus (VMH) DBS in freely moving vervet monkeys to modulate food intake as a model for the potential treatment of eating disorders. Methods. Deep brain stimulation electrodes were bilaterally implanted into the VMH of 2 adult male vervet monkeys by using the stereotactic techniques utilized in DBS in humans. Stimulators were implanted subcutaneously on the upper back, allowing ready access to program stimulation parameters while the animal remained conscious and freely moving. In anesthetized animals, intraoperatively and 6-10 weeks postsurgery, VMH DBS parameters were selected according to minimal cardiovascular and autonomic nervous system responses. Thereafter, conscious animals were subjected to 2 cycles of VMH DBS for periods of 8 and 3 days, and food intake and behavior were monitored. Animals were then killed for histological verification of probe placement. Results. During VMH DBS, total food consumption increased. The 3-month bilateral implant of electrodes and subsequent periods of high-frequency VMH stimulation did not result in significant adverse behavioral effects. Conclusions. This is the first study in which techniques of hypothalamic DBS in humans have been applied in freely moving nonhuman primates. Future studies can now be conducted to determine whether VMH DBS can change hypothalamic responsivity to endocrine signals associated with adiposity for long-term modulation of food intake. C1 [De Salles, Antonio A. F.; Gorgulho, Alessandra A.; Krahl, Scott E.; Frighetto, Leonardo; Behnke, Eric J.] Univ Calif Los Angeles, David Gaffen Sch Med, Dept Surg, Div Neurosurg, Los Angeles, CA 90024 USA. [Lacan, Goran; Melega, William P.] Univ Calif Los Angeles, David Gaffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90024 USA. [De Salles, Antonio A. F.; Krahl, Scott E.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP De Salles, AAF (reprint author), 200 UCLA Med Plaza,Suite 504, Los Angeles, CA 90095 USA. EM adesalles@mednet.ucla.edu NR 56 TC 27 Z9 28 U1 0 U2 4 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD FEB PY 2008 VL 108 IS 2 BP 336 EP 342 DI 10.3171/JNS/2008/108/2/0336 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 259JB UT WOS:000252934500020 PM 18240931 ER PT J AU Erickson, JI Daniels, AA Smith, ME Vega-Barachowitz, CD AF Erickson, Jeanette Ives Daniels, Ann A. Smith, Mary Ellin Vega-Barachowitz, Carmen D. TI Recognizing clinical excellence at all levels of practice SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article ID PROGRAM AB The authors describe the development and implementation of a program to recognize the clinical practice of clinicians from 6 different disciplines: nursing, occupational therapy, physical therapy, respiratory therapy, social work, and speech-language pathology. The program, which is grounded on skill acquisition theory, offers direct care practitioners a well-defined pathway for clinical development by recognizing and celebrating all levels of practice, from the beginning practitioner to the seasoned expert. C1 [Erickson, Jeanette Ives; Daniels, Ann A.; Smith, Mary Ellin; Vega-Barachowitz, Carmen D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Erickson, JI (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Bulfinch 230, Boston, MA 02114 USA. EM JlvesErickson@Partners.org NR 11 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD FEB PY 2008 VL 38 IS 2 BP 68 EP 75 DI 10.1097/01.NNA.0000310716.15474.be PG 8 WC Nursing SC Nursing GA 267AV UT WOS:000253481400005 PM 18300838 ER PT J AU Nuernberg, AM Boyce, PD Cavallari, JM Fang, SC Eisen, EA Christiani, DC AF Nuernberg, Amy M. Boyce, Paul D. Cavallari, Jennifer M. Fang, Shona C. Eisen, Ellen A. Christiani, David C. TI Urinary 8-isoprostane and 8-OHdG concentrations in boilermakers with welding exposure SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID OXIDATIVE DNA-DAMAGE; OCCUPATIONAL-EXPOSURE; CIGARETTE-SMOKING; LUNG-CANCER; METAL FUME; BIOMARKER; WELDERS; STRESS; ASTHMA; RISK AB Objective: To investigate the association of exposure to fine particulate matter (PM2.5) with DNA damage and oxidative stress in boilermakers exposed to welding fumes. Methods: Forty-one workers were monitored over 24 hours during which baseline, postshift, bedtime, and next morning measurements were collected. Twenty-two workers participated as controls. Results: Linear regression was used to model pairwise change in u-8-isoprostane and u-8-OHdG: pre- to postshift, preshift to bedtime, postshift to bedtime, and postshift to next morning. In the models, pre- to postshift change in 8-OHdG was statistically significant, whereas postshift to bedtime change in 8-isoprostane showed an unexpected inverse relationship with PM2.5. Conclusions: Acute welding exposure is associated with a postshift blunting of systemic inflammation in chronically exposed boilermakers, as measured by 8-isoprostane. The level of oxidative DNA damage as measured by 8-OHdG is less clear. C1 [Nuernberg, Amy M.; Boyce, Paul D.; Cavallari, Jennifer M.; Fang, Shona C.; Eisen, Ellen A.; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Nuernberg, Amy M.; Boyce, Paul D.; Christiani, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit, Boston, MA USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave,Bldg 1,Room 1407, Boston, MA 02115 USA. EM dchris@hohp.harvard.edu FU NIEHS NIH HHS [ES00002, ES009860]; NIOSH CDC HHS [T42 OH008416] NR 35 TC 20 Z9 20 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD FEB PY 2008 VL 50 IS 2 BP 182 EP 189 DI 10.1097/JOM.0b013e31815cf6cc PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 263KX UT WOS:000253217100011 PM 18301175 ER PT J AU Cunningham, LL Dodson, TB Feinberg, SE Le, AD Wohlford, ME Zuniga, JR AF Cunningham, Larry L., Jr. Dodson, Thomas B. Feinberg, Stephen E. Le, Anh D. Wohlford, Mark E. Zuniga, John R. TI 2007 research summit: At the forefront of innovation SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Editorial Material ID SURGICAL SIMULATION CASS; RISK; TRANSPLANTATION; CLEFTS C1 [Cunningham, Larry L., Jr.] Univ Kentucky, Dept Oral & Maxillofacial Surg, Lexington, KY 40506 USA. [Dodson, Thomas B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Feinberg, Stephen E.] Univ Michigan Hlth Syst, Dept Oral & Maxillofacial Surg, Ann Arbor, MI USA. [Zuniga, John R.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. RP Cunningham, LL (reprint author), Univ Kentucky, Dept Oral & Maxillofacial Surg, Lexington, KY 40506 USA. OI zuniga, john/0000-0002-8602-2811 NR 14 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD FEB PY 2008 VL 66 IS 2 BP 215 EP 222 DI 10.1016/j.joms.2007.10.003 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 256TV UT WOS:000252753700002 PM 18201599 ER PT J AU Susarla, SM Cbuang, SK Dodson, TB AF Susarla, Srinivas M. Cbuang, Sung-Kiang Dodson, Thomas B. TI Delayed versus immediate loading of implants: Survival analysis and risk factors for dental implant failure SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID INTERFACE; STRATEGY AB Purpose: The purpose of this study was to estimate 1-year survival for delayed versus immediately loaded implants and identify risk factors for implant failure. Materials and Methods: This was a retrospective cohort study, consisting of a sample of subjects who had greater than or equal to 1 Bicon dental implant (Bicon, Boston, MA) placed over a 13-year period. The primary predictor variable was method of implant loading: delayed (3 to 6 months after placement) or immediately after insertion. Secondary predictor variables were classified as demographic, anatomic, implant/abutment, and reconstructive. The outcome variable was implant failure, defined as removal of the implant, and was recorded as months of survival. Descriptive, Kaplan-Meier, and univariate Cox proportional hazards statistics were computed. Univariate associations with P <= .15 and biologically relevant variables (eg, age, gender) were included in a marginal multiple Cox regression model. In the multiple model, a P value of <= .05 was considered statistically significant. Results: The study sample consisted of 677 subjects who had 2,349 delayed-loaded dental implants and 178 patients who had 477 immediate-loaded implants. The unadjusted 1-year survival estimates for the delayed and immediate loading groups were 95.5% and 90.3%, respectively (P <.01). In the marginal multiple Cox regression model, immediate loading, current tobacco use, maxillary implants, and shorter implants were associated with failure (P <= .05). Conclusion: in this study, implants loaded immediately were 2.7 times (after adjusting) more likely to fail at I year compared with delayed-loaded implants. (c) 2008 American Association of Oral and Maxillofacial Surgeons. C1 [Susarla, Srinivas M.; Cbuang, Sung-Kiang; Dodson, Thomas B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Ctr Appl Clin Invest, Boston, MA 02114 USA. RP Susarla, SM (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Ctr Appl Clin Invest, 55 Fruit St,Warren 1201, Boston, MA 02114 USA. EM smsusarla@gmail.com OI Susarla, Srinivas/0000-0003-0155-8260 NR 16 TC 28 Z9 30 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD FEB PY 2008 VL 66 IS 2 BP 251 EP 255 DI 10.1016/j.joms.2007.09.012 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 256TV UT WOS:000252753700007 PM 18201604 ER PT J AU Casarett, D Pickard, A Bailey, FA Ritchie, C Furman, C Rosenfeld, K Shreve, S Shea, JA AF Casarett, David Pickard, Amy Bailey, F. Amos Ritchie, Christine Furman, Christian Rosenfeld, Ken Shreve, Scott Shea, Judy A. TI Important aspects of end-of-life care among veterans: Implications for measurement and quality improvement SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE end-of-life care; quality improvement; measurement; veterans ID ILL HOSPITALIZED ADULTS; FAMILY-MEMBERS; CARDIOPULMONARY-RESUSCITATION; ADVANCE DIRECTIVES; SYMPTOM ASSESSMENT; CANCER-PATIENTS; PATIENT; PREFERENCES; SATISFACTION; VALIDATION AB To identify aspects of end-of-life care in the U.S. Department of Veterans Affairs (VA) health care system that are not assessed by existing survey instruments and to identify issues that may be unique to veterans, telephone interviews using open-ended questions were conducted with family members of veterans who had received care from a VA facility in the last month of life. Responses were compared to validated end-of-life care assessment instruments in common use. The study took place in four VA medical centers and one family member per patient was invited to participate, selected from medical records using predefined eligibility criteria. These family members were asked to describe positive and negative aspects of the care the veteran received in the last month of life. Interview questions elicited perceptions of care both at VA sites and at non-VA sites. Family reports were coded and compared with items in five existing prospective and retrospective instruments that assess the quality of care that patients receive near the end of life. Interviews were completed with 66 family members and revealed 384 codes describing both positive and negative aspects of care during the last month of life. Almost half of these codes were not represented in any of the five reference instruments (n = 174; 45%). These codes, some of which are unique to the veteran population, were grouped into eight categories: information about VA benefits (n = 36; 55%), inpatient care (n = 36; 55%), access to care (n = 33; 50%), transitions in care (n = 32; 48%), care that the veteran received at the time of death (n = 31; 47%), home care (n = 26; 40%), health care facilities (n = 12; 18%), and mistakes and complications (n = 18; 27%). Although most of the reference instruments assessed some aspect of these categories, they did not fully capture the experiences described by our respondents. These data suggest that many aspects of veterans' end-of-life care that are important to their families are-not assessed by existing survey instruments. VA efforts to evaluate end-of-life care for veterans should not only measure common aspects of care (e.g., pain management), but also examine performance in areas that are more specific to the veteran population. C1 [Casarett, David] Childrens Hosp, Philadelphia, PA 19104 USA. [Casarett, David; Pickard, Amy; Shea, Judy A.] Philadelphia Vet Affairs Ctr Hlth Equity Res, Philadelphia, PA USA. [Bailey, F. Amos; Ritchie, Christine] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Furman, Christian] Louisville Vet Affairs Med Ctr, Louisville, KY USA. [Rosenfeld, Ken] Greater Los Angeles Vet Affairs Med Ctr, Los Angeles, CA USA. [Shreve, Scott] Lebanon Vet Affairs Ctr, Lebanon, PA USA. RP Casarett, D (reprint author), Childrens Hosp, 3615 Chestnut St, Philadelphia, PA 19104 USA. EM casarett@mail.med.upenn.edu NR 42 TC 18 Z9 18 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2008 VL 35 IS 2 BP 115 EP 125 DI 10.1016/j.jpainsymman.2007.03.008 PG 11 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 262YZ UT WOS:000253186100001 PM 18053680 ER PT J AU Perrin, JM Kuhlthau, K Chughtai, A Romm, D Kirschner, BS Ferry, GD Cohen, SA Gold, BD Heyman, MB Baldassano, RN Winter, HS AF Perrin, James M. Kuhlthau, Karen Chughtai, Aziz Romm, Diane Kirschner, Barbara S. Ferry, George D. Cohen, Stanley A. Gold, Benjamin D. Heyman, Melvin B. Baldassano, Robert N. Winter, Harland S. TI Measuring quality of life in pediatric patients with inflammatory bowel disease: Psychometric and clinical characteristics SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE Crohn disease; ulcerative colitis; wellbeing; disease activity; functional status ID GENERIC CORE SCALES; CROHNS-DISEASE; ADOLESCENT PATIENTS; ULCERATIVE-COLITIS; ACTIVITY INDEX; CHILDREN; HEALTH; RELIABILITY; VALIDITY; PEDSQL(TM) AB Objective: To extend development of a pediatric inflammatory bowel disease (IBD) health-related quality of life (HRQoL) measure by determining its factor structure and associations of factors with generic HRQoL measures and clinical variables. Patients and Methods: Cross-sectional survey of children and adolescents ages 8 years to 18 years and their parents attending any of 6 US IBD centers, recruited from either existing registry of age-eligible subjects or visits to participating centers, The survey included generic (Pediatric Quality of Life Inventory) and IBD-specific (Impact Questionnaire) quality of life measures, disease activity, and other clinical indicators. We carried out factor analysis of Impact responses, comparing resulting factors with results on the generic HRQoL and the clinical measures. Results: We included 220 subjects (161 with Crohn disease and 59 with ulcerative colitis). Initial confirmatory factor analysis did not support the 6 proposed Impact domains. Exploratory factor analysis indicated 4 factors with good to excellent reliability for IBD responses: general well-being and symptoms, emotional functioning, social interactions, and body image. Two items did not load well on any factor. The 4 factors correlated well with the Pediatric Quality of Life Inventory and subscales. Children, with higher disease activity scores and other indicators of clinical activity reported lower HRQoL. Conclusions: This study provides further characteristics of a HRQoL measure specific to pediatric IBD and indicates ways to score the measure based on the resulting factor structure. The measure correlates appropriately with generic HRQoL measures and clinical severity indicators. C1 [Perrin, James M.; Kuhlthau, Karen; Chughtai, Aziz; Romm, Diane; Winter, Harland S.] MassGen Hosp Children, Dept Pediat, Boston, MA USA. [Kirschner, Barbara S.] Univ Chicago, Comer Childrens Hosp, Chicago, IL 60637 USA. [Ferry, George D.] Baylor Coll Med, Houston, TX 77030 USA. [Cohen, Stanley A.; Gold, Benjamin D.] Childrens Healthcare Atlanta, Atlanta, GA USA. [Heyman, Melvin B.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Baldassano, Robert N.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. RP Perrin, JM (reprint author), 50 Staniford St,Suite 901, Boston, MA 02114 USA. EM jperrin@partners.org FU NIDDK NIH HHS [DK 062927, DK 060617, R03 DK062937-02, K24 DK060617] NR 34 TC 38 Z9 39 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD FEB PY 2008 VL 46 IS 2 BP 164 EP 171 PG 8 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 254XF UT WOS:000252620600007 PM 18223375 ER PT J AU Friedmann, AM Weinstein, HJ AF Friedmann, Alison M. Weinstein, Howard J. TI The evolving standard of care for Hodgkin lymphoma SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Editorial Material ID INVOLVED-FIELD RADIATION; DISEASE; TRIAL C1 [Friedmann, Alison M.; Weinstein, Howard J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Friedmann, AM (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Yawkey 8B, Boston, MA 02114 USA. EM afriedmann@partners.org NR 7 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD FEB PY 2008 VL 30 IS 2 BP 121 EP 123 PG 3 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 266TW UT WOS:000253460900003 PM 18376263 ER PT J AU Auriti, C Kieran, MW Deb, G Devito, R Pasquini, L Danhaive, O AF Auriti, Cinzia Kieran, Mark W. Deb, Giovanni Devito, Rita Pasquini, Luciano Danhaive, Olivier TI Remission of infantile generalized myofibromatosis after interferon alpha therapy SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE angiogenesis; vascular endothelial growth factor; basic fibroblast growth factor; visceral myofibroma; interferon alpha-2b ID ENDOTHELIAL GROWTH-FACTOR; PEDIATRIC-PATIENTS; ANTIANGIOGENIC THERAPY; SPASTIC DIPLEGIA; ANGIOGENESIS; TUMORS; RECURRENT; PATIENT; CANCER; TRIAL AB Infantile myofibromatosis is the most common fibrous tumor of infancy. Solitary or generalized myofibromas without visceral involvement usually regress within a few months. The multifocal disease infantile generalized myofibromatosis, with visceral involvement, is associated with a significant mortality due to the effect of tumors on vital organs. We report a case of infantile generalized myofibromatosis with visceral involvement, including 2 right atrium tumors. The infant expressed high circulating vascular endothelial growth factor and fibroblast growth factor-2 levels, and interferon alpha-2b was started as antiangiogenic treatment, aimed at triggering regression of the life-threatening cardiac lesions. The tumors regressed and vascular endothelial growth factor and fibroblast growth factor-2 levels were reduced after treatment discontinuation. C1 [Auriti, Cinzia; Danhaive, Olivier] Bambino Gesu Pediat Hosp, Dept Neonatol, I-00165 Rome, Italy. [Pasquini, Luciano] Bambino Gesu Pediat Hosp, Dept Cardiol, I-00165 Rome, Italy. [Deb, Giovanni] Bambino Gesu Pediat Hosp, Div Oncol, I-00165 Rome, Italy. [Devito, Rita] Bambino Gesu Pediat Hosp, Div Pathol, I-00165 Rome, Italy. [Kieran, Mark W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. RP Auriti, C (reprint author), Bambino Gesu Pediat Hosp, Dept Neonatol, 4 Piazza St Onofrio, I-00165 Rome, Italy. EM auriti@opbg.net OI Kieran, Mark/0000-0003-2184-7692 NR 25 TC 7 Z9 7 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD FEB PY 2008 VL 30 IS 2 BP 179 EP 181 PG 3 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 266TW UT WOS:000253460900015 PM 18376275 ER PT J AU Kellogg, DL Zhao, JL Wu, Y AF Kellogg, Dean L., Jr. Zhao, Joan L. Wu, Yubo TI Neuronal nitric oxide synthase control mechanisms in the cutaneous vasculature of humans in vivo SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID SYMPATHETIC VASODILATOR NERVES; VASOACTIVE-INTESTINAL-PEPTIDE; SKIN BLOOD-FLOW; HEAT-STRESS; ACTIVE VASODILATION; 7-NITRO INDAZOLE; SWEAT GLANDS; BODY; INHIBITION; ACETYLCHOLINE AB The physiological roles of constituitively expressed nitric oxide synthase (NOS) isoforms in humans, in Vivo, are unknown. Cutaneous vasodilatation during both central nervous system-mediated, thermoregulatory reflex responses to whole-body heat stress and during peripheral axon reflex-mediated, local responses to skin warming in humans depend on nitric oxide (NO) generation by constituitively expressed NOS of uncertain isoform. We hypothesized that neuronal NOS (nNOS, NOS 1) effects cutaneous vasodilatation during whole-body heat stress, but not during local skin warming. We examined the effects of the nNOS inhibitor 7-nitroindazole (7-NI) administered by intradermal microdialysis on vasodilatation induced by whole-body heat stress or local skin warming. Skin blood flow (SkBF) was monitored by laser-Doppler flowmetry (LDF). Blood pressure (MAP) was monitored and cutaneous vascular conductance calculated (CVC = LDF/MAP). In protocol 1, whole-body heat stress was induced with water-perfused suits. In protocol 2, local skin warming was induced through local warming units at LDF sites. At the end of each protocol, 56 mM sodium nitroprusside was perfused at microdialysis sites to raise SkBF to maximal levels for data normalization. 7-NI significantly attenuated CVC increases during whole-body heat stress (P < 0.05), but had no effect on CVC increases induced by local skin warming (P > 0.05). These diametrically opposite effects of 7-NI on two NO-dependent processes verify selective nNOS antagonism, thus proving that the nNOS isoform affects NO increases and hence vasodilatation during centrally mediated, reflex responses to whole-body heat stress, but not during locally mediated, axon reflex responses to local skin warming. We conclude that the constituitively expressed nNOS isoform has distinct physiological roles in cardiovascular control mechanisms in humans, in vivo. C1 [Zhao, Joan L.; Wu, Yubo] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Geriatr & Gerontol, San Antonio, TX 78229 USA. [Kellogg, Dean L., Jr.] Audie L Murphy Mem Vet Hosp Div, S Texas Vet Hlth Care Syst, Dept Vet Affairs, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78229 USA. RP Kellogg, DL (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Geriatr & Gerontol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM kelloggd@uthscsa.edu NR 60 TC 65 Z9 68 U1 2 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD FEB 1 PY 2008 VL 586 IS 3 BP 847 EP 857 DI 10.1113/jphysiol.2007.144642 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 265PL UT WOS:000253373300018 PM 18048451 ER PT J AU Pan, S Rush, J Peskind, ER Galasko, D Chung, K Quinn, J Jankovic, J Leverenz, JB Zabetian, C Pan, C Wang, Y Oh, JH Gao, J Zhang, JP Montine, T Zhang, J AF Pan, Sheng Rush, John Peskind, Elaine R. Galasko, Douglas Chung, Kathryn Quinn, Joseph Jankovic, Joseph Leverenz, James B. Zabetian, Cyrus Pan, Catherine Wang, Yan Oh, Jung Hun Gao, Jean Zhang, Jianpeng Montine, Thomas Zhang, Jing TI Application of targeted quantitative proteomics analysis in human cerebrospinal fluid using a liquid chromatography matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometer (LC MALDI TOF/TOF) platform SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE mass spectrometry; quantitative proteomics; matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometer (MALDI TOF/TOF); cerebrospinal fluid; biomarker; aging; Parkinson's disease; Alzheimer's disease ID PROTEIN BIOMARKER DISCOVERY; NOVO SEQUENCE-ANALYSIS; ION TRAP-TIME; FRAGMENTATION CHARACTERISTICS; DESORPTION IONIZATION; CONTAINING PEPTIDES; ALZHEIMER-DISEASE; HIGH-RESOLUTION; MS/MS ANALYSIS; FTICR-MS AB Targeted quantitative proteomics by mass spectrometry aims to selectively detect one or a panel of peptides/proteins in a complex sample and is particularly appealing for novel biomarker verification/validation because it does not require specific antibodies. Here, we demonstrated the application of targeted quantitative proteomics in searching, identifying, and quantifying selected peptides in human cerebrospinal spinal fluid (CSF) using a matrix-assisted laser desorption/ ionization time-of-flight tandem mass spectrometer (MALDI TOF/TOF)-based platform. The approach involved two major components: the use of isotopic-labeled synthetic peptides as references for targeted identification and quantification and a highly selective mass spectrometric analysis based on the unique characteristics of the MALDI instrument. The platform provides high confidence for targeted peptide detection in a complex system and can potentially be developed into a high-throughput system. Using the liquid chromatography (LC) MALDI TOF/TOF platform and the complementary identification strategy, we were able to selectively identify and quantify a panel of targeted peptides in the whole proteome of CSF without prior depletion of abundant proteins. The effectiveness and robustness of the approach associated with different sample complexity, sample preparation strategies, as well as mass spectrometric quantification were evaluated. Other issues related to chromatography separation and the feasibility for high-throughput analysis were also discussed. Finally, we applied targeted quantitative proteomics to analyze a subset of previously identified candidate markers in CSF samples of patients with Parkinson's disease (PD) at different stages and Alzheimer's disease (AD) along with normal controls. C1 [Pan, Sheng; Pan, Catherine; Wang, Yan; Zhang, Jianpeng; Montine, Thomas; Zhang, Jing] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Rush, John] Cell Signaling Technol Inc, Danvers, MA 01915 USA. [Peskind, Elaine R.; Leverenz, James B.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Galasko, Douglas] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Chung, Kathryn; Quinn, Joseph] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Quinn, Joseph] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. [Leverenz, James B.; Zabetian, Cyrus] Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98195 USA. [Leverenz, James B.; Zabetian, Cyrus] VA Puget Sound Hlth Care Syst, VA Northwest Network Mental Illness Res Educ & Cl, Seattle, WA 98108 USA. [Zabetian, Cyrus] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Oh, Jung Hun; Gao, Jean] Univ Texas Arlington, Dept Comp Sci & Engn, Arlington, TX 76019 USA. RP Pan, S (reprint author), Univ Washington, Dept Pathol, Seattle, WA 98195 USA. EM span@u.washington.edu; zhangj@u.washington.edu OI Zabetian, Cyrus/0000-0002-7739-4306 FU NIA NIH HHS [AG025327, AG05136, NIA AG05136]; NIEHS NIH HHS [ES012703]; NINDS NIH HHS [NS060252] NR 69 TC 45 Z9 49 U1 1 U2 17 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD FEB PY 2008 VL 7 IS 2 BP 720 EP 730 DI 10.1021/pr700630x PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 258JO UT WOS:000252864400025 PM 18186601 ER PT J AU Montezuma, SR Lessell, S Pineda, R AF Montezuma, Sandra R. Lessell, Simmons Pineda, Roberto TI Optic neuropathy after epi-LASIK SO JOURNAL OF REFRACTIVE SURGERY LA English DT Article ID IN-SITU KERATOMILEUSIS; FIBER LAYER THICKNESS; SCANNING LASER POLARIMETRY; STEROID-INDUCED ELEVATION; INTRAOCULAR-PRESSURE; TOMOGRAPHY; MIGRAINE AB PURPOSE: To report a case of optic neuropathy after epi-LASIK. METHODS: A 24-year-old man developed optic neuropathy after epi-LASIK, possibly related to the barotrauma created by the suction ring. Optic neuropathy and steroid-induced ocular hypertension were diagnosed. Prednisolone drops were discontinued and timolol was started. RESULTS: After 2 weeks, his symptoms improved and the pain resolved. CONCLUSIONS: Optic neuropathy is a potentially vision-threatening complication of epi-LASIK. Barotrauma from a transient increase in intraocular pressure created by the suction ring can be an important factor in this entity. C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Med Sch, Dept Ophthalmol, Boston, MA USA. RP Montezuma, SR (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM Sandra_Montezuma@meei.harvard.edu NR 25 TC 4 Z9 4 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-597X J9 J REFRACT SURG JI J. Refractive Surg. PD FEB PY 2008 VL 24 IS 2 BP 204 EP 208 PG 5 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 263HO UT WOS:000253208400016 PM 18297947 ER PT J AU Logemanin, JA Gensler, G Robbins, J Lindblad, AS Brandt, D Hind, JA Kosek, S Dikernan, K Kazandiian, M Grarnigna, GD Lundy, D McGarvey-Toler, S Gardner, PJM AF Logemanin, Jeri A. Gensler, Gary Robbins, JoAnne Lindblad, Anne S. Brandt, Diane Hind, Jacqueline A. Kosek, Steven Dikernan, Karen Kazandiian, Marto Grarnigna, Gary D. Lundy, Donna McGarvey-Toler, Susan Gardner, Patricia J. Miller TI A randomized study of three interventions for aspiration of thin liquids in patients with dementia or Parkinson's disease SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article DE dementia; Parkinson's disease; aspiration; thickened liquids; posture ID SPEECH-LANGUAGE PATHOLOGIST; ALZHEIMERS-DISEASE; THICKENED LIQUIDS; PRACTICE PATTERNS; HEAD ROTATION; DYSPHAGIA; SWALLOW; MANAGEMENT; MANEUVERS; SEVERITY AB Purpose: This study was designed to identify which of 3 treatments for aspiration on thin liquids-chin-down posture, nectar-thickened liquids, or honey-thickened liquids-results in the most successful immediate elimination of aspiration on thin liquids during the videofluorographic swallow study in patients with dementia and/or Parkinson's disease. Method: This randomized clinical trial included 711 patients ages 50 to 95 years who aspirated on thin liquids as assessed videofluorographically. All patients received all 3 interventions in a randomly assigned order during the videofluorographic swallow study. Results: immediate elimination of aspiration on thin liquids occurred most often with honey-thickened liquids for patients in each diagnostic category, followed by nectar-thickened liquids and chin-down posture. Patients with most severe dementia exhibited least effectiveness on all interventions. Patient preference was best for chin-down posture followed closely by nectar-thickened liquids. Conclusion: To identify best short-term intervention to prevent aspiration of thin liquid in patients with dementia and/or Parkinson's disease, a videofluorographic swallow assessment is needed. Evidence-based practice requires taking patient preference into account when designing a dysphagic patient's management plan. The longer-term impact of short-term prevention of aspiration requires further study. C1 [Logemanin, Jeri A.] Northwestern Univ, Dept Commun Sci & Disorders, Evanston, IL 60208 USA. [Gensler, Gary; Lindblad, Anne S.; Brandt, Diane] EMMES Corp, Rockville, MD USA. [Robbins, JoAnne] Univ Wisconsin, Madison, WI USA. [Hind, Jacqueline A.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. [Kosek, Steven] Minneapolis VA Med Ctr, Minneapolis, MN USA. [Dikernan, Karen; Kazandiian, Marto] New York Hosp Med Ctr, Flushing, NY USA. [Grarnigna, Gary D.] VA Boston Healthcare Syst, Roxbury, MA USA. [Lundy, Donna] Univ Miami, Med Ctr, Miami, FL 33152 USA. [McGarvey-Toler, Susan] Richard L Roudebush VA Med Ctr, Indianapolis, IN USA. [Gardner, Patricia J. Miller] Amer Speech Language Hearing Assoc, Clin Trials Res Grp, Rockville, MD USA. RP Logemanin, JA (reprint author), Northwestern Univ, Dept Commun Sci & Disorders, 2240 Campus Dr,3-358, Evanston, IL 60208 USA. EM j-logemann@northwestem.edu FU NCRR NIH HHS [M01 RR003186, M01 RR003186-190295]; NIDCD NIH HHS [U01 DC003206, U01 DC003206-07] NR 38 TC 104 Z9 109 U1 2 U2 18 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1092-4388 J9 J SPEECH LANG HEAR R JI J. Speech Lang. Hear. Res. PD FEB PY 2008 VL 51 IS 1 BP 173 EP 183 DI 10.1044/1092-4388(2008/013) PG 11 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 265PN UT WOS:000253373500013 PM 18230864 ER PT J AU Raymer, AM Beeson, P Holland, A Kendall, D Maher, LM Martin, N Murray, L Rose, M Thompson, CK Turkstra, L Altmann, L Boyle, M Conway, T Hula, W Kearns, K Rapp, B Simmons-Mackie, N Rothi, LIG AF Raymer, Anastasia M. Beeson, Pelogie Holland, Audrey Kendall, Diane Maher, Lynn M. Martin, Nadine Murray, Laura Rose, Miranda Thompson, Cynthia K. Turkstra, Lyn Altmann, Lori Boyle, Mary Conway, Tim Hula, William Kearns, Kevin Rapp, Brenda Simmons-Mackie, Nina Rothi, Leslie J. Gonzalez TI Translational research in aphasia: from neuroscience to neurorehabilitation SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Review DE aphasia; rehabilitation; plasticity ID INDUCED MOVEMENT THERAPY; LEXICAL ACCESS; POSTSTROKE APHASIA; SPEECH PRODUCTION; BRAIN PLASTICITY; CORTICAL REORGANIZATION; LANGUAGE TREATMENT; NONFLUENT APHASIA; RIGHT-HEMISPHERE; FLUENT APHASIA AB Purpose: In this article, the authors encapsulate discussions of the Language Work Group that took place as part of the Workshop in Plasticity/NeuroRehabilitation Research at the University of Florida in April 2005. Method: In this narrative review, they define neuroplasticity and review studies that demonstrate neural changes associated with aphasia recovery and treatment. The authors then summarize basic science evidence from animals, human cognition, and computational neuroscience that is relevant to aphasia treatment research. They then turn to the aphasia treatment literature in which evidence exists to support several of the neuroscience principles. Conclusion: Despite the extant aphasia treatment literature, many questions remain regarding how neuroscience principles can be manipulated to maximize aphasia recovery and treatment. They propose a framework, incorporating some of these principles, that may serve as a potential roadmap for future investigations of aphasia treatment and recovery. In addition to translational investigations from basic to clinical science, the authors propose several areas in which translation can occur from clinical to basic science to contribute to the fundamental knowledge base of neurorehabilitation. This article is intended to reinvigorate interest in delineating the factors influencing successful recovery from aphasia through basic, translational, and clinical research. C1 [Raymer, Anastasia M.] Old Dominion Univ, Norfolk, VA 23529 USA. [Beeson, Pelogie; Holland, Audrey] Univ Arizona, Tucson, AZ USA. [Kendall, Diane; Rothi, Leslie J. Gonzalez] VA Brain Rehabil Res Ctr, Gainesville, FL USA. [Kendall, Diane; Altmann, Lori; Conway, Tim; Rothi, Leslie J. Gonzalez] Univ Florida, Gainesville, FL USA. [Maher, Lynn M.] DeBakey VA Med Ctr, Houston, TX USA. [Turkstra, Lyn] Baylor Coll Med, Houston, TX 77030 USA. [Martin, Nadine] Temple Univ, Philadelphia, PA 19122 USA. [Murray, Laura] Indiana Univ, Bloomington, IN 47405 USA. [Rose, Miranda] La Trobe Univ, Melbourne, Vic, Australia. [Thompson, Cynthia K.] Northwestern Univ, Chicago, IL 60611 USA. [Turkstra, Lyn] Univ Wisconsin, Madison, WI USA. RP Raymer, AM (reprint author), Old Dominion Univ, 110 Child Study Ctr, Norfolk, VA 23529 USA. EM sraymer@odu.edu RI Maher, Lynn/L-7074-2015; Rose, Miranda/P-7995-2015 OI Rose, Miranda/0000-0002-8892-0965 NR 132 TC 59 Z9 64 U1 7 U2 38 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1092-4388 J9 J SPEECH LANG HEAR R JI J. Speech Lang. Hear. Res. PD FEB PY 2008 VL 51 IS 1 BP S259 EP S275 DI 10.1044/1092-4388(2008/020) PG 17 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 265PN UT WOS:000253373500020 PM 18230850 ER PT J AU Eddy, KT Doyle, AC Hoste, RR Herzog, DB Le Grange, D AF Eddy, Kamryn T. Doyle, Angela Celio Hoste, Renee Rienecke Herzog, David B. Le Grange, Daniel TI Eating disorder not otherwise specified in adolescents SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE eating disorder not otherwise specified; eating disorder; classification; DSM-V ID BECK DEPRESSION INVENTORY; ANOREXIA-NERVOSA; BULIMIA-NERVOSA; DSM-V; CHILDREN; OVERWEIGHT; VALIDITY; EDNOS; NOS AB Objective: To examine the frequency, type, and clinical severity of eating disorder not otherwise specified (EDNOS) in adolescents seeking treatment through an outpatient eating disorders service. Method: Two hundred eighty-one consecutive referrals to an eating disorders program were assessed using the Eating Disorder Examination (EDE) and self-report measures of depression and self-esteem. Results: The majority of adolescents presented with EDNOS (59.1%; n = 166) relative to anorexia nervosa (AN; 20.3%; n = 57) and bulimia nervosa (BN; 20.6%; n = 58). Most EDNOS youths could be described as subthreshold AN (SAN; 27.7%; n = 46), subthreshold BN (SBN; 19.9%; n = 33), EDNOS purging (27.7%; n = 46), or EDNOS bingeing (6.0%; n = 10); yet 31 (18.7%) could not be categorized as such (EDNOS "other"). Overall differences in eating disorder pathology, depressive symptoms, and self-esteem emerged between the EDNOS types, wherein adolescents with EDNOS bulimic variants (SBN, EDNOS purging, and EDNOS bingeing) had more pathology than youths with SAN or EDNOS "other." There were no differences in these variables between AN and SAN; in contrast, compared with BN, youths with EDNOS bulimic variants reported lower EDE scores and higher self-esteem, although there were no between-group differences in depression. Conclusions: As in adults with eating disorders, EDNOS predominates and is heterogeneous with regard to eating disorder pathology and associated features in an adolescent clinical sample. Lack of differences between AN and SAN suggests that the strict criteria for AN could be relaxed; differences between BN and EDNOS bulimic variants do not support their combination. C1 [Eddy, Kamryn T.; Herzog, David B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Eddy, Kamryn T.; Herzog, David B.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Doyle, Angela Celio; Hoste, Renee Rienecke; Le Grange, Daniel] Univ Chicago, Chicago, IL 60637 USA. RP Eddy, KT (reprint author), Massachusetts Gen Hosp, 2 Longfellow Pl,Suite 200, Boston, MA 02114 USA. EM kamryn@gmail.com RI Le Grange, Daniel/A-2649-2011 FU NIMH NIH HHS [MH 070620]; OMHHE CDC HHS [K23 MN 01923] NR 37 TC 82 Z9 86 U1 4 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD FEB PY 2008 VL 47 IS 2 BP 156 EP 164 DI 10.1097/chi.0b013e31815cd9cf PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 253MR UT WOS:000252522800009 PM 18176335 ER PT J AU Armstrong, A Idriss, S Kimball, A Bernhard, J AF Armstrong, April Idriss, Shereene Kimball, Alexandra Bernhard, Jeffrey TI Fate of manuscripts rejected by the journal of the American Academy of Dermatology SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Academy-of-Dermatology CY FEB 01-05, 2008 CL San Antonio, TX SP Amer Acad Dermatol C1 [Armstrong, April; Kimball, Alexandra] Harvard Univ, Massachusetts Gen Hosp, Dept Dermatol, Cambridge, MA 02138 USA. [Idriss, Shereene] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bernhard, Jeffrey] Univ Massachusetts, Sch Med, Amherst, MA 01003 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD FEB PY 2008 VL 58 IS 2 SU 2 BP AB74 EP AB74 PG 1 WC Dermatology SC Dermatology GA 256AT UT WOS:000252700800295 ER PT J AU Boker, A Rolz-Cruz, G Cumbie, B Kimball, A AF Boker, Andreas Rolz-Cruz, Gabriella Cumbie, Bill Kimball, Alexandra TI A single-center, prospective, open-label, pilot study of the safety, local tolerability, and efficacy of ultraviolet-C (UVC) phototherapy for the treatment of great toenail onychomycosis SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Academy-of-Dermatology CY FEB 01-05, 2008 CL San Antonio, TX SP Amer Acad Dermatol C1 [Boker, Andreas] Harvard Univ, Brigham & Womens Hosp, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. [Rolz-Cruz, Gabriella] Harvard Univ, Brigham & Womens Hosp, Massachusetts Gen Hosp, Sch Med,Dept Dermatol, Cambridge, MA 02138 USA. [Cumbie, Bill] Keraderm, LLC, Hampton, VA USA. [Kimball, Alexandra] Harvard Univ, Brigham & Womens Hosp, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 3 Z9 3 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD FEB PY 2008 VL 58 IS 2 SU 2 BP AB82 EP AB82 PG 1 WC Dermatology SC Dermatology GA 256AT UT WOS:000252700800327 ER PT J AU Kazanis, M Kimball, A Armstrong, A AF Kazanis, Maryanne Kimball, Alexandra Armstrong, April TI Understanding incentives for research subjects in clinical trials SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Academy-of-Dermatology CY FEB 01-05, 2008 CL San Antonio, TX SP Amer Acad Dermatol C1 [Kazanis, Maryanne; Kimball, Alexandra; Armstrong, April] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD FEB PY 2008 VL 58 IS 2 SU 2 BP AB78 EP AB78 PG 1 WC Dermatology SC Dermatology GA 256AT UT WOS:000252700800310 ER PT J AU Tierney, E Kimball, AB AF Tierney, Emily Kimball, Alexa Boer TI Dermatology workforce shortage: Geographic maldistribution of dermatologists and entry of dermatology providers to fill gaps SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Academy-of-Dermatology CY FEB 01-05, 2008 CL San Antonio, TX SP Amer Acad Dermatol C1 [Tierney, Emily; Kimball, Alexa Boer] Massachusetts Gen Hosp, Brigham & Womens Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD FEB PY 2008 VL 58 IS 2 SU 2 BP AB77 EP AB77 PG 1 WC Dermatology SC Dermatology GA 256AT UT WOS:000252700800305 ER PT J AU Bilimoria, KY Stewart, AK Palis, BE Bentrern, DJ Talamonti, MS Ko, CY AF Bilimoria, Karl Y. Stewart, Andrew K. Palis, Bryan E. Bentrern, David J. Talamonti, Mark S. Ko, Clifford Y. TI Adequacy and importance of lymph node evaluation for colon cancer in the elderly SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID COLORECTAL-CANCER; MINIMUM NUMBER; STAGE-III; ADJUVANT CHEMOTHERAPY; HOSPITAL VOLUME; SURVIVAL; SURGERY; RESECTION; RECOMMENDATIONS; PROGNOSIS AB BACKGROUND: Studies have demonstrated improved survival when 12 or more nodes are examined for colon cancer. The elderly comprise a major proportion of patients with colon cancer, but it is unknown if examination of 12 or more nodes is appropriate for older patients. Our objective was to assess differences in lymph node evaluation by age and to determine whether adequate nodal evaluation (12 or more nodes) is associated with improved survival in the elderly. STUDY DESIGN: From the National Cancer Data Base (1998 to 2004), we identified 142,009 N0M0 patients who underwent colectomy for adenocarcinoma. Logistic regression was used to determine whether age is associated with adequate nodal examination. Multivariable modeling stratified by age was used to determine whether evaluation of 12 or more nodes is associated with improved survival. RESULTS: The median number of nodes examined was similar with increasing age (less than 67 years: 11 nodes; 67 to 78 years: 10 nodes; greater than 78 years: 10 nodes). Patients older than 78 years underwent evaluation of 12 or more nodes less frequently than patients less than 67 years old: 47.7% versus 41.4% (p < 0.0001). When adjusted for patient, tumor, treatment, and hospital characteristics, patients greater than 78 years were less likely to have 12 or more nodes examined (odds ratio 0.68, 95% CI 0.65 to 0.70, p < 0.0001). Regardless of age, patients who had 12 or more nodes examined had better survival than those with less than 12 nodes examined (p < 0.0001). CONCLUSIONS: The elderly account for nearly half of patients with colon cancer. Older patients undergo inadequate lymph node evaluation more frequently than younger patients do. Improving lymph node evaluation will result in more accurate pathologic staging for the elderly. C1 [Bilimoria, Karl Y.; Bentrern, David J.; Talamonti, Mark S.] NW Mem Hosp, Dept Surg, Feinberg Sch Med, Chicago, IL 60611 USA. [Bilimoria, Karl Y.; Stewart, Andrew K.; Palis, Bryan E.; Ko, Clifford Y.] Amer Coll Surg, Canc Program, Chicago, IL USA. [Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Bilimoria, KY (reprint author), NW Mem Hosp, Dept Surg, Feinberg Sch Med, 251 E Huron St,Galter 3-150, Chicago, IL 60611 USA. NR 30 TC 45 Z9 45 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD FEB PY 2008 VL 206 IS 2 BP 247 EP 254 DI 10.1016/j.jamcollsurg.2007.07.044 PG 8 WC Surgery SC Surgery GA 257UA UT WOS:000252822900006 PM 18222376 ER PT J AU McCoy, LC Wehler, CJ Rich, SE Garcia, RI Miller, DR Jones, JA AF McCoy, Linda C. Wehler, Carolyn J. Rich, Sharron E. Garcia, Raul I. Miller, Donald R. Jones, Judith A. TI Adverse events associated with chlorhexidine use - Results from the department of veterans affairs dental diabetes study SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article DE chlorhexidine gluconate; mouthrinse; periodontal disease; diabetes ID DIGLUCONATE; GINGIVITIS; GLUCONATE; EFFICACY; 6-MONTH; DESIGN AB Background. The authors report adverse events, (AEs) related to the use of chlorhexidine gluconate mouthrinse in a clinical trial of the efficacy of periodontal treatment in older adults with diabetes. Methods. Participants were U.S. veterans with uncontrolled diabetes (hemoglobin A(1c) value >= 8.5 percent) and periodontal disease. Treatment included periodontal scaling, 0.12 percent chlorhexidine lavage during ultrasonic scaling and use of chlorhexidine mouthrinse at home. Results. Forty-four (31 percent) of 140 subjects reported having AEs. Most common were taste changes and tooth. staining, sore mouth and/or throat, tongue irritation and wheezing/shortness of breath; the latter was reported more commonly before chlorhexidine use than after. Only body mass index greater than 30 was significantly related to AEs. Conclusions. AEs are common among subjects using chlorhexidine mouthrinse: Most AEs (taste change and staining) were resolved easily by subjects' discontinuing mouthrinse use and receiving dental prophylaxis. No serious AEs were reported. Clinical Implications. Clinicians should advise patients using. chlorhexidine mouthrinse of possible side effects If necessary, patients, should discontinue mouthrinse use and obtain medical care. Careful monitoring of AEs in patients using chlorhexidine is warranted. C1 [McCoy, Linda C.] Edith Nourse Rogers Mem Vet Adm Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA. [Wehler, Carolyn J.; Rich, Sharron E.; Jones, Judith A.] Boston Univ, Grad Sch Dent Med, Dept Gen Dent, Boston, MA 02215 USA. [Garcia, Raul I.] Boston Univ, Grad Sch Dent Med, Dept Hlth Policy & Hlth Serv Res, Boston, MA 02215 USA. [Garcia, Raul I.] VA Boston Healthcare Syst, Boston, MA USA. [Miller, Donald R.] Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Miller, Donald R.] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. RP McCoy, LC (reprint author), Edith Nourse Rogers Mem Vet Adm Hosp, Ctr Hlth Qual Outcomes & Econ Res, 200 Springs Rd 152, Bedford, MA 01730 USA. EM mccoyl@bu.edu FU NIDCR NIH HHS [K24 DE 00419, K24 DE 018211] NR 32 TC 20 Z9 23 U1 0 U2 3 PU AMER DENTAL ASSOC PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD FEB PY 2008 VL 139 IS 2 BP 178 EP 183 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 263GZ UT WOS:000253206900017 PM 18245686 ER PT J AU Gray, SL Anderson, ML Crane, PK Breitner, JCS McCormick, W Bowen, JD Teri, L Larson, E AF Gray, Shelly L. Anderson, Melissa L. Crane, Paul K. Breitner, John C. S. McCormick, Wayne Bowen, James D. Teri, Linda Larson, Eric TI Antioxidant vitamin supplement use and risk of dementia or Alzheimer's disease in older adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT Alzheimers-Associations International Conference on Prevention of Dementia CY JUN 09-12, 2007 CL Washington, DC SP Alzheimers Assoc DE Alzheimer's disease; antioxidant supplements; pharmacoepidemiology ID DIETARY-INTAKE; COGNITIVE FUNCTION; APOLIPOPROTEIN-E; CONTROLLED-TRIAL; METAANALYSIS; TOCOPHEROL; MORTALITY AB OBJECTIVES: To examine whether use of vitamins C or E alone or in combination was associated with lower incidence of dementia or Alzheimer's disease (AD). DESIGN: Prospective cohort study. SETTING: Group Health Cooperative, Seattle, Washington. PARTICIPANTS: Two thousand nine hundred sixty-nine participants aged 65 and older without cognitive impairment at baseline in the Adult Changes in Thought study. MEASUREMENTS: Participants were followed biennially to identify incident dementia and AD diagnosed according to standard criteria. Participants were considered to be users of vitamins C or E if they self-reported use for at least 1 week during the month before baseline. RESULTS: Over a mean follow-up +/- standard deviation of 5.5 +/- 2.7 years, 405 subjects developed dementia (289 developed AD). The use of vitamin E was not associated with dementia (adjusted hazard ratio (HR)=0.98, 95% confidence interval (CI)=0.77-1.25) or with AD (HR=1.04; 95% CI=0.78-1.39). No association was found between vitamin C alone (dementia: HR=0.90, 95% CI=0.71-1.13; AD: HR=0.95, 95% CI=0.72-1.25) or concurrent use of vitamin C and E (dementia: HR=0.93, 95% CI=0.72-1.20; AD: HR=1.00, 95% CI=0.73-1.35) and either outcome. CONCLUSION: In this study, the use of supplemental vitamin E and C, alone or in combination, did not reduce risk of AD or overall dementia over 5.5 years of follow-up. C1 [Gray, Shelly L.] Univ Washington, Sch Pharm, Seattle, WA 98195 USA. [Crane, Paul K.; Breitner, John C. S.] Univ Washington, Div Gen Internal Med, Seattle, WA 98195 USA. [McCormick, Wayne] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. [Bowen, James D.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Teri, Linda] Univ Washington, Dept Psychosocial & Community Hlth, Seattle, WA 98195 USA. [Teri, Linda] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Teri, Linda] Univ Washington, Dept Psychol, Seattle, WA 98195 USA. [Anderson, Melissa L.; Larson, Eric] Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. [Breitner, John C. S.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Gray, SL (reprint author), Univ Washington, Sch Pharm, Box 357630, Seattle, WA 98195 USA. EM slgray@u.washington.edu RI Crane, Paul/C-8623-2014; OI Crane, Paul/0000-0003-4278-7465 FU PHS HHS [AL 06781] NR 24 TC 49 Z9 53 U1 0 U2 11 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD FEB PY 2008 VL 56 IS 2 BP 291 EP 295 DI 10.1111/j.1532-5415.2007.01531.x PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 256FO UT WOS:000252713300014 PM 18047492 ER PT J AU Liu, F Brezniceanu, ML Wei, CC Chenier, I Sachetelli, S Zhang, SL Filep, JG Ingelfinger, JR Chan, JSD AF Liu, Fang Brezniceanu, Marie-Luise Wei, Chih-Chang Chenier, Isabelle Sachetelli, Sebastien Zhang, Shao-Ling Filep, Janos G. Ingelfinger, Julie R. Chan, John S. D. TI Overexpression of angiotensinogen increases tubular apoptosis in diabetes SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GLOMERULOTUBULAR JUNCTION ABNORMALITIES; RENAL PROXIMAL TUBULE; II INDUCES APOPTOSIS; GENE-EXPRESSION; TRANSGENIC MICE; RAT-KIDNEY; ATUBULAR GLOMERULI; EPITHELIAL-CELLS; BLOOD-PRESSURE; HIGH GLUCOSE AB The intrarenal renin-angiotensin system (RAS) plays an important role in the progression of diabetic nephropathy. We have previously reported that mice overexpressing angiotensinogen in renal proximal tubular cells (RPTC) develop hypertension, albuminuria, and renal injury. Here, we investigated whether activation of the intrarenal RAS contributes to apoptosis of RPTC in diabetes. Induction of diabetes with streptozotocin in these transgenic mice led to significant increases in BP, albuminuria, RPTC apoptosis, and proapoptotic gene expression compared with diabetic nontransgenic littermates. Insulin and/or RAS blockers markedly attenuated these changes. Hydralazine prevented hypertension but not albuminuria, RPTC apoptosis, or proapoptotic gene expression. In vitro, high-glucose medium significantly increased apoptosis and caspase-3 activity in rat immortalized RPTC overexpressing angiotensinogen compared with control cells, and these changes were prevented by insulin and/or RAS blockers. In conclusion, intrarenal RAS activation and high glucose may act in concert to increase tubular apoptosis in diabetes, independent of systemic hypertension. C1 [Liu, Fang; Brezniceanu, Marie-Luise; Wei, Chih-Chang; Chenier, Isabelle; Sachetelli, Sebastien; Zhang, Shao-Ling; Chan, John S. D.] Univ Montreal, CHUM, Hotel Dieu, Res Ctr Pavillon Masson, Montreal, PQ H2W 1T8, Canada. [Filep, Janos G.] Univ Montreal, Hop Maison Neuve Rosemont, Res Ctr, Montreal, PQ, Canada. [Ingelfinger, Julie R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Nephrol Unit, Boston, MA USA. RP Chan, JSD (reprint author), Univ Montreal, CHUM, Hotel Dieu, Res Ctr Pavillon Masson, 3500 St Urban St, Montreal, PQ H2W 1T8, Canada. EM john.chan@umontreal.ca FU NHLBI NIH HHS [HL-48455] NR 48 TC 45 Z9 50 U1 0 U2 10 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD FEB PY 2008 VL 19 IS 2 BP 269 EP 280 DI 10.1681/ASN.2007010074 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 265DW UT WOS:000253340300014 PM 18057217 ER PT J AU Boffa, DJ Allen, MS Grab, JD Gaissert, HA Harpole, DH Wright, CD AF Boffa, Daniel J. Allen, Mark S. Grab, Joshua D. Gaissert, Henning A. Harpole, David H. Wright, Cameron D. TI Data from the society of thoracic surgeons general thoracic surgery database: The surgical management of primary lung tumors SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 87th Annual Meeting of the American-Association-for-Thoracic-Surgery CY MAY 05-09, 2007 CL Washington, DC SP Amer Assoc Thorac Surg ID CANCER SURGERY; UNITED-STATES; MORTALITY; MEDIASTINOSCOPY; COMPLICATIONS; EXPERIENCE; MORBIDITY; OUTCOMES; VOLUME AB Objective: Our objective was to investigate the surgical management of primary lung cancer by board-certified thoracic surgeons participating in the general thoracic surgery portion of The Society of Thoracic Surgeons database. Methods: We identified all pulmonary resections recorded in the general thoracic surgery prospective database from 1999 to 2006. Among the 49,029 recorded operations, 9033 pulmonary resections for primary lung cancer were analyzed. Results: There were 4539 men and 4494 women with a median age of 67 years (range 20-94 years). Comorbidity affected 79% of patients and included hypertension in 66%, coronary artery disease in 26%, body mass index of 30 kg/m(2) or more in 25.7%, and diabetes mellitus in 13%. The type of resection was a wedge resection in 1649 (18.1%), segmentectomy in 394 (4.4%), lobectomy in 6042 (67%), bilobectomy in 357 (4.0%), and pneumonectomy in 591 (6.5%). Mediastinal lymph nodes were evaluated in 5879 (65%) patients; via mediastinoscopy in 1928 (21%), nodal dissection 3722 (41%), nodal sampling in 1124 (12.4%), and nodal biopsy in 729 (8%). Median length of stay was 5 days (range 0-277 days). Operative mortality was 2.5% (179 patients). One or more postoperative events occurred in 2911 (32%) patients. Conclusion: The patients in the general thoracic surgery database are elderly, gender balanced, and afflicted by multiple comorbid conditions. Mediastinal lymph node evaluation is common and the pneumonectomy rate is low. The length of stay is short and operative mortality is low, despite frequent postoperative events. C1 [Allen, Mark S.] Mayo Clin, Div Gen Thorac Surg, Sch Med, Rochester, MN 55905 USA. [Boffa, Daniel J.] Cleveland Clin, Dept Thorac & Cardiovasc Surg, Cleveland, OH 44106 USA. [Grab, Joshua D.] Duke Univ, Duke Clin Res Inst, Durham, NC USA. [Harpole, David H.] Massachusetts Gen Hosp, Dept Gen Thorac Surg, Boston, MA 02114 USA. [Harpole, David H.] Duke Univ, Dept Gen Thorac Surg, Durham, NC USA. RP Allen, MS (reprint author), Mayo Clin, Div Gen Thorac Surg, Sch Med, 200 1st St,SW, Rochester, MN 55905 USA. EM allen.mark@mayo.edu NR 20 TC 229 Z9 239 U1 0 U2 8 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD FEB PY 2008 VL 135 IS 2 BP 247 EP 254 DI 10.1016/j.jtcvs.2007.07.060 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 257WU UT WOS:000252830400004 PM 18242243 ER PT J AU Krysan, K Lee, JM Dohadwala, M Gardner, BK Reckamp, KL Garon, E John, MS Sharma, S Dubinett, SM AF Krysan, Kostyantyn Lee, Jay M. Dohadwala, Mariam Gardner, Brian K. Reckamp, Karen L. Garon, Edward John, Maie St. Sharma, Sherven Dubinett, Steven M. TI Inflammation, epithelial to mesenchymal transition, and epidermal growth factor receptor tyrosine kinase inhibitor resistance SO JOURNAL OF THORACIC ONCOLOGY LA English DT Editorial Material DE EGFR TK inhibitor; G-protein coupled receptors; inflammation; cyclooxygenase-2; PGE2; epithelial to mesenchymal transition; drug resistance; NSCLC ID CELL LUNG-CANCER; PROTEIN-COUPLED RECEPTORS; SMOOTH-MUSCLE-CELLS; CYCLOOXYGENASE-2-DEPENDENT INVASION; TUMOR PROGRESSION; EGF RECEPTOR; E-CADHERIN; GEFITINIB; TRANSACTIVATION; SENSITIVITY AB Inflammation is an important contributor to lung tumor development and progression. In addition, inflammatory signaling may promote epithelial to mesenchymal transition, development of aggressive metastatic tumor phenotypes, and play a role in resistance to targeted therapies. New insights in inflammatory signaling have led to the evaluation of combination therapies that target these specific pathways. In addition to developing the optimal combination of targeted agents, biomarker-based selection of patients who will likely benefit will be critical to the success of this strategy. Here we focus on the potential contribution of inflammatory mediator-induced resistance to epidermal growth factor receptor tyrosine kinase inhibitors. C1 [Krysan, Kostyantyn; Dohadwala, Mariam; Gardner, Brian K.; Garon, Edward] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Lee, Jay M.; John, Maie St.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Lee, Jay M.; Dubinett, Steven M.] Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Lung Canc Res Program, Los Angeles, CA 90095 USA. [Reckamp, Karen L.] City Hope Natl Med Ctr, Beckman Res Inst, Dept Med Oncol & Therapeut Res, Duarte, CA 91010 USA. [Sharma, Sherven; Dubinett, Steven M.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Dubinett, Steven M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol, Los Angeles, CA 90095 USA. RP Krysan, K (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. EM KKrysan@mednet.ucla.edu OI Reckamp, Karen/0000-0002-9213-0325 FU NCI NIH HHS [5 K12 CA076095, K23 CA131577]; PHS HHS [P50 90388] NR 44 TC 26 Z9 27 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD FEB PY 2008 VL 3 IS 2 BP 107 EP 110 DI 10.1097/JTO.0b013e3181630ece PG 4 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 264MS UT WOS:000253292300003 PM 18303428 ER PT J AU Garcia, DA Regan, S Henault, LE Upadhyay, A Baker, J Othman, M Hylek, EM AF Garcia, David A. Regan, Susan Henault, Lori E. Upadhyay, Ashish Baker, Jaclyn Othman, Mohamed Hylek, Elaine M. TI Risk of thromboembolism with short-term interruption of warfarin SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Meeting Abstract C1 [Garcia, David A.; Othman, Mohamed] Univ New Mexico, Hlth Sci Ctr, Dept Internal Med, Albuquerque, NM 87131 USA. [Regan, Susan] Massachusetts Gen Hosp, Dept Med, Gen Med Unit, Boston, MA 02114 USA. [Henault, Lori E.; Baker, Jaclyn; Hylek, Elaine M.] Boston Univ, Sch Med, Dept Med, Res Unit,Sect Gen Internal Med, Boston, MA 02118 USA. [Upadhyay, Ashish] Tufts Univ, Sch Med, Dept Med, Caritas St Elizabeths Med Ctr, Boston, MA 02111 USA. OI Regan, Susan/0000-0003-0940-2017 NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD FEB PY 2008 VL 25 IS 1 BP 116 EP 116 DI 10.1007/s11239-007-0124-7 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 248QF UT WOS:000252168600044 ER PT J AU Kudsk, KA Hermsen, JL Genton, L Faucher, L Gomez, FE AF Kudsk, Kenneth A. Hermsen, Joshua L. Genton, Laurence Faucher, Lee Gomez, F. Enrique TI Injury stimulates an innate respiratory immunoglobulin A immune response in humans SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article; Proceedings Paper CT 66th Annual Meeting of the American-Association-for-the-Surgery-of-Trauma CY SEP 27-29, 2007 CL Las Vegas, NV SP Amer Assoc Surg Trauma DE immunoglobulin A; injury; mucosal immunity; innate immunity; respiratory tract ID NOSOCOMIAL PNEUMONIA; SEPTIC MORBIDITY; MUCOSAL IMMUNITY; ABDOMINAL-TRAUMA; LYMPHOID-TISSUE; TRACT IMMUNITY; NUTRITION; IGA; CYTOKINES; SEPSIS AB Background: Secretory immunoglobulin A (SIgA) is the specific immune antibacterial defense. Since pneumonia frequently complicates the course of trauma patients, we studied early airway immune responses after injury. Methods: Twelve severely injured, intubated (expected for >= 5 d) patients had tracheal and bilateral lung lavage (BAL) within 30 hours of injury (n=12). Epithelial lining fluid (ELF) volume and SIgA were measured by urea dilution and enzyme-linked immunosorbent assay (ELISA), respectively. Control BAL specimens were obtained from eight healthy elective surgical patients. Anatomically based comparisons were made between groups with Welch's impaired t test. To verify human data, 30 male mice received no injury (time 0, n=7) or injury with abdominal and neck incisions and were killed for airway IgA at 4 (n=7), 8 (n=8), and 24 (n=8) hours. Analysis of variance (ANOVA) and Fisher's protected least significant difference testing was used to analyze animal data. Results: Initial trauma patient SIgA concentration (SIgA/mL ELF) increased compared with control in the lungs bilaterally (p < 0.05 both right and left). ELF volume was significantly higher in the right lung (p=0.02) and just missed statistical significance (p=0.07) on the left. Mouse IgA increased 8 hours after stress (p < 0.05 versus 0, 4, and 24 hours) and returned to normal by 24 hours. Conclusion: A previously unrecognized innate human airway mucosal immune response with increased airway SIgA and ELF occurs after severe injury and is reproducible experimentally. This accessible, quantifiable human response allows study of clinical strategies to reduce infections via mucosal immune therapies. C1 [Kudsk, Kenneth A.] William S Middleton Mem Vet Adm Med Ctr, Vet Adm Surg Serv, Madison, WI USA. [Kudsk, Kenneth A.; Hermsen, Joshua L.; Genton, Laurence; Faucher, Lee; Gomez, F. Enrique] Univ Wisconsin, Coll Med & Publ Hlth, Dept Surg, Madison, WI USA. [Genton, Laurence] Univ Hosp Geneva, Dept Clin Nutr, Geneva, Switzerland. RP Kudsk, KA (reprint author), 600 Highland Ave,H4-736 CSC, Madison, WI 53792 USA. EM kudsk@surgery.wisc.edu FU NIGMS NIH HHS [R01 GM53439] NR 35 TC 14 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5282 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD FEB PY 2008 VL 64 IS 2 BP 316 EP 323 DI 10.1097/TA.0b013e3181627586 PG 8 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 264KV UT WOS:000253287100014 PM 18301193 ER PT J AU Linzel, D Ring, D Jupiter, J AF Linzel, Durk Ring, David Jupiter, Jesse TI Diaphyseal fracture of the radius with dislocation of the proximal radioulnar joint SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article ID SHAFT FRACTURE; GALEAZZI FRACTURES; ELBOW DISLOCATION; HEAD DISLOCATION C1 [Ring, David] Massachusetts Gen Hosp, Yawkee Ctr, Boston, MA 02114 USA. [Linzel, Durk; Ring, David; Jupiter, Jesse] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extremity Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Yawkee Ctr, Suite 2100,55 Fruit Str, Boston, MA 02114 USA. EM dring@partners.org NR 18 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5282 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD FEB PY 2008 VL 64 IS 2 BP 503 EP 506 DI 10.1097/TA.0b013e31802e70ea PG 4 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 264KV UT WOS:000253287100051 PM 18301222 ER PT J AU Suvak, M Maguen, S Litz, BT Silver, RC Holman, EA AF Suvak, Michael Maguen, Shira Litz, Brett T. Silver, Roxane Cohen Holman, E. Alison TI Indirect exposure to the September 11 terrorist attacks: Does symptom structure resemble PTSD? SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; CONFIRMATORY FACTOR-ANALYSIS; PSYCHOMETRIC PROPERTIES; LATENT STRUCTURE; EVENT SCALE; CHECKLIST; DIMENSIONALITY; PREDICTORS; RESPONSES; VETERANS AB The authors conducted confirmatory factor analyses of reports of posttraumatic stress reactions using a national probability sample of individuals indirectly exposed to the terrorist attacks of September 11, 2001 (n = 675). Reactions at three time points in the year after the attacks were best accounted for by a lower-order 4-factor solution (Reexperiencing, Strategic Avoidance, Emotional Numbing, and Hyperarousal Symptoms). Indirect exposure to a traumatic event appears to induce a response with a similar symptom structure as responses to direct exposure. C1 [Suvak, Michael] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Maguen, Shira] San Francisco Vet Adm Med Ctr, San Francisco, CA USA. [Maguen, Shira] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Litz, Brett T.] Boston VA Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Litz, Brett T.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Silver, Roxane Cohen] Univ Calif Irvine, Dept Psychol & Social Behav, Irvine, CA USA. [Silver, Roxane Cohen] Univ Calif Irvine, Dept Med, Irvine, CA 92717 USA. [Holman, E. Alison] Univ Calif Irvine, Coll Hlth Sci, Nursing Sci Program, Irvine, CA USA. RP Suvak, M (reprint author), VA Boston Healthcare Syst 116B5, 150 S Huntington Ave, Boston, MA 02130 USA. EM suvakmi@yahoo.com NR 41 TC 14 Z9 15 U1 5 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD FEB PY 2008 VL 21 IS 1 BP 30 EP 39 DI 10.1002/jts.20289 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 274RU UT WOS:000254019500005 PM 18302169 ER PT J AU Miller, MW Fogler, JM Wolf, EJ Kaloupek, DG Keane, TM AF Miller, Mark W. Fogler, Jason M. Wolf, Erika J. Kaloupek, Danny G. Keane, Terence M. TI The internalizing and externalizing structure of psychiatric comorbidity in combat veterans SO JOURNAL OF TRAUMATIC STRESS LA English DT Article; Proceedings Paper CT 21st Annual Meeting of the International-Society-for-Traumatic-Stress-Studies (ISTSS) CY NOV 02-05, 2005 CL Toronto, CANADA SP Int Soc Traumat Stress Studies, Natl Inst Ment Hlth ID POSTTRAUMATIC-STRESS-DISORDER; COMMON MENTAL-DISORDERS; DSM-IV ANXIETY; MAJOR DEPRESSION; MOOD DISORDERS; TWIN PAIRS; III-R; PTSD; PERSONALITY; ALCOHOLISM AB This study examined the latent structure of psychiatric disorders in a sample with a high prevalence of PTSD. A series of confirmatory factor analyses tested competing models for the covariation between Structured Clinical Interview for DSM-III-R diagnoses among 1,325 Vietnam veterans. The best-fitting solution was a 3-factor model that included two correlated internalizing factors: anxious-misery, defined by PTSD and major depression, and fear, defined by panic disorder/agoraphobia and obsessive-compulsive disorder. The third factor externalizing, was defined by antisocial personality disorder, alcohol abuse/dependence, and drug abuse/dependence. Both substance-related disorders also showed significant, albeit smaller cross-loadings on the anxious-misery factor. These findings shed new light on the structure of psychiatric comorbidity in a treatment-seeking sample characterized by high rates of PTSD. C1 [Miller, Mark W.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Miller, MW (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 150 S Huntington Ave,116B-2, Boston, MA 02130 USA. EM mark.miller5@va.gov RI Miller, Mark/G-7322-2011; OI Miller, Mark/0000-0001-6393-8563; Wolf, Erika/0000-0003-2666-2435; Kaloupek, Danny/0000-0002-0795-593X FU CSRD VA [I01 CX000431]; NIMH NIH HHS [F31 MH074267, R01 MH079806] NR 43 TC 61 Z9 61 U1 7 U2 11 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD FEB PY 2008 VL 21 IS 1 BP 58 EP 65 DI 10.1002/jts.20303 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 274RU UT WOS:000254019500008 PM 18302181 ER PT J AU Vogt, DS Samper, RE King, DW King, LA Martin, JA AF Vogt, Dawne S. Samper, Rita E. King, Daniel W. King, Lynda A. Martin, James A. TI Deployment stressors and posttraumatic stress symptomatology: comparing active duty and National Guard/Reserve personnel from Gulf War I SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID MALE VIETNAM VETERANS; MILITARY PERSONNEL; DESERT-STORM; DISORDER; HEALTH; IRAQ; PTSD; AFGHANISTAN; RECOVERY; FEMALE AB The increased use of National Guard and Reserve (NG/R) military personnel in current conflicts raises the question of whether deployment experiences and their associations with posttraumatic stress symptomatology differ for active duty and NG/R military personnel. To date, very few studies are available on this topic. Moreover, it is unclear whether the impact of military status differs for women and men. We addressed these research issues in a sample of 311 female and male Gulf War I veterans. Several differences were observed in deployment stressor exposures and results based on differential associations generally suggested more negative impacts of deployment experiences for active duty women and NG/R men. The potential role of unit cohesion in explaining these findings is discussed. C1 [Vogt, Dawne S.; Samper, Rita E.; King, Lynda A.] VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA 02130 USA. [King, Daniel W.] VA Boston Healthcare Syst, Natl Ctr PTSD, Behav Sci Div, Boston, MA 02130 USA. [Vogt, Dawne S.; King, Daniel W.; King, Lynda A.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [King, Daniel W.; King, Lynda A.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Martin, James A.] Bryn Mawr Coll, Grad Sch Social Work & Social Res, Bryn Mawr, PA 19010 USA. RP Vogt, DS (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, 116B-5,150 S Huntington Ave, Boston, MA 02130 USA. EM Dawne.Vogr@va.gov NR 43 TC 51 Z9 52 U1 1 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD FEB PY 2008 VL 21 IS 1 BP 66 EP 74 DI 10.1002/jts.20306 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 274RU UT WOS:000254019500009 PM 18302185 ER PT J AU Turley, RS Hamilton, RJ Terris, MK Kane, CJ Aronson, WJ Presti, JC Amling, CL Freedland, SJ AF Turley, Ryan S. Hamilton, Robert J. Terris, Martha K. Kane, Christopher J. Aronson, William J. Presti, Joseph C., Jr. Amling, Christopher L. Freedland, Stephen J. CA SEARCH Database Study Grp TI Small transrectal ultrasound volume predicts clinically significant Gleason score upgrading after radical prostatectomy: Results from the SEARCH database SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; biopsy; needle; prostatectomy ID CANCER; BIOPSY; GRADE; SPECIMENS; SIZE; RISK AB Purpose: Needle biopsy Gleason scores are often upgraded after pathological examination of the prostate following radical prostatectomy. It has been suggested that larger prostates would be associated with a greater risk of upgrading since a smaller percentage of the gland is sampled and, thus, the highest grade disease would more likely be missed, assuming an equal number of cores is taken from similar locations. We examined the likelihood of clinically relevant upgrading after radical prostatectomy as a function of transrectal ultrasound volume. Materials and Methods: We examined the association between transrectal ultrasound volume and upgrading (higher Gleason score category in the radical prostatectomy specimen than in the biopsy) in 586 men treated with radical prostatectomy between 1995 and 2006 in the SEARCH database who underwent at least a sextant biopsy using multivariate logistic regression. Transrectal ultrasound volume was categorized as 20 or less (in 71), 21 to 40 (in 334), 41 to 60 (in 123) and greater than 60 cm(3) (in 58). Gleason score was examined as a categorical variable of 2-6, 3 + 4 and 4 + 3 or greater. Results: Overall 138 cases (24%) were upgraded, 80 (14%) were downgraded, and 368 (62%) had identical biopsy and pathological Gleason sum groups. Larger transrectal ultrasound volume was significantly associated with decreased likelihood of upgrading (p trend < 0.001). For transrectal ultrasound volumes greater than 60, 41 to 60, 21 to 40 and 20 cm(3) or less, the estimated multivariate adjusted probability of upgrading was 12.6%, 27.5%, 36.4% and 45.5% for Gleason 2-6 tumors, and 6.1%, 8.5%, 18.9% and 20.9% for Gleason 3 + 4 tumors, respectively. Conclusions: Larger transrectal ultrasound volumes were at decreased risk for clinically significant upgrading after radical prostatectomy. This fact should be kept in mind when deciding on treatment decisions for men with apparently low grade prostate cancer on biopsy. C1 [Turley, Ryan S.; Hamilton, Robert J.; Freedland, Stephen J.] Duke Prostate Ctr, Div Urol Surg, Durham, NC USA. [Freedland, Stephen J.] Duke Univ, Sch Med, Dept Pathol, Div Urol, Durham, NC 27710 USA. [Freedland, Stephen J.] Vet Affairs Med Ctr, Urol Sect, Durham, NC USA. [Terris, Martha K.] Vet Affairs Med Ctr, Urol Sect, Augusta, GA USA. [Terris, Martha K.] Med Coll Georgia, Urol Sect, Augusta, GA 30912 USA. [Kane, Christopher J.] Vet Affairs Med Ctr, Urol Sect, San Francisco, CA 94121 USA. [Kane, Christopher J.] Univ Calif San Francisco, Sch Med, Dept Urol, San Francisco, CA 94143 USA. [Aronson, William J.] Vet Affairs Greater Los Angeles Healthcare Syst, Urol Sect, Los Angeles, CA USA. [Aronson, William J.] Univ Calif Los Angeles, Dept Urol, Los Angeles, CA USA. [Presti, Joseph C., Jr.] Stanford Univ, Sch Med, Dept Urol, Palo Alto, CA 94304 USA. [Presti, Joseph C., Jr.] Vet Affairs Med Ctr, Urol Sect, Palo Alto, CA 94304 USA. [Amling, Christopher L.] Univ Alabama, Div Urol, Birmingham, AL USA. RP Freedland, SJ (reprint author), Duke Univ, Sch Med, Dept Pathol, Div Urol, Box 2626, Durham, NC 27710 USA. EM steve.freedland@duke.edu OI Hamilton, Robert/0000-0002-6715-5934; Terris, Martha/0000-0002-3843-7270 FU NCI NIH HHS [P50 CA92131-01A1, R01CA100938] NR 17 TC 37 Z9 41 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD FEB PY 2008 VL 179 IS 2 BP 523 EP 527 DI 10.1016/j.juro.2007.09.078 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 251JP UT WOS:000252369600036 PM 18076952 ER PT J AU Shoskes, DA Berger, R Elmi, A Landis, JR Propert, KJ Zeitlin, S AF Shoskes, Daniel A. Berger, Richard Elmi, Angelo Landis, J. Richard Propert, Kathleen J. Zeitlin, Scott CA Chronic Prostatitis Collaborative TI Muscle tenderness in men with chronic prostatitis/chronic pelvic pain syndrome: The chronic prostatitis cohort study SO JOURNAL OF UROLOGY LA English DT Article DE prostatitis; pelvic pain AB Purpose: Myofascial pain is a possible etiology for category III chronic prostatitis/chronic pelvic pain syndrome, either secondary to infection/inflammation or as the primary cause. We documented tenderness on physical examination in a large multicenter cohort of patients with chronic pelvic pain syndrome and compared to controls. Materials and Methods: Data were reviewed from the National Institutes of Health Chronic Prostatitis Cohort study on 384 men with chronic pelvic pain syndrome and 121 asymptomatic controls who had complete unblinded physical examination data from 7 clinical centers between October 1998 and August 2001. Tenderness in 11 sites including prostate, genitals, abdomen and pelvic floor together with prostate size and consistency was evaluated. Data were correlated with cultures and symptoms. Results: Overall 51% of patients with chronic pelvic pain syndrome and 7% of controls had any tenderness. The most common site was prostate (41% chronic pelvic pain syndrome, 5% controls), followed by external and internal pelvic floor (13% and 14% chronic pelvic pain syndrome, 0 controls) and suprapubic area (9% chronic pelvic pain syndrome, 0 controls). Of patients with chronic pelvic pain syndrome 25% had 1 tender site, 11% had 2 and 6% had 3 tender sites. Tenderness did not correlate with inflammation or infection in the prostate fluid. Prostate consistency was normal in 79% of patients with chronic pelvic pain syndrome and in 95% of controls, and did not correlate with symptom severity. Patients with chronic pelvic pain syndrome with any tenderness had significantly higher Chronic Prostatitis Symptom Index scores at baseline and at 1 year (24.1 vs 21.2 and 20.2 vs 17.5, p < 0.0001) compared to patients without tenderness. Conclusions: Abdominal/pelvic tenderness is present in half of the patients with chronic pelvic pain syndrome but only 7% of controls. Extraprostatic tenderness may identify a cohort of patients with a neuromuscular source of pain. C1 [Shoskes, Daniel A.] Cleveland Clin, Glickman Urol & Kidney Inst, Cleveland, OH 44915 USA. [Berger, Richard] Univ Washington, Seattle, WA 98195 USA. [Elmi, Angelo; Landis, J. Richard; Propert, Kathleen J.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Zeitlin, Scott] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. [Zeitlin, Scott] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Shoskes, DA (reprint author), Cleveland Clin, Glickman Urol & Kidney Inst, 9500 Euclid Ave,Desk A100, Cleveland, OH 44915 USA. EM dshoskes@mac.com RI Landis, J. Richard/A-9330-2010; OI Landis, J Richard/0000-0001-8099-0988 FU NIDDK NIH HHS [R01 DK53736, R01 DK053732, R01 DK053752, R01 DK053752-03S1, R01 DK53730, R01 DK53732, R01 DK53734, R01 DK53746, R01 DK53752, U01 DK065189-04] NR 7 TC 34 Z9 39 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD FEB PY 2008 VL 179 IS 2 BP 556 EP 560 DI 10.1016/j.juro.2007.09.088 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 251JP UT WOS:000252369600045 PM 18082223 ER PT J AU Jones, J Otu, HH Grall, F Spentzos, D Can, H Aivado, M Belldegrun, AS Pantuck, AJ Libermann, TA AF Jones, Jon Otu, Hasan H. Grall, Franck Spentzos, Dimitrios Can, Handan Aivado, Manuel Belldegrun, Arie S. Pantuck, Allan J. Libermann, Towia A. TI Proteomic identification of interleukin-2 therapy response in metastatic renal cell cancer SO JOURNAL OF UROLOGY LA English DT Article DE kidney; carcinoma; renal cell; proteomics; spectrometry; mass; matrix-assisted laser desorption-ionization; interleukin-2 ID CARBONIC-ANHYDRASE-IX; TERM SURVIVAL UPDATE; SELDI-TOF-MS; RADICAL NEPHRECTOMY; PREDICT SURVIVAL; CARCINOMA; IMMUNOTHERAPY; TUMOR; STAGE AB Purpose: To detect a predictive protein profile that distinguishes interleukin-2 therapy responders and nonresponders among patients with metastatic renal cell carcinoma we used surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Materials and Methods: Protein extracts from 56 patients with metastatic clear cell patients renal cell carcinoma obtained from radical nephrectomy specimens before interleukin-2 therapy were applied to protein chip arrays of different chromatographic properties and analyzed using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. A class prediction algorithm was applied to identify a subset of protein peaks with expression values associated with interleukin-2 response status. Multivariate analysis was performed to assess the association between the proteomic profile and interleukin-2 response status, controlling for the effect of lymphadenopathy. Results: From 513 protein peaks we discovered a predictor set of 11 that performed optimally for predicting interleukin-2 response status with 86% accuracy (Fisher's p < 0.004, permutation p < 0.01). Results were validated in an independent data set with 72% overall accuracy (p < 0.05, permutation p < 0.01). On multivariate analysis the proteomic profile was significantly associated with the interleukin-2 response when corrected for lymph node status (p < 0.04). Conclusions: We identified and validated a proteomic pattern that is an independent predictor of the interleukin-2 response. The ability to predict the probability of the interleukin-2 response could permit targeted selection of the patients most likely to respond to interleukin-2, while avoiding unwanted toxicity in patients less likely to respond. This proteomic predictor has the potential to significantly aid clinicians in the decision making of appropriate therapy for patients with metastatic renal cell carcinoma. C1 [Jones, Jon; Otu, Hasan H.; Grall, Franck; Spentzos, Dimitrios; Can, Handan; Aivado, Manuel; Libermann, Towia A.] Beth Israel Deaconess Med Ctr Genom Ctr, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Jones, Jon; Spentzos, Dimitrios] Harvard Univ, Sch Med, Harvard Inst Med, Boston, MA 02115 USA. [Jones, Jon; Otu, Hasan H.; Grall, Franck; Spentzos, Dimitrios; Aivado, Manuel; Libermann, Towia A.] Dana Farber Harvard Canc Ctr Canc Proteom Core, Boston, MA USA. [Spentzos, Dimitrios] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. [Jones, Jon] Univ Frankfurt, Dept Urol & Pediat Urol, Frankfurt, Germany. [Belldegrun, Arie S.; Pantuck, Allan J.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Dept Urol, Univ Calif Los Angeles Kidney Canc Program, Los Angeles, CA 90024 USA. [Belldegrun, Arie S.; Pantuck, Allan J.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Dept Med, Univ Calif Los Angeles Kidney Canc Program, Los Angeles, CA 90024 USA. [Belldegrun, Arie S.; Pantuck, Allan J.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. [Otu, Hasan H.; Can, Handan] Yeditepe Univ, Dept Genet & Bioengn, Istanbul, Turkey. RP Jones, J (reprint author), Beth Israel Deaconess Med Ctr Genom Ctr, Beth Israel Deaconess Med Ctr, 4 Blackfan Circle, Boston, MA 02115 USA. EM jjones6@bidmc.harvard.edu RI Libermann, Towia/F-9866-2010; OI Libermann, Towia/0000-0002-4006-8179; Otu, Hasan/0000-0002-9253-8152 FU NCI NIH HHS [R01 CA085467, 1R01 CA85467, K23 CA095151, K23CA095151-01, P50 CA090381] NR 19 TC 12 Z9 13 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD FEB PY 2008 VL 179 IS 2 BP 730 EP 736 DI 10.1016/j.juro.2007.00.016 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 251JP UT WOS:000252369600089 PM 18082202 ER PT J AU d'Othe, BJ Faintuch, S Schirmang, T Lang, EV AF d'Othe, Bertrand Janne Faintuch, Salomao Schirmang, Todd Lang, Elvira V. TI Endovenous laser ablation of the saphenous veins: Bilateral versus unilateral single-session procedures SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID TUMESCENT TECHNIQUE; MEDICAL PROCEDURES; RANDOMIZED-TRIAL; PAIN; ANESTHESIA; ANALGESIA; RESPONSES AB PURPOSE: To assess the feasibility of bilateral endovenous laser ablation (EVLA) of saphenous veins in a single session with use of diluted lidocaine for tumescent anesthesia. MATERIALS AND METHODS: Among 122 consecutive EVLA procedures (112 patients; mean age, 49 years; 75% women) over a 12-month period, there were 75 unilateral procedures (n = 67) and 47 bilateral interventions (n = 45). Tumescent anesthesia consisted of lidocaine diluted to 0.10% for unilateral procedures versus 0.05% for bilateral cases (lidocaine dose <4.5 mg/kg body weight). Procedural data, immediate success rates on an intent-to-treat basis, and outcomes at: 3-6-month follow-up were compared between groups with nonparametric tests. RESULTS: Bilateral procedures could be performed successfully with low lidocaine dilutions with a similar success rate (96%) as unilateral procedures (100%). No significant variation in systolic and diastolic blood pressure and heart rate was observed between bilateral and unilateral groups. No patient experienced signs of lidocaine toxicity. After adjusting for length of vein treated, there were no significant differences in the total lidocaine dose used, tumescent anesthesia volume, or procedure duration. CONCLUSIONS: Bilateral saphenous vein ablation in a single session appears safe and effective when tumescent anesthesia is given with very dilute lidocaine (0.05%). This approach may help meet patients' requests for simultaneous bilateral treatment and reduce duration of postprocedural discomfort. C1 [d'Othe, Bertrand Janne] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol Cardiovasc Imaging & Intervent, Boston, MA 02115 USA. [d'Othe, Bertrand Janne; Faintuch, Salomao; Schirmang, Todd; Lang, Elvira V.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA USA. RP d'Othe, BJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol Cardiovasc Imaging & Intervent, 55 Fruit St,GRB-290, Boston, MA 02115 USA. EM bjannedothee@partners.org RI Janne d'Othee, Bertrand/E-8467-2010 NR 23 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD FEB PY 2008 VL 19 IS 2 BP 211 EP 215 DI 10.1016/j.jvir.2007.09.010 PN 1 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 261HX UT WOS:000253070800010 ER PT J AU Matsumura, JS Cambria, RP Dake, MD Moore, RD Svensson, LG Snyder, S AF Matsumura, Jon S. Cambria, Richard P. Dake, Michael D. Moore, Randy D. Svensson, Lars G. Snyder, Scott CA TX2 Clinical Trial Investigators TI International controlled clinical trial of thoracic endovascular aneurysm repair with the Zenith TX2 endovascular graft: 1-year results SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 19th Annual Meeting of the American-Venous-Forum CY FEB 14-17, 2007 CL San Diego, CA SP Amer Venous Forum ID OPEN-SURGICAL REPAIR; AORTIC-ANEURYSMS; EXPERIENCE AB Purpose: This trial evaluated the safety and effectiveness of thoracic endovascular aortic repair (TEVAR) with a contemporary endograft system compared with open surgical repair (open) of descending thoracic aortic aneurysms and large ulcers. Methods: Forty-two international trial sites enrolled 230 subjects with descending thoracic aortic aneurysms or ulcers. The study compared 160 TEVAR subjects treated with the Zenith TX2 Endovascular Graft (William Cook Europe, ApS, Bjaeverskov, Denmark) with 70 open subjects. Subjects were evaluated preprocedure, predischarge, 1, 6, and 12 months, and yearly through 5 years with medical examination, laboratory testing, chest radiographs, and computed tomography scans. Mortality rates, prespecified severe morbidity composite index, major morbidity, clinical utility, aneurysm rupture, and secondary interventions were compared. The TEVAR subjects were evaluated by a core laboratory for device performance, including change in aneurysm size, endoleak, migration, and device integrity. Results: The 30-day survival rate was noninferior (P < .01) for the TEVAR group compared with the open group (98.1% vs 94.3%). The severe morbidity composite index was lower for TEVAR (0.2 +/- 0.7 vs 0.7 +/- 1.2; P <.01). Cumulative major morbidity scores were significantly lower at 30 days for the TEVAR group compared with the open group (1.3 +/- 3.0 vs 2.9 +/- 3.6, P <.01). The TEVAR patients had fewer cardiovascular, pulmonary, and vascular adverse events, although neurologic events were not significantly different. Clinical utility for the TEVAR patients was superior to that of the open patients. No ruptures or conversions occurred in the first year. Reintervention rates were similar in both groups. At 12 months, aneurysm growth was identified in 7.1% (8/112), endoleak in 3.9% (4/103), migration (>10 mm) in 2.8% (3/107), and other device issues were rare. None of the patients with migration experienced endoleak, aneurysm growth, or required a secondary intervention. Conclusions: Thoracic endovascular aortic repair with the TX2 is a safer and effective alternative to open surgical repair for the treatment of anatomically suitable descending thoracic aortic aneurysms and ulcers at 1 year of follow-up. Device performance issues are infrequent, but careful planning and regular follow-up with imaging remain a necessity. C1 [Cambria, Richard P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Dake, Michael D.] Univ Virginia, Charlottesville, VA USA. [Svensson, Lars G.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Moore, Randy D.] Univ Calgary, Calgary, AB, Canada. [Snyder, Scott] MED Inst, W Lafayette, IN USA. [Matsumura, Jon S.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Chicago, IL 60611 USA. RP Matsumura, JS (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Surg, 201 E Huron,Ste 10-105, Chicago, IL 60611 USA. EM j-matsumura@northwestern.edu NR 19 TC 178 Z9 180 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD FEB PY 2008 VL 47 IS 2 BP 247 EP 257 DI 10.1016/j.jvs.2007.10.032 PG 11 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 255VE UT WOS:000252685000001 PM 18241743 ER PT J AU Reddy, KR Govindarajan, S Marcellin, P Bernstein, D Dienstag, JL Bodenheimer, H Rakela, J Messinger, D Schmidt, G Ackrill, A Hadziyannis, SJ AF Reddy, K. R. Govindarajan, S. Marcellin, P. Bernstein, D. Dienstag, J. L. Bodenheimer, H., Jr. Rakela, J. Messinger, D. Schmidt, G. Ackrill, A. Hadziyannis, S. J. TI Hepatic steatosis in chronic hepatitis C: baseline host and viral characteristics and influence on response to therapy with peginterferon alpha-2a plus ribavirin SO JOURNAL OF VIRAL HEPATITIS LA English DT Article DE baseline predictors; chronic hepatitis C virus; HCV genotype; metabolic syndrome; peginterferon alpha-2a; steatosis; sustained virological response ID BODY-MASS INDEX; VIRUS-INFECTION; FIBROSIS PROGRESSION; INSULIN-RESISTANCE; DIABETES-MELLITUS; LIVER FIBROSIS; GENOTYPE; DISEASE; OBESITY; IMPACT AB Hepatic steatosis is common in hepatitis C virus (HCV)-infected patients and may be associated with the metabolic syndrome. We studied steatosis in patients treated with peginterferon alpha-2a plus ribavirin. Forty-five of 207 patients (22%) had >5% hepatic steatosis at baseline. Significantly more patients with steatosis than without were HCV genotype 3 (51%vs 14%; P <0.0001) had higher HCV-RNA (P = 0.0045), body weight (P = 0.0176), body mass index (BMI, P = 0.0352) and serum triglycerides (TG) (P = 0.0364), hypertriglyceridaemia (P = 0.0009), elevated blood pressure/history of hypertension (P = 0.0229) and lower cholesterol (P = 0.0009). Significant steatosis predictors were genotype 3 (OR 9.04, 95% CI 3.85-21.21, P <0.0001), HCV-RNA (OR 2.96, 1.49-5.88, P = 0.0019) and triglycerides (OR 1.06, 1.02-1.11, P = 0.0071). In genotype 3 patients, HCV-RNA was the only significant predictor (OR 11.15, 2.60-47.81, P = 0.0012). In non-genotype 3 patients, hypertriglyceridaemia was the only significant predictor (OR 1.07, 1.02-1.12, P = 0.0041). 134 of 207 patients (65%) achieved an sustained virological response (SVR) with peginterferon alpha-2a plus ribavirin, similar to the overall response rate. In genotype 3 patients with an SVR, steatosis decreased from 48% to 13% (baseline to end-point). No change was seen in the steatosis rate in non-genotype 3 patients with an SVR. This large and comprehensive analysis of a large data base from a multinational trial further adds to the observations that chronic HCV is associated with hepatic steatosis in approximately a fifth of patients. Further, features of the metabolic syndrome are associated with hepatic steatosis in most of these patients. Steatosis is significantly more common in genotype 3 compared with other genotypes, and in these patients, an SVR is associated with steatosis clearance. C1 [Reddy, K. R.] Univ Penn, GI Div, Philadelphia, PA 19104 USA. [Govindarajan, S.] Rancho Los Amigos Med Ctr, Downey, CA USA. [Marcellin, P.] Hop Beaujon, Clichy, France. [Bernstein, D.] N Shore Univ Hosp, Manhasset, NY USA. [Dienstag, J. L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit Med Serv, Boston, MA USA. [Dienstag, J. L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Bodenheimer, H., Jr.] Albert Einstein Coll Med, Beth Israel Med Ctr, New York, NY USA. [Rakela, J.] Mayo Clin, Phoenix, AZ USA. [Messinger, D.; Schmidt, G.] IST GmbH, Mannheim, Germany. [Hadziyannis, S. J.] Henry Dunant Hosp, Dept Med & Hepatol, Athens, Greece. RP Reddy, KR (reprint author), Univ Penn, GI Div, Philadelphia, PA 19104 USA. EM rajender.reddy@uphs.upenn.edu NR 29 TC 35 Z9 37 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1352-0504 J9 J VIRAL HEPATITIS JI J. Viral Hepatitis PD FEB PY 2008 VL 15 IS 2 BP 129 EP 136 DI 10.1111/j.1365-2893.2007.00901.x PG 8 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA 246LY UT WOS:000252009700007 PM 18184196 ER PT J AU Kaur, A Di Mascio, M Barabasz, A Rosenzweig, M McClure, HM Perelson, AS Ribeiro, RM Johnson, RP AF Kaur, Amitinder Di Mascio, Michele Barabasz, Amy Rosenzweig, Michael McClure, Harold M. Perelson, Alan S. Ribeiro, Ruy M. Johnson, R. Paul TI Dynamics of T- and B-lymphocyte turnover in a natural host of simian immunodeficiency virus SO JOURNAL OF VIROLOGY LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; HIV-INFECTED PATIENTS; SOOTY MANGABEYS; RHESUS MACAQUES; SIV INFECTION; RAPID TURNOVER; CELL TURNOVER; IN-VIVO; CD4(+); CD8(+) AB Increased lymphocyte turnover is a hallmark of pathogenic lentiviral infection. To investigate perturbations in lymphocyte dynamics in natural hosts with nonpathogenic simian immunodeficiency virus (SIV) infection, the nucleoside analog bromodeoxyuridine (BrdU) was administered to six naturally SIV-infected and five SIV-negative sooty mangabeys. As a measure of lymphocyte turnover, we estimated the mean death rate by fitting a mathematical model to the fraction of BrdU-labeled cells during a 2-week labeling and a median 10-week delabeling period. Despite significantly lower total T- and B-lymphocyte counts in SIV-infected sooty mangabeys than in SIV-negative mangabeys, the turnover rate of B lymphocytes and CD4(+) and CD8(+) T lymphocytes was not increased in the SIV-infected animals. A small, rapidly proliferating CD45RA(+) memory subset and a large, slower-proliferating CD45RA(-) central memory subset of CD4(+) T lymphocytes identified in the peripheral blood of sooty mangabeys also did not show evidence of increased turnover in the context of SIV infection. Independently of SIV infection, the turnover of CD4(+) T lymphocytes in sooty mangabeys was significantly higher (P < 0.01) than that of CD8(+) T lymphocytes, a finding hitherto not reported in rhesus macaques or humans. The absence of aberrant T-lymphocyte turnover along with an inherently high rate of CD4(+) T-lymphocyte turnover may help to preserve the pool of central memory CD4(+) T lymphocytes in viremic SIV-infected sooty mangabeys and protect against progression to AIDS. C1 [Kaur, Amitinder; Barabasz, Amy; Rosenzweig, Michael; Johnson, R. Paul] Harvard Univ, Sch Med, Div Immunol, New England Reg Primate Res Ctr, Southborough, MA 01772 USA. [Di Mascio, Michele] NIAID, NIH, Off Clin Res, Biostat Res Branch, Bethesda, MD 20892 USA. [McClure, Harold M.] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. [Perelson, Alan S.; Ribeiro, Ruy M.] Los Alamos Natl Lab, Los Alamos, NM 87545 USA. [Johnson, R. Paul] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02115 USA. [Johnson, R. Paul] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02115 USA. RP Kaur, A (reprint author), Harvard Univ, Sch Med, Div Immunol, New England Reg Primate Res Ctr, 1 Pine Hill Dr,POB 9102, Southborough, MA 01772 USA. EM amitinder_kaur@hms.harvard.edu OI Ribeiro, Ruy/0000-0002-3988-8241 FU NCRR NIH HHS [P20-RR18754, P51 RR000168, R01 RR006555, RR 00168, RR06555, K26 RR000168, P20 RR018754]; PHS HHS [A149809] NR 32 TC 33 Z9 33 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 2008 VL 82 IS 3 BP 1084 EP 1093 DI 10.1128/JVI.02197-07 PG 10 WC Virology SC Virology GA 253JH UT WOS:000252514000003 PM 18032490 ER PT J AU Fuhr, P Martinez, B Williams, M AF Fuhr, Patti Martinez, Bethany Williams, Michael TI Caregivers with visual impairments: A preliminary study SO JOURNAL OF VISUAL IMPAIRMENT & BLINDNESS LA English DT Editorial Material ID QUALITY-OF-LIFE; MACULAR DEGENERATION; OLDER-ADULTS; VISION REHABILITATION; CARE; SATISFACTION; POPULATION; DISTRESS; PATTERNS; OUTCOMES C1 [Fuhr, Patti; Martinez, Bethany] Birmingham VA Med Ctr, Low Vis Optometry Dept, Birmingham, AL 35233 USA. [Williams, Michael] Atlanta VA Med Ctr, Rehabil Res & Dev Ctr Excellence Aging Vet Vis Lo, Decatur, GA 30033 USA. RP Fuhr, P (reprint author), Birmingham VA Med Ctr, Low Vis Optometry Dept, Room 124,700 S 19th St, Birmingham, AL 35233 USA. EM patti.fuhr@va.gov; bethany.martinez@va.gov; mike.williams2@va.gov NR 37 TC 3 Z9 3 U1 1 U2 2 PU AMER FOUNDATION BLIND PI NEW YORK PA J VISUAL IMPAIRMENT BLINDNESS 11 PENN PLAZA SUITE 300, NEW YORK, NY 10001 USA SN 0145-482X J9 J VISUAL IMPAIR BLIN JI J. Vis. Impair. Blind. PD FEB PY 2008 VL 102 IS 2 BP 89 EP 96 PG 8 WC Rehabilitation SC Rehabilitation GA 268CN UT WOS:000253555600005 ER PT J AU Rudolph, JL Ramlawi, B Kuchel, GA McElhaney, JE Xie, DX Sellke, FW Khabbaz, K Levkoff, SE Marcantonio, ER AF Rudolph, James L. Ramlawi, Basel Kuchel, George A. McElhaney, Janet E. Xie, Dongxu Sellke, Frank W. Khabbaz, Kamal Levkoff, Sue E. Marcantonio, Edward R. TI Chemokines are associated with delirium after cardiac surgery SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE inflammation; delirium; cardiac surgery; chemokines; cytokines ID BLOOD-BRAIN-BARRIER; BEAD ARRAY ASSAYS; CARDIOPULMONARY BYPASS; POSTOPERATIVE CONFUSION; INFLAMMATORY RESPONSE; CNS INFLAMMATION; CYTOKINES; INTERLEUKIN-6; INJURY; SENSITIVITY AB Background. Delirium has been hypothesized to be a central nervous system response to systemic inflammation during a state of blood-brain barrier compromise. The purpose of this study was to compare postoperative changes in groups of inflammatory markers in persons who developed delirium following cardiac surgery and matched controls without delirium. Methods. Serum samples were drawn from 42 patients undergoing cardiac surgery preoperatively and postoperatively at 6 hours and postoperative day 4. The serum concentrations of 28 inflammatory markers were determined with a microsphere flow cytometer. A priori, inflammatory markers were assigned to five classes of cytokines. A class 7 score was calculated by averaging the standardized, normalized levels of the markers in each class. Beginning on postoperative day 2, patients underwent a daily delirium assessment. Results. Twelve patients with delirium were matched by surgical duration, age, and baseline cognition to 12 patients without delirium. At the 6-hour time point, patients who went on to develop delirium had higher increases of chemokines compared to matched controls (class z score 0.3 +/- 1.0, p < .05). Among the five classes of cytokines, there were no other significant differences between patients with or without delirium at either the 6 hour or postoperative day 4 assessments. Conclusion. After cardiac surgery, chemokine levels were elevated in patients who developed delirium in the early postoperative period. Because chemokines are capable of disrupting blood-brain barrier integrity in vitro, future studies are needed to define the relationship of these inflammatory mediators to delirium pathogenesis. C1 [Rudolph, James L.] VA Boston Healthcare Syst, Ctr Geriatr Res Educ & Clin, Boston, MA 02130 USA. [Ramlawi, Basel] Univ Western Ontario, Div Cardiac Surg, London, ON, Canada. [McElhaney, Janet E.; Xie, Dongxu] Univ Connecticut, Sch Med, Ctr Immunotherapy Canc & Infect Dis, Farmington, CT USA. [Kuchel, George A.; McElhaney, Janet E.; Xie, Dongxu] Univ Connecticut, Ctr Hlth, Univ Connecticut Ctr Aging, Farmington, CT USA. [McElhaney, Janet E.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Ramlawi, Basel; Sellke, Frank W.; Khabbaz, Kamal] Beth Israel Deaconess Med Ctr, Div Cardiac Surg, Boston, MA 02215 USA. [Marcantonio, Edward R.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Marcantonio, Edward R.] Beth Israel Deaconess Med Ctr, Div Gerontol, Boston, MA 02215 USA. [Levkoff, Sue E.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Rudolph, James L.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. RP Rudolph, JL (reprint author), VA Boston Healthcare Syst, Ctr Geriatr Res Educ & Clin, 150 S Huntington Ave JP-182, Boston, MA 02130 USA. EM jrudolph@partners.org FU NHLBI NIH HHS [R01 HL046716, HL46716, R01 HL046716-17]; NIA NIH HHS [AG00294-18, AG08812-14, K12 AG000294, P60 AG008812, P60 AG008812-15S2, R03 AG029861, R03 AG029861-01A1, Z01 AG000294]; NIAID NIH HHS [AI68265, R01 AI068265, R01 AI068265-07] NR 36 TC 62 Z9 65 U1 0 U2 4 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD FEB PY 2008 VL 63 IS 2 BP 184 EP 189 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 301FV UT WOS:000255882700012 PM 18314455 ER PT J AU Patel, TV Cornell, L Wolf, M AF Patel, T. V. Cornell, L. Wolf, M. TI Renal metastases SO KIDNEY INTERNATIONAL LA English DT Editorial Material C1 [Patel, T. V.; Wolf, M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. [Cornell, L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Wolf, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Bartlett 917,55 Fruit St, Boston, MA 02114 USA. EM mswolf@partners.org NR 4 TC 1 Z9 2 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD FEB PY 2008 VL 73 IS 3 BP 370 EP 370 DI 10.1038/sj.ki.5002594 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 251QK UT WOS:000252388300027 PM 18195706 ER PT J AU BuSaba, NY Cunningham, MJ AF BuSaba, Nicolas Y. Cunningham, Michael J. TI Connexin 26 and 30 Genes Mutations in Patients with Chronic Rhinosinusitis SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Annual Meeting of the Western Section of the Triological-Society CY FEB 15-18, 2007 CL Marco Isl, FL SP Triol Soc, Western Sect DE Chronic rhinosinusitis; recurrent acute rhinosinusitis; mucociliary clearance; connexin 26 gene; connexin 30 gene; gene mutation ID HEARING-LOSS; GAP-JUNCTIONS; SINUSITIS; POPULATION; EXPRESSION; GJB2 AB Objectives: Connexin proteins play an important role in cell-to-cell communication. Mutations in the genes that encode for these connexins may potentially lead to dysfunction in mucociliary clearance predisposing to chronic rhinosinusitis (CRS) or recurrent acute rhinosinusitis (RARS). The objective of this study was to assess for the presence of connexin 26 and 30 gene mutations in patients with CRS and RARS. Study Design: Prospective case series. Methods: Forty-six consecutive patients who were diagnosed with CRS or RARS at a single tertiary care facility were included in the study. Patients with known dysfunction in mucociliary clearance were excluded. The following clinical data were collected: age, gender, duration of disease and age at onset, personal history of otitis media and/or sensorineural hearing loss (SNHL), and family history of paranasal sinus disease and SNHL. Buccal swab deoxyribonucleic acid (DNA) specimens were sequenced for connexin 26 and 30 genes. Results: The study group consisted of 32 females and 14 males, 8 children and 38 adults. Adequate sequencing of connexin 30 gene was possible in all 46 specimens, but in only 19 specimens for connexin 26 gene. Connexin 30 gene mutations were not detected in any of the 46 specimens. Two of the 19 specimens had heterozygous mutations in the connexin 26 gene; there was one V371 mutation and one 35dG mutation. Both patients were adults; the patient with 35dG mutation had SNHL. Conclusion: Mutations in connexin 26 and 30 genes are rare in patients with CRS or RARS and do not seem to play a contributory role in the pathogensis of these disorders. C1 [BuSaba, Nicolas Y.; Cunningham, Michael J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [BuSaba, Nicolas Y.] VA Boston HealthCare Syst, Div Otolaryngol, Boston, MA USA. [BuSaba, Nicolas Y.; Cunningham, Michael J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP BuSaba, NY (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM nicolas_busaba@meei.harvard.edu NR 18 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD FEB PY 2008 VL 118 IS 2 BP 310 EP 313 DI 10.1097/MLG.0b013e31815744b6 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 368ZE UT WOS:000260661500023 PM 17989577 ER PT J AU White, WM Makin, IRS Slayton, MH Barthe, PG Gliklich, R AF White, W. Matthew Makin, Inder Raj S. Slayton, Michael H. Barthe, Peter G. Gliklich, Richard TI Selective transcutaneous delivery of energy to porcine soft tissues using Intense Ultrasound (IUS) SO LASERS IN SURGERY AND MEDICINE LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the American-Society-for-Laser-Medicine-and-Surgery CY APR 05-09, 2006 CL Boston, MA SP Amer Soc Laser Med & Surg DE nonablative devices; porcine tissue; ex vivo; aging face; collagen; ultrasound; Intense Ultrasound; skin; SMAS; muscle ID CARBON-DIOXIDE LASER; FOCUSED ULTRASOUND; THERMAL-INJURY; SKIN; PHOTOTHERMOLYSIS; REJUVENATION; CONTRACTION; ABLATION; SURGERY; THERAPY AB Objective: Various energy delivery systems have been utilized to treat superficial rhytids in the aging face. The Intense Ultrasound System JUS) is a novel modality capable of transcutaneously delivering controlled thermal energy at various depths while sparing the overlying tissues. The purpose of this feasibility study was to evaluate the response of porcine tissues to various IUS energy source conditions. Further evaluation was performed of the built-in imaging capabilities of the device. Materials and Methods: Simulations were performed on ex vivo porcine tissues to estimate the thermal dose distribution in tissues after IUS exposures to determine the unique source settings that would produce thermal injury zones (TIZs) at given depths. Exposures were performed at escalating power settings and different exposure times (in the range of 1-7.6 J) using three JUS handpieces with unique frequencies and focal depths. Ultrasound imaging was performed before and after IUS exposures to detect changes in tissue consistency. Porcine tissues were examined using nitro-blue tetrazolium chloride (NBTC) staining sensitive for thermal lesions, both grossly and histologically. The dimensions and depth of the TIZs were measured from digital photographs and compared. Results: IUS can reliably achieve discrete, TIZ at various depths within tissue without surface disruption. Changes in the TIZ dimensions and shape were observed as source settings were varied. As the source energy was increased, the thermal lesions became larger by growing proximally towards the tissue surface. Maximum lesion depth closely approximated the pre-set focal depth of a given handpiece. Ultrasound imaging detected well-demarcated TIZ at depths within the porcine muscle tissue. Conclusion: This study demonstrates the response of porcine tissue to various energy dose levels of Intense Ultrasound. Further study, especially on human facial tissue, is necessary in order to understand the utility of this modality in treating the aging face and potentially, other cosmetic applications. C1 [White, W. Matthew; Gliklich, Richard] Harvard Univ, Sch Med, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm,Div Facial Plast &, Boston, MA 02114 USA. [Makin, Inder Raj S.; Slayton, Michael H.; Barthe, Peter G.] Ulthera Inc, Mesa, AZ USA. RP Gliklich, R (reprint author), Harvard Univ, Sch Med, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm,Div Facial Plast &, 243 Charles St, Boston, MA 02114 USA. EM richard_gliklich@meei.harvard.edu NR 26 TC 29 Z9 29 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD FEB PY 2008 VL 40 IS 2 BP 67 EP 75 DI 10.1002/lsm.20613 PG 9 WC Dermatology; Surgery SC Dermatology; Surgery GA 269SQ UT WOS:000253670900002 PM 18306156 ER PT J AU Park, JM Tsao, H Tsao, S AF Park, Jong Min Tsao, Hensin Tsao, Sandy TI Combined use of intense pulsed light and Q-switched ruby laser for complex dyspigmentation among Asian patients SO LASERS IN SURGERY AND MEDICINE LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the American-Society-for-Laser-Medicine-and-Surgery CY APR 11-15, 2007 CL Grapevine, TX SP Amer Soc Laser Med & Surg DE dyspigmentation; Asian ID ACQUIRED BILATERAL NEVUS; OTA-LIKE MACULES; PIGMENTED LESIONS; ALEXANDRITE LASER; HORIS NEVUS; YAG LASER; THERAPY; MELASMA; ND AB Background: Dyspigmentation is a common cosmetic concern among Asians. Many individuals exhibit mixed pigmentary entities including melasma, flat/small seborrheic keratoses, ephelides, solar lentigines and acquired bilateral nevus-of-Ota-like macules (ABNOM). We term this phenomenon complex dyspigmentation (CD) and suggest that a combination strategy may be more efficacious than any singular modality. Objective: To determine the effectiveness of combined intense-pulsed light (IPL) for global photorejuvenation along, with Q-switched ruby laser (QSRL) for targeted pigment dissolution. Study Design/Materials and Methods: Twenty-five Korean women with CD (defined as > 2 types of facial pigmentary disorders) were initially treated with IPL followed by repeat treatments every 3-4 weeks as needed. The QSRL treatments, set at low fluence, were added either during the same session or within 1 week of the IPL treatment. Improvement was assessed by the patient, the treating physician and a blinded evaluation of pre- and post-treatment photographs. Results: Using a 4-point scale (1 = poor, 2 = fair, 3 = good, 4 = excellent), 19/25 patients (76%) reporting good-to-excellent response (score "3" or "4"). Two independent physician assessment revealed that 15/25 patients (60%) showed 76-100% improvement while 19/25 patients (76%) showed at least 50% improvement. Side-effects were minimal: 3 patients had transient post-inflammatory hyperpigmentation (12%) and 1 patient (4%) had linear hypopigmentation. Conclusions: Combination treatment with IPL and QSRL is an effective and safe treatment for CD among Asian patients. C1 [Park, Jong Min; Tsao, Hensin; Tsao, Sandy] Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, Boston, MA 02114 USA. [Tsao, Sandy] Massachusetts Gen Hosp, MGH Dermatol Laser & Cosmet Ctr, Boston, MA 02114 USA. RP Tsao, S (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, Bartlett 6,48 Blossom St, Boston, MA 02114 USA. EM stsao@partners.org NR 16 TC 29 Z9 30 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD FEB PY 2008 VL 40 IS 2 BP 128 EP 133 DI 10.1002/lsm.20603 PG 6 WC Dermatology; Surgery SC Dermatology; Surgery GA 269SQ UT WOS:000253670900010 PM 18306166 ER PT J AU Anderson, KC Kyle, RA Rajkumar, SV Stewart, AK Weber, D Richardson, P AF Anderson, K. C. Kyle, R. A. Rajkumar, S. V. Stewart, A. K. Weber, D. Richardson, P. CA ASH FDA Panel Clinical Endpoints M TI Clinically relevant end points and new drug approvals for myeloma SO LEUKEMIA LA English DT Article; Proceedings Paper CT ASH/FDA Workshop on Clinical End Points in Multiple Myeloma CY OCT 26, 2006 CL Washington, DC SP ASH, FDA DE myeloma; novel therapies; drug approval ID STEM-CELL TRANSPLANTATION; DIAGNOSED MULTIPLE-MYELOMA; COOPERATIVE-ONCOLOGY-GROUP; UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHY; MAINTENANCE THERAPY; PLUS DEXAMETHASONE; IMPROVES SURVIVAL; RANDOMIZED TRIAL; PREDNISONE AB This manuscript summarizes the recommendations of the American Society of Hematology/US Food and Drug Administration Workshop on Clinical Endpoints in Multiple Myeloma, which brought together clinical investigators in multiple myeloma, the United States Food and Drug Administration, pharmaceutical companies, patient advocates and other concerned scientists and physicians to provide guidance, consensus and consistency in the definition of clinically relevant end points to expedite new drug approvals for multiple myeloma in the appropriate trial design settings. This manuscript will therefore be a most valuable resource to provide the framework for the design of appropriate clinical trial strategies for more rapid new drug approval in myeloma. C1 [Anderson, K. C.; Richardson, P.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kyle, R. A.; Rajkumar, S. V.] Mayo Clin, Div Hematol, Rochester, MN USA. [Stewart, A. K.] Mayo Clin, Div Hematol, Scottsdale, AZ USA. [Weber, D.] MD Anderson Canc Ctr, Dept Med, Houston, TX USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Mayer 557,44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu OI Rajkumar, S. Vincent/0000-0002-5862-1833 NR 56 TC 98 Z9 99 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD FEB PY 2008 VL 22 IS 2 BP 231 EP 239 DI 10.1038/sj.leu.2405016 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 262RY UT WOS:000253166900001 PM 17972944 ER PT J AU Palumbo, A Rajkumar, SV Dimopoulos, MA Richardson, PG Miguel, JS Barlogie, B Harousseau, J Zonder, JA Cavo, M Zangari, M Attal, M Belch, A Knop, S Joshua, D Sezer, O Ludwig, H Vesole, D Blade, J Kyle, R Westin, J Weber, D Bringhen, S Niesvizky, R Waage, A von Lilienfeld-Toal, M Lonial, S Morgan, GJ Orlowski, RZ Shimizu, K Anderson, KC Boccadoro, M Durie, BG Sonneveld, P Hussein, MA AF Palumbo, A. Rajkumar, S. V. Dimopoulos, M. A. Richardson, P. G. Miguel, J. San Barlogie, B. Harousseau, J. Zonder, J. A. Cavo, M. Zangari, M. Attal, M. Belch, A. Knop, S. Joshua, D. Sezer, O. Ludwig, H. Vesole, D. Blade, J. Kyle, R. Westin, J. Weber, D. Bringhen, S. Niesvizky, R. Waage, A. von Lilienfeld-Toal, M. Lonial, S. Morgan, G. J. Orlowski, R. Z. Shimizu, K. Anderson, K. C. Boccadoro, M. Durie, B. G. Sonneveld, P. Hussein, M. A. CA Int Myeloma Working Grp TI Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma SO LEUKEMIA LA English DT Article DE thrombosis; prophylaxis; risk factors; thalidomide; lenalidomide ID DEEP-VEIN THROMBOSIS; REFRACTORY MULTIPLE-MYELOMA; MOLECULAR-WEIGHT HEPARIN; HOSPITALIZED MEDICAL PATIENTS; CENTRAL VENOUS CATHETERS; NEWLY-DIAGNOSED MYELOMA; PATIENTS RECEIVING THALIDOMIDE; PREVIOUSLY TREATED PATIENTS; STEM-CELL TRANSPLANTATION; PLACEBO-CONTROLLED TRIAL AB The incidence of venous thromboembolism (VTE) is more than 1%omicron annually in the general population and increases further in cancer patients. The risk of VTE is higher in multiple myeloma (MM) patients who receive thalidomide or lenalidomide, especially in combination with dexamethasone or chemotherapy. Various VTE prophylaxis strategies, such as low-molecular-Weight heparin (LMWH), warfarin or aspirin, have been investigated in small, uncontrolled clinical studies. This manuscript summarizes the available evidence and recommends a prophylaxis strategy according to a risk-assessment model. Individual risk factors for thrombosis associated with thalidomide/lenalidomide-based therapy include age, history of VTE, central venous catheter, comorbidities (infections, diabetes, cardiac disease), immobilization, surgery and inherited thrombophilia. Myeloma-related risk factors include diagnosis and hyperviscosity. VTE is very high in patients who receive high-dose dexamethasone, doxorubicin or multiagent chemotherapy in combination with thalidomide or lenalidomide, but not with bortezomib. The panel recommends aspirin for patients with <= 1 risk factor for VTE. LMWH (equivalent to enoxaparin 40 mg per day) is recommended for those with two or more individual/myeloma-related risk factors. LMWH is also recommended for all patients receiving concurrent high-dose dexamethasone or doxorubicin. Full-dose warfarin targeting a therapeutic INR of 2-3 is an alternative to LMWH, although there are limited data in the literature with this strategy. In the absence of clear data from randomized studies as a foundation for recommendations, many of the following proposed strategies are the results of common sense or derive from the extrapolation of data from many studies not specifically designed to answer these questions. Further investigation is needed to define the best VTE prophylaxis. C1 [Palumbo, A.; Bringhen, S.; Boccadoro, M.] Univ Turin, Azienda Ospidaliera San Giovanni Battista, Div Ematol, I-10126 Turin, Italy. [Rajkumar, S. V.] Mayo Clin, Coll Med, Div Hematol, Rochester, MN USA. [Dimopoulos, M. A.] Univ Athens, Sch Med, Dept Clin Therapeut, GR-11527 Athens, Greece. [Richardson, P. G.; Anderson, K. C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Miguel, J. San] Hosp Clin Univ Salamanca, Dept Hematol, Salamanca, Spain. [Barlogie, B.; Zangari, M.] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Div Hematol Oncol, Little Rock, AR USA. [Harousseau, J.] Hop Hotel Dieu, Serv Hematol, Nantes, France. [Zonder, J. A.] Wayne State Univ, Sch Med, Karmanos Canc Ctr, Div Hematol Oncol, Detroit, MI USA. [Cavo, M.] Univ Bologna, Inst Hematol & Med Oncol Seragnoli, Bologna, Italy. [Attal, M.] Hop Purpan, Serv Hematol, Toulouse, France. [Belch, A.] Cross Canc Inst, Dept Hematol Oncol, Edmonton, AB T6G 1Z2, Canada. [Knop, S.] Tuebingen Univ Hosp, Dept Hematol Oncol, Tubingen, Germany. [Joshua, D.] Royal Prince Alfred Hosp, Inst Hematol, Sydney, NSW, Australia. [Ludwig, H.] Wilhelminenspital Stadt Wien, Dept Med 1, Ctr Oncol & Hematol, Vienna, Austria. [Vesole, D.] St Vincents Comprehens Canc Ctr, Dept Med, New York, NY USA. [Blade, J.] Univ Barcelona, Hosp Clin, IDIBAPS, Inst Hematol & Oncol,Hematol Dept, Barcelona, Spain. [Kyle, R.] Mayo Clin & Mayo Grad Sch Med, Lab Med, Div Hematol, Rochester, MN USA. [Westin, J.] Lund Univ, Dept Med, Div Hematol, Lund, Sweden. [Weber, D.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Lymphoma Myeloma, Houston, TX 77030 USA. [Niesvizky, R.] Cornell Univ, New York Presbytarian Hosp, Cornell Med Ctr,Ctr Excellence Lymphoma & Myeloma, Weill Med Coll,Div Hematol & Med Oncol, New York, NY USA. [Waage, A.] Univ Trondheim Hosp, Dept Hematol, Trondheim, Norway. [von Lilienfeld-Toal, M.] St James Univ Hosp, Bone Marrow Transplant Unit, Leeds LS9 7TF, W Yorkshire, England. [Lonial, S.] Emory Univ, Winship Canc Ctr, Div Hematol Oncol, Atlanta, GA 30322 USA. [Morgan, G. J.] Royal Marsden Hosp, Sect Haematooncol, London SW3 6JJ, England. [Morgan, G. J.] Inst Canc Res, London SW3 6JB, England. [Orlowski, R. Z.] Univ N Carolina, Div Hematol Oncol, Chapel Hill, NC USA. [Shimizu, K.] Nagoya City Midori Gen Hosp, Dept Med, Nagoya, Aichi, Japan. [Durie, B. G.] Cedars Sinai Comprehens Canc Ctr, Los Angeles, CA USA. [Sonneveld, P.] Erasmus MC, Dept Hematol, Rotterdam, Netherlands. [Hussein, M. A.] Cleveland Clin Taussing Canc Ctr, Multiple Myeloma Multidisciplinary Clin Res Progr, Dept Interdisciplinary Oncol, Cleveland, OH USA. [Sezer, O.] Charite, Dept Hematol & Oncol, D-10117 Berlin, Germany. RP Palumbo, A (reprint author), Univ Turin, Azienda Ospidaliera San Giovanni Battista, Div Ematol, Via Genova 3, I-10126 Turin, Italy. EM appalumbo@yahoo.com RI 2008, Ibsal/A-1268-2012; Waage, Anders/D-7705-2013; OI CAVO, MICHELE/0000-0003-4514-3227; Rajkumar, S. Vincent/0000-0002-5862-1833 NR 99 TC 377 Z9 390 U1 2 U2 23 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD FEB PY 2008 VL 22 IS 2 BP 414 EP 423 DI 10.1038/sj.leu.2405062 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 262RY UT WOS:000253166900025 PM 18094721 ER PT J AU Delgado-Borrego, A Liu, YS Jordan, SH Agrawal, S Zhang, H Christofi, M Casson, D Cosimi, B Chung, RT AF Delgado-Borrego, Aymin Liu, Yun-Sheen Jordan, Sergio H. Agrawal, Saurabh Zhang, Hui Christofi, Marielle Casson, Deborah Cosimi, Benedict Chung, Raymond T. TI Prospective study of liver transplant recipients with HCV infection: Evidence for a causal relationship between HCV and insulin resistance SO LIVER TRANSPLANTATION LA English DT Article ID HEPATITIS-C VIRUS; DIABETES-MELLITUS; CARDIOVASCULAR-DISEASE; MYCOPHENOLATE-MOFETIL; HEART-DISEASE; RISK-FACTORS; STEATOSIS; FIBROSIS; PROGRESSION; HYPERINSULINEMIA AB An association between hepatitis C virus (HCV) infection and insulin resistance (IR) has been recently reported. However, causality has not been established. The cross-sectional nature of most reported studies and varying degrees of fibrosis have limited definitive conclusions about the independent role of HCV in development of IR. We sought to evaluate whether HCV induces IR by prospectively analyzing a cohort of adult liver transplant (LT) recipients. A total of 34 adults (14 HCV(+) and 20 HCV(-)) who underwent consecutive LT were followed during the first year posttransplantation. IR was estimated using the homeostasis model assessment (HOMA). Univariate and multivariate repeated measures analyses and Cox regression models were used. There were no significant differences between the groups with respect to age, body mass index (BMI), family history of diabetes, alcohol consumption, or laboratory indices. The cohort had no or minimal fibrosis. There was lower prednisone use in the HCV(+) group, and no difference in the use of tacrolimus between the two groups was found. IR was 77% higher in HCV(+) subjects during the first year post-LT when controlling for BMI (P = 0.035). Subjects with high HCV ribonucleic acid (RNA) levels reached high HOMA-IR significantly earlier than those with lower HCV RNA (P = 0.03). Following the first month post-LT, HCV(+) subjects were 4 times more likely to become diabetic than HCV(-) controls (P < 0.01). In conclusion, there is significantly higher IR in the HCV(+) group during the first year post-LT. This cannot be explained by differences in BMI, medications used, alcohol consumption, or degree of fibrosis. Higher HCV RNA levels were associated with earlier elevations in HOMA-IR. Collectively, these results provide strong evidence that HCV induces the development of IR. C1 [Delgado-Borrego, Aymin; Liu, Yun-Sheen; Jordan, Sergio H.; Agrawal, Saurabh; Casson, Deborah; Chung, Raymond T.] Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. [Delgado-Borrego, Aymin] Univ Miami, Miller Sch Med, Dept Pediat, Div Gastroenterol, Miami, FL 33152 USA. [Delgado-Borrego, Aymin] Univ Miami, Miller Sch Med, Dept Pediat, Div Clin Res, Miami, FL 33152 USA. [Delgado-Borrego, Aymin; Christofi, Marielle] Childrens Hosp, Dept Med, Boston, MA 02115 USA. [Zhang, Hui] Massachusetts Gen Hosp, Ctr Biostat, Dept Med, Boston, MA 02114 USA. [Cosimi, Benedict; Chung, Raymond T.] Massachusetts Gen Hosp, Dept Surg, Transplantat Unit, Boston, MA 02114 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, 55 Fruit St,GRJ 724, Boston, MA 02114 USA. EM rtchung@partners.org FU NIDDK NIH HHS [K08 DK070022, K08 DK070022-05, R01 DK57857, R01 DK057857] NR 31 TC 39 Z9 42 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD FEB PY 2008 VL 14 IS 2 BP 193 EP 201 DI 10.1002/lt.21267 PG 9 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 260WA UT WOS:000253039900013 PM 18236394 ER PT J AU Singh, N Wannstedt, C Keyes, L Mayher, D Tickerhoof, L Akoad, M Wagener, MM Cacciarelli, TV AF Singh, Nina Wannstedt, Cheryl Keyes, Lois Mayher, Debra Tickerhoof, Lisa Akoad, Mohamed Wagener, Marilyn M. Cacciarelli, Thomas V. TI Valganciclovir as preemptive therapy for cytomegalovirus in cytomegalovirus-seronegative liver transplant recipients of cytomegalovirus-seropositive donor allografts SO LIVER TRANSPLANTATION LA English DT Article ID DISEASE; INFECTION; PROPHYLAXIS; GANCICLOVIR; PREVENTION; EFFICACY; METAANALYSIS; IMPACT AB The efficacy of valganciclovir as preemptive therapy for the prevention of cytomegalovirus (CMV) disease and its impact on indirect sequelae of CMV were assessed in recipient-negative/donor-positive (R-/D+) liver transplant recipients. Of 187 consecutive liver transplant recipients at our institution since July 2001, 36 (19.2%) belonged to the R-/D+ group. Surveillance tests for CMV were performed on all patients at weeks 2, 4, 6, 8, 10,12, and 16. In all, 27 patients with asymptomatic viremia received preemptive therapy with valganciclovir. At a total follow-up of 62.8 patient years (median: 19 months, range: 3 months to 5.6 years), no episodes of CMV disease were documented in these patients. The incidence of rejection, retransplantation, and bacterial or fungal infections and the probability of survival did not differ for R-/D+ patients and all non-R-/D+ patients treated preemptively with valganciclovir (P > 0.20 for all variables). Thus, preemptive therapy with valganciclovir in R-/D+ patients was not associated with CMV disease during the period of surveillance monitoring or at anytime thereafter (late-onset CMV disease). The indirect outcomes with the use of valganciclovir in R-/D+ patients were comparable to the outcomes of other subgroups of liver transplant recipients receiving preemptive therapy. C1 [Singh, Nina; Wagener, Marilyn M.] VA Pittsburgh Healthcare Syst, Dept Med, Div Infect Dis, Pittsburgh, PA USA. [Wannstedt, Cheryl; Keyes, Lois; Mayher, Debra; Tickerhoof, Lisa; Akoad, Mohamed; Cacciarelli, Thomas V.] VA Pittsburgh Healthcare Syst, Dept Surg, Div Liver Transplant, Pittsburgh, PA USA. RP Singh, N (reprint author), Vet Adm Med Ctr, Univ Dr C, Pittsburgh, PA 15240 USA. EM nis5@pitt.edu NR 17 TC 39 Z9 42 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD FEB PY 2008 VL 14 IS 2 BP 240 EP 244 DI 10.1002/lt.21362 PG 5 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 260WA UT WOS:000253039900020 PM 18236404 ER PT J AU Helmer, DA Tseng, CL Rajan, M Crystal, S Shen, YJ Miller, DR Safford, MM Tiwari, A Pogach, L AF Helmer, Drew A. Tseng, Chin-Lin Rajan, Mangala Crystal, Stephen Shen, Yujing Miller, Donald R. Safford, Monika M. Tiwari, Anjali Pogach, Leonard TI Can ambulatory care prevent hospitalization for metabolic decompensation? SO MEDICAL CARE LA English DT Article DE diabetes mellitus; ambulatory care; quality indicators; health care; diabetic ketoacidosis; veterans ID DIABETIC-KETOACIDOSIS; SENSITIVE CONDITIONS; INSULIN THERAPY; HEALTH-CARE; VETERANS; ACCESS AB Objective: Metabolic decompensations (MD) are hospitalizations considered preventable with appropriate ambulatory care. We tested for associations between diabetes care and MD. Research Design: We retrospectively compared care between cases (MD; n = 2714) and controls (without MD; n = 10,856) using merged Veterans Health Administration and Medicare data. Logistic regression tested for associations between MD and diabetes care controlling for patient characteristics. Subjects: Veterans Health Administration users with diabetes stratified into high [hemoglobin Alc (HA1c) >= 9%; n = 2532] and low (HA1c <9%; n = 6176) risk groups. Measures: The outcome was hospitalization for MD. Care was defined as quarterly or semiannual diabetes visits and HAIc testing during individualized 12-month baseline periods. Results: Cases averaged more diabetes visits and HAIc tests than controls (P < 0.001 for both) in the 12-month baseline period. Among the high-risk, 29.8% of cases made 4 quarterly visits compared with 29.6% of controls (P = 0.004); among the low-risk, there was no difference in semiannual visits. Among the high-risk, models showed having no visit was associated with higher odds of MD (adjusted odds ratio: 3.05; 95% confidence interval: 1.69-5.49) compared with 4 visits; individuals with 1-4 visits had similar odds of MD. More HA1c testing was weakly associated with higher odds of MD. Conclusions: MD was associated with more diabetes care, even controlling for patient characteristics. This inconsistency with the theoretical association between appropriate ambulatory care and lower MD rates indicates that MD rates may not accurately reflect diabetes care quality. C1 [Helmer, Drew A.; Tseng, Chin-Lin; Rajan, Mangala; Shen, Yujing; Tiwari, Anjali; Pogach, Leonard] Vet Adm New Jersey Hlth Care Syst, Ctr Healthcare Knowledge Management, E Orange, NJ USA. [Helmer, Drew A.; Tseng, Chin-Lin; Pogach, Leonard] Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. [Crystal, Stephen; Shen, Yujing] Rutgers State Univ, Inst Hlth Hlth Care Policy & Aging Res, New Brunswick, NJ 08903 USA. [Miller, Donald R.] VA New England Hlth Care Syst, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Miller, Donald R.] Boston Univ, Boston, MA 02215 USA. [Safford, Monika M.] Birmingham VA Med Ctr, Deep S Ctr Effectiveness, Birmingham, AL USA. [Safford, Monika M.] Univ Alabama, Birmingham, AL USA. RP Helmer, DA (reprint author), Michael E DeBakey VA Med Ctr, 2002 Holcombe Blvd 111PC, Houston, TX 77030 USA. EM drew.helmer@va.gov NR 31 TC 3 Z9 3 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD FEB PY 2008 VL 46 IS 2 BP 148 EP 157 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 258AQ UT WOS:000252841200008 PM 18219243 ER PT J AU Pugh, MJV Rosen, AK Montez-Rath, M Amuan, ME Fincke, BG Burk, M Bierman, A Cunningham, F Mortensen, EM Berlowitz, DR AF Pugh, Mwy Jo V. Rosen, Amy K. Montez-Rath, Maria Amuan, Megan E. Fincke, Benjamin G. Burk, Muriel Bierman, Arlene Cunningham, Francesca Mortensen, Eric M. Berlowitz, Dan R. TI Potentially inappropriate prescribing for the elderly - Effects of geriatric care at the patient and health core system level SO MEDICAL CARE LA English DT Article DE geriatric health services; quality of health care; innovation diffusion; clinical practice variation ID MEDICATION USE; EXPLICIT CRITERIA; DRUG-USE; VETERANS; POPULATION; MORTALITY; QUALITY; US AB Background: Many studies have identified patient characteristics associated with potentially inappropriate prescribing in the elderly (PIPE), however, little attention has been directed toward how health care system factors such as geriatric care may affect this patient safety issue. Objective: This study examines the association between geriatric care and PIPE in a community dwelling elderly population. Research Design: Cross-sectional retrospective database study. Subjects: Veterans age >= 65 years who received health care in the VA system during Fiscal Years (FY99-00), and also received at medications from the Veterans Administration in FY00. Measures: PIPE was identified using the Zhan adaptation of the Beers criteria. Geriatric care penetration was calculated as the proportion of patients within a facility who received at least I geriatric outpatient clinic or inpatient visit. Analyses: Logistic regression models with generalized estimating equations were used to assess the relationship between geriatric care and PIPE after controlling for patient and health care system characteristics. Results: Patients receiving geriatric care were less likely to have PIPE exposure (odds ratio, 0.64; 95% confidence interval, 0.59-0.73). There was also a weak effect for geriatric care penetration, with a trend for patients in low geriatric care penetration facilities having higher risk for PIPE regardless of individual geriatric care exposure (odds ratio, 1.14; 95% confidence interval, 0.99-1.30). Conclusions: Although geriatric care is associated with a lower risk of PIPE, additional research is needed to determine if heterogeneity in the organization and delivery of geriatric care resulted in the weak effect of geriatric care penetration, or whether this is a result of low power. C1 [Pugh, Mwy Jo V.; Mortensen, Eric M.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Pugh, Mwy Jo V.; Mortensen, Eric M.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Rosen, Amy K.; Montez-Rath, Maria; Amuan, Megan E.; Fincke, Benjamin G.; Berlowitz, Dan R.] Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Rosen, Amy K.; Berlowitz, Dan R.] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Burk, Muriel; Cunningham, Francesca] Pharm Benefits Managements Strateg Hlth Grp, Dept Vet Affairs, Hines, IL USA. [Bierman, Arlene] Ctr Res Inner City Hlth, Toronto, ON, Canada. RP Pugh, MJV (reprint author), STVHCS ALMD, VERDICT, 7400 Merton Minter Blvd 11C6, San Antonio, TX 78229 USA. EM pughm@uthscsa.edu OI Mortensen, Eric/0000-0002-3880-5563 NR 35 TC 25 Z9 26 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD FEB PY 2008 VL 46 IS 2 BP 167 EP 173 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 258AQ UT WOS:000252841200010 PM 18219245 ER PT J AU Taylor, BB Marcantonio, ER Pagovich, O Carbo, A Bergmann, M Davis, RB Bates, DW Phillips, RS Weingart, SN AF Taylor, Benjamin B. Marcantonio, Edward R. Pagovich, Odelya Carbo, Alexander Bergmann, Margaret Davis, Roger B. Bates, David W. Phillips, Russell S. Weingart, Saul N. TI Do medical inpatients who report poor service quality experience more adverse events and medical errors? SO MEDICAL CARE LA English DT Article; Proceedings Paper CT 29th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 27-29, 2006 CL Los Angeles, CA SP Soc Gen Internal Med DE adverse events; medical errors; service quality; patient-doctor communication ID PHYSICIAN-PATIENT COMMUNICATION; TECHNICAL QUALITY; HOSPITAL-CARE; HEALTH-CARE; MALPRACTICE CLAIMS; SATISFACTION; COMPLAINTS; NEGLIGENT AB Purpose: Service quality deficiencies are common in health care. However, little is known about the relationship between service quality and the occurrence of adverse events and medical errors. We hypothesized that patients who reported poor service quality were at increased risk of experiencing adverse events and medical errors. Subjects and Methods: Patients were interviewed during and after their admissions regarding problems experienced during the hospitalizations. We used this information to identify service quality deficiencies. We then performed a blinded, retrospective chart review to independently identify adverse events and errors. We used multivariable methods to analyze whether patients who reported service quality deficiencies (obtained by patient report) experienced any adverse event, close call, or low risk error (ascertained by chart review). Results: The 228 participants (mean age 63 years, 37% male) reported 183 service quality deficiencies. Of the 52 incidents identified on chart review, patients experienced 34 adverse events, 11 close calls, and 7 low risk errors. The presence of any service quality deficiency more than doubled the odds of any adverse event, close call, or low risk error (adjusted odds ratio = 2.5; 95% confidence interval = 1.2-5.4). Service quality deficiencies involving poor coordination of care (adjusted odds ratio = 4.4; 95% confidence interval = 1.4-14.0) were associated with the occurrence of adverse events and medical errors. Conclusions: Patient-reported service quality deficiencies were associated with adverse events and medical errors. Patients who report service quality incidents may help to identify patient safety hazards. C1 [Weingart, Saul N.] Dana Farber Canc Inst, Ctr Patient Safety, Boston, MA 02115 USA. [Taylor, Benjamin B.; Marcantonio, Edward R.; Carbo, Alexander; Bergmann, Margaret; Davis, Roger B.; Phillips, Russell S.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Marcantonio, Edward R.; Carbo, Alexander; Davis, Roger B.; Bates, David W.; Phillips, Russell S.; Weingart, Saul N.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Bates, David W.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. [Pagovich, Odelya] Beth Israel Deaconess Med Ctr, New York, NY 10003 USA. RP Weingart, SN (reprint author), Dana Farber Canc Inst, Ctr Patient Safety, 44 Binney St, Boston, MA 02115 USA. EM saul_weingart@dfci.harvard.edu FU AHRQ HHS [1 K08 HS 11644] NR 22 TC 29 Z9 31 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD FEB PY 2008 VL 46 IS 2 BP 224 EP 228 PG 5 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 258AQ UT WOS:000252841200017 PM 18219252 ER PT J AU Rivard, PE Luther, SL Christiansen, CL Zhao, SB Loveland, S Elixhauser, A Romano, PS Rosen, AK AF Rivard, Peter E. Luther, Stephen L. Christiansen, Cindy L. Zhao, Shibei Loveland, Susan Elixhauser, Anne Romano, Patrick S. Rosen, Amy K. TI Using patient safety indicators to estimate the impact of potential adverse events on outcomes SO MEDICAL CARE RESEARCH AND REVIEW LA English DT Article DE patient safety; patient safety indicators; outcomes; mortality; cost ID QUALITY-OF-CARE; IN-HOSPITAL MORTALITY; HEALTH-CARE; ADMINISTRATIVE DATA; UNITED-STATES; RISK-FACTORS; DRUG EVENTS; MEDICARE BENEFICIARIES; EXCESS LENGTH; COSTS AB The authors estimated the impact of potentially preventable patient safety events, identified by Agency for Healthcare Research and Quality (AHRQ) Patient Safety Indicators (PSIs), on patient outcomes: mortality, length of stay (LOS), and cost. The PSIs were applied to all acute inpatient hospitalizations at Veterans Health Administration (VA) facilities in fiscal 2001. Two methods-regression analysis and multivariable case matching-were used independently to control for patient and facility characteristics while predicting the effect of the PSI on each outcome. The authors found statistically significant (p < .0001) excess mortality, LOS, and cost in all groups with PSIs. The magnitude of the excess varied considerably across the PSIs. These VA findings are similar to those from a previously published study of nonfederal hospitals, despite differences between VA and non-VA systems. This study contributes to the literature measuring outcomes of medical errors and provides evidence that AHRQ PSIs may be useful indicators for comparison across delivery systems. C1 [Rivard, Peter E.] VA Boston Healthcare Syst, Boston, MA USA. [Christiansen, Cindy L.] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Romano, Patrick S.] Univ Calif Davis, Davis, CA 95616 USA. RP Rivard, PE (reprint author), VA Boston Healthcare Syst, Boston, MA USA. RI Romano, Patrick/N-4225-2014; OI Romano, Patrick/0000-0001-6749-3979; Christiansen, Cindy/0000-0001-9951-480X NR 55 TC 45 Z9 46 U1 3 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1077-5587 J9 MED CARE RES REV JI Med. Care Res. Rev. PD FEB PY 2008 VL 65 IS 1 BP 67 EP 87 DI 10.1177/1077558707309611 PG 21 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 251UW UT WOS:000252401800003 PM 18184870 ER PT J AU Suzuki, K Yoshida, H Nappi, J Armato, SG Dachman, AH AF Suzuki, Kenji Yoshida, Hiroyuki Naeppi, Janne Armato, Samuel G., III Dachman, Abraham H. TI Mixture of expert 3D massive-training ANNs for reduction of multiple types of false positives in CAD for detection of polyps in CT colonography SO MEDICAL PHYSICS LA English DT Article DE virtual colonoscopy; colon cancer; mixture of expert networks; CT colonography; computer-aided diagnosis; false-positive reduction; artificial neural network ID ARTIFICIAL NEURAL-NETWORK; COMPUTER-AIDED DIAGNOSIS; COLONIC POLYPS; LUNG NODULES; TOMOGRAPHIC COLONOGRAPHY; VIRTUAL COLONOSCOPY; VOLUMETRIC FEATURES; AUTOMATED DETECTION; CHEST RADIOGRAPHS; SMALL NUMBER AB One of the major challenges in computer-aided detection (CAD) of polyps in CT colonography (CTC) is the reduction of false-positive detections (FPs) without a concomitant reduction in sensitivity. A large number of FPs is likely to confound the radiologist's task of image interpretation, lower the radiologist's efficiency, and cause radiologists to lose their confidence in CAD as a useful tool. Major sources of FPs generated by CAD schemes include haustral folds, residual stool, rectal tubes, the ileocecal valve, and extra-colonic structures such as the small bowel and stomach. Our purpose in this study was to develop a method for the removal of various types of FPs in CAD of polyps while maintaining a high sensitivity. To achieve this, we developed a "mixture of expert" three-dimensional (3D) massive-training artificial neural networks (MTANNs) consisting of four 3D MTANNs that were designed to differentiate between polyps and four categories of FPs: (1) rectal tubes, (2) stool with bubbles, (3) colonic walls with haustral folds, and (4) solid stool. Each expert 3D MTANN was trained with examples from a specific non-polyp category along with typical polyps. The four expert 3D MTANNs were combined with a mixing artificial neural network (ANN) such that different types of FPs could be removed. Our database consisted of 146 CTC datasets obtained from 73 patients whose colons were prepared by standard pre-colonoscopy cleansing. Each patient was scanned in both supine and prone positions. Radiologists established the locations of polyps through the use of optical-colonoscopy reports. Fifteen patients had 28 polyps, 15 of which were 5-9 mm and 13 were 10-25 mm in size. The CTC cases were subjected to our previously reported CAD method consisting of centerline-based extraction of the colon, shape-based detection of polyp candidates, and a Bayesian-ANN-based classification of polyps. The original CAD method yielded 96.4% (27/28) by-polyp sensitivity with an average of 3.1 (224/73) FPs per patient. The mixture of expert 3D MTANNs removed 63% (142/224) of the FPs without the loss of any true positive; thus, the FP rate of our CAD scheme was improved to 1.1 (82/73) FPs per patient while the original sensitivity was maintained. By use of the mixture of expert 3D MTANNs, the specificity of a CAD scheme for detection of polyps in CTC was substantially improved while a high sensitivity was maintained. (C) 2008 American Association of Physicists in Medicine. C1 [Suzuki, Kenji; Armato, Samuel G., III; Dachman, Abraham H.] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. [Yoshida, Hiroyuki; Naeppi, Janne] Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Yoshida, Hiroyuki; Naeppi, Janne] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Suzuki, K (reprint author), Univ Chicago, Dept Radiol, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM suzuki@uchicago.edu RI Nappi, Janne/B-9424-2008; Suzuki, Kenji/A-1284-2007 OI Nappi, Janne/0000-0002-0108-0992; Suzuki, Kenji/0000-0002-3993-8309 FU NCI NIH HHS [R01CA120549] NR 54 TC 48 Z9 50 U1 2 U2 5 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD FEB PY 2008 VL 35 IS 2 BP 694 EP 703 DI 10.1118/1.2829870 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 264VL UT WOS:000253318400032 PM 18383691 ER PT J AU Wu, ZJ Rietzel, E Boldea, V Sarrut, D Sharp, GC AF Wu, Ziji Rietzel, Eike Boldea, Vlad Sarrut, David Sharp, Gregory C. TI Evaluation of deformable registration of patient lung 4DCT with subanatomical region segmentations SO MEDICAL PHYSICS LA English DT Article DE deformable image registration; validation; 4DCT ID GUIDED RADIATION-THERAPY; IMAGE REGISTRATION; RESPIRATORY MOTION; DOSE CALCULATION; PROSTATE-CANCER; MONTE-CARLO; RADIOTHERAPY; DEFORMATIONS; OPTIMIZATION; ALGORITHM AB Deformable registration is needed for a variety of tasks in establishing the voxel correspondence between respiratory phases. Most registration algorithms assume or imply, that the deformation field is smooth and continuous everywhere. However, the lungs are contained within closed invaginated sacs called pleurae and are allowed to slide almost independently along the chest wall. This sliding motion is characterized by a discontinuous vector field, which cannot be generated using standard deformable registration methods. The authors have developed a registration method that can create discontinuous vector fields at the boundaries of anatomical subregions. Registration is performed independently on each subregion, with a boundary-matching penalty used to prevent gaps. This method was implemented and tested using both the B-spline and Demons registration algorithms in the Insight Segmentation and Registration Toolkit. The authors have validated this method on four patient 4DCT data sets for registration of the end-inhalation and end-exhalation volumes. Multiple experts identified homologous points in the lungs and along the ribs in the two respiratory phases. Statistical analyses of the mismatch of the homologous points before and after registration demonstrated improved overall accuracy for both algorithms. (C) 2008 American Association of Physicists in Medicine. C1 [Wu, Ziji; Sharp, Gregory C.] Harvard Univ, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Rietzel, Eike] Siemens Med Solut, D-91052 Erlangen, Germany. [Boldea, Vlad] Univ Lyon 2, LIRIS Lab, Lyon, France. [Sarrut, David] Leon Berard Anti Canc Ctr, F-69373 Lyon, France. [Sarrut, David] CNRS, CREATIS Lab, UMR 5220, INSERM U630, Lyon, France. RP Wu, ZJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA. EM zwmedphy@gmail.com RI Sarrut, David/F-4849-2010 OI Sarrut, David/0000-0002-4854-4141 FU NCI NIH HHS [R01 CA 111590] NR 31 TC 76 Z9 77 U1 0 U2 6 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD FEB PY 2008 VL 35 IS 2 BP 775 EP 781 DI 10.1118/1.2828378 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 264VL UT WOS:000253318400041 PM 18383700 ER PT J AU Hawkins, VN Foster-Schubert, K Chubak, J Sorensen, B Ulrich, CM Stancyzk, FZ Plymate, S Stanford, J White, E Potter, JD McTiernan, A AF Hawkins, Vivian N. Foster-Schubert, Karen Chubak, Jessica Sorensen, Bess Ulrich, Cornelia M. Stancyzk, Frank Z. Plymate, Stephen Stanford, Janet White, Emily Potter, John D. McTiernan, Anne TI Effect of exercise on serum sex hormones in men: a 12-month randomized clinical trial SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE aerobic exercise; androgens; human males; adiposity ID MIDDLE-AGED MEN; BODY-FAT DISTRIBUTION; BINDING GLOBULIN; RESISTANCE EXERCISE; OLDER MEN; METABOLIC SYNDROME; ADIPOSE-TISSUE; ENDURANCE EXERCISE; INSULIN-RESISTANCE; ELDERLY-MEN AB Purpose: The effect of exercise on androgens in middle-aged to older men is poorly understood, and it could have implications for several aspects of health. This analysis was conducted to examine the effects of long-term aerobic exercise on serum sex hormones in middle-aged to older men. Methods: One hundred two sedentary men, ages 40-75 yr, were randomly assigned to a 12-month exercise intervention or a control group (no change in activity). The combined facility- and home-based exercise program consisted of moderate/vigorous-intensity aerobic activity for 60 min.d(-1), 6 d.wk(-1). Serum concentrations of testosterone, free testosterone, dilrydrotestosterone (DHT), 3 alpha-androstanediol glucuronide (3 alpha-Diol-G), estradiol, free estradiol, and sex hormone binding globulin (SHBG) were measured at baseline, 3, and 12 months. Results: Exercisers trained a mean of 370 min.wk(-1) (102% of goal), with only two dropouts. Cardiopulmonary fitness (VO2max) increased 10.8% in exercisers and decreased by 1.8% in controls (P<0.001). DHT increased 14.5% in exercisers versus 1.7% in controls at 3 months (P=0.04); at 12 months, it remained 8.6% above baseline in exercisers versus a 3.1% decrease in controls (P=0.03). SHBG increased 14.3% in exercisers versus 5.7% in controls at 3 months (P=0.04); at 12 months, it remained 8.9% above baseline in exercisers versus 4.0% in controls (P=0.13). There were significant trends toward increasing DHT and SHBG, with greater increases in VO2max at 3 and 12 months in exercisers. No statistically significant differences were observed for testosterone, free testosterone, 3a-Diol-G, estradiol, or free estradiol in exercisers versus controls. Conclusions: A yearlong, moderate-intensity aerobic exercise program increased DHT and SHBG, but it had no effect on other androgens in middle-aged to older men. C1 [Hawkins, Vivian N.; Foster-Schubert, Karen; Chubak, Jessica; Sorensen, Bess; Ulrich, Cornelia M.; White, Emily; Potter, John D.; McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98109 USA. [Hawkins, Vivian N.; Chubak, Jessica; Ulrich, Cornelia M.; Stanford, Janet; White, Emily; Potter, John D.; McTiernan, Anne] Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. [Foster-Schubert, Karen; Ulrich, Cornelia M.; Plymate, Stephen; McTiernan, Anne] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Stancyzk, Frank Z.] Univ So Calif, Sch Med, Los Angeles, CA USA. [Plymate, Stephen] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res & Educ Clin Ctr, Seattle, WA USA. [Stanford, Janet] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. RP McTiernan, A (reprint author), Fred Hutchinson Canc Res Ctr, Canc Prevent Program, POB 19024,M4-B402, Seattle, WA 98109 USA. EM amctiern@fhcrc.org RI Perez , Claudio Alejandro/F-8310-2010; OI Perez , Claudio Alejandro/0000-0001-9688-184X; Potter, John/0000-0001-5439-1500 FU NCATS NIH HHS [TL1 TR000422, UL1 TR000423]; NCI NIH HHS [R25 CA 94880, P20 CA 103728, P20 CA103728, R01 CA 77572, R01 CA077572, R25 CA094880, U54 CA 116847, U54 CA116847]; NCRR NIH HHS [K12 RR 023265-03, K12 RR023265, KL2 RR025015, KL2 RR025015-01] NR 66 TC 26 Z9 30 U1 7 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD FEB PY 2008 VL 40 IS 2 BP 223 EP 233 DI 10.1249/mss.0b013e31815cbba9 PG 11 WC Sport Sciences SC Sport Sciences GA 254SM UT WOS:000252608300006 PM 18202581 ER PT J AU Kawasaki, T Ohnishi, M Suemoto, Y Kirkner, GJ Liu, Z Yamamoto, H Loda, M Fuchs, CS Ogino, S AF Kawasaki, Takako Ohnishi, Mutsuko Suemoto, Yuko Kirkner, Gregory J. Liu, Zhiqian Yamamoto, Hiroyuki Loda, Massimo Fuchs, Charles S. Ogino, Shuji TI WRN promoter methylation possibly connects mucinous differentiation, microsatellite instability and CpG island methylator phenotype in colorectal cancer SO MODERN PATHOLOGY LA English DT Article DE colon cancer; WRN; mucin; DNA methylation; CIMP; MSI ID CULTURED SKIN FIBROBLASTS; POPULATION-BASED SAMPLE; REPLICATION PROTEIN-A; WERNERS-SYNDROME; DNA METHYLATION; BRAF MUTATION; COLON-CANCER; CIMP; GLYCOSAMINOGLYCANS; P53 AB Werner syndrome is a premature aging syndrome characterized by early onset of cancer and abnormal cellular metabolism of glycosaminoglycan. The WRN helicase plays an important role in the maintenance of telomere function. WRN promoter methylation and gene silencing are common in colorectal cancer with the CpG island methylator phenotype (CIMP), which is associated with microsatellite instability (MSI) and mucinous tumors. However, no study has examined the relationship between mucinous differentiation, WRN methylation, CIMP and MSI in colorectal cancer. Utilizing 903 population-based colorectal cancers and real-time PCR (MethyLight), we quantified DNA methylation in WRN and eight other promoters (CACNA1G, CDKN2A, CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1) known to be specific for CIMP. Supporting WRN as a good CIMP marker, WRN methylation was correlated well with CIMP-high diagnosis (>= 6/8 methylated promoters), demonstrating 89% sensitivity and 81% specificity. WRN methylation was associated with the presence of any mucinous component and >= 50% mucinous component (P<0.0001). Because both MSI and CIMP were associated with mucinous tumors and WRN methylation, we stratified tumors into 9 MSI/CIMP subtypes, to examine whether the relationship between WRN methylation and mucin still persisted. In each MSI/CIMP subtype, tumors with mucinous component were persistently more common in WRN-methylated tumors than WRN-unmethylated tumors (P=0.004). No relations of WRN methylation with other variables (age, sex, tumor location, poor differentiation, signet ring cells, lymphocytic reactions, KRAS, BRAF, p53, p21 or 18q loss of heterozygosity) persisted after tumors were stratified by CIMP status. In conclusion, WRN methylation is associated with mucinous differentiation independent of CIMP and MSI status. Our data suggest a possible role of WRN methylation in mucinous differentiation, and may provide explanation to the enigmatic association between mucin and MSI/CIMP. C1 [Kawasaki, Takako; Kirkner, Gregory J.; Loda, Massimo; Fuchs, Charles S.; Ogino, Shuji] Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Sch Med, Boston, MA 02115 USA. [Kawasaki, Takako; Ohnishi, Mutsuko; Suemoto, Yuko; Liu, Zhiqian; Loda, Massimo; Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kirkner, Gregory J.; Fuchs, Charles S.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA USA. [Yamamoto, Hiroyuki] Sapporo Med Univ, Dept Internal Med 1, Sapporo, Hokkaido, Japan. RP Ogino, S (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Sch Med, 75 Francis St, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu FU NCI NIH HHS [P01 CA 55075, P01 CA 87969] NR 48 TC 17 Z9 17 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2008 VL 21 IS 2 BP 150 EP 158 DI 10.1038/modpathol.3800996 PG 9 WC Pathology SC Pathology GA 255MU UT WOS:000252662900010 PM 18084250 ER PT J AU Hoang, MP Dresser, KA Kapur, P High, WA Mahalingam, M AF Hoang, Mai P. Dresser, Karen A. Kapur, Payal High, Whitney A. Mahalingam, Meera TI Microcystic adnexal carcinoma: an immunohistochemical reappraisal SO MODERN PATHOLOGY LA English DT Article DE microcystic adnexal carcinoma; squamous cell carcinoma with ductal differentiation; desmoplastic trichoepithelioma; infiltrative basal cell carcinoma; cytokeratin 15; BerEP4 ID BASAL-CELL CARCINOMA; SWEAT GLAND CARCINOMA; FOLLICLE STEM-CELLS; MONOCLONAL-ANTIBODY; SQUAMOUS-CELL; SEBACEOUS DIFFERENTIATION; SYRINGOMATOUS CARCINOMA; CYTOKERATIN 15; BER EP4; SKIN AB Even though immunohistochemical comparisons of microcystic adnexal carcinoma vs infiltrative basal cell carcinoma and desmoplastic trichoepithelioma exist, they are mostly restricted to the use of a single stain. In addition, a comparison with squamous cell carcinoma has not been reported previously. In this study, we compare the expression of cytokeratin (CK) 15, CK7, CK20, CK903, carcinoembryonic antigen (CEA), CD10, CD15 and BerEP4 in 13 microcystic adnexal carcinoma, eight desmoplastic trichoepithelioma, 10 infiltrative basal cell carcinoma, and eight squamous cell carcinoma of which five exhibited ductal differentiation. We found that the majority of microcystic adnexal carcinoma (92%) and desmoplastic trichoepithelioma (100%) cases expressed CK15 while the infiltrative basal cell carcinoma and squamous cell carcinoma cases were all negative. Forty percent of infiltrative basal cell carcinoma expressed CK7; while only two microcystic adnexal carcinoma cases (15%) and one squamous cell carcinoma with ductal differentiation (12%) expressed CK7 in the remaining three tumor categories. None of the desmoplastic trichoepithelioma expressed CK7. All tumors were strongly positive for CK903. While the neoplastic cells were negative, luminal staining of ductal structures was noted for CK7, CD15 and CEA in some of the microcystic adnexal carcinoma, desmoplastic trichoepithelioma and squamous cell carcinoma with ductal differentiation cases. Sixty percent of infiltrative basal cell carcinoma, 31% of microcystic adnexal carcinoma, and 25% of squamous cell carcinoma express CD10. BerEP4 expression was noted in 38% of microcystic adnexal carcinoma, 57% of desmoplastic trichoepithelioma, 100% of infiltrative basal cell carcinoma, and 38% of squamous cell carcinoma. In conclusion, we found CK15 to be a useful marker in distinguishing microcystic adnexal carcinoma from infiltrative basal cell carcinoma and squamous cell carcinoma with ductal differentiation. Our experience indicates that microcystic adnexal carcinoma and desmoplastic trichoepithelioma have a similar immunohistochemical profile that is, CK15+ and BerEP4+/-; thus, additional studies are needed to separate these two entities. C1 [Hoang, Mai P.; Dresser, Karen A.; Mahalingam, Meera] UMass Med Sch, Dept Pathol, Worcester, MA USA. [Kapur, Payal] Univ Texas Dallas, SW Med Ctr, Dept Pathol, Dallas, TX USA. [High, Whitney A.] Univ Colorado, Hlth Sci Ctr, Dept Dermatol, Aurora, CO USA. RP Hoang, MP (reprint author), Massachusetts Gen Hosp, Dermatopathol Unit, 55 Fruit St,Warren 820, Boston, MA 02114 USA. EM mhoang@partners.org OI Mahalingam, Meera/0000-0002-2800-9985 NR 42 TC 40 Z9 44 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2008 VL 21 IS 2 BP 178 EP 185 DI 10.1038/modpathol.3801000 PG 8 WC Pathology SC Pathology GA 255MU UT WOS:000252662900013 PM 18065959 ER PT J AU Oh, R Ho, R Mar, L Gertsenstein, M Paderova, J Hsien, J Squire, JA Higgins, MJ Nagy, A Lefebvre, L AF Oh, Rosemary Ho, Rita Mar, Lynn Gertsenstein, Marina Paderova, Jana Hsien, John Squire, Jeremy A. Higgins, Michael J. Nagy, Andras Lefebvre, Louis TI Epigenetic and phenotypic consequences of a truncation disrupting the imprinted domain on distal mouse chromosome 7 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID BECKWITH-WIEDEMANN-SYNDROME; EMBRYONIC STEM-CELLS; MOUSE H19 GENE; REPRESSIVE HISTONE METHYLATION; PATERNAL DUPLICATION; GROWTH-RETARDATION; MAMMALIAN-CELLS; DNA METHYLATION; HUMAN TELOMERES; MICE AB The distal end of mouse chromosome 7 (Chr 7) contains a large cluster of imprinted genes. In this region two cis-acting imprinting centers, IC1 (H19 DMR) and IC2 (KvDMR1), define proximal and distal subdomains, respectively. To assess the functional independence of ICI in the context of Chr 7, we developed a recombinase- mediated chromosome truncation strategy in embryonic stem cells and generated a terminal deletion allele, DelTel7, with a breakpoint in between the two subdomains. We obtained germ line transmission of the truncated Chr 7 and viable paternal heterozygotes, confirming the absence of developmentally required paternally expressed genes distal of Ins2. Conversely, maternal transmission of DelTel7 causes a midgestational lethality, consistent with loss of maternally expressed genes in the IC2 subdomain. Expression and DNA methylation analyses on DelTel7 heterozygotes demonstrate the independent imprinting of ICI in absence of the entire IC2 subdomain. The evolutionarily conserved linkage between the subdomains is therefore not required for IC1 imprinting on Chr 7. Importantly, the developmental phenotype of maternal heterozygotes is rescued fully by a paternally inherited deletion of IC2. Thus, all the imprinted genes located in the region and required for normal development are silenced by an IC2-dependent mechanism on the paternal allele. C1 [Oh, Rosemary; Ho, Rita; Lefebvre, Louis] Univ British Columbia, Dept Med Genet, Life Sci Ctr, Mol Epigenet Grp,Life Sci Inst, Vancouver, BC V6T 1Z3, Canada. [Gertsenstein, Marina; Hsien, John; Nagy, Andras] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Mar, Lynn] Dana Farber Canc Inst, Boston, MA 02115 USA. [Paderova, Jana; Squire, Jeremy A.] Princess Margaret Hosp, Ontario Canc Inst, Toronto, ON M5G 2M9, Canada. [Squire, Jeremy A.] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 2M9, Canada. [Higgins, Michael J.] Roswell Pk Canc Inst, Dept Canc Genet, Buffalo, NY 14263 USA. RP Lefebvre, L (reprint author), Univ British Columbia, Dept Med Genet, Life Sci Ctr, Mol Epigenet Grp,Life Sci Inst, 5503-2350 Hlth Sci Mall, Vancouver, BC V6T 1Z3, Canada. EM louis.lefebvre@ubc.ca RI Nagy, Andras/G-6465-2013; Lefebvre, Louis/O-9309-2016; OI Lefebvre, Louis/0000-0001-5664-9480; Squire, Jeremy/0000-0002-9863-468X NR 71 TC 10 Z9 10 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 2008 VL 28 IS 3 BP 1092 EP 1103 DI 10.1128/MCB.01019-07 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 254RQ UT WOS:000252606100020 PM 18039841 ER PT J AU Trotter, KW Fan, HY Ivey, ML Kingston, RE Archer, TK AF Trotter, Kevin W. Fan, Hua-Ying Ivey, Melissa L. Kingston, Robert E. Archer, Trevor K. TI The HSA domain of BRG1 mediates critical interactions required for glucocorticoid receptor-dependent transcriptional activation in vivo SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CHROMATIN-REMODELING COMPLEX; BREAST-CANCER CELLS; NUCLEAR RECEPTORS; ESTROGEN-RECEPTOR; SWI/SNF COMPLEXES; RESPONSIVE GENES; SUBUNITS; PROTEINS; FAMILY; DNA AB The packaging of eukaryotic DNA into chromatin can create an impediment to transcription by hindering binding of essential factors required for transcription. The mammalian SWI/SNF remodeling complex has been shown to alter local chromatin structure and facilitate recruitment of transcription factors. BRG1 (or hBrm), the central ATPase of the human SWI/SNF complex, is a critical factor for the functional activity of nuclear receptor complexes. Analysis using BRG1/SNF2h chimeras suggests BRG1 may contain previously uncharacterized functional motifs important for SWI/SNF. To identify these regions, BRG1 truncation and deletion mutants were designed, characterized, and utilized in a series of assays to evaluate transcriptional activation and chromatin remodeling by the glucocorticoid receptor. We identified a domain within the N terminus of BRG1 that mediates critical protein interactions within SWI/SNF. We find the HSA domain of BRG1 is required to mediate the interaction with BAF250a/ARIDIA and show this association is necessary for transcriptional activation from chromatin mouse mammary tumor virus or endogenous promoters in vivo. These studies suggest BAF250a is a necessary facilitator of BRG1-mediated chromatin remodeling required for SWI/SNF-dependent transcriptional activation. C1 [Trotter, Kevin W.; Ivey, Melissa L.; Archer, Trevor K.] NIEHS, NIH, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. [Fan, Hua-Ying; Kingston, Robert E.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Fan, Hua-Ying] Fox Chase Canc Ctr, Div Basic Sci, Philadelphia, PA 19111 USA. [Fan, Hua-Ying; Kingston, Robert E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Archer, TK (reprint author), NIEHS, NIH, Mol Carcinogenesis Lab, POB 12233, Res Triangle Pk, NC 27709 USA. EM archer1@me.nih.gov FU Intramural NIH HHS; NCI NIH HHS [K01 CA093660, CA-093660] NR 40 TC 30 Z9 31 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 2008 VL 28 IS 4 BP 1413 EP 1426 DI 10.1128/MCB.01301-07 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 260SD UT WOS:000253029800020 PM 18086889 ER PT J AU Fischer, S Kleinschnitz, C Muller, M Kobsar, I Ip, CW Rollins, BJ Martini, R AF Fischer, Stefan Kleinschnitz, Christoph Mueller, Marcus Kobsar, Igor Ip, Chi Wang Rollins, Barrett J. Martini, Rudolf TI Monocyte chemoattractant protein-1 is a pathogenic component in a model for a hereditary peripheral neuropathy SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article DE Schwarm cell; myelin; macrophages; MCP-1; P0 ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MICE HETEROZYGOUSLY DEFICIENT; CENTRAL-NERVOUS-SYSTEM; LYMPHOCYTIC CHORIOMENINGITIS; MACROPHAGE RECRUITMENT; ANIMAL-MODEL; EXPRESSION; INJURY; MYELIN; CELLS AB Macrophages are critically involved in the pathogenesis of genetically caused demyelination, as it occurs in models for inherited demyelinating neuropathies. It is presently unknown which factors link the Scbwann cell-based myelin mutation to the activation of endoneurial macrophages. Here we identified the chemokine monocyte chemoattractant protein-1 (MCP-1) as a first and crucial factor upregulated in Schwann cells of mice heterozygously deficient for the myelin protein zero. The chemokine could be identified as an important mediator of macrophage immigration into peripheral nerves. Furthermore, a 50% reduction of chemokine expression by crossbreeding with MCP-1-deficient mice reduced the increase in macrophage numbers in the mutant nerves and lead to a robust amelioration of pathology. Surprisingly, the complete absence of MCP-1 aggravated the disease. Our findings show that reducing but not eliminating chemokine expression can rescue genetically caused demyelination that may be an interesting target in treating demyelinating diseases of the peripheral nervous system. (C) 2007 Elsevier Inc. All rights reserved. C1 [Fischer, Stefan; Kobsar, Igor; Ip, Chi Wang; Martini, Rudolf] Univ Wurzburg, Dept Neurol Dev Neurobiol, D-97080 Wurzburg, Germany. [Kleinschnitz, Christoph] Univ Wurzburg, Dept Neurol Neuroimmunol Multiple Sclerosis Res, D-97080 Wurzburg, Germany. [Mueller, Marcus] Univ Munster, Dept Neurol, D-4400 Munster, Germany. [Rollins, Barrett J.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Martini, R (reprint author), Univ Wurzburg, Dept Neurol Dev Neurobiol, Josef Schneider Str 11, D-97080 Wurzburg, Germany. EM rudolf.martini@mail.uni-wuerzburg.de OI Martini, Rudolf/0000-0002-5463-5592 NR 35 TC 23 Z9 24 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD FEB PY 2008 VL 37 IS 2 BP 359 EP 366 DI 10.1016/j.mcn.2007.10.012 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 263ON UT WOS:000253226500015 PM 18326085 ER PT J AU Liddle, FJ Frank, DA AF Liddle, Forrester J. Frank, David A. TI STAT1 expression is not required for polyp formation in min mice SO MOLECULAR CARCINOGENESIS LA English DT Article DE tumorigenesis; signal transduction; colon polyps; colon cancer; transcription factors ID INTERFERON-GAMMA; TARGETED DISRUPTION; TUMOR PROGRESSION; CARCINOMA-CELLS; INTERLEUKIN-6; RECEPTOR; GROWTH; CANCER; MOUSE; NEOPLASIA AB Recent studies have suggested the importance of interleukin (IL)-6 signaling in the development of colon cancer. Expression of IL-6 and the IL-6 receptor have been found to be elevated in colorectal carcinoma tissue, and IL-6 has been found to be critical for tumor formation in mouse models of colon cancer. IL-6 mediated activation of the transcription factor STAT1 has been shown to be important in protection of colorectal carcinoma cells from apoptotic signals. To test the hypothesis that the IL-6-STAT1 axis plays a role in early stages of colon cancer development, we examined the role of this pathway in the mouse multiple intestinal neoplasia (Min) model of intestinal tumorigenesis. Due to low fecundity, we were unable to generate Min mice lacking expression of IL-6. We then focused on the role of STAT1 in intestinal polyp formation in these animals. Min mice lacking STAT1 or heterozygous for STAT1, developed polyps in similar numbers as those expressing STAT1. Furthermore, the anatomic distribution and histological characteristics of these polyps did not vary among these populations. These results indicate that STAT1 does not play a role in the pathogenesis of the Min model for colon cancer. However, they do not rule out the possibility that STAT1 plays a role in other stages of colon cancer development. (C) 2007 Wiley-Liss, Inc. C1 [Liddle, Forrester J.; Frank, David A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Liddle, Forrester J.; Frank, David A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA USA. RP Frank, DA (reprint author), Dana Farber Canc Inst, Room M552B,44 Binney St, Boston, MA 02115 USA. NR 21 TC 4 Z9 4 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD FEB PY 2008 VL 47 IS 2 BP 75 EP 79 DI 10.1002/mc.20371 PG 5 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 261LB UT WOS:000253079000001 PM 17683066 ER PT J AU Ko, S Shi, L Kim, S Song, CS Chatterjee, B AF Ko, Soyoung Shi, Liheng Kim, Soyoung Song, Chung S. Chatterjee, Bandana TI Interplay of nuclear factor-kappa B and B-myb in the negative regulation of androgen receptor expression by tumor necrosis factor alpha SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID PROSTATE-CANCER CELLS; ACID-SULFOTRANSFERASE SULT2A1; HISTONE DEACETYLASE; TRANSCRIPTIONAL REPRESSION; INDUCED APOPTOSIS; N-COR; GENE; RESISTANCE; GROWTH; RNA AB Increased androgen receptor (AR) levels are associated with prostate cancer progression to androgen independence and therapy resistance. Evidence has suggested that chronic inflammation is closely linked to various cancers including prostate cancer. Herein we show that the proinflammatory cytokine TNF alpha negatively regulates AR mRNA and protein expression and reduces androgen sensitivity in androgen-dependent LNCaP human prostate cancer cells. Decreased AR expression results from transcription repression involving essential in cis interaction of nuclear factor-kappa B (NF-kappa B) with the B- myb transcription factor at a composite genomic element in the 5'-untranslated region of AR. The negative regulation was abrogated when NF-kappa B activity was inhibited by a superrepressor of the inhibitory kappa B protein. In contrast, androgen- independent C4-2 (LNCaP-derived) cells fail to show AR down- regulation by TNF alpha, despite expression of B-myb and TNF alpha-induced NF-kappa B activity similar to that in LNCaP cells. The negatively regulated AR gene chromatin region showed TNF alpha-dependent enrichment of B-myb and the NF-kappa B proteins p65 and p50. In parallel, the histone deacetylase 1, corepressor silencing mediator of retinoid and thyroid hormone receptor and the corepressor-associated scaffold protein mSin3A were recruited to the inhibitory site. In C4-2 cells, neither NF-kappa B and B-myb, nor any of the corepressor components, were detected at the negative site in response to TNF alpha. Apoptosis was induced in TNF alpha- treated LNCaP cells, likely in part due to the down- regulation of AR. The androgen- independent, AR-expressing C4-2 and C4-2B (derived from C4-2) cells were resistant to TNF alpha- induced apoptosis. The results linking androgen dependence to the NF- kappa B and AR pathways may be insightful in identifying novel treatment targets for prostate cancer. C1 [Ko, Soyoung; Shi, Liheng; Kim, Soyoung; Song, Chung S.; Chatterjee, Bandana] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, Inst Biotechnol, San Antonio, TX 78245 USA. [Chatterjee, Bandana] Audie L Murphy Vet Affairs Hosp, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Chatterjee, B (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, Inst Biotechnol, 15355 Lambda Dr, San Antonio, TX 78245 USA. EM chatterjee@uthscsa.edu FU NIA NIH HHS [AG 19660, R01 AG010486, AG 10486, R01 AG019660, R37 AG010486] NR 40 TC 25 Z9 25 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD FEB PY 2008 VL 22 IS 2 BP 273 EP 286 DI 10.1210/me.2007-0332 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 255SV UT WOS:000252678600006 PM 17975021 ER PT J AU Hou, XY Arvisais, EW Jiang, C Chen, DB Roy, SK Pate, JL Hansen, TR Rueda, BR Davis, JS AF Hou, Xiaoying Arvisais, Edward W. Jiang, Chao Chen, Dong-Bao Roy, Shyamal K. Pate, Joy L. Hansen, Thomas R. Rueda, Bo R. Davis, John S. TI Prostaglandin F2 alpha stimulates the expression and secretion of transforming growth factor B1 via induction of the early growth response 1 gene (EGR1) in the bovine corpus luteum SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; SIGNAL-TRANSDUCTION PATHWAYS; TRANSCRIPTION FACTOR EGR-1; ACTIVATED PROTEIN-KINASE; SERUM RESPONSE FACTOR; FACTOR-I; FACTOR-BETA-1 GENE; MAMMALIAN OVARY; TGF-BETA; A EGR-1 AB In most mammals, prostaglandin F2 alpha (PGF2 alpha) is believed to be a trigger that induces the regression of the corpus luteum (CL), whereby progesterone synthesis is inhibited, the luteal structure involutes, and the reproductive cycle resumes. Studies have shown that the early growth response 1 (EGR1) protein can induce the expression of proapoptotic proteins, suggesting that EGR1 may play a role in luteal regression. Our hypothesis is that EGR1 mediates the actions of PGF2 alpha by inducing the expression of TGF beta 1 (TGFB1), a key tissue remodeling protein. The levels of EGR1 mRNA and protein were up-regulated in the bovine CL during PGF2 alpha-induced luteolysis in vivo and in PGF2 alpha-treated luteal cells in vitro. Using chemical and genetic approaches, the RAF/MAPK kinase (MEK) 1/ERK pathway was identified as a proximal signaling event required for the induction of EGR1 in PGF2 alpha-treated cells. Treatment with PGF2 alpha increased the expression of TGFB1 mRNA and protein as well as the binding of EGR1 protein to TGFB1 promoter in bovine luteal cells. The effect of PGF2 alpha on TGFB1 expression was mimicked by a protein kinase C (PKC)/RAF/MEK1/ERK activator or adenoviral-mediated expression of EGR1. The stimulatory effect of PGF2 alpha on TGFB1 mRNA and TGFB1 protein secretion was inhibited by blockade of MEK1/ERK signaling and by adenoviral-mediated expression of NAB2, an EGR1 binding protein that inhibits EGR1 transcriptional activity. Treatment of luteal cells with TGFB1 reduced progesterone secretion, implicating TGFB1 in luteal regression. These studies demonstrate that PGF2 alpha stimulates the expression of EGR1 and TGFB1 in the CL. We suggest that EGR1 plays a role in the expression of genes whose cognate proteins coordinate luteal regression. C1 [Hou, Xiaoying; Arvisais, Edward W.; Davis, John S.] Dept Vet Affairs Med Ctr, Omaha, NE 68105 USA. [Hou, Xiaoying; Arvisais, Edward W.; Jiang, Chao; Davis, John S.] Univ Nebraska Med Ctr, Ctr Womens Hlth, Omaha, NE 68198 USA. [Roy, Shyamal K.] Univ Nebraska Med Ctr, Dept Obstet & Gynecol, Omaha, NE 68198 USA. [Roy, Shyamal K.] Univ Nebraska Med Ctr, Dept Physiol & Biophys, Omaha, NE 68198 USA. [Davis, John S.] Univ Nebraska Med Ctr, Dept Biochem & Mol Biol, Omaha, NE 68198 USA. [Davis, John S.] Univ Nebraska Med Ctr, Dept Pharmacol & Expt Neurosci, Omaha, NE 68198 USA. [Chen, Dong-Bao] Univ Calif San Diego, Med Ctr, Dept Reprod Med, La Jolla, CA 92093 USA. [Pate, Joy L.] Ohio State Univ, Dept Anim Sci, Wooster, OH 44691 USA. [Hansen, Thomas R.] Colorado State Univ, Dept Biomed Sci, Ft Collins, CO 80523 USA. [Rueda, Bo R.] Massachusetts Gen Hosp, Vincent Reprod Biol, Boston, MA 02114 USA. [Rueda, Bo R.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Davis, JS (reprint author), Nebraska Med Ctr, Omaha, NE 68198 USA. EM jsdavis@unmc.edu FU NICHD NIH HHS [R01 HD 35934-08, HD 048754, R01 HD035934, R03 HD048754] NR 48 TC 30 Z9 33 U1 1 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD FEB PY 2008 VL 22 IS 2 BP 403 EP 414 DI 10.1210/me.2007-0272 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 255SV UT WOS:000252678600015 PM 17916653 ER PT J AU Wilcox, WR Oliveira, JP Hopkin, RJ Ortiz, A Banikazemi, M Feldt-Rasmussen, U Sims, K Waldek, S Pastores, GM Lee, P Eng, CM Marodi, L Stanford, KE Breunig, F Wanner, C Warnock, DG Lemay, RM Germain, DP AF Wilcox, William R. Oliveira, Joao Paulo Hopkin, Robert J. Ortiz, Alberto Banikazemi, Maryam Feldt-Rasmussen, Ulla Sims, Katherine Waldek, Stephen Pastores, Gregory M. Lee, Philip Eng, Christine M. Marodi, Laszlo Stanford, Kevin E. Breunig, Frank Wanner, Christoph Warnock, David G. Lemay, Roberta M. Germain, Dominique P. TI Females with Fabry disease frequently have major organ involvement: Lessons from the Fabry Registry SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE fabry disease; heterozygote; alpha-galactosidase a; enzyme replacement; chronic kidney disease; proteinuria; cardiomyopathy; stroke ID ENZYME REPLACEMENT THERAPY; QUALITY-OF-LIFE; GLOMERULAR-FILTRATION-RATE; GALACTOSIDASE-A ACTIVITY; AGALSIDASE-BETA THERAPY; CLINICAL-MANIFESTATIONS; NATURAL-HISTORY; OUTCOME SURVEY; ALPHA-GALACTOSIDASE; HEMODIALYSIS-PATIENTS AB Fabry disease (FD) is an X-linked lysosomal storage disease caused by alpha-galactosidase A deficiency. The Fabry Registry is a global clinical effort to collect longitudinal data on FD. In the past, most "carrier" females were usually thought to be clinically unaffected. A systematic effort has been made to enroll all FD females, regardless of symptomology. Of the 1077 enrolled females in the Registry, 69.4% had symptoms and signs of FD. The median age at symptom onset among females was 13 years, and even though 84.1 % had a positive family history, the diagnosis was not made until a median age of 31 years. Twenty percent experienced major cerebrovascular, cardiac, or renal events, at a median age of 46 years. Among adult females with estimated glomerular filtration rate (eGFR) data (N = 638), 62.5% had an eGFR <90 ml/min/1.73M(2) and 19.0% had eGFR <60 ml/min/1.73 m(2). Proteinuria >= 300 mg/day was present in 39.0% of females, and 22.2% had >1 gram/day. Quality of life (QoL), as measured by the SF-36((R)) survey, was impaired at a later age than in males, but both genders experience significantly impaired QoL from the third decade of life onward. Thus, females with FD have a significant risk for major organ involvement and decreased QoL. Females should be regularly monitored for signs and symptoms of FD, and considered for enzyme replacement therapy. C1 [Wilcox, William R.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Wilcox, William R.] Univ Calif Los Angeles, Sch Med, Dept Pediat, Los Angeles, CA 90024 USA. [Oliveira, Joao Paulo] Hosp Sao Joao, Oporto, Portugal. [Hopkin, Robert J.] Cincinnati Childrens Hosp, Cincinnati, OH USA. [Ortiz, Alberto] Fdn Jimenez Diaz, E-28040 Madrid, Spain. [Banikazemi, Maryam; Pastores, Gregory M.] NYU, New York, NY USA. [Feldt-Rasmussen, Ulla] Univ Copenhagen, Rigshosp, Dept Med Endocrinol, DK-1168 Copenhagen, Denmark. [Sims, Katherine] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. [Waldek, Stephen] Hope Hosp, Salford, England. [Lee, Philip] Natl Hosp Neurol & Neurosurg, London, England. [Eng, Christine M.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Marodi, Laszlo] Univ Debrecen, Med & Hlth Sci Ctr, Dept Infect & Pediat Immunol, Debrecen, Hungary. [Stanford, Kevin E.] Univ Cincinnati, Coll Med, Dept Psychiat, Cincinnati, OH USA. [Breunig, Frank] Univ Hosp, Dept Med, Div Nephrol, Wurzburg, Germany. [Wanner, Christoph] Univ Hosp, Dept Med, Wurzburg, Germany. [Warnock, David G.] Univ Alabama, Birmingham, AL USA. [Lemay, Roberta M.] Genzyme Corp, Biomed Operat, Genzyme, WY USA. [Germain, Dominique P.] Hop Paris, Ctr Reference Maladie Fabry Maladies Hereditaires, Paris, France. [Germain, Dominique P.] Univ Versailles, St Quentin en Yvelines, France. RP Wilcox, WR (reprint author), Cedars Sinai Med Ctr, Inst Med Genet, 8700 Beverly Blvd,SSB, Los Angeles, CA 90048 USA. EM william.wilcox@cshs.org RI Oliveira, Joao Paulo/C-2154-2012; OI Oliveira, Joao Paulo/0000-0002-5016-1967; Hopkin, Robert/0000-0003-0770-5516; Ortiz Arduan, Alberto/0000-0002-9805-9523 NR 65 TC 236 Z9 248 U1 2 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2008 VL 93 IS 2 BP 112 EP 128 DI 10.1016/j.ymgme.2007.09.013 PG 17 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 265KT UT WOS:000253358500003 PM 18037317 ER PT J AU Adams, H Mink, JW Jordan, R Kwon, J Marshall, FJ Rothberg, PG Vierhile, A Deblieck, EA Pearce, DA AF Adams, Heather Mink, Jonathan W. Jordan, Rachel Kwon, Jennifer Marshall, Frederick J. Rothberg, Paul G. Vierhile, Amy deBlieck, Elisabeth A. Pearce, David A. TI Genotype-phenotype associations in Juvenile neuronal ceroid lipofuseinosis (JNCL; CLN3) SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 4th Annual World Symposium of the Lysosomal-Disease-Network CY FEB 13-15, 2008 CL Las Vegas, NV SP Lysosomal Dis Network C1 [Adams, Heather; Mink, Jonathan W.; Kwon, Jennifer; Marshall, Frederick J.; Rothberg, Paul G.; Vierhile, Amy; deBlieck, Elisabeth A.; Pearce, David A.] Univ Rochester, Med Ctr, Rochester, NY 14627 USA. [Jordan, Rachel] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2008 VL 93 IS 2 BP S14 EP S14 DI 10.1016/j.ymgme.2007.10.013 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 265KT UT WOS:000253358500018 ER PT J AU Slaugenhatipt, S Curcio-Morelli, C Venugopal, B Varro, A Michaud, N Nanthakumar, N Walkley, S Pickel, J Marsha, B AF Slaugenhatipt, Susan Curcio-Morelli, Cyntia Venugopal, Bhuvaramurthy Varro, Andrea Michaud, Norman Nanthakumar, Nanda Walkley, Steven Pickel, James Marsha, Browning TI A murine model for mucolipidosis type IV SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 4th Annual World Symposium of the Lysosomal-Disease-Network CY FEB 13-15, 2008 CL Las Vegas, NV SP Lysosomal Dis Network C1 [Slaugenhatipt, Susan; Curcio-Morelli, Cyntia; Venugopal, Bhuvaramurthy; Nanthakumar, Nanda; Marsha, Browning] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Varro, Andrea] Univ Liverpool, Liverpool L69 3BX, Merseyside, England. [Michaud, Norman] Massachusetts Eye & Ear Infirm, Boston, MA USA. [Walkley, Steven] Albert Einstein Coll Med, Bronx, NY USA. [Pickel, James] Natl Inst Hlth, Bethesda, MD USA. RI Varro, Andras/M-2647-2016 OI Varro, Andras/0000-0003-0745-3603 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2008 VL 93 IS 2 MA 92 BP S38 EP S38 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 265KT UT WOS:000253358500109 ER PT J AU Thurberg, B Rennke, H Colvin, R Dikman, S Gordon, R O'Callaghan, M AF Thurberg, Beth Rennke, Hehnut Colvin, Robert Dikman, Steven Gordon, Ronald O'Callaghan, Michael TI Pathology of Fabry nephropathy: Renal fibrosis may begin in adolescence SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 4th Annual World Symposium of the Lysosomal-Disease-Network CY FEB 13-15, 2008 CL Las Vegas, NV SP Lysosomal Dis Network C1 [Thurberg, Beth; O'Callaghan, Michael] Genzyme Corp, Framingham, MA USA. [Rennke, Hehnut] Brigham & Womens Hosp, Boston, MA 02115 USA. [Colvin, Robert] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Dikman, Steven; Gordon, Ronald] Mt Sinai Sch Med, New York, NY 10029 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2008 VL 93 IS 2 MA 96 BP S39 EP S39 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 265KT UT WOS:000253358500113 ER PT J AU Zimran, A Cappellini, M Cox, T Gianini, E Grabowski, GA Hwu, WL Mankin, H Martins, AM Sawyer, C vom Dahl, S Weinreb, N Yeh, M AF Zimran, Ari Cappellini, Maria Cox, Timothy Gianini, Edward Grabowski, Gregory A. Hwu, Wuh-Liang Mankin, Henry Martins, Anna Maria Sawyer, Carolyn vom Dahl, Stephan Weinreb, Neal Yeh, Michael TI Development of a disease severity scoring system for type I Gaucher disease SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 4th Annual World Symposium of the Lysosomal-Disease-Network CY FEB 13-15, 2008 CL Las Vegas, NV SP Lysosomal Dis Network C1 [Zimran, Ari] Shaare Zedek Med Ctr, Jerusalem, Israel. [Cappellini, Maria] Univ Milan, I-20122 Milan, Italy. [Cox, Timothy] Univ Cambridge, Cambridge CB2 1TN, England. [Grabowski, Gregory A.] Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. [Hwu, Wuh-Liang] Natl Taiwan Univ Hosp, Taipei, Taiwan. [Mankin, Henry] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Martins, Anna Maria] Univ Fed Sao Paulo, Sao Paulo, Brazil. [Sawyer, Carolyn; Yeh, Michael] Genzyme Corp, Cambridge, MA USA. [vom Dahl, Stephan] St Franziskus Hosp, Cologne, Germany. [Weinreb, Neal] Univ Res Fdn Lysosomal Storage Disorders, Coral Gables, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2008 VL 93 IS 2 BP S45 EP S45 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 265KT UT WOS:000253358500134 ER PT J AU Stayrook, KR Rogers, PM Savkur, RS Wang, YJ Su, C Varga, G Bu, X Wei, T Nagpal, S Liu, XS Burris, TP AF Stayrook, Keith R. Rogers, Pamela M. Savkur, Rajesh S. Wang, Yongjun Su, Chen Varga, Gabor Bu, Xin Wei, Tao Nagpal, Sunil Liu, Xiaole Shirley Burris, Thomas P. TI Regulation of human 3 alpha-hydroxysteroid dehydrogenase (AKR1C4) expression by the liver x receptor alpha SO MOLECULAR PHARMACOLOGY LA English DT Article ID 7-ALPHA-HYDROXYLASE GENE CYP7A1; LXR-ALPHA; MACROPHAGES; INHIBITION; ACTIVATION; PROMOTER; ISOFORMS; PATHWAY; TARGET; RAT AB Type I human hepatic 3 alpha-hydroxysteroid dehydrogenase (AKR1C4) plays a significant role in bile acid biosynthesis, steroid hormone metabolism, and xenobiotic metabolism. Utilization of a hidden Markov model for predictive modeling of nuclear hormone receptor response elements coupled with chromatin immunoprecipitation/microarray technology revealed a putative binding site in the AKR1C4 promoter for the nuclear hormone receptor known as liver X receptor alpha, (LXR alpha [NR1H3]), which is the physiological receptor for oxidized cholesterol metabolites. The putative LXR alpha response element (LXRE), identified by chromatin immunoprecipitation, was similar to 1.5 kilobase pairs upstream of the transcription start site. LXR alpha was shown to bind specifically to this LXRE and mediate transcriptional activation of the AKR1C4 gene, leading to increased AKR1C4 protein expression. These data suggest that LXR alpha may modulate the bile acid biosynthetic pathway at a unique site downstream of CYP7A1 and may also modulate the metabolism of steroid hormones and certain xenobiotics. C1 [Rogers, Pamela M.; Wang, Yongjun; Burris, Thomas P.] Louisiana State Univ, Pennington Biomed Res Ctr, Nucl Receptor Biol Lab, Baton Rouge, LA 70808 USA. [Stayrook, Keith R.; Savkur, Rajesh S.; Bu, Xin; Nagpal, Sunil] Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. [Su, Chen; Varga, Gabor] Lilly Res Labs, Greenfield, IN 46140 USA. [Liu, Xiaole Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Burris, TP (reprint author), Louisiana State Univ, Pennington Biomed Res Ctr, Nucl Receptor Biol Lab, 6400 Perkins Rd, Baton Rouge, LA 70808 USA. EM thomas.burris@pbrc.edu RI Nagpal, Sunil/A-8007-2009; Burris, Thomas/H-5078-2011; Burris, Thomas/B-3886-2016 OI Burris, Thomas/0000-0003-2922-4449 NR 25 TC 15 Z9 15 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD FEB PY 2008 VL 73 IS 2 BP 607 EP 612 DI 10.1124/mol.107.039099 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 254PA UT WOS:000252597300034 PM 18024509 ER PT J AU Motter, AE Gulbahce, N Almaas, E Barabasi, AL AF Motter, Adilson E. Gulbahce, Natali Almaas, Eivind Barabasi, Albert-Laszlo TI Predicting synthetic rescues in metabolic networks SO MOLECULAR SYSTEMS BIOLOGY LA English DT Article DE complex networks; genetic interactions; genetic recovery; metabolism; systems biology ID ESCHERICHIA-COLI MG1655; GENETIC INTERACTIONS; CELL BIOLOGY; YEAST; GENOME; EVOLUTION; GROWTH; OPTIMIZATION; ORGANIZATION; FERMENTATION AB An important goal of medical research is to develop methods to recover the loss of cellular function due to mutations and other defects. Many approaches based on gene therapy aim to repair the defective gene or to insert genes with compensatory function. Here, we propose an alternative, network-based strategy that aims to restore biological function by forcing the cell to either bypass the functions affected by the defective gene, or to compensate for the lost function. Focusing on the metabolism of single-cell organisms, we computationally study mutants that lack an essential enzyme, and thus are unable to grow or have a significantly reduced growth rate. We show that several of these mutants can be turned into viable organisms through additional gene deletions that restore their growth rate. In a rather counterintuitive fashion, this is achieved via additional damage to the metabolic network. Using flux balance-based approaches, we identify a number of synthetically viable gene pairs, in which the removal of one enzyme-encoding gene results in a non-viable phenotype, while the deletion of a second enzyme-encoding gene rescues the organism. The systematic network-based identification of compensatory rescue effects may open new avenues for genetic interventions. C1 [Motter, Adilson E.] Northwestern Univ, Dept Phys & Astron, Evanston, IL 60208 USA. [Motter, Adilson E.] Northwestern Univ, Norwegian Inst Complex Syst, Evanston, IL 60208 USA. [Gulbahce, Natali] Los Alamos Natl Lab, Div Theoret, Los Alamos, NM USA. [Gulbahce, Natali] Los Alamos Natl Lab, Ctr Nonlinear Studies, Los Alamos, NM 87545 USA. [Gulbahce, Natali] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. [Gulbahce, Natali; Barabasi, Albert-Laszlo] Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA. [Gulbahce, Natali] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Almaas, Eivind] Lawrence Livermore Natl Lab, Biosci & Biotechnol Div, Network Biol & Microbial Syst Grp, Livermore, CA USA. [Barabasi, Albert-Laszlo] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. [Barabasi, Albert-Laszlo] Northeastern Univ, Dept Biol, Boston, MA 02115 USA. [Barabasi, Albert-Laszlo] Northeastern Univ, Dept Comp Sci, Boston, MA 02115 USA. [Barabasi, Albert-Laszlo] Univ Notre Dame, Ctr Complex Network Res, Notre Dame, IN 46556 USA. [Barabasi, Albert-Laszlo] Univ Notre Dame, Dept Phys, Notre Dame, IN 46556 USA. [Barabasi, Albert-Laszlo] Univ Notre Dame, Dept Comp Sci, Notre Dame, IN 46556 USA. RP Motter, AE (reprint author), Northwestern Univ, Dept Phys & Astron, 2145 Sheridan Rd, Evanston, IL 60208 USA. EM motter@northwestern.edu OI Almaas, Eivind/0000-0002-9125-326X FU NCI NIH HHS [1P20 CA11300-01]; PHS HHS [U01 A1070499-01] NR 53 TC 68 Z9 68 U1 3 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1744-4292 J9 MOL SYST BIOL JI Mol. Syst. Biol. PD FEB PY 2008 VL 4 AR 168 DI 10.1038/msb.2008.1 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 271AM UT WOS:000253761300001 PM 18277384 ER PT J AU Cornu, TI Thibodeau-Beganny, S Guhl, E Alwin, S Eichtinger, M Joung, J Cathomen, T AF Cornu, Tatjana I. Thibodeau-Beganny, Stacey Guhl, Eva Alwin, Stephen Eichtinger, Magdalena Joung, J. K. Cathomen, Toni TI DNA-binding specificity is a major determinant of the activity and toxicity of zinc-finger Nucleases SO MOLECULAR THERAPY LA English DT Article ID DOUBLE-STRAND BREAKS; ARTIFICIAL TRANSCRIPTION FACTORS; HOMOLOGOUS RECOMBINATION; ADENOASSOCIATED VIRUS; RESTRICTION ENZYMES; CHIMERIC NUCLEASES; CRYSTAL-STRUCTURE; PROTEIN-DNA; HUMAN-CELLS; RECOGNITION AB The engineering of proteins to manipulate cellular genomes has developed into a promising technology for biomedical research, including gene therapy. In particular, zinc-finger nucleases (ZFNs), which consist of a nonspecific endonuclease domain tethered to a tailored zinc-finger (ZF) DNA-binding domain, have proven invaluable for stimulating homology-directed gene repair in a variety of cell types. However, previous studies demonstrated that ZFNs could be associated with significant cytotoxicity due to cleavage at off-target sites. Here, we compared the in vitro affinities and specificities of nine ZF DNA-binding domains with their performance as ZFNs in human cells. The results of our cell-based assays reveal that the DNA-binding specificity - in addition to the affinity - is a major determinant of ZFN activity and is inversely correlated with ZFN-associated toxicity. In addition, our data provide the first evidence that engineering strategies, which account for context-dependent DNA-binding effects, yield ZFs that function as highly efficient ZFNs in human cells. C1 [Cornu, Tatjana I.; Guhl, Eva; Alwin, Stephen; Cathomen, Toni] CBF, Charite Med Sch, Inst Virol, D-12203 Berlin, Germany. [Thibodeau-Beganny, Stacey; Eichtinger, Magdalena; Joung, J. K.] Massachusetts Gen Hosp, Mol Pathol Unit, Canc Res Ctr, Charlestown, MA USA. [Thibodeau-Beganny, Stacey; Eichtinger, Magdalena; Joung, J. K.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA USA. [Eichtinger, Magdalena; Joung, J. K.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Cathomen, T (reprint author), CBF, Charite Med Sch, Inst Virol, Hindenburgdamm 27, D-12203 Berlin, Germany. EM toni.cathomen@charite.de OI Cathomen, Toni/0000-0002-7757-4630 NR 48 TC 140 Z9 145 U1 2 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD FEB PY 2008 VL 16 IS 2 BP 352 EP 358 DI 10.1038/sj.mt.6300357 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 256RY UT WOS:000252748600017 PM 18026168 ER PT J AU Vilardaga, JP Nikolaev, VO Lorenz, K Ferrandon, S Zhuang, ZJ Lohse, MJ AF Vilardaga, Jean-Pierre Nikolaev, Viacheslav O. Lorenz, Kristina Ferrandon, Sebastien Zhuang, Zhenjie Lohse, Martin J. TI Conformational cross-talk between alpha(2A)-adrenergic and mu-opioid receptors controls cell signaling SO NATURE CHEMICAL BIOLOGY LA English DT Article ID PROTEIN-COUPLED-RECEPTOR; RESONANCE ENERGY-TRANSFER; LIVING CELLS; MEMBRANE MICRODOMAINS; MOLECULAR-BASIS; LIVE CELLS; ACTIVATION; DIMER; HETERODIMERIZATION; HOMODIMERIZATION AB Morphine, a powerful analgesic, and norepinephrine, the principal neurotransmitter of sympathetic nerves, exert major inhibitory effects on both peripheral and brain neurons by activating distinct cell-surface G protein-coupled receptors-the mu-opioid receptor (MOR) and alpha(2A)-adrenergic receptor (alpha(2A)-AR), respectively. These receptors, either singly or as a heterodimer, activate common signal transduction pathways mediated through the inhibitory G proteins (G(i) and G(o)). Using fluorescence resonance energy transfer microscopy, we show that in the heterodimer, the MOR and alpha(2A)-AR communicate with each other through a cross-conformational switch that permits direct inhibition of one receptor by the other with subsecond kinetics. We discovered that morphine binding to the MOR triggers a conformational change in the norepinephrine-occupied alpha(2A)-AR that inhibits its signaling to Gi and the downstream MAP kinase cascade. These data highlight a new mechanism in signal transduction whereby a G protein-coupled receptor heterodimer mediates conformational changes that propagate from one receptor to the other and cause the second receptor's rapid inactivation. C1 [Vilardaga, Jean-Pierre; Ferrandon, Sebastien; Zhuang, Zhenjie] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Vilardaga, Jean-Pierre; Ferrandon, Sebastien; Zhuang, Zhenjie] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Vilardaga, Jean-Pierre; Ferrandon, Sebastien; Zhuang, Zhenjie] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Nikolaev, Viacheslav O.; Lohse, Martin J.] Univ Wurzburg, Inst Pharmacol & Toxicol, D-98078 Wurzburg, Germany. [Nikolaev, Viacheslav O.; Lorenz, Kristina; Lohse, Martin J.] Univ Wurzburg, Rudolf Virchow Ctr, DFG Res Ctr Expt Biomed, D-98078 Wurzburg, Germany. RP Vilardaga, JP (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, CPZN 8-218,185 Cambridge St, Boston, MA 02114 USA. EM vilardaga.jeanpierre@mgh.harvard.edu RI Lohse, Martin/A-7160-2012; Lorenz, Kristina/F-3522-2016 OI Lohse, Martin/0000-0002-0599-3510; Lorenz, Kristina/0000-0002-5747-2207 NR 39 TC 165 Z9 170 U1 2 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1552-4450 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD FEB PY 2008 VL 4 IS 2 BP 126 EP 131 DI 10.1038/nchembio.64 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 254KL UT WOS:000252585400012 PM 18193048 ER PT J AU Yachimski, PS Friedman, LS AF Yachimski, Patrick S. Friedman, Lawrence S. TI Gastrointestinal bleeding in the elderly SO NATURE CLINICAL PRACTICE GASTROENTEROLOGY & HEPATOLOGY LA English DT Review DE colonoscopy; elderly; gastrointestinal bleeding; gastrointestinal endoscopy; gastrointestinal hemorrhage ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; DOUBLE-BALLOON ENTEROSCOPY; HEMORRHAGIC RADIATION PROCTITIS; RANDOMIZED CONTROLLED-TRIAL; WIRELESS CAPSULE ENDOSCOPY; AGED 80 YEARS; PEPTIC-ULCER; RISK-FACTORS; DIAGNOSTIC YIELD; DIVERTICULAR HEMORRHAGE AB Gastrointestinal bleeding affects a substantial number of elderly people and is a frequent indication for hospitalization. Bleeding can originate from either the upper or lower gastrointestinal tract, and patients with gastrointestinal bleeding present with a range of symptoms. In the elderly, the nature, severity, and outcome of bleeding are influenced by the presence of medical comorbidities and the use of antiplatelet medication. This Review discusses trends in the epidemiology and outcome of gastrointestinal bleeding in elderly patients. Specific causes of upper and lower gastrointestinal bleeding are discussed, and recommendations for approaches to endoscopic diagnosis and therapy are given. C1 [Friedman, Lawrence S.] Newton Wellesley Hosp, Dept Med, Newton, MA 02462 USA. [Yachimski, Patrick S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Cambridge, MA 02138 USA. RP Friedman, LS (reprint author), Newton Wellesley Hosp, Dept Med, 2014 Washington St, Newton, MA 02462 USA. EM lfriedman@partners.org NR 104 TC 23 Z9 25 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1743-4378 J9 NAT CLIN PRACT GASTR JI Nat. Clin. Pract. Gastroenterol. Hepatol. PD FEB PY 2008 VL 5 IS 2 BP 80 EP 93 DI 10.1038/ncpgasthep1034 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 258FU UT WOS:000252854600009 PM 18253137 ER PT J AU Corsello, SM Kantoff, PW AF Corsello, Steven M. Kantoff, Philip W. TI Does androgen deprivation therapy in men with prostate cancer increase cardiovascular morbidity? SO NATURE CLINICAL PRACTICE UROLOGY LA English DT Editorial Material DE androgen deprivation therapy; cardiovascular; hormone; morbidity; prostate cancer C1 [Kantoff, Philip W.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Corsello, Steven M.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Kantoff, PW (reprint author), Dana Farber Canc Inst, 44 Binney St,Dana1230, Boston, MA 02115 USA. EM philip_kantoff@dfci.harvard.edu NR 6 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1743-4270 J9 NAT CLIN PRACT UROL JI Nat. Clin. Pract. Urol. PD FEB PY 2008 VL 5 IS 2 BP 80 EP 81 DI 10.1038/ncpuro1015 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 259IU UT WOS:000252933800009 PM 18087294 ER PT J AU Kathiresan, S Melander, O Guiducci, C Surti, A Burtt, NP Rieder, MJ Cooper, GM Roos, C Voight, BF Havulinna, AS Wahlstrand, B Hedner, T Corella, D Tai, ES Ordovas, JM Berglund, G Vartiainen, E Jousilahti, P Hedblad, B Taskinen, MR Newton-Cheh, C Salomaa, V Peltonen, L Groop, L Altshuler, DM Orho-Melander, M AF Kathiresan, Sekar Melander, Olle Guiducci, Candace Surti, Aarti Burtt, Noel P. Rieder, Mark J. Cooper, Gregory M. Roos, Charlotta Voight, Benjamin F. Havulinna, Aki S. Wahlstrand, Bjorn Hedner, Thomas Corella, Dolores Tai, E. Shyong Ordovas, Jose M. Berglund, Goran Vartiainen, Erkki Jousilahti, Pekka Hedblad, Bo Taskinen, Marja-Riitta Newton-Cheh, Christopher Salomaa, Veikko Peltonen, Leena Groop, Leif Altshuler, David M. Orho-Melander, Marju TI Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans SO NATURE GENETICS LA English DT Article ID CORONARY-HEART-DISEASE; PLASMA-LEVELS; CARDIOVASCULAR RISK; GENERAL-POPULATION; HDL CHOLESTEROL; LIPASE; POLYMORPHISM; CONTRIBUTES; HAPLOTYPES; PROTEIN AB Blood concentrations of lipoproteins and lipids are heritable(1) risk factors for cardiovascular disease(2,3). Using genome-wide association data from three studies (n = 8,816 that included 2,758 individuals from the Diabetes Genetics Initiative specific to the current paper as well as 1,874 individuals from the FUSION study of type 2 diabetes and 4,184 individuals from the SardiNIA study of aging-associated variables reported in a companion paper in this issue(4)) and targeted replication association analyses in up to 18,554 independent participants, we show that common SNPs at 18 loci are reproducibly associated with concentrations of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and/or triglycerides. Six of these loci are new (P < 5 x 10(-8) for each new locus). Of the six newly identified chromosomal regions, two were associated with LDL cholesterol (1p13 near CELSR2, PSRC1 and SORT1 and 19p13 near CILP2 and PBX4), one with HDL cholesterol (1q42 in GALNT2) and five with triglycerides (7q11 near TBL2 and MLXIPL, 8q24 near TRIB1, 1q42 in GALNT2, 19p13 near CILP2 and PBX4 and 1p31 near ANGPTL3). At 1p13, the LDL-associated SNP was also strongly correlated with CELSR2, PSRC1, and SORT1 transcript levels in human liver, and a proxy for this SNP was recently shown to affect risk for coronary artery disease(5). Understanding the molecular, cellular and clinical consequences of the newly identified loci may inform therapy and clinical care. C1 [Kathiresan, Sekar; Newton-Cheh, Christopher] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Kathiresan, Sekar; Guiducci, Candace; Surti, Aarti; Burtt, Noel P.; Voight, Benjamin F.; Newton-Cheh, Christopher; Peltonen, Leena; Altshuler, David M.] MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Kathiresan, Sekar; Guiducci, Candace; Surti, Aarti; Burtt, Noel P.; Voight, Benjamin F.; Newton-Cheh, Christopher; Peltonen, Leena; Altshuler, David M.] Harvard Univ, Cambridge, MA 02142 USA. [Kathiresan, Sekar; Newton-Cheh, Christopher; Altshuler, David M.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Melander, Olle] Lund Univ, Malmo Univ Hosp, Dept Clin Sci Hypertens & Cardiovasc Dis, S-20502 Malmo, Sweden. [Rieder, Mark J.; Cooper, Gregory M.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Roos, Charlotta; Groop, Leif; Orho-Melander, Marju] Lund Univ, Malmo Univ Hosp, Dept Clin Sci Diabet & Endocrinol, S-20502 Malmo, Sweden. [Voight, Benjamin F.; Altshuler, David M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Voight, Benjamin F.; Altshuler, David M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Havulinna, Aki S.; Vartiainen, Erkki; Jousilahti, Pekka; Salomaa, Veikko; Peltonen, Leena] Natl Publ Hlth Inst, SF-00300 Helsinki, Finland. [Wahlstrand, Bjorn; Hedner, Thomas] Sahlgrens Univ Hosp, Dept Clin Pharmacol, S-41345 Gothenburg, Sweden. [Corella, Dolores] Univ Valencia, Sch Med, Dept Prevent Med, Valencia 46010, Spain. [Tai, E. Shyong] Singapore Gen Hosp, Dept Endocrinol, Singapore 169608, Singapore. [Ordovas, Jose M.] Tufts Univ, Nutr & Genom Lab, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Berglund, Goran] Lund Univ, Malmo Univ Hosp, Dept Internal Med, S-20502 Malmo, Sweden. [Hedblad, Bo] Lund Univ, Malmo Univ Hosp, Dept Epidemiol Res, S-20502 Malmo, Sweden. [Taskinen, Marja-Riitta] Univ Helsinki, Dept Med, Helsinki 00029, Finland. [Peltonen, Leena] Univ Helsinki, Dept Med Genet, Helsinki 00029, Finland. [Peltonen, Leena] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Groop, Leif] Helsinki Univ Hosp, Dept Med, Helsinki 00029, Finland. [Altshuler, David M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Kathiresan, S (reprint author), Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. EM skathiresan@partners.org; marju.orho-melander@med.lu.se RI Altshuler, David/A-4476-2009; Cooper, Gregory/D-6914-2011; Voight, Benjamin/F-1775-2011; OI Altshuler, David/0000-0002-7250-4107; Cooper, Gregory/0000-0001-5509-9923; Ordovas, Jose/0000-0002-7581-5680; Tai, E Shyong/0000-0003-2929-8966 FU Wellcome Trust [089061] NR 30 TC 789 Z9 807 U1 2 U2 40 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD FEB PY 2008 VL 40 IS 2 BP 189 EP 197 DI 10.1038/ng.75 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 256MJ UT WOS:000252732900017 PM 18193044 ER PT J AU von Boehmer, H Nolting, J AF von Boehmer, Harald Nolting, Jens TI What turns on Foxp3? SO NATURE IMMUNOLOGY LA English DT Editorial Material ID REGULATORY T-CELLS; EXPRESSION AB Inducible regulatory T cells respond to TGF-beta upregulating Foxp3 expression. Tone and colleagues identify an enchancer site in Foxp3 that binds transcription factors Smad3 and NFAT, suggesting a means by which TGF-beta regulates Foxp3 expression. C1 [von Boehmer, Harald; Nolting, Jens] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM harald_von_boehmer@dfci.harvard.edu NR 10 TC 12 Z9 12 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD FEB PY 2008 VL 9 IS 2 BP 121 EP 122 DI 10.1038/ni0208-121 PG 2 WC Immunology SC Immunology GA 253FB UT WOS:000252503000006 PM 18204423 ER PT J AU Cai, GF Anumanthan, A Brown, JA Greenfield, EA Zhu, B Freeman, GJ AF Cai, Guifang Anumanthan, Anukanth Brown, Julia A. Greenfield, Edward A. Zhu, Baogong Freeman, Gordon J. TI CD160 inhibits activation of human CD4(+) T cells through interaction with herpesvirus entry mediator SO NATURE IMMUNOLOGY LA English DT Article ID MHC CLASS-I; NK CELLS; LYMPHOCYTE ATTENUATOR; RECEPTOR FAMILY; SIMPLEX VIRUS-1; CUTTING EDGE; B-LYMPHOCYTE; HLA-C; LIGHT; HVEM AB CD160, a glycosylphosphatidylinositol-anchored member of the immunoglobulin superfamily, is expressed on both cytolytic lymphocytes and some unstimulated CD4(+) T cells. Here we show that CD160 expression was increased after activation of human CD4(+) T cells and that crosslinking CD160 with monoclonal antibody strongly inhibited CD3- and CD28-mediated activation. We found that herpesvirus entry mediator (HVEM) was a ligand of CD160 that acted as a 'bidirectional switch' for T cell activation, producing a positive or negative outcome depending on the engagement of HVEM by CD160 and known HVEM ligands such as B and T lymphocyte attenuator (BTLA) and the T lymphocyte receptor LIGHT. Inhibition of CD4(+) T cell activation by HVEM-transfected cells was dependent on CD160 and BTLA; when the cysteine-rich domain 1 of HVEM was deleted, this inhibition was lost, resulting in strong T cell activation. CD160 thus serves as a negative regulator of CD4(+) T cell activation through its interaction with HVEM. C1 [Cai, Guifang; Anumanthan, Anukanth; Brown, Julia A.; Greenfield, Edward A.; Zhu, Baogong; Freeman, Gordon J.] Harvard Univ, Sch Med, Dept Med, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02115 USA. RP Freeman, GJ (reprint author), Harvard Univ, Sch Med, Dept Med, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02115 USA. EM gordon_freeman@dfci.harvard.edu FU NIAID NIH HHS [AI39671, AI56299] NR 35 TC 159 Z9 173 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD FEB PY 2008 VL 9 IS 2 BP 176 EP 185 DI 10.1038/ni1554 PG 10 WC Immunology SC Immunology GA 253FB UT WOS:000252503000014 PM 18193050 ER PT J AU Danial, NN Walensky, LD Zhang, CY Choi, CS Fisher, JK Molina, AJA Datta, SR Pitter, KL Bird, GH Wikstrom, JD Deeney, JT Robertson, K Morash, J Kulkarni, A Neschen, S Kim, S Greenberg, ME Corkey, BE Shirihai, OS Shulman, GI Lowell, BB Korsmeyer, SJ AF Danial, Nika N. Walensky, Loren D. Zhang, Chen-Yu Choi, Cheol Soo Fisher, Jill K. Molina, Anthony J. A. Datta, Sandeep Robert Pitter, Kenneth L. Bird, Gregory H. Wikstrom, Jakob D. Deeney, Jude T. Robertson, Kirsten Morash, Joel Kulkarni, Ameya Neschen, Susanne Kim, Sheene Greenberg, Michael E. Corkey, Barbara E. Shirihai, Orian S. Shulman, Gerald I. Lowell, Bradford B. Korsmeyer, Stanley J. TI Dual role of proapoptotic BAD in insulin secretion and beta cell survival SO NATURE MEDICINE LA English DT Article ID GLUCOSE-HOMEOSTASIS; DIABETES-MELLITUS; PANCREATIC-ISLETS; GLUCOKINASE GENE; BH3 DOMAIN; KINASE; PHOSPHORYLATION; PROTEIN; GROWTH; MODEL AB The proapoptotic BCL-2 family member BAD resides in a glucokinase-containing complex that regulates glucose-driven mitochondrial respiration. Here, we present genetic evidence of a physiologic role for BAD in glucose- stimulated insulin secretion by beta cells. This novel function of BAD is specifically dependent upon the phosphorylation of its BH3 sequence, previously defined as an essential death domain. We highlight the pharmacologic relevance of phosphorylated BAD BH3 by using cell-permeable, hydrocarbon-stapled BAD BH3 helices that target glucokinase, restore glucose- driven mitochondrial respiration and correct the insulin secretory response in Bad-deficient islets. Our studies uncover an alternative target and function for the BAD BH3 domain and emphasize the therapeutic potential of phosphorylated BAD BH3 mimetics in selectively restoring beta cell function. Furthermore, we show that BAD regulates the physiologic adaptation of beta cell mass during high-fat feeding. Our findings provide genetic proof of the bifunctional activities of BAD in both beta cell survival and insulin secretion. C1 [Danial, Nika N.; Fisher, Jill K.; Robertson, Kirsten; Lowell, Bradford B.; Korsmeyer, Stanley J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Walensky, Loren D.; Pitter, Kenneth L.; Bird, Gregory H.; Morash, Joel] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Danial, Nika N.; Walensky, Loren D.; Fisher, Jill K.; Pitter, Kenneth L.; Bird, Gregory H.; Robertson, Kirsten; Morash, Joel] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Danial, Nika N.; Walensky, Loren D.; Fisher, Jill K.; Pitter, Kenneth L.; Bird, Gregory H.; Robertson, Kirsten; Morash, Joel] Dana Farber Canc Inst, Program Canc Chem Biol, Boston, MA 02115 USA. [Walensky, Loren D.; Pitter, Kenneth L.; Bird, Gregory H.; Morash, Joel] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Zhang, Chen-Yu] Nanjing Univ, Sch Life Sci, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Peoples R China. [Choi, Cheol Soo; Kulkarni, Ameya; Neschen, Susanne; Kim, Sheene; Shulman, Gerald I.; Korsmeyer, Stanley J.] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA. [Choi, Cheol Soo; Kulkarni, Ameya; Neschen, Susanne; Kim, Sheene; Shulman, Gerald I.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [Molina, Anthony J. A.; Wikstrom, Jakob D.; Shirihai, Orian S.] Tufts Univ, Sch Med, Dept Pharmacol & Expt Therapeut, Boston, MA 02111 USA. [Datta, Sandeep Robert; Greenberg, Michael E.] Childrens Hosp, Dept Neurol, Neurobiol Program, Boston, MA 02115 USA. [Deeney, Jude T.; Corkey, Barbara E.] Boston Univ, Med Ctr, Evans Dept Med, Obes Res Ctr, Boston, MA 02118 USA. [Lowell, Bradford B.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Endocrionol, Boston, MA 02215 USA. RP Danial, NN (reprint author), Harvard Univ, Sch Med, Dept Pathol, 44 Binney St, Boston, MA 02115 USA. EM nika_danial@dfci.harvard.edu OI Wikstrom, Jakob/0000-0002-4287-1774; Corkey, Barbara/0000-0002-5467-1630; Deeney, Jude/0000-0003-0988-9419 FU NCI NIH HHS [K01 CA106596, K01 CA106596-01, K01 CA106596-02, K01 CA106596-03, K01 CA106596-04, K01CA10659, R01 CA050239, 5R01CA50239]; NHLBI NIH HHS [5K08HL074049, K08 HL074049]; NICHD NIH HHS [P01 HD024926, P30 HD018655]; NIDDK NIH HHS [U24 DK059635, 5R01DK68781, R01 DK040936, R01 DK068781] NR 50 TC 175 Z9 178 U1 0 U2 18 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD FEB PY 2008 VL 14 IS 2 BP 144 EP 153 DI 10.1038/nm1717 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 259NT UT WOS:000252946700022 PM 18223655 ER PT J AU Sackstein, R Merzaban, JS Cain, DW Dagia, NM Spencer, JA Lin, CP Wohlgemuth, R AF Sackstein, Robert Merzaban, Jasmeen S. Cain, Derek W. Dagia, Nilesh M. Spencer, Joel A. Lin, Charles P. Wohlgemuth, Roland TI Ex vivo glycan engineering of CD44 programs human multipotent mesenchymal stromal cell trafficking to bone SO NATURE MEDICINE LA English DT Article ID HUMAN HEMATOPOIETIC-CELLS; L-SELECTIN LIGAND; SIALYL-LEWIS-X; STEM-CELLS; ADHESION MOLECULE-1; P-SELECTIN; MARROW; EXPRESSION; BINDING; FUCOSYLATION AB The capacity to direct migration ('homing') of blood-borne cells to a predetermined anatomic compartment is vital to stem cell based tissue engineering and other adoptive cellular therapies. Although multipotent mesenchymal stromal cells (MSCs, also termed 'mesenchymal stem cells') hold the potential for curing generalized skeletal diseases, their clinical effectiveness is constrained by the poor osteotropism of infused MSCs (refs. 1-3). Cellular recruitment to bone occurs within specialized marrow vessels that constitutively express vascular E-selectin(4,5), a lectin that recognizes sialofucosylated determinants on its various ligands. We show here that human MSCs do not express E-selectin ligands, but express a CD44 glycoform bearing alpha-2,3-sialyl modifications. Using an alpha-1,3-fucosyltransferase preparation and enzymatic conditions specifically designed for treating live cells, we converted the native CD44 glycoform on MSCs into hematopoietic cell E-selectin/L-selectin ligand (HCELL)(6), which conferred potent E-selectin binding without effects on cell viability or multipotency. Real-time intravital microscopy in immunocompromised (NOD/SCID) mice showed that intravenously infused HCELL+ MSCs infiltrated marrow within hours of infusion, with ensuing rare foci of endosteally localized cells and human osteoid generation. These findings establish that the HCELL glycoform of CD44 confers tropism to bone and unveil a readily translatable roadmap for programming cellular trafficking by chemical engineering of glycans on a distinct membrane glycoprotein. C1 [Sackstein, Robert; Merzaban, Jasmeen S.; Cain, Derek W.; Dagia, Nilesh M.] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [Sackstein, Robert; Merzaban, Jasmeen S.; Cain, Derek W.; Dagia, Nilesh M.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Sackstein, Robert; Merzaban, Jasmeen S.; Cain, Derek W.; Dagia, Nilesh M.] Harvard Skin Dis Res Ctr, Boston, MA 02115 USA. [Sackstein, Robert] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Spencer, Joel A.; Lin, Charles P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Wohlgemuth, Roland] Sigma Aldrich, CH-9470 Buchs, Switzerland. RP Sackstein, R (reprint author), Brigham & Womens Hosp, Dept Dermatol, 75 Francis St, Boston, MA 02115 USA. EM rsackstein@rics.bwh.harvard.edu RI Spencer, Joel/A-4590-2013 FU NHLBI NIH HHS [R01 HL60528, R01 HL73714] NR 30 TC 265 Z9 278 U1 0 U2 20 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD FEB PY 2008 VL 14 IS 2 BP 181 EP 187 DI 10.1038/nm1703 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 259NT UT WOS:000252946700027 PM 18193058 ER PT J AU Ott, HC Matthiesen, TS Goh, SK Black, LD Kren, SM Netoff, TI Taylor, DA AF Ott, Harald C. Matthiesen, Thomas S. Goh, Saik-Kia Black, Lauren D. Kren, Stefan M. Netoff, Theoden I. Taylor, Doris A. TI Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart SO NATURE MEDICINE LA English DT Article ID CARDIAC TISSUE; RECELLULARIZATION; TRANSPLANTATION; SCAFFOLD; CELLS AB About 3,000 individuals in the United States are awaiting a donor heart; worldwide, 22 million individuals are living with heart failure. A bioartificial heart is a theoretical alternative to transplantation or mechanical left ventricular support. Generating a bioartificial heart requires engineering of cardiac architecture, appropriate cellular constituents and pump function. We decellularized hearts by coronary perfusion with detergents, preserved the underlying extracellular matrix, and produced an acellular, perfusable vascular architecture, competent acellular valves and intact chamber geometry. To mimic cardiac cell composition, we reseeded these constructs with cardiac or endothelial cells. To establish function, we maintained eight constructs for up to 28 d by coronary perfusion in a bioreactor that simulated cardiac physiology. By day 4, we observed macroscopic contractions. By day 8, under physiological load and electrical stimulation, constructs could generate pump function (equivalent to about 2% of adult or 25% of 16-week fetal heart function) in a modified working heart preparation. C1 [Matthiesen, Thomas S.; Goh, Saik-Kia; Kren, Stefan M.; Taylor, Doris A.] Univ Minnesota, Ctr Cardiovasc Repair, Minneapolis, MN 55455 USA. [Ott, Harald C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Black, Lauren D.; Netoff, Theoden I.] Univ Minnesota, Dept Biomed Engn, Minneapolis, MN 55455 USA. [Taylor, Doris A.] Univ Minnesota, Dept Integrat Biol & Physiol, Minneapolis, MN 55455 USA. RP Taylor, DA (reprint author), Univ Minnesota, Ctr Cardiovasc Repair, 312 Church St SE,7-105A NHH, Minneapolis, MN 55455 USA. EM dataylor@umn.edu RI Sano, Michael/E-1715-2011; OI Black, Lauren/0000-0002-7486-5811 NR 26 TC 1062 Z9 1126 U1 29 U2 302 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD FEB PY 2008 VL 14 IS 2 BP 213 EP 221 DI 10.1038/nm1684 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 259NT UT WOS:000252946700032 PM 18193059 ER PT J AU Wurdinger, T Badr, C Pike, L de Kleine, R Weissleder, R Breakefield, XO Tannous, BA AF Wurdinger, Thomas Badr, Christian Pike, Lisa de Kleine, Ruben Weissleder, Ralph Breakefield, Xandra O. Tannous, Bakhos A. TI A secreted luciferase for ex vivo monitoring of in vivo processes SO NATURE METHODS LA English DT Article ID REPORTER GENE-EXPRESSION; LIVING MICE; BIOLUMINESCENCE; CANCER; VECTOR AB Luciferases are widely used to monitor biological processes. Here we describe the naturally secreted Gaussia princeps luciferase (Gluc) as a highly sensitive reporter for quantitative assessment of cells in vivo by measuring its concentration in blood. The Gluc blood assay complements in vivo bioluminescence imaging, which has the ability to localize the signal and provides a multifaceted assessment of cell viability, proliferation and location in experimental disease and therapy models. C1 [Wurdinger, Thomas; Badr, Christian; Pike, Lisa; Breakefield, Xandra O.; Tannous, Bakhos A.] Harvard Univ, Sch Med, Mol Neurogenet Unit, Dept Neurol, Charlestown, MA 02129 USA. [Wurdinger, Thomas; de Kleine, Ruben; Weissleder, Ralph; Breakefield, Xandra O.; Tannous, Bakhos A.] Harvard Univ, Sch Med, Ctr Mol Imaging Res, Dept Radiol, Charlestown, MA 02129 USA. [Wurdinger, Thomas; Breakefield, Xandra O.; Tannous, Bakhos A.] Harvard Univ, Sch Med, Program Neurosci, Charlestown, MA 02129 USA. [Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Tannous, Bakhos A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Tannous, BA (reprint author), Harvard Univ, Sch Med, Mol Neurogenet Unit, Dept Neurol, 149 13th St, Charlestown, MA 02129 USA. EM btannous@hms.harvard.edu FU NCI NIH HHS [P50 CA086355, 1K99CA126839-01, P50 CA86355-04, K99 CA126839, P50 CA086355-02S1] NR 13 TC 149 Z9 159 U1 1 U2 22 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 J9 NAT METHODS JI Nat. Methods PD FEB PY 2008 VL 5 IS 2 BP 171 EP 173 DI 10.1038/NMETH.1177 PG 3 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 256SR UT WOS:000252750700019 PM 18204457 ER PT J AU Letai, AG AF Letai, Anthony G. TI Diagnosing and exploiting cancer's addiction to blocks in apoptosis SO NATURE REVIEWS CANCER LA English DT Review ID CYTOCHROME-C RELEASE; BCL-2 FAMILY-MEMBERS; PROGRAMMED CELL-DEATH; MITOCHONDRIAL-MEMBRANE PERMEABILIZATION; CHRONIC LYMPHOCYTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; BH3 MIMETIC ABT-737; BH3-ONLY PROTEINS; BREAST-CANCER; CHROMOSOMAL BREAKPOINT AB Cancer cells survive despite violating rules of normal cellular behaviour that ordinarily provoke apoptosis. The blocks in apoptosis that keep cancer cells alive are therefore attractive candidates for targeted therapies. Recent studies have significantly increased our understanding of how interactions among proteins in the BCL2 family determine cell survival or death. It is now possible to systematically determine how individual cancers escape apoptosis. Such a determination can help predict not only whether cells are likely to be killed by antagonism of BCL2, but also whether they are likely to be sensitive to chemotherapy that kills by the intrinsic apoptotic pathway. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02052 USA. RP Letai, AG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02052 USA. EM anthony_letai@dfci.harvard.edu NR 94 TC 303 Z9 307 U1 2 U2 23 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD FEB PY 2008 VL 8 IS 2 BP 121 EP 132 DI 10.1038/nrc2297 PG 12 WC Oncology SC Oncology GA 255RA UT WOS:000252673900013 PM 18202696 ER PT J AU Orford, KW Scadden, DT AF Orford, Keith W. Scadden, David T. TI Deconstructing stem cell self-renewal: genetic insights into cell-cycle regulation SO NATURE REVIEWS GENETICS LA English DT Review ID BONE-MARROW-CELLS; HEMATOPOIETIC STEM; IN-VIVO; PROLIFERATIVE CAPACITY; DROSOPHILA OVARY; PROGENITOR PROLIFERATION; DEVELOPMENTAL REGULATORS; SERIAL TRANSPLANTATION; RELATIVE QUIESCENCE; DEPENDENT KINASES AB The regulation of stem cell self-renewal must balance the regenerative needs of tissues that persist throughout life with the potential for cell overgrowth, transformation and cancer. Here, we attempt to deconstruct the relationship that exists between cell-cycle progression and the self-renewal versus commitment cell-fate decision in embryonic and adult stem cells. Recent genetic studies in mice have provided insights into the regulation of the cell cycle in stem cells, including its potential modulation by the stem cell niche. Although the dynamics of the embryonic and adult stem cell cycles are profoundly dissimilar, we suggest that shared principles underlie the governance of this important decision point in diverse stem cell types. C1 [Orford, Keith W.; Scadden, David T.] Harvard Univ, Massachusetts Gen Hosp, MGH Ctr Regenerat Med, Boston, MA 02114 USA. RP Scadden, DT (reprint author), Harvard Univ, Massachusetts Gen Hosp, MGH Ctr Regenerat Med, 182 Cambridge St,CPZN Room 4265A, Boston, MA 02114 USA. EM scadden.david@mgh.harvard.edu NR 117 TC 425 Z9 434 U1 5 U2 49 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0056 J9 NAT REV GENET JI Nat. Rev. Genet. PD FEB PY 2008 VL 9 IS 2 BP 115 EP 128 DI 10.1038/nrg2269 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 252OI UT WOS:000252455400010 PM 18202695 ER PT J AU Stuart, LM Ezekowitz, RA AF Stuart, Lynda M. Ezekowitz, R. Alan TI Phagocytosis and comparative innate immunity: learning on the fly SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID FC-GAMMA-R; APOPTOTIC CELLS; DROSOPHILA-MELANOGASTER; MEDIATED PHAGOCYTOSIS; CROSS-PRESENTATION; RHO-GTPASES; RECOGNITION PROTEIN; EXOGENOUS ANTIGENS; SCAVENGER RECEPTOR; ADAPTIVE IMMUNITY AB Phagocytosis, the engulfment of material by cells, is a highly conserved process that arose before the development of multicellularity. Phagocytes have a key role in embryogenesis and also guard the portals of potential pathogen entry. They discriminate between diverse particles through the array of receptors expressed on their surface. In higher species, arguably the most sophisticated function of phagocytes is the processing and presentation of antigens derived from internalized material to stimulate lymphocytes and long-lived specific immunity. Central to these processes is the generation of a phagosome, the organelle that forms around internalized material. As we discuss in this Review, over the past two decades important insights into phagocytosis have been gleaned from studies in the model organism Drosophila melanogaster. C1 [Stuart, Lynda M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Boston, MA 02144 USA. [Ezekowitz, R. Alan] Merck Res Labs, Rahway, NJ 07065 USA. RP Stuart, LM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, 55 Fruit St, Boston, MA 02144 USA. EM lstuart@partners.org NR 101 TC 132 Z9 139 U1 5 U2 33 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD FEB PY 2008 VL 8 IS 2 BP 131 EP 141 DI 10.1038/nri2240 PG 11 WC Immunology SC Immunology GA 255QE UT WOS:000252671700014 PM 18219310 ER PT J AU Hedestam, GBK Fouchier, RAM Phogat, S Burton, DR Sodroski, J Wyatt, RT AF Hedestam, Gunilla B. Karlsson Fouchier, Ron A. M. Phogat, Sanjay Burton, Dennis R. Sodroski, Joseph Wyatt, Richard T. TI The challenges of eliciting neutralizing antibodies to HIV-1 and to influenza virus SO NATURE REVIEWS MICROBIOLOGY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; GP120 ENVELOPE GLYCOPROTEIN; HUMAN MONOCLONAL-ANTIBODY; CORECEPTOR BINDING-SITE; X-RAY CRYSTALLOGRAPHY; T-CELL RESPONSES; RECEPTOR-BINDING; PROTECTIVE IMMUNITY; PANDEMIC INFLUENZA; VACCINE DESIGN AB The ability to elicit broadly neutralizing antibody responses against HIV-1 is a crucial goal for a prophylactic HIV-1 vaccine. Here, we discuss the difficulties of achieving broad HIV-1 neutralization in the context of both the effective annual human influenza virus vaccine and the need to develop a pandemic influenza vaccine. Immunogen-design strategies are underway to target functionally conserved regions of the HIV-1 envelope glycoproteins, and similar strategies might be applicable to pandemic influenza virus vaccine development. Efforts to develop broadly neutralizing vaccines against either HIV-1 or influenza virus might establish a paradigm for future vaccines against highly variable pathogens. C1 [Phogat, Sanjay; Wyatt, Richard T.] NIAID, NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Hedestam, Gunilla B. Karlsson] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm 17177, Sweden. [Hedestam, Gunilla B. Karlsson] Swedish Inst Infect Dis Control, Solna 17182, Sweden. [Fouchier, Ron A. M.] Erasmus MC, Natl Influenza Ctr, NL-3015GE Rotterdam, Netherlands. [Fouchier, Ron A. M.] Erasmus MC, Dept Virol, NL-3015GE Rotterdam, Netherlands. [Burton, Dennis R.] Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. [Burton, Dennis R.] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. [Sodroski, Joseph] Harvard Univ, Sch Med, Div AIDS, Dana Farber Canc Inst,Dept Cancer Immunol & AIDS, Boston, MA 02115 USA. RP Wyatt, RT (reprint author), NIAID, NIH, Vaccine Res Ctr, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM richardwyatt@nih.gov RI Fouchier, Ron/A-1911-2014 OI Fouchier, Ron/0000-0001-8095-2869 NR 134 TC 169 Z9 170 U1 3 U2 41 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1740-1526 J9 NAT REV MICROBIOL JI Nat. Rev. Microbiol. PD FEB PY 2008 VL 6 IS 2 BP 143 EP 155 DI 10.1038/nrmicro1819 PG 13 WC Microbiology SC Microbiology GA 252DZ UT WOS:000252426700013 ER PT J AU James, MF Lelke, JM MacCollin, M Plotkin, SR Stemmer-Rachamimov, AO Ramesh, V Gusella, JF AF James, Marianne F. Lelke, Johanna M. MacCollin, Mia Plotkin, Scott R. Stemmer-Rachamimov, Anat O. Ramesh, Vijaya Gusella, James F. TI Modeling NF2 with human arachnoidal and meningioma cell culture systems: NF2 silencing reflects the benign character of tumor growth SO NEUROBIOLOGY OF DISEASE LA English DT Article DE merlin; NF2; neurofibromatosis 2; meningioma; arachnoidal; senescence; actin cytoskeleton; alpha-catenin; contact inhibition; RNA interference ID HUMAN SCHWANNOMA CELLS; SUPPRESSOR GENE-PRODUCT; NEUROFIBROMATOSIS TYPE-2; EZRIN/RADIXIN/MOESIN PROTEINS; EXTRACELLULAR-MATRIX; ACTIN POLYMERIZATION; LEPTOMENINGEAL CELLS; MOUSE MODELS; MERLIN; EXPRESSION AB Meningiomas, common tumors arising from arachnoidal cells of the meninges, may occur sporadically, or in association with the inherited disorder, neurofibromatosis 2 (NF2). Most sporadic meningiomas result from NF2 inactivation, resulting in loss of tumor suppressor merlin, implicated in regulating membrane-cytoskeletal organization. To investigate merlin function in an authentic target cell type for NF2 tumor formation, we established primary cultures from genetically-matched meningioma and normal arachnoidal tissues. Our studies revealed novel and distinct cell biological and biochemical properties unique to merlin-deficient meningioma cells compared to merlin-expressing arachnoidal and meningioma cells, and other NF2-deficient cell types. Merlin-deficient meningioma cells displayed cytoskeletal and cell contact defects, altered cell morphology and growth properties, most notably cell senescence, implicating the activation of senescence pathways in limiting benign meningioma growth. Merlin suppression by RNAi in arachnoidal cells replicated merlin-deficient meningioma features, thus establishing these cell systems as disease-relevant models for studying NF2 tumorigenesis. (C) 2007 Elsevier Inc. All rights reserved. C1 [James, Marianne F.; Lelke, Johanna M.; Ramesh, Vijaya; Gusella, James F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Boston, MA 02114 USA. [MacCollin, Mia; Plotkin, Scott R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Stemmer-Rachamimov, Anat O.] Massachusetts Gen Hosp, Dept Pathol, Mol Neurooncol Lab, Charlestown, MA 02129 USA. RP Gusella, JF (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Richard B Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM gusella@helix.mgh.harvard.edu FU NINDS NIH HHS [P30 NS045776-03, P30 NS045776, P01 NS024279-140001, P30 NS045776-04, P30 NS045776-019003, P30 NS045776-01, P01 NS024279-120001, P30 NS045776-02, R01 NS041917-02, P01 NS024279-15A10010, R01 NS041917-03, P01 NS024279-130001, R01 NS041917-04, NS024279, P30 NS045776-019001, P30 NS045776-05, R01 NS041917, P01 NS024279-160010, NS045776, NS041917, P01 NS024279, R01 NS041917-01, R01 NS041917-05] NR 62 TC 16 Z9 16 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD FEB PY 2008 VL 29 IS 2 BP 278 EP 292 DI 10.1016/j.nbd.2007.09.002 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 255GW UT WOS:000252647000011 PM 17962031 ER PT J AU Schaechter, JD Perdue, KL Wang, RP AF Schaechter, Judith D. Perdue, Katherine L. Wang, Ruopeng TI Structural damage to the corticospinal tract correlates with bilateral sensorimotor cortex reorganization in. stroke patients SO NEUROIMAGE LA English DT Article ID PRIMARY MOTOR CORTEX; TRANSCRANIAL MAGNETIC STIMULATION; WELL-RECOVERED PATIENTS; ISCHEMIC BRAIN-INJURY; DIFFUSION TENSOR MRI; WALLERIAN DEGENERATION; CAPSULAR STROKE; INTERINDIVIDUAL VARIABILITY; FUNCTIONAL REORGANIZATION; CEREBRAL INFARCTION AB Damage to the corticospinal tract (CST) in stroke patients has been associated with functional reorganization in the ipsilesional and contralesional sensorimotor cortices. However, it is unknown whether a quantitative relationship exists between the extent of structural damage to the CST and functional reorganization in stroke patients. The purpose of the current study was to examine the relationship between structural CST damage and motor task-related cortical activity in chronic herniparetic stroke patients. In 10 chronic herniparetic stroke patients with heterogeneous lesions, CST damage was quantified using conventional structural magnetic resonance imaging and tractography based on diffusion tensor imaging. Cortical activity was measured using functional magnetic resonance imaging during repetitive flexion/extension movements of the digits. We found that the two measures of CST damage were strongly correlated. Moreover, greater CST damage was significantly and linearly correlated with increased activation during affected hand movement in the hand area of the contralesional primary sensorimotor cortex (M1/S1) and in the ipsilesional M1/S1 ventral to the hand area. To our knowledge, this is the first demonstration of a quantitative relationship between the extent of structural damage to the CST and functional reorganization in stroke patients. This relationship was observed in stroke patients with heterogeneous lesions, suggesting that CST damage is a factor relevant to the variation in functional reorganization in the clinical population. (c) 2007 Elsevier Inc. All rights reserved. C1 [Schaechter, Judith D.; Perdue, Katherine L.; Wang, Ruopeng] Massachusetts Gen Hosp, MIT, HMS, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Schaechter, Judith D.; Perdue, Katherine L.; Wang, Ruopeng] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Schaechter, JD (reprint author), Massachusetts Gen Hosp, MIT, HMS, Athinoula A Martinos Ctr Biomed Imaging, 13th St,Bldg 149,Room 2301, Charlestown, MA 02129 USA. EM judith@nmr.mgh.har-vard.edu RI Perdue, Katherine/D-4306-2013 OI Perdue, Katherine/0000-0003-2846-3149 FU NCRR NIH HHS [P41 RR014075, P41-RR14075]; NICHD NIH HHS [K23-HD044425, K23 HD044425, K23 HD044425-01, K23 HD044425-02, K23 HD044425-03, K23 HD044425-04, K23 HD044425-05] NR 81 TC 66 Z9 70 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD FEB 1 PY 2008 VL 39 IS 3 BP 1370 EP 1382 DI 10.1016/j.neuroimage.2007.09.071 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 255XN UT WOS:000252691800042 PM 18024157 ER PT J AU Tourville, JA Reilly, KJ Guenther, FH AF Tourville, Jason A. Reilly, Kevin J. Guenther, Frank H. TI Neural mechanisms underlying auditory feedback control of speech SO NEUROIMAGE LA English DT Article DE auditory feedback control; speech production; neural modeling; functional magnetic resonance imaging; structural equation modeling; effective connectivity ID EVENT-RELATED FMRI; PHASE BIMANUAL MOVEMENTS; CEREBRAL-BLOOD-FLOW; SENSORIMOTOR ADAPTATION; VERBAL FEEDBACK; FUNCTIONAL MRI; BRAIN ACTIVATION; MOTOR CORTEX; OVERT SPEECH; SHORT-TERM AB The neural substrates underlying auditory feedback control of speech were investigated using a combination of functional magnetic resonance imaging (fMRI) and computational modeling. Neural responses were measured while subjects spoke monosyllabic words under two conditions: (i) normal auditory feedback of their speech and (ii) auditory feedback in which the first formant frequency of their speech was unexpectedly shifted in real time. Acoustic measurements showed compensation to the shift within approximately 136 ms of onset. Neuroimaging revealed increased activity in bilateral superior temporal cortex during shifted feedback, indicative of neurons coding mismatches between expected and actual auditory signals, as well as right prefrontal and Rolandic cortical activity. Structural equation modeling revealed increased influence of bilateral auditory cortical areas on right frontal areas during shifted speech, indicating that projections from auditory error cells in posterior superior temporal cortex to motor correction cells in right frontal cortex mediate auditory feedback control of speech. (c) 2007 Elsevier Inc. All rights reserved. C1 [Tourville, Jason A.; Reilly, Kevin J.; Guenther, Frank H.] Boston Univ, Dept Cognit & Neural Syst, Boston, MA 02215 USA. [Guenther, Frank H.] Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Guenther, Frank H.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Guenther, Frank H.] MIT, Elect Res Lab, Cambridge, MA 02139 USA. RP Tourville, JA (reprint author), Boston Univ, Dept Cognit & Neural Syst, 677 Beacon St, Boston, MA 02215 USA. EM jtour@cns.bu.cdu FU NCRR NIH HHS [P41 RR014075, P41RR14075]; NIDCD NIH HHS [R01 DC02852, R01 DC002852] NR 91 TC 199 Z9 203 U1 3 U2 28 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD FEB 1 PY 2008 VL 39 IS 3 BP 1429 EP 1443 DI 10.1016/j.neuroimage.2007.09.054 PG 15 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 255XN UT WOS:000252691800047 PM 18035557 ER PT J AU Kovelman, L Shalinsky, MH Berens, MS Petitto, LA AF Kovelman, Loulia Shalinsky, Mark H. Berens, Melody S. Petitto, Laura-Ann TI Shining new light on the brain's "bilingual signature": A functional Near Infrared Spectroscopy investigation of semantic processing SO NEUROIMAGE LA English DT Review ID SPANISH-ENGLISH BILINGUALS; INFERIOR FRONTAL-CORTEX; AMERICAN SIGN LANGUAGE; CRITICAL PERIOD; WORKING-MEMORY; PREFRONTAL CORTEX; WORD RECOGNITION; VISUAL-CORTEX; 2ND LANGUAGE; ACQUISITION AB Decades of research have shown that, from an early age, proficient bilinguals can speak each of their two languages separately (similar to monolinguals) or rapidly switch between them (dissimilar to monolinguals). Thus we ask, do monolingual and bilingual brains process language similarly or dissimilarly, and is this affected by the language context? Using an innovative brain imaging technology, functional Near Infrared Spectroscopy (fNIRS), we investigated how adult bilinguals process semantic information, both in speech and in print, in a monolingual language context (one language at a time) or in a bilingual language context (two languages in rapid alternation). While undergoing fNIRS recording, ten early exposed, highly proficient Spanish-English bilinguals completed a Semantic Judgment task in monolingual and bilingual contexts and were compared to ten English monolingual controls. Two hypotheses were tested: the Signature Hypothesis predicts that early, highly proficient bilinguals will recruit neural tissue to process language differently from monolinguals across all language contexts. The Switching Hypothesis predicts that bilinguals will recruit neural tissue to process language similarly to monolinguals, when using one language at a time. Supporting the Signature Hypothesis, in the monolingual context, bilinguals and monolinguals showed differences in both hemispheres in the recruitment of DLPFC (BA 46/9) and IFC (BA 47/11), but similar recruitment of Broca's area (BA 44/45). In particular, in the monolingual context, bilinguals showed greater signal intensity in channels maximally overlaying DLPFC and IFC regions as compared to monolinguals. In the bilingual context, bilinguals demonstrated a more robust recruitment of right DLPFC and right IFC. These findings reveal how extensive early bilingual exposure modifies language organization in the brain-thus imparting a possible "bilingual signature." They further shed fascinating new light on how the bilingual brain may reveal the biological extent of the neural architecture underlying all human language and the language processing potential not fully recruited in the monolingual brain. (c) 2007 Elsevier Inc. All rights reserved. C1 [Berens, Melody S.; Petitto, Laura-Ann] Univ Toronto Scarborough, Dept Psychol, Toronto, ON MIC 1A4, Canada. [Kovelman, Loulia] MIT, Cambridge, MA 02139 USA. [Shalinsky, Mark H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Anthinoula A Martinos Ctr Biomed Imaging, Cambridge, MA 02138 USA. RP Petitto, LA (reprint author), Univ Toronto Scarborough, Dept Psychol, 1265 Mil Trail, Toronto, ON MIC 1A4, Canada. EM petitto@utsc.utoronto.ca OI Kovelman, Ioulia/0000-0003-4287-6986 FU NICHD NIH HHS [R21 HD050558-03, R01 HD045822-01A2, R21 HD050558-01A1, R01 HD045822-04, R21 HD050558, R21HD050558-01, R01 HD045822, R01HD045822-01] NR 108 TC 11 Z9 11 U1 4 U2 21 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD FEB 1 PY 2008 VL 39 IS 3 BP 1457 EP 1471 DI 10.1016/j.neuroimage.2007.10.017 PG 15 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 255XN UT WOS:000252691800049 PM 18054251 ER PT J AU Goff, DC Lamberti, JS Leon, AC Green, MF Miller, AL Patel, J Manschreck, T Freudenreich, O Johnson, SA AF Goff, Donald C. Lamberti, J. Steven Leon, Andrew C. Green, Michael F. Miller, Alexander L. Patel, Jayendra Manschreck, Theo Freudenreich, Oliver Johnson, Steven A. TI A placebo-controlled add-on trial of the Ampakine, CX516, for cognitive deficits in schizophrenia SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Ampakine; glutamate; schizophrenia; cognition ID NEGATIVE SYNDROME SCALE; LONG-TERM POTENTIATION; GLUTAMATE RECEPTORS; ANTIPSYCHOTIC-DRUGS; KAINATE RECEPTORS; RATING-SCALE; CLOZAPINE; HALOPERIDOL; MODULATORS; MEMORY AB AMPA-receptor-positive modulators (Ampakines) facilitate learning and memory in animal models and in preliminary trials in human subjects. CX516 is the first Ampakine to be studied for cognitive enhancement in schizophrenia. Stable schizophrenia patients treated with clozapine (n= 52), olanzapine (n= 40), or risperidone (n= 13) were randomly assigned to add-on treatment with CX516 900 mg three times daily or placebo for 4 weeks. Subjects were assessed with a cognitive battery at baseline, week 4, and at 4-week follow-up. Clinical scales and safety monitoring were also performed. The primary endpoint was the change from baseline in a composite cognitive score at week 4 for the intent-to-treat sample. Additional analyses examined change in symptom rating scores and examined drug effects on patients treated with clozapine separately from patients treated with either olanzapine or risperidone. A total of 105 patients were randomized and 95 (90%) completed the 4-week trial. Patients treated with CX516 did not differ from placebo in change from baseline on the composite cognitive score, or on any cognitive test at weeks 4 or 8. The between groups effect size at week 4 for the cognitive composite score was -0.19 for clozapine-treated patients and 0.24 for patients treated with olanzapine or risperidone. The placebo group improved more on the PANSS total score than the CX516 group; no other clinical rating differed between treatment groups. CX516 was associated with fatigue, insomnia and epigastric discomfort compared to placebo, but was generally well tolerated. CX516 was not effective for cognition or for symptoms of schizophrenia when added to clozapine, olanzapine, or risperidone. C1 [Goff, Donald C.; Freudenreich, Oliver] Massachusetts Gen Hosp, Dept Psychiat, Freedom Trial Clin, Boston, MA 02114 USA. [Goff, Donald C.; Freudenreich, Oliver] Harvard Univ, Boston, MA 02115 USA. [Lamberti, J. Steven] Univ Rochester, Med Ctr, Dept Psychiat, Rochester, NY 14642 USA. [Leon, Andrew C.] Cornell Univ, Weill Med Coll, Dept Psychiat, New York, NY USA. [Green, Michael F.] Univ Calif Los Angeles, Semel Neuropsychiat Inst, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. [Miller, Alexander L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Patel, Jayendra] Univ Massachusetts, Sch Med, Ctr Psychopharmacol Res & Treatment, Dept Psychiat, Worcester, MA 01605 USA. [Manschreck, Theo] Harvard Univ, Sch Med, Dr John C Corrigan Mental Hlth Ctr, Dept Psychiat, Fall River, MA USA. [Johnson, Steven A.] Cortex Pharmaceut Inc, Irvine, CA USA. RP Goff, DC (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Freedom Trial Clin, 25 Staniford St,2nd Floor, Boston, MA 02114 USA. EM goff@psych.mgh.harvard.edu FU NIMH NIH HHS [R44 MH059450, 1R43 MH59450, K24 MH002025, K24 MH002025-10, K24 MH02025, R44 MH059450-02A1] NR 69 TC 100 Z9 102 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD FEB PY 2008 VL 33 IS 3 BP 465 EP 472 DI 10.1038/sj.npp.1301444 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 250LE UT WOS:000252300700001 PM 17487227 ER PT J AU Barr, RS Culhane, MA Jubelt, LE Mufti, RS Dyer, MA Weiss, AP Deckersbach, T Kelly, JF Freudenreich, O Goff, DC Evins, AE AF Barr, Ruth S. Culhane, Melissa A. Jubelt, Lindsay E. Mufti, Rana S. Dyer, Michael A. Weiss, Anthony P. Deckersbach, Thilo Kelly, John F. Freudenreich, Oliver Goff, Donald C. Evins, A. Eden TI The effects of transdermal nicotine on cognition in nonsmokers with schizophrenia and nonpsychiatric controls SO NEUROPSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT 11th International Congress on Schizophrenia Research/8th Biennial Mt Sinai Conference on Cognition in Schizophrenia CY MAR 27-APR 01, 2007 CL Colorado Springs, CO DE schizophrenia; nicotine; smoking; cognition; attention; nonsmokers ID CONTINUOUS PERFORMANCE-TEST; IDENTICAL PAIRS VERSION; PURSUIT EYE-MOVEMENTS; CIGARETTE-SMOKING; WORKING-MEMORY; SMOOTH-PURSUIT; NEUROCOGNITIVE DEFICITS; SUBCUTANEOUS NICOTINE; RECEPTOR MECHANISMS; RESPONSE-INHIBITION AB Abundant evidence indicates that the neuronal nicotinic acetylcholine receptor (nAChR) system is integral to regulation of attentional processes and is dysregulated in schizophrenia. Nicotinic agonists may have potential for the treatment of cognitive impairment in this disease. This study investigated the effects of transdermal nicotine on attention in individuals with schizophrenia (n = 28) and healthy controls (n = 32). All participants were nonsmokers in order to eliminate confounding effects of nicotine withdrawal and reinstatement that may occur in the study of smokers. Subjects received 14 mg transdermal nicotine and identical placebo in a randomized, placebo-controlled, crossover design. A cognitive battery was conducted before and 3 h after each patch application. The primary outcome measure was performance on the Continuous Performance Test Identical Pairs (CPT-IP) Version. Nicotine significantly improved the performance on the CPT-IP as measured by hit reaction time, hit reaction time standard deviation and random errors in both groups. In addition, nicotine reduced commission errors on the CPT-IP and improved the performance on a Card Stroop task to a greater extent in those with schizophrenia vs controls. In summary, nicotine improved attentional performance in both groups and was associated with greater improvements in inhibition of impulsive responses in subjects with schizophrenia. These results confirm previous findings that a single dose of nicotine improves attention and suggest that nicotine may specifically improve response inhibition in nonsmokers with schizophrenia. C1 [Barr, Ruth S.; Culhane, Melissa A.; Mufti, Rana S.; Dyer, Michael A.; Kelly, John F.; Evins, A. Eden] Massachusetts Gen Hosp, Addict Res Program, Boston, MA 02114 USA. [Barr, Ruth S.; Culhane, Melissa A.; Jubelt, Lindsay E.; Mufti, Rana S.; Dyer, Michael A.; Weiss, Anthony P.; Freudenreich, Oliver; Goff, Donald C.; Evins, A. Eden] Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA 02114 USA. [Barr, Ruth S.; Mufti, Rana S.; Weiss, Anthony P.; Deckersbach, Thilo; Kelly, John F.; Freudenreich, Oliver; Goff, Donald C.; Evins, A. Eden] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Deckersbach, Thilo] Massachusetts Gen Hosp, Cognit Neurosci Program, Boston, MA 02114 USA. RP Evins, AE (reprint author), Massachusetts Gen Hosp, Addict Res Program, 25 Staniford St, Boston, MA 02114 USA. EM a_eden_evins@hms.harvard.edu FU NIDA NIH HHS [K23 DA00510] NR 86 TC 120 Z9 122 U1 5 U2 17 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD FEB PY 2008 VL 33 IS 3 BP 480 EP 490 DI 10.1038/sj.npp.1301423 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 250LE UT WOS:000252300700003 PM 17443126 ER PT J AU Moore, EE Jackson, SL Boyko, EJ Scholes, D Fihn, SD AF Moore, Elya E. Jackson, Sara L. Boyko, Edzvard J. Scholes, Delia Fihn, Stephan D. TI Urinary incontinence and urinary tract infection - Temporal relationships in postmenopausal women SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID RISK-FACTORS; HYSTERECTOMY; PREVALENCE; PREDICTORS; STRESS; URGE AB OBJECTIVE: To estimate the temporal relationship between self-reported urine loss and incident, symptomatic, microbiologically confirmed urinary tract infection (UTI). METHODS: We used daily diaries to collect information on incontinent episodes during a 2-year prospective study of incident UTI among 913 healthy postmenopausal health maintenance organization enrollees. We calculated the monthly rate of urine loss to assess for association with incident UTI. We also estimated the basal rate of urinary incontinence among women who experienced a UTI (excluding the 14-day time period pre- and post-UTI) and compared this to urine loss during the 3-day time period after UTI, to evaluate changes after infection. RESULTS: Sixty percent of women reported urinary incontinence, at a mean rate of 4.7 times per month. The monthly mean rate of urine loss was 2.64 times per month among women who did not experience a UTI compared with 4.60 times per among women who developed a UTI (P=.04). Among women who developed a UTI (n=78), the rate of urine loss during the 3 days after UTI onset was 1.5 times higher than the basal rate (0.23 compared with 0.15 reports per day, P=.26). CONCLUSION: After eliminating episodes of incontinence surrounding a UTI, the basal rate of urine loss was higher among women who experienced UTIs compared with those who did not. Additionally, among women who experienced a UTI, an increase in urine loss occurred in the immediate 3-day time period post-UTI, compared with infection-free periods. Urinary incontinence characterizes women who experience UTIs, both intercurrently and during an acute episode. C1 [Moore, Elya E.; Jackson, Sara L.; Boyko, Edzvard J.; Scholes, Delia; Fihn, Stephan D.] Grp Hlth Ctr Hlth Studies, Grp Hlth Cooperat, Seattle, WA USA. [Moore, Elya E.; Jackson, Sara L.; Boyko, Edzvard J.; Scholes, Delia; Fihn, Stephan D.] Univ Washington, Hlth Serv Res & Dev Ctr Excellence, VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA 98195 USA. [Moore, Elya E.; Jackson, Sara L.; Boyko, Edzvard J.; Scholes, Delia; Fihn, Stephan D.] Seattle ERIC, VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Moore, EE (reprint author), Royal Childrens Hosp, Murdoch Childrens Res Inst, Flemington Rd, Parkville, Vic 3052, Australia. EM elya.moore@mcri.edu.au FU NIAID NIH HHS [T32AI07140]; NIDDK NIH HHS [K23DK02660, R01 DK43134] NR 26 TC 23 Z9 23 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD FEB PY 2008 VL 111 IS 2 BP 317 EP 323 DI 10.1097/AOG.0b013e318160d64a PN 1 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 256XD UT WOS:000252762300009 PM 18238968 ER PT J AU Rigotti, NA Park, ER Chang, YC Regan, S AF Rigotti, Nancy A. Park, Elyse R. Chang, Yuchiao Regan, Susan TI Smoking cessation medication use among pregnant and postpartum smokers SO OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 13th Annual Meeting of the Society-for-Research-in-Nicotine-and-Tobacco CY FEB 23, 2007 CL Austin, TX SP Soc Res Nicotine & Tobacco ID NICOTINE REPLACEMENT THERAPY; RANDOMIZED CONTROLLED-TRIAL; OBSTETRICIANS; GYNECOLOGISTS; GUIDELINES; DEPENDENCE; UPDATE; WOMEN AB OBJECTIVE: To assess how often pregnant and postpartum smokers use medications and how often obstetric providers recommend them. METHODS: We analyzed end-of-pregnancy and 3-month postpartum surveys of 296 pregnant smokers enrolled in a randomized controlled trial of telephone counseling for smoking cessation that did not include medication. Patients were asked whether any obstetric provider discussed cessation medication and whether they had used medication. RESULTS: At end of pregnancy, 29.3% of respondents reported discussing a cessation medication with their obstetric providers, more often nicotine replacement (26.5%) than bupropion (12.2%) (P=.001). Ten percent of trial respondents used a medication while pregnant (7.4% nicotine replacement, 3.4% bupropion, P=.023). Obstetricians discussed medication with 29.4% of smokers at the postpartum visit; 14.3% of postpartum smokers used medication. Contrary to guidelines, women who smoked more cigarettes per day or had already tried quitting during pregnancy were not more likely to use medication or to discuss medication with their provider. Medication use was associated with older age, more education, living with a partner, a previous birth, having an obstetric provider who discussed medication, and having private health insurance in a state whose Medicaid program did not cover cessation medications (all P<.05). CONCLUSION: Pregnant women are more reluctant to use cessation medications than clinical guidelines recommend. More pregnant smokers might use cessation medications if their obstetricians discussed them routinely and if health insurance covered their cost. C1 [Rigotti, Nancy A.; Park, Elyse R.; Chang, Yuchiao; Regan, Susan] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. [Rigotti, Nancy A.; Park, Elyse R.; Chang, Yuchiao; Regan, Susan] Tobacco Res & Treatment Ctr, Dept Med, Boston, MA USA. [Rigotti, Nancy A.; Park, Elyse R.; Chang, Yuchiao; Regan, Susan] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Rigotti, NA (reprint author), Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM nrigotti@partners.org NR 36 TC 20 Z9 20 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD FEB PY 2008 VL 111 IS 2 BP 348 EP 355 DI 10.1097/01.AOG.0000297305.54455.2e PN 1 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 256XD UT WOS:000252762300013 PM 18238972 ER PT J AU Haglund, KE Viswanathan, AN AF Haglund, Karl E. Viswanathan, Akila N. TI Computed tomography-based radiation therapy of ovarian remnants for symptomatic persistent endometriosis SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID ABLATION AB BACKGROUND: Endometriosis, a major cause of pelvic pain in women, is driven by estrogen. Ovarian remnant irradiation may alleviate pelvic pain by eliminating estrogen production in appropriately selected women with endometriosis. CASE: Three patients with endometriosis causing incapacitating pelvic pain received 3D-imaging-based external beam radiation to doses of 1,500 to 2,100 cGy. All had pre-irradiation premenopausal follicle stimulating hormone levels and imaging evidence of ovarian remnants. None were candidates for further medical or surgical interventions. By 3 months after radiation, follicle stimulating hormone levels reached postmenopausal levels in all three patients, with complete resolution of the severe pelvic pain. CONCLUSION: Radiation therapy effectively induced menopause and relieved refractory pain from endometriosis. Careful selection of patients is necessary, given the potential for an increased long-term risk of radiation-related complications. C1 [Haglund, Karl E.; Viswanathan, Akila N.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Haglund, Karl E.; Viswanathan, Akila N.] Harvard Radiat Oncol Program, Boston, MA USA. RP Viswanathan, AN (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St,ASB1-L2, Boston, MA 02115 USA. EM aviswanathan@lroc.harvard.edu NR 9 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD FEB PY 2008 VL 111 IS 2 BP 579 EP 583 DI 10.1097/01.AOG.0000299877.71874.91 PN 2 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 256XF UT WOS:000252762500038 PM 18239029 ER PT J AU Schutte, J Reichardt, P Schlemmer, M Wendtner, CM Demetri, GD AF Schuette, J. Reichardt, P. Schlemmer, M. Wendtner, C. -M. Demetri, G. D. TI Efficacy and safety of sunitinib in patients with gastrointestinal stromal tumour resistant or intolerant of prior imatinib therapy: Results from a worldwide treatment-use study SO ONKOLOGIE LA English DT Meeting Abstract C1 [Schuette, J.] Marien Hosp, Klin Onkol & Hamatol, Dusseldorf, Germany. [Reichardt, P.] HELIOS Klin, Bad Saarow Pieskow, Germany. [Schlemmer, M.] Klinikum Univ Munich Grosshadern, Munich, Germany. [Wendtner, C. -M.] Klinikum Univ Koln, Cologne, Germany. [Demetri, G. D.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-584X J9 ONKOLOGIE JI Onkologie PD FEB PY 2008 VL 31 SU 1 BP 77 EP 77 PG 1 GA 265PG UT WOS:000253372800244 ER PT J AU Feke, GT Pasquale, LR AF Feke, Gilbert T. Pasquale, Louis R. TI Retinal blood flow response to posture change in glaucoma patients compared with healthy subjects SO OPHTHALMOLOGY LA English DT Article ID OPEN-ANGLE GLAUCOMA; NORMAL-TENSION GLAUCOMA; NORMAL-PRESSURE GLAUCOMA; LASER-DOPPLER VELOCIMETRY; OPTIC DISC HEMORRHAGES; PERFUSION-PRESSURE; INTRAOCULAR-PRESSURE; VASCULAR DYSREGULATION; OCULAR HYPERTENSION; ISOMETRIC-EXERCISE AB Purpose: To characterize the retinal vascular autoregulatory response to ocular perfusion pressure (OPP) changes in patients with glaucoma and in healthy control subjects. Design: Observational cohort study. Participants: Eighteen patients with open-angle glaucoma (OAG) and 8 control subjects, all females ages 40 to 60 years, were studied. Only subjects with known maximum intraocular pressure less than 22 mmHg in both eyes were included. Methods: Arterial diameter and blood speed in the inferior temporal retinal artery of the left eye were measured simultaneously at baseline while sitting, while reclining for approximately 30 minutes, and once again sitting using a retinal laser Doppler instrument. Blood flow rate was computed automatically. Brachial artery blood pressure and heart rate also were measured. Main Outcome Measure: Change in blood flow rate while reclining for approximately 30 minutes compared with baseline blood flow rate measured while seated. Results. In control subjects, arterial diameter decreased by 7.5 +/- 3.4% (P = 0.0003) and blood speed increased by 24.6 +/- 10.8% (P = 0.004) while reclining compared with baseline. The concomitant change in the blood flow rate (6.5 +/- 12.0%; P = 0.15) compared with baseline was not statistically significant. In contrast, OAG patients showed a much broader range of blood flow changes in response to posture change (14.9 +/- 37.7%; P = 0.086) compared with baseline. Although there were no significant differences in the flow changes compared with baseline in either group, there was a significant difference in the variance of the blood flow changes in the OAG patients compared with the controls (P = 0.0025). Division of the OAG patients into subgroups revealed a significant (P = 0.031) association between baseline OPP and the retinal blood flow response to posture change. Conclusions: The authors describe the hemodynamic details of retinal vascular autoregulation in response to posture-induced changes in OPP in healthy subjects and document the lack of such autoregulation in a selected group of patients with OAG. C1 [Feke, Gilbert T.] Schepens Retina Associates Fdn, Boston, MA 02215 USA. [Pasquale, Louis R.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Feke, Gilbert T.; Pasquale, Louis R.] Schepens Eye Res Inst, Boston, MA USA. [Feke, Gilbert T.; Pasquale, Louis R.] Harvard Univ, Sch Med, Boston, MA USA. RP Feke, GT (reprint author), Schepens Retina Associates Fdn, 1 Autumn St,6th Floor, Boston, MA 02215 USA. EM feke@schepens.com NR 54 TC 75 Z9 78 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD FEB PY 2008 VL 115 IS 2 BP 246 EP 252 DI 10.1016/j.ophtha.2007.04.055 PG 7 WC Ophthalmology SC Ophthalmology GA 258AJ UT WOS:000252840500005 PM 17689612 ER PT J AU Pavan-Langston, D AF Pavan-Langston, Deborah TI Herpes zoster - Antivirals and pain management SO OPHTHALMOLOGY LA English DT Review ID PLACEBO-CONTROLLED TRIAL; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; SIMPLEX VIRUS TYPE-1; POSTHERPETIC NEURALGIA; ORAL ACYCLOVIR; NEUROPATHIC PAIN; RANDOMIZED-TRIAL; GRANULOMATOUS-ANGIITIS; IMMUNOCOMPETENT ADULTS; OPHTHALMIC ZOSTER AB Topic: Evaluation of evidence-based strategies for managing herpes zoster (HZ) and the pain of postherpetic neuralgia (PHN). Clinical Relevance: Approximately 20% of the world's population suffers from herpes zoster at least once in a lifetime, with 10% to 20% having ophthalmic involvement. Treatment of the acute disease with oral antivirals may reduce the incidence and severity of complications but does not reliably prevent PHN or postherpetic itch (PHI). The acute pain abates as the acute phase resolves; the long-term pain of PHN or PHI may be severe and difficult to manage. Although many therapeutic agents have efficacy in the management of these complications, relief is frequently partial for months to the remainder of the lifetime. Methods: Literature review was performed using the resources of the Harvard Medical School/Massachusetts Eye and Ear Infirmary Ophthalmic library as well as the National Library of Medicine and the National Institutes of Health PubMed service searching by pertinent topics, authors, and journals. Results: If started within 72 hours of the onset of the acute HZ rash, the oral antiviral agents acyclovir, valacyclovir, and famciclovir significantly shorten the periods of acute pain, virus shedding, rash, acute and late-onset anterior segment complications, and, in the case of valacyclovir and famciclovir, the incidence and severity of PHN. However, these medications do not prevent PHN, which remains a common and debilitating complication of HZ in older patients, requiring assiduous pain management. Tricyclic antidepressants, antiseizure drugs, opioids, and topical analgesics all offer some pain relief, and may be combined. Conclusion: Options are available to manage HZ and reduce the pain of PHN. However, prevention, now possible with the HZ vaccine, is preferable to treatment. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. RP Pavan-Langston, D (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM deborah.langston@meei.harvard.edu NR 110 TC 21 Z9 24 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD FEB PY 2008 VL 115 IS 2 SU S BP S13 EP S20 DI 10.1016/j.ophtha.2007.10.012 PG 8 WC Ophthalmology SC Ophthalmology GA 259RV UT WOS:000252957400003 PM 18243927 ER PT J AU Pavan-Langston, D Dohman, CH AF Pavan-Langston, Deborah Dohman, Claes H. TI Boston keratoprosthesis treatment of herpes zoster neurotrophic keratopathy SO OPHTHALMOLOGY LA English DT Article AB Topic: The successful use of the Boston keratoprosthesis in a severely inflamed ulcer in herpes zoster neurotrophic keratopathy. Clinical Relevance: Approximately 10% to 20% of patients with herpes zoster will develop herpes zoster ophthalmicus (HZO). Antiviral medication forms the foundation of pharmacologic treatment for acute herpes zoster, but management of HZO is supplemented with topical and,systemic antimicrobials and corticosteroid agents as well as surgical interventions. However, HZO is associated with poor healing, as evidenced by a high occurrence of ulceration, superinfection, and surgical failure. Methods: A 95-year-old man was referred for corneal edema in the right eye. There was a history of acute herpes zoster in the right eye 10 months previously. Slit-lamp examination revealed lagophthalmos, ectropion, total corneal anesthesia, and marked inferior corneal edema. Despite surgical repair of all lid abnormalities and aggressive lubrication and management of rosacea blepharitis, the corneal surface remained unhealthy. Four months later, the patient presented with an inflamed hypopyon ulcer, culture positive for abundant Pseudomonas and Candida albicans. The ulcer progressed to descemetocele in the face of aggressive antimicrobial therapy, vision was light perception (LP), and perforation became imminent. A Boston kerato prosthesis was used to replace the severely damaged cornea, and extracapsular cataract extraction of a mature cataract was also performed. Results: One week after surgery, the inflammation was almost entirely resolved, and cultures of the host button were negative for any organisms. Vision gradually increased from LIP to 20/60 over the ensuing 4 months. Conclusion: The Boston keratoprosthesis procedure successfully salvaged and restored vision in this high-risk herpes zoster eye in which standard keratoplasty would almost certainly have failed. C1 [Pavan-Langston, Deborah; Dohman, Claes H.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. RP Pavan-Langston, D (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM deborah.langston@schepens.harvard.edu NR 6 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD FEB PY 2008 VL 115 IS 2 SU S BP S21 EP S23 DI 10.1016/j.ophtha.2007.10.013 PG 3 WC Ophthalmology SC Ophthalmology GA 259RV UT WOS:000252957400004 PM 18243928 ER PT J AU Hunziker, EB Kapfinger, E Martin, J Buckwalter, J Morales, TI AF Hunziker, E. B. Kapfinger, E. Martin, J. Buckwalter, J. Morales, T. I. TI Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) is closely associated with the chondrocyte nucleus in human articular cartilage SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE insulin-like growth factor-1 (IGF-1); IGF-binding protein-3 (IGFBP-3); human osteoarthritis; cartilage; nuclear ID FACTOR-BINDING PROTEIN-3; FACTOR-I; FACTOR BINDING-PROTEIN-3; OSTEOARTHRITIC CARTILAGE; INCREASED EXPRESSION; LOCALIZATION; MORPHOLOGY; APOPTOSIS; TRANSPORT; EXPLANTS AB Objective: Insulin-like growth factor-1 (IGF-1) is critically involved in the control of cartilage matrix metabolism. It is well known that IGF-binding protein-3 (IGFBP-3) is increased during osteoarthritis (OA), but its function(s) is not known. In other cells, IGFBP-3 can regulate IGF-1 action in the extracellular environment and can also act independently inside the cell; this includes transcriptional gene control in the nucleus. These studies were undertaken to localize IGFBP-3 in human articular cartilage, particularly within cells. Design: Cartilage was dissected from human femoral heads derived from arthroplasty for OA, and OA grade assessed by histology. Tissue slices were further characterized by extraction and assay of IGFBPs by IGF ligand blot (LB) and by enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry (IHC) for IGF-1 and IGFBP-3 was performed on cartilage from donors with mild, moderate and severe OA. Indirect fluorescence and immunogold-labeling IHC studies were included. Results: LBs of chondrocyte lysates showed a strong signal for IGFBP-3. IHC of femoral cartilage sections at all OA stages showed IGF-1 and IGFBP-3 matrix stain particularly in the top zones, and closely associated with most cells. A prominent perinuclear/nuclear IGFBP-3 signal was seen. Controls using non-immune sera or antigen-blocked antibody showed negative or strongly reduced stain. In frozen sections of human ankle cartilage, immunofluorescent IGFBP-3 stain co- localized with the nuclear 4',6-diamidino-2-phenyl indole (DAPI) stain in greater than 90% of the cells. Immunogold IHC of thin sections and transmission electron immunogold microscopy of ultra-thin sections showed distinct intra-nuclear staining. Conclusions: IGFBP-3 in human cartilage is located in the matrix and within chondrocytes in the cytoplasm and nuclei. This new finding indicates that the range of IGFBP-3 actions in articular cartilage is likely to include IGF-independent roles and opens the door to studies of its nuclear actions, including the possible regulation of hormone receptors or transcriptional complexes to control gene action. (c) 2007 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. C1 [Morales, T. I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02114 USA. [Hunziker, E. B.; Kapfinger, E.] ITI Res Inst Dent & Skeletal Biol, Bern, Switzerland. [Martin, J.; Buckwalter, J.] Univ Iowa, Iowa City, IA USA. [Martin, J.; Buckwalter, J.] Iowa City Vet Med Ctr, Iowa City, IA USA. RP Morales, TI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Jackson 1223,55 Fruit St, Boston, MA 02114 USA. EM tmorales@partners.org FU NIAMS NIH HHS [P50 AR48939, AR48304, P50 AR048939, R01 AR048304, R01 AR048304-01A1, R01 AR048304-02, R01 AR048304-03, R01 AR048304-04] NR 34 TC 13 Z9 15 U1 3 U2 9 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD FEB PY 2008 VL 16 IS 2 BP 185 EP 194 DI 10.1016/j.joca.2007.06.008 PG 10 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 269GW UT WOS:000253638500004 PM 17693100 ER PT J AU Radulescu, VC Gerrard, M Moertel, C Grundy, PE Mathias, L Feusner, J Diller, L Dome, JS AF Radulescu, Vlad C. Gerrard, Mary Moertel, Chris Grundy, Paul E. Mathias, Liesl Feusner, James Diller, Lisa Dome, Jeffrey S. TI Treatment of recurrent clear cell sarcoma of the kidney with brain metastasis SO PEDIATRIC BLOOD & CANCER LA English DT Article DE CCSK; chemotherapy; relapse; stem cell ID NATIONAL WILMS-TUMOR AB Background Clear cell sarcoma of the kidney (CCSK) is known for its propensity to metastasize to bone, but it also spreads to other sites including the brain. This study was undertaken to describe the treatment and outcomes of patients with recurrent CCSK involving the brain. Methods. A retrospective records review was conducted on eight patients with CCSK who developed brain metastases after complete responses to initial therapy. Results. The recurrences occurred at a median of 24.5 months after initial diagnosis (range, 12-53 months). At the time of recurrence, patients were treated with multimodal therapy including biopsy or resection, radiation therapy, and chemotherapy. All patients received a variable number of courses of ifosfamide, carboplatin, and etoposide (ICE), with or without other agents. Four patients received high-dose chemotherapy with autologous stem cell rescue. One patient died from complications of bacteremia 8 weeks after starting chemotherapy. The other seven patients achieved a complete response after either surgery or ICE chemotherapy. Of these, six patients were alive without disease with a median follow-up of 30 months from the time of recurrence (range, 24 to 71 months). All six survivors received radiation therapy and four had gross total resections. Three survivors received high-dose chemotherapy with stem cell rescue. Conclusion. Patients with recurrent CCSK involving the brain can have durable survival after recurrence. ICE chemotherapy, together with radiation therapy and surgery, provides a reasonable salvage regimen for recurrent CCSK. It is unclear whether high-dose chemotherapy confers a benefit compared to conventional-dose chemotherapy. C1 [Radulescu, Vlad C.] E Tennessee State Univ, Johnson City, TN 37614 USA. [Radulescu, Vlad C.] Univ Kentucky, Lexington, KY USA. [Gerrard, Mary] Sheffield Childrens Hosp, Sheffield, S Yorkshire, England. [Moertel, Chris] Childrens Hosp & Clin Minnesota, St Paul, MN USA. [Grundy, Paul E.] Stollery Childrens Hosp, Edmonton, AB, Canada. [Mathias, Liesl] Loma Linda Univ, Med Ctr, Loma Linda, CA USA. [Feusner, James] Childrens Hosp Oakland, Oakland, CA USA. [Diller, Lisa] Dana Farber Canc Inst, Boston, MA 02115 USA. [Dome, Jeffrey S.] St Jude Childrens Hosp, Memphis, TN 38105 USA. RP Dome, JS (reprint author), Childrens Natl Med Ctr, Div Oncol, 111 Michigan Ave,NW, Washington, DC 20010 USA. EM jdome@cnmc.org FU NCI NIH HHS [CA-21765] NR 14 TC 14 Z9 14 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD FEB PY 2008 VL 50 IS 2 BP 246 EP 249 DI 10.1002/pbc.21131 PG 4 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 246KN UT WOS:000252006000013 PM 17226850 ER PT J AU Nestoridi, E Kushak, RI Tsukurov, O Grabowski, EF Ingelfinger, JR AF Nestoridi, Eirini Kushak, Rafail I. Tsukurov, Olga Grabowski, Eric F. Ingelfinger, Julie R. TI Role of the renin angiotensin system in TNF-alpha and Shiga-toxin-induced tissue factor expression SO PEDIATRIC NEPHROLOGY LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the American-Society-of-Nephrology CY NOV 08-13, 2005 CL Philadelphia, PA SP Amer Soc Nephrol DE angiotensin II; tissue factor; Shiga-toxin; hemolytic uremic syndrome; human glomerular endothelial cells ID HEMOLYTIC-UREMIC SYNDROME; ENDOTHELIAL-CELLS; COAGULATION; ACTIVATION; RAT; PATHOPHYSIOLOGY; PATHOGENESIS; MONOCYTES AB Current evidence implicates a prothrombotic state in the development of Shiga-toxin (Stx)-mediated hemolytic uremic syndrome (HUS). We recently reported that Stx modulates procoagulant activity by enhancing functional tissue factor (TF) activity on cytokine-activated human glomerular endothelial cells (HGECs). Since angiotensin II (Ang II), the key effector of the renin angiotensin system (RAS), has been shown to increase TF expression in vascular tissue, we examined the possible involvement of Ang II in TF expression in HGECs. HGECs were exposed to tumor necrosis factor (TNF)-alpha +/- Stx-1 +/- Ang II. Exogenous Ang II significantly increased TF activity and TF mRNA in TNF-alpha- +/- Stx-1-activated HGECs. This increase was mediated via Ang II type I receptor (AT(1)R), as losartan, an AT(1)R inhibitor, attenuated Ang-II-induced TF activity. To study the effect of endogenous Ang II in TF expression by TNF-alpha +/- Stx-1, HGECs were incubated with losartan or an AT(2)R inhibitor (PD 123319) or an angiotensin-converting enzyme inhibitor (enalapril). Losartan but not PD 123319 decreased TF activity induced by TNF-alpha +/- Stx-1 (P < 0.05). Enalapril, also, dose dependently, downregulated TF expression in HGECs exposed to TNF-alpha +/- Stx-1 (P < 0.05). AT(1)R mRNA was upregulated in TNF-alpha- +/- Stx-1-activated HGECs (P<0.05). These data indicate that TF expression in TNF-alpha- and Stx-1-activated HGECs is enhanced by exogenous Ang II and that endogenous Ang II production may be upregulated by TNF-alpha +/- Stx-1. Hence, local RAS activation may be important in the development of the thrombotic microangiopathy observed in HUS. C1 [Nestoridi, Eirini; Tsukurov, Olga; Ingelfinger, Julie R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, MassGen Hosp Children,Pediat Nephrol Lab, Boston, MA 02114 USA. [Nestoridi, Eirini; Kushak, Rafail I.; Grabowski, Eric F.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, MassGen Hosp Children,Cardiovasc Thrombosis Lab, Boston, MA 02114 USA. RP Ingelfinger, JR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, MassGen Hosp Children,Pediat Nephrol Lab, Yawkey 6C,55 Fruit St, Boston, MA 02114 USA. EM jingelfinger@partners.org FU NHLBI NIH HHS [R01 HL033095, R01 HL089332, HL 33095]; NIDDK NIH HHS [DK 58950, DK 71253] NR 34 TC 14 Z9 17 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0931-041X J9 PEDIATR NEPHROL JI Pediatr. Nephrol. PD FEB PY 2008 VL 23 IS 2 BP 221 EP 231 DI 10.1007/s00467-007-0636-6 PG 11 WC Pediatrics; Urology & Nephrology SC Pediatrics; Urology & Nephrology GA 250KK UT WOS:000252298600007 PM 18060435 ER PT J AU Friedmann, AM AF Friedmann, Alison M. TI Evaluation and management of lymphadenopathy in children SO PEDIATRICS IN REVIEW LA English DT Review ID PERIPHERAL LYMPHADENOPATHY; CHILDHOOD; BIOPSY; NECK C1 Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. RP Friedmann, AM (reprint author), Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. NR 7 TC 15 Z9 18 U1 1 U2 4 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0191-9601 J9 PEDIATR REV JI Pediatr. Rev. PD FEB PY 2008 VL 29 IS 2 BP 53 EP 60 DI 10.1542/pir.29-2-53 PG 8 WC Pediatrics SC Pediatrics GA 259OB UT WOS:000252947500002 PM 18245301 ER PT J AU Canter, JA Haas, DW Kallianpur, AR Ritchie, MD Robbins, GK Shafer, RW Clifford, DB Murdock, DG Hulgan, T AF Canter, J. A. Haas, D. W. Kallianpur, A. R. Ritchie, M. D. Robbins, G. K. Shafer, R. W. Clifford, D. B. Murdock, D. G. Hulgan, T. TI The mitochondrial pharmacogenomics of haplogroup T: MTND2*LHON4917G and antiretroviral therapy-associated peripheral neuropathy SO PHARMACOGENOMICS JOURNAL LA English DT Article DE MTND2*LHON4917G; mitochondrial DNA; peripheral neuropathy; antiretroviral therapy ID HEREDITARY OPTIC NEUROPATHY; HUMAN-IMMUNODEFICIENCY-VIRUS; PARKINSONS-DISEASE; ALZHEIMER-DISEASE; HUMAN-EVOLUTION; DNA DEPLETION; COMPLEX I; NUCLEOSIDE; AIDS; INFECTION AB Peripheral neuropathy (PN) due to mitochondrial injury complicates HIV therapy with some nucleoside reverse transcriptase inhibitors (NRTIs). Variation in the mitochondrial genome may influence susceptibility to NRTI toxicities. Two non-synonymous mitochondrial DNA polymorphisms, MTND1*LHON4216C (4216C) and MTND2*LHON4917G (4917G) were characterized in HIV-infected participants exposed to NRTIs in a randomized clinical trial. Among 250 self-identified white, non-Hispanic participants, symptomatic PN (X grade 1) developed in 70 (28%). Both 4216C (odds ratio (OR) = 1.98 (95% confidence interval (CI) 1.05-3.75); P = 0.04) and 4917G (OR = 2.93 (95% CI 1.25-6.89); P = 0.01) were more frequent in PN cases. These two polymorphisms remained independently associated with PN after adjusting for age, baseline CD4 count, plasma HIV RNA level, and NRTI randomization arm; 4216C (OR = 2.0 (95% CI 1.1-4.0) P 0.04) and 4917G (OR = 5.5 (95% CI 1.6-18.7) P<0.01). When 4917G individuals were excluded from the analysis, the association with 4216C was no longer seen. The mitochondrial 4917G polymorphism may increase susceptibility to NRTI-associated PN. C1 [Canter, J. A.; Ritchie, M. D.; Murdock, D. G.] Vanderbilt Univ, Sch Med, Ctr Human Genet Res, Dept Mol Physiol & Biophys,Med Ctr, Nashville, TN 37212 USA. [Haas, D. W.; Hulgan, T.] Vanderbilt Univ, Sch Med, Div Infect Dis, Nashville, TN 37212 USA. [Haas, D. W.] Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, Nashville, TN 37212 USA. [Kallianpur, A. R.] Vanderbilt Univ, Sch Med, Dept Med, Div Gen Internal Med & Publ Hlth, Nashville, TN 37212 USA. [Robbins, G. K.] Harvard Univ, Massachusetts Gen Hosp, Dept Med, Boston, MA 02115 USA. [Shafer, R. W.] Stanford Univ, Dept Med Infect Dis, Stanford, CA 94305 USA. [Clifford, D. B.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Clifford, D. B.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. RP Canter, JA (reprint author), Vanderbilt Univ, Sch Med, Ctr Human Genet Res, Dept Mol Physiol & Biophys,Med Ctr, 519 Light Hall, Nashville, TN 37212 USA. EM jeff.canter@vanderbilt.edu RI Robbins, Gregory/F-7988-2011; Ritchie, Marylyn/C-1114-2012; Murdock, Deborah/C-3483-2012; Hulgan, Todd/B-3947-2014 OI Hulgan, Todd/0000-0002-3339-067X FU NIAID NIH HHS [AI 27666, AI 002508, AI 27659, AI 54999] NR 48 TC 34 Z9 35 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD FEB PY 2008 VL 8 IS 1 BP 71 EP 77 DI 10.1038/sj.tpj.6500470 PG 7 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 252OK UT WOS:000252455600010 PM 17684475 ER PT J AU Huang, CK Huang, W Zuk, P Jarrahy, R Rudkin, GH Ishida, K Yamaguchi, DT Miller, TA AF Huang, Catherine K. Huang, Weibiao Zuk, Pat Jarrahy, Reza Rudkin, George H. Ishida, Kenji Yamaguchi, Dean T. Miller, Timothy A. TI Genetic markers of osteogenesis and angiogenesis are altered in processed lipoaspirate cells when cultured on three-dimensional scaffolds SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article; Proceedings Paper CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res ID MESENCHYMAL STEM-CELLS; MARROW STROMAL CELLS; HUMAN ADIPOSE-TISSUE; BONE REGENERATION; BIODEGRADABLE SCAFFOLDS; TRICALCIUM PHOSPHATE; BIOACTIVE GLASS; IN-VIVO; PART II; DIFFERENTIATION AB Background: Liposuction-derived stem cells (processed lipoaspirate) have recently been shown to be capable of differentiating into bone. Most studies on osteoblastic growth and differentiation have been conducted in a conventional two-dimensional culture system; however, in native bone, osteoblasts are situated in a three-dimensional configuration. There have been limited studies of processed lipoaspirate behavior in three-dimensional systems. The authors studied the influence a three-dimensional scaffold has on the expression of genes related to osteogenesis and angiogenesis in processed lipoaspirate cells. Methods: One million processed lipoaspirate cells were seeded onto two-dimensional poly(L-lactide-co-glycolide) films or in three-dimensional poly (L-lactide-co-glycolide) scaffolds and incubated in osteogenic medium up to 21 days. RNA was extracted and analyzed with quantitative real-time polymerase chain reaction. Results: When an inert three-dimensional poly(L-lactide-co-glycolide) scaffold was introduced, the pattern and sequence of gene expression changed significantly. Processed lipoaspirate cells cultured onto three-dimensional scaffolds had increased expression of interleukin-8 and vascular endothelial growth factor compared with two-dimensional controls at early time points. Osteogenesis markers-alkaline phosphatase, collagen type I, osteocalcin, osteonectin, and osteopontin-were significantly up-regulated in three-dimensional cultures relative to two-dimensional controls after 24 hours and persisted throughout the 21 days. Conclusions: In human processed lipoaspirate cells, the introduction of a three-dimensional scaffold significantly enhances gene markers of angiogenesis and osteogenesis. On three-dimensional scaffolds, processed lipoaspirate cells first upregulate genes involved with vascular ingrowth and then those involved in bone formation. We believe these differences will significantly impact the design of a bone graft substitute for clinical application. C1 [Huang, Catherine K.; Huang, Weibiao; Zuk, Pat; Jarrahy, Reza; Rudkin, George H.; Ishida, Kenji; Yamaguchi, Dean T.; Miller, Timothy A.] Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Hlthcare Syst, Plast Surg Res Lab, Los Angeles, CA 90095 USA. [Huang, Catherine K.; Huang, Weibiao; Zuk, Pat; Jarrahy, Reza; Rudkin, George H.; Ishida, Kenji; Yamaguchi, Dean T.; Miller, Timothy A.] Univ Calif Los Angeles, Dept Head & Neck Surg, Los Angeles, CA USA. [Huang, Catherine K.; Huang, Weibiao; Zuk, Pat; Jarrahy, Reza; Rudkin, George H.; Ishida, Kenji; Yamaguchi, Dean T.; Miller, Timothy A.] Univ Calif Los Angeles, Div Plast & Reconstruct Surg, Los Angeles, CA USA. RP Huang, CK (reprint author), Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Hlthcare Syst, Plast Surg Res Lab, Los Angeles, CA 90095 USA. NR 32 TC 10 Z9 12 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD FEB PY 2008 VL 121 IS 2 BP 411 EP 423 DI 10.1097/01.prs.0000298510.03226.5f PG 13 WC Surgery SC Surgery GA 261KC UT WOS:000253076500007 PM 18300957 ER PT J AU Carpizo, KH Saran, MJ Huang, W Ishida, K Roostaeian, J Bischoff, D Huang, CK Rudkin, GH Yamaguchi, DT Miller, TA AF Carpizo, Katherine H. Saran, Madeleine J. Huang, Weibiao Ishida, Kenji Roostaeian, Jason Bischoff, David Huang, Catherine K. Rudkin, George H. Yamaguchi, Dean T. Miller, Timothy A. TI Pretreatment of poly(L-lactide-co-glycolide) scaffolds with sodium hydroxide enhances osteoblastic differentiation and slows proliferation of mouse preosteoblast cells SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article; Proceedings Paper CT 51st Annual Meeting of the Research-Council-of-Plastic-Surgery CY MAY 17-20, 2006 CL Dana Point, CA SP Res Council Plast Surg ID GROWTH-FACTORS; IN-VITRO; ADHESION; EXPRESSION; POLYMER; HYDROLYSIS; REPAIR AB Background: Surface topography is important in the creation of a scaffold for tissue engineering. Chemical etching of poly (L-lactide-co-glycolide) with sodium hydroxide has been shown to enhance adhesion and function of numerous cell types. The authors investigated the effects of sodium hydroxide pretreatment of three-dimensional poly (L-lactide-co-glycolide) scaffolds on the adhesion, differentiation, and proliferation of MC3T3-E1 murine preosteoblasts. Methods: MC3T3-E1 cells were seeded onto three-dimensional poly(L-lactide-co-glycolide) scaffolds with and without 1 M sodium hydroxide pretreatment. Cells were then cultured in osteogenic medium and harvested at varying time points for RNA extraction. Quantitative real-time reverse-transcriptase polymerase chain reaction was performed to measure mRNA expression of several osteogenic marker genes. In addition, cell numbers were determined at varying time points during the culture period. All experiments were performed in triplicate. Results: Pretreatment of three-dimensional poly(L-lactide-co-glycolide) scaffolds with sodium hydroxide resulted in statistically significant up-regulation of mRNA expression of alkaline phosphatase, bone sialoprotein, osteocalcin, and vascular endothelial growth factor during the first 10 days of culture. Histologic analysis demonstrated a striking increase in mineralized cell matrix deposition in the sodium hydroxide-treated group. Cell number was statistically higher in the sodium hydroxide-treated group immediately after cell seeding, suggesting improved adhesion. During the first 24 hours of culture, cells grew faster in the control group than in the sodium hydroxide-treated group. Conclusions: Chemical etching of poly (L-lactide-co-glycolide) scaffolds with sodium hydroxide strongly influences the behavior of MC3T3-E1 preosteoblasts in vitro by enhancing adhesion and differentiation and slowing proliferation. Sodium hydroxide treatment may represent a simple and inexpensive way of improving scaffolds for use in bone tissue engineering. C1 [Carpizo, Katherine H.; Saran, Madeleine J.; Huang, Weibiao; Ishida, Kenji; Roostaeian, Jason; Bischoff, David; Huang, Catherine K.; Rudkin, George H.; Yamaguchi, Dean T.; Miller, Timothy A.] Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Hlthcare Syst, Plast Surg Sect, Los Angeles, CA 90095 USA. [Carpizo, Katherine H.; Saran, Madeleine J.; Huang, Weibiao; Ishida, Kenji; Roostaeian, Jason; Bischoff, David; Huang, Catherine K.; Rudkin, George H.; Yamaguchi, Dean T.; Miller, Timothy A.] Univ Calif Los Angeles, Dept Surg, Div Plast & Reconstruct Surg, Los Angeles, CA USA. RP Carpizo, KH (reprint author), Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Hlthcare Syst, Plast Surg Sect, Los Angeles, CA 90095 USA. NR 18 TC 6 Z9 6 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD FEB PY 2008 VL 121 IS 2 BP 424 EP 434 DI 10.1097/01.prs.0000298366.74273.da PG 11 WC Surgery SC Surgery GA 261KC UT WOS:000253076500008 PM 18300958 ER PT J AU Yaremchuk, MJ AF Yaremchuk, Michael J. TI Secondary malar implant surgery SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID AUGMENTATION; COMPLICATIONS; APPEARANCE AB Background: Iatrogenic problems may occur after malar implant surgery. These include asymmetry, displeasing contours (too wide, too large, too low, or too prominent) with time, and symptoms related to infraorbital nerve damage. Methods: Implant removal at the time of secondary surgery leaves depressions in the cheek resulting from implant-induced bone erosion and soft-tissue contracture. Secondary surgery requires implant removal, implant replacement with appropriately positioned and sized implants, and cheek resuspension (subperiosteal midface lift) to mask and redistribute implant-induced soft-tissue distortions. Results: Twenty of the 22 patients were satisfied with their secondary operation. One patient requested another revision and, later, implant removal. Another patient who had been previously treated for infection developed another infection requiring implant removal. Conclusion: Malar implant related midface deformities can be corrected by implant removal, deficiency specific implant replacement, and subperiosteal midface resuspension. C1 [Yaremchuk, Michael J.] Massachusetts Gen Hosp, Wang Ambulatory Care Ctr, Div Plast Surg, Dept Surg, Boston, MA 02114 USA. [Yaremchuk, Michael J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Yaremchuk, MJ (reprint author), Massachusetts Gen Hosp, Wang Ambulatory Care Ctr, Div Plast Surg, Dept Surg, Suite 453,15 Parkman St, Boston, MA 02114 USA. EM dr.y@dryaremchuk.com NR 26 TC 9 Z9 9 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD FEB PY 2008 VL 121 IS 2 BP 620 EP 628 DI 10.1097/01.prs.0000298094.57441.63 PG 9 WC Surgery SC Surgery GA 261KC UT WOS:000253076500033 PM 18300983 ER PT J AU Listgarten, J Brumme, Z Kadie, C Gao, XJ Walker, B Carrington, M Goulder, P Heckerman, D AF Listgarten, Jennifer Brumme, Zabrina Kadie, Carl Gao Xiaojiang Walker, Bruce Carrington, Mary Goulder, Philip Heckerman, David TI Statistical Resolution of Ambiguous HLA Typing Data SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID EXPECTATION-MAXIMIZATION ALGORITHM; HAPLOTYPE FREQUENCY ESTIMATION; MAXIMUM-LIKELIHOOD-ESTIMATION; C VIRUS-INFECTION; POPULATION-DATA; INFORMATION; INFERENCE; ALLELES; POLYMORPHISMS; GENOTYPE AB High-resolution HLA typing plays a central role in many areas of immunology, such as in identifying immunogenetic risk factors for disease, in studying how the genomes of pathogens evolve in response to immune selection pressures, and also in vaccine design, where identification of HLA-restricted epitopes may be used to guide the selection of vaccine immunogens. Perhaps one of the most immediate applications is in direct medical decisions concerning the matching of stem cell transplant donors to unrelated recipients. However, high-resolution HLA typing is frequently unavailable due to its high cost or the inability to re-type historical data. In this paper, we introduce and evaluate a method for statistical, in silico refinement of ambiguous and/or low-resolution HLA data. Our method, which requires an independent, high-resolution training data set drawn from the same population as the data to be refined, uses linkage disequilibrium in HLA haplotypes as well as four-digit allele frequency data to probabilistically refine HLA typings. Central to our approach is the use of haplotype inference. We introduce new methodology to this area, improving upon the Expectation-Maximization (EM)based approaches currently used within the HLA community. Our improvements are achieved by using a parsimonious parameterization for haplotype distributions and by smoothing the maximum likelihood (ML) solution. These improvements make it possible to scale the refinement to a larger number of alleles and loci in a more computationally efficient and stable manner. We also show how to augment our method in order to incorporate ethnicity information (as HLA allele distributions vary widely according to race/ethnicity as well as geographic area), and demonstrate the potential utility of this experimentally. A tool based on our approach is freely available for research purposes at http://microsoft.com/science. C1 [Listgarten, Jennifer; Kadie, Carl; Heckerman, David] Microsoft Res, Redmond, WA USA. [Brumme, Zabrina; Walker, Bruce; Goulder, Philip] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Boston, MA USA. [Gao Xiaojiang; Carrington, Mary] NCI, SAIC Frederick, Frederick, MD 21701 USA. [Walker, Bruce] Howard Hughes Med Inst, Frederick, MD USA. [Goulder, Philip] Univ Oxford, Dept Paediat, Oxford, England. RP Listgarten, J (reprint author), Microsoft Res, Redmond, WA USA. EM jennl@microsoft.com; heckerma@microsoft.com FU National Cancer Institute; National Institutes of Health [N01-CO-12400]; Center for Cancer Research FX This publication has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400. The content of this publication does not necessarily reflect the views of policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. This research was supported in part by the Intramural Research Program of NIH, National Cancer Institute, Center for Cancer Research. NR 48 TC 35 Z9 35 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-734X J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD FEB PY 2008 VL 4 IS 2 AR e1000016 DI 10.1371/journal.pcbi.1000016 PG 15 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 492WI UT WOS:000269692800016 PM 18392148 ER PT J AU Zou, LH Sriswasdi, S Ross, B Missiuro, PV Liu, J Ge, H AF Zou, Lihua Sriswasdi, Sira Ross, Brian Missiuro, Patrycja V. Liu, Jun Ge, Hui TI Systematic Analysis of Pleiotropy in C. elegans Early Embryogenesis SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID PROTEIN-INTERACTION NETWORK; CAENORHABDITIS-ELEGANS; MODULAR ORGANIZATION; GENE; GENOME; RNAI; BETWEENNESS; SET AB Pleiotropy refers to the phenomenon in which a single gene controls several distinct, and seemingly unrelated, phenotypic effects. We use C. elegans early embryogenesis as a model to conduct systematic studies of pleiotropy. We analyze high-throughput RNA interference (RNAi) data from C. elegans and identify "phenotypic signatures", which are sets of cellular defects indicative of certain biological functions. By matching phenotypic profiles to our identified signatures, we assign genes with complex phenotypic profiles to multiple functional classes. Overall, we observe that pleiotropy occurs extensively among genes involved in early embryogenesis, and a small proportion of these genes are highly pleiotropic. We hypothesize that genes involved in early embryogenesis are organized into partially overlapping functional modules, and that pleiotropic genes represent "connectors" between these modules. In support of this hypothesis, we find that highly pleiotropic genes tend to reside in central positions in protein-protein interaction networks, suggesting that pleiotropic genes act as connecting points between different protein complexes or pathways. C1 [Zou, Lihua; Liu, Jun] Harvard Univ, Dept Stat, Cambridge, MA 02138 USA. [Zou, Lihua] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Sriswasdi, Sira; Ross, Brian; Missiuro, Patrycja V.; Ge, Hui] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. RP Zou, LH (reprint author), Harvard Univ, Dept Stat, Cambridge, MA 02138 USA. EM hge@wi.mit.edu OI Ross, Brian/0000-0003-2432-4678 FU Whitehead Institute for Biomedical Research; NIH [R01-GM078990]; NSF [DMS-0706989] FX SS, BR, PVM, and HG are supported by the Whitehead Institute for Biomedical Research. LZ and JL are supported by NIH R01-GM078990 and NSF DMS-0706989. NR 26 TC 14 Z9 14 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-734X J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD FEB PY 2008 VL 4 IS 2 AR e1000003 DI 10.1371/journal.pcbi.1000003 PG 10 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 492WI UT WOS:000269692800007 PM 18463698 ER PT J AU Ebert, BL Galili, N Tamayo, P Bosco, J Mak, R Pretz, J Tanguturi, S Ladd-Acosta, C Stone, R Golub, TR Raza, A AF Ebert, Benjamin L. Galili, Naomi Tamayo, Pablo Bosco, Jocelyn Mak, Raymond Pretz, Jennifer Tanguturi, Shyam Ladd-Acosta, Christine Stone, Richard Golub, Todd R. Raza, Azra TI An erythroid differentiation signature predicts response to lenalidomide in myelodysplastic syndrome SO PLOS MEDICINE LA English DT Article ID COMMONLY DELETED REGION; SET ENRICHMENT ANALYSIS; THALIDOMIDE; CLASSIFICATION; APOPTOSIS; PROLIFERATION; CHROMOSOME-5; DISCOVERY; DISEASES; TISSUES AB Background Lenalidomide is an effective new agent for the treatment of patients with myelodysplastic syndrome (MDS), an acquired hematopoietic disorder characterized by ineffective blood cell production and a predisposition to the development of leukemia. Patients with an interstitial deletion of Chromosome 5q have a high rate of response to lenalidomide, but most MDS patients lack this deletion. Approximately 25% of patients without 5q deletions also benefit from lenalidomide therapy, but response in these patients cannot be predicted by any currently available diagnostic assays. The aim of this study was to develop a method to predict lenalidomide response in order to avoid unnecessary toxicity in patients unlikely to benefit from treatment. Methods and Findings Using gene expression profiling, we identified a molecular signature that predicts lenalidomide response. The signature was defined in a set of 16 pretreatment bone marrow aspirates from MDS patients without 5q deletions, and validated in an independent set of 26 samples. The response signature consisted of a cohesive set of erythroid-specific genes with decreased expression in responders, suggesting that a defect in erythroid differentiation underlies lenalidomide response. Consistent with this observation, treatment with lenalidomide promoted erythroid differentiation of primary hematopoietic progenitor cells grown in vitro. Conclusions These studies indicate that lenalidomide-responsive patients have a defect in erythroid differentiation, and suggest a strategy for a clinical test to predict patients most likely to respond to the drug. The experiments further suggest that the efficacy of lenalidomide, whose mechanism of action in MDS is unknown, may be due to its ability to induce erythroid differentiation. C1 [Ebert, Benjamin L.; Tamayo, Pablo; Bosco, Jocelyn; Mak, Raymond; Pretz, Jennifer; Tanguturi, Shyam; Ladd-Acosta, Christine; Golub, Todd R.] Broad Inst Harvard, Cambridge, MA USA. [Ebert, Benjamin L.; Tamayo, Pablo; Bosco, Jocelyn; Mak, Raymond; Pretz, Jennifer; Tanguturi, Shyam; Ladd-Acosta, Christine; Golub, Todd R.] MIT, Cambridge, MA 02139 USA. [Ebert, Benjamin L.; Bosco, Jocelyn; Mak, Raymond; Pretz, Jennifer; Tanguturi, Shyam; Ladd-Acosta, Christine; Golub, Todd R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Ebert, Benjamin L.; Stone, Richard] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Galili, Naomi; Raza, Azra] St Vincents Comprehens Canc Ctr, New York, NY USA. [Golub, Todd R.] Childrens Hosp, Boston, MA 02115 USA. [Golub, Todd R.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Raza, A (reprint author), Broad Inst Harvard, Cambridge, MA USA. EM araza@aptiumoncology.com OI Tanguturi, Shyam/0000-0001-6479-1946 FU NHGRI NIH HHS [1R01-HG003945-01, R01 HG003945]; NHLBI NIH HHS [K08-HL078818-01, K08 HL078818] NR 36 TC 95 Z9 96 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD FEB PY 2008 VL 5 IS 2 BP 312 EP 322 AR e35 DI 10.1371/journal.pmed.0050035 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 287PK UT WOS:000254928800021 PM 18271621 ER PT J AU Gold, MC Ehlinger, HD Cook, MS Smyk-Pearson, SK Wille, PT Ungerleider, RM Lewinsohn, DA Lewinsohn, DM AF Gold, Marielle C. Ehlinger, Heather D. Cook, Matthew S. Smyk-Pearson, Susan K. Wille, Paul T. Ungerleider, Ross M. Lewinsohn, Deborah A. Lewinsohn, David M. TI Human innate mycobacterium tuberculosis reactive alpha beta TCR(+) thymocytes SO PLOS PATHOGENS LA English DT Article ID T-CELL RESPONSE; DENDRITIC CELLS; LYMPHOCYTES-T; IFN-GAMMA; INFECTION; THYMUS; RECOGNITION; ACTIVATION; RESISTANCE; IMMUNOLOGY AB The control of Mycobacterium tuberculosis (Mtb) infection is heavily dependent on the adaptive Th1 cellular immune response. Paradoxically, optimal priming of the Th1 response requires activation of priming dendritic cells with Th1 cytokine IFN-gamma. At present, the innate cellular mechanisms required for the generation of an optimal Th1 T cell response remain poorly characterized. We hypothesized that innate Mtb-reactive T cells provide an early source of IFN-gamma to fully activate Mtb-exposed dendritic cells. Here, we report the identification of a novel population of Mtb-reactive CD4(-) alpha beta TCR(+) innate thymocytes. These cells are present at high frequencies, respond to Mtb-infected cells by producing IFN-gamma directly ex vivo, and display characteristics of effector memory T cells. This novel innate population of Mtb-reactive T cells will drive further investigation into the role of these cells in the containment of Mtb following infectious exposure. Furthermore, this is the first demonstration of a human innate pathogen-specific alpha beta TCR(+) T cell and is likely to inspire further investigation into innate T cells recognizing other important human pathogens. C1 [Gold, Marielle C.; Lewinsohn, David M.] Oregon Hlth & Sci Univ, Dept Pulm & Crit Care Med, Portland VA Med Ctr, Portland, OR 97201 USA. [Ehlinger, Heather D.; Cook, Matthew S.; Smyk-Pearson, Susan K.; Lewinsohn, Deborah A.] Oregon Hlth & Sci Univ, Dept Pediat, Portland, OR 97201 USA. [Wille, Paul T.; Lewinsohn, Deborah A.; Lewinsohn, David M.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. [Ungerleider, Ross M.] Oregon Hlth & Sci Univ, Doernbecher Mem Hosp Children, Portland, OR 97201 USA. RP Gold, MC (reprint author), Oregon Hlth & Sci Univ, Dept Pulm & Crit Care Med, Portland VA Med Ctr, 3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. EM goldm@ohsu.edu RI Lewinsohn, David/I-4936-2013; OI Lewinsohn, David/0000-0001-9906-9494; Gold, Marielle/0000-0003-2505-3291 FU NHLBI NIH HHS [F32 HL087129, F32 HL087129-01]; NIAID NIH HHS [R01 AI048090-06, R01 AI048090] NR 42 TC 10 Z9 10 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD FEB PY 2008 VL 4 IS 2 AR e39 DI 10.1371/journal.ppat.0040039 PG 9 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 294OR UT WOS:000255415900022 PM 18282101 ER PT J AU Koh, AY Kohler, JR Coggshall, KT Van Rooijen, N Pier, GB AF Koh, Andrew Y. Kohler, Julia R. Coggshall, Kathleen T. Van Rooijen, Nico Pier, Gerald B. TI Mucosal damage and neutropenia are required for Candida albicans dissemination SO PLOS PATHOGENS LA English DT Article ID SUSTAINED GASTROINTESTINAL COLONIZATION; EXPERIMENTAL RENAL CANDIDIASIS; INVASIVE FUNGAL-INFECTIONS; IMMUNOCOMPROMISED MICE; SYSTEMIC CANDIDOSIS; PSEUDOMONAS-AERUGINOSA; ACTIVATED MACROPHAGES; GAMMA-INTERFERON; CANCER-PATIENTS; MURINE MODEL AB Candida albicans fungemia in cancer patients is thought to develop from initial gastrointestinal (GI) colonization with subsequent translocation into the bloodstream after administration of chemotherapy. It is unclear what components of the innate immune system are necessary for preventing C. albicans dissemination from the GI tract, but we have hypothesized that both neutropenia and GI mucosal damage are critical for allowing widespread invasive C. albicans disease. We investigated these parameters in a mouse model of C. albicans GI colonization that led to systemic spread after administration of immunosuppression and mucosal damage. After depleting resident GI intestinal flora with antibiotic treatment and achieving stable GI colonization levels of C. albicans, it was determined that systemic chemotherapy with cyclophosphamide led to 100% mortality, whereas selective neutrophil depletion, macrophage depletion, lymphopenia or GI mucosal disruption alone resulted in no mortality. Selective neutrophil depletion combined with GI mucosal disruption led to disseminated fungal infection and 100% mortality ensued. GI translocation and dissemination by C. albicans was also dependent on the organism's ability to transform from the yeast to the hyphal form. This mouse model of GI colonization and fungemia is useful for studying factors of innate host immunity needed to prevent invasive C. albicans disease as well as identifying virulence factors that are necessary for fungal GI colonization and dissemination. The model may also prove valuable for evaluating therapies to control C. albicans infections. C1 [Koh, Andrew Y.; Coggshall, Kathleen T.; Pier, Gerald B.] Harvard Univ, Sch Med, Channing Lab, Brigham & Womens Hosp,Dept Med, Boston, MA 02115 USA. [Koh, Andrew Y.] Childrens Hosp, Dept Med Hematol Oncol, Boston, MA 02115 USA. [Koh, Andrew Y.; Kohler, Julia R.] Childrens Hosp, Dept Med Infect Dis, Boston, MA 02115 USA. [Koh, Andrew Y.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Van Rooijen, Nico] Free Univ Amsterdam, Dept Cell Biol & Immunol, Amsterdam, Netherlands. RP Koh, AY (reprint author), Harvard Univ, Sch Med, Channing Lab, Brigham & Womens Hosp,Dept Med, Boston, MA 02115 USA. EM Andrew_koh@dfci.harvard.edu OI Pier, Gerald/0000-0002-9112-2331 FU NIAID NIH HHS [AI22535, AI62983, K08 AI062983, R01 AI022535, R21 AI064715] NR 64 TC 124 Z9 133 U1 1 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD FEB PY 2008 VL 4 IS 2 AR e35 DI 10.1371/journal.ppat.0040035 PG 10 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 294OR UT WOS:000255415900019 PM 18282097 ER PT J AU Tomarken, A Holland, J Schachter, S Vanderwerker, L Zuckerman, E Nelson, C Coups, E Ramirez, PM Prigerson, H AF Tomarken, Alexis Holland, Jimmie Schachter, Sherry Vanderwerker, Lauren Zuckerman, Enid Nelson, Christian Coups, Elliot Ramirez, Paul Michael Prigerson, Holly TI Factors of complicated grief pre-death in caregivers of cancer patients SO PSYCHO-ONCOLOGY LA English DT Article DE cancer; oncology; caregivers; complicated grief; pre-death ID STRUCTURED CLINICAL INTERVIEW; DSM-III-R; TRAUMATIC GRIEF; SOCIAL SUPPORT; DISTINGUISHING OPTIMISM; BEREAVEMENT; RELIABILITY; ADJUSTMENT; DEPRESSION; DISORDERS AB Purpose: Over the past decade, Prigerson and her colleagues have shown that symptoms of 'compticated grief'-intense yearning, difficulty accepting the death, excessive bitterness, numbness, emptiness, and feeling uneasy moving on and that the future is bleak-are distinct from depression and anxiety and are independently associated with substantial morbidity. Little is known about complicated grief experienced by family caregivers prior to the death. This study sought to examine differences in caregiver age groups and potential risk factors for complicated grief pre-death. Method: Two hundred and forty eight caregivers from multiple sites nationwide (20-86 years of age) identified themselves as primary caregivers to a terminally ill cancer patient. Each caregiver was interviewed using the following measures: the Pre-Death Inventory of Complicated Grief-Caregiver Version; the Brief Interpersonal Support Evaluation List; the Structured Clinical Interview for the DSM-IV Axis 1; the Life Orientation Test-Revised; the SEPRATE Measure of Stressful Life Events; the Covinsky Family Impact Survey; and mental health access questions. Results: The study found that those under 60 years old had higher levels of complicated grief pre-death than caregivers 60 and older (t(246) = 2.30, p < 0.05). Significant correlations were also found between levels of complicated grief pre-loss and the following psychosocial factors: perceived social support (r = -0.415, p < 0.001); history of depression (r = -0.169, p < 0.05); current depression (r = -0.158, p < 0.05); current annual income (Spearman rho = -0.210, p < 0.01); annual income at time of patient's diagnosis (Spearman rho = -0.155, p = 0.05); pessimistic thinking (r = 0.320, p < 0.001); and number of moderate to severe stressful life events (Spearman rho = 0.218, p = 0.001). In a multi-variate analysis (R-2 = 0.368), pessimistic thinking (Beta = 0.208, p < 0.05) and severity of stressful life events (Beta = 0.222, p < 0.05) remained as important factors to developing complicated grief pre-death. Conclusions: These results suggest that mental health professionals who work with caregivers should pay particular attention to pessimistic thinking and stressful life events, beyond the stress of the loved one's illness, that caretakers experience. Additionally, although not reaching significance, mental health professionals should also consider younger caregivers at greater risk for complicated grief pre-loss. Copyright (C) 2007 John Wiley & Sons, Ltd. C1 [Tomarken, Alexis; Holland, Jimmie; Zuckerman, Enid; Nelson, Christian; Coups, Elliot] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Schachter, Sherry] Calvary Hosp, Bronx, NY USA. [Vanderwerker, Lauren; Prigerson, Holly] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Tomarken, A (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. EM tomorkeo@.mskcc.org FU NCI NIH HHS [R01 CA106370-01, R01 CA106370]; NIMH NIH HHS [MH63892, R01 MH063892] NR 29 TC 53 Z9 53 U1 3 U2 14 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD FEB PY 2008 VL 17 IS 2 BP 105 EP 111 DI 10.1002/pon.1188 PG 7 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 265AF UT WOS:000253330800001 PM 17443644 ER PT J AU Pirl, WF Greer, JA Goode, M Smith, MR AF Pirl, William F. Greer, Joseph A. Goode, Melissa Smith, Matthew R. TI Prospective study of depression and fatigue in men with advanced prostate cancer receiving hormone therapy SO PSYCHO-ONCOLOGY LA English DT Article DE depression; fatigue; prostate cancer treatment ID ANDROGEN DEPRIVATION THERAPY; QUALITY-OF-LIFE; TESTOSTERONE REPLACEMENT THERAPY; ASYMPTOMATIC MEN; HYPOGONADAL MEN; MOOD; CARCINOMA; SURVIVAL; HEALTH AB Purpose: We prospectively examined the development of depressive symptoms and fatigue among men with locally advanced prostate cancer receiving hormone therapy. Methods: Fifty-two men with advanced or recurrent prostate cancer were randomly assigned to receive either parenteral leuprolide or oral bicalutamide. Patients completed the Beck Depression Inventory (BDI) and Fatigue Severity Scale (FSS) at pretreatment baseline, 6 months, and 12 months. Results: Rates of at least mild depression ranged from 10.4 to 16.3% over the 12 months and were not significantly different at each time point. Mean change in BDI scores from baseline to 6 months for the entire sample was 0.91 (SE = 0.73), and from baseline to 12 months was 0.35 (SE = 0.67). Mean FSS scores increased significantly from baseline (M = 24.43, SD = 11.75) to 6 months (M = 27.93, SD = 13.52) and remained steady at 12 months (M = 27.80, SD = 14.44). There were no significant differences in depression between the two types of hormone therapy. Conclusion: Hormone therapy does not appear to cause clinically significant changes in depression among men with locally advanced prostate cancer. However, fatigue increased significantly over the study period. Copyright (C) 2007 John Wiley & Sons, Ltd. C1 [Pirl, William F.; Greer, Joseph A.; Goode, Melissa; Smith, Matthew R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Pirl, WF (reprint author), Massachusetts Gen Hosp, Ctr Canc, Yawkey 9A,55 Fruit St, Boston, MA 02114 USA. EM wpirl@partners.org FU NCI NIH HHS [K24 CA121990, K24 CA121990-03] NR 32 TC 35 Z9 35 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD FEB PY 2008 VL 17 IS 2 BP 148 EP 153 DI 10.1002/pon.1206 PG 6 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 265AF UT WOS:000253330800006 PM 17443645 ER PT J AU Pizzagalli, DA Evins, AE Schetter, EC Frank, MJ Pajtas, PE Santesso, DL Culhane, M AF Pizzagalli, Diego A. Evins, A. Eden Schetter, Erika Cowman Frank, Michael J. Pajtas, Petra E. Santesso, Diane L. Culhane, Melissa TI Single dose of a dopamine agonist impairs reinforcement learning in humans: Behavioral evidence from a laboratory-based measure of reward responsiveness SO PSYCHOPHARMACOLOGY LA English DT Article DE dopamine; D2 agonists; reward processing; depression; mesolimbic system; addiction ID HEALTHY-VOLUNTEERS; PARKINSONS-DISEASE; NUCLEUS-ACCUMBENS; D-AMPHETAMINE; ENDOCRINE FUNCTIONS; RECEPTOR AGONISTS; DEFICIENT MICE; PRAMIPEXOLE; MODULATION; PREDICTION AB Rationale The dopaminergic system, particularly D2-like dopamine receptors, has been strongly implicated in reward processing. Animal studies have emphasized the role of phasic dopamine (DA) signaling in reward-related learning, but these processes remain largely unexplored in humans. Objectives To evaluate the effect of a single, low dose of a D2/D3 agonist-pramipexole-on reinforcement learning in healthy adults. Based on prior evidence indicating that low doses of DA agonists decrease phasic DA release through autoreceptor stimulation, we hypothesized that 0.5 mg of pramipexole would impair reward learning due to presynaptic mechanisms. Materials and methods Using a double-blind design, a single 0.5-mg dose of pramipexole or placebo was administered to 32 healthy volunteers, who performed a probabilistic reward task involving a differential reinforcement schedule as well as various control tasks. Results As hypothesized, response bias toward the more frequently rewarded stimulus was impaired in the pramipexole group, even after adjusting for transient adverse effects. In addition, the pramipexole group showed reaction time and motor speed slowing and increased negative affect; however, when adverse physical side effects were considered, group differences in motor speed and negative affect disappeared. Conclusions These findings show that a single low dose of pramipexole impaired the acquisition of reward-related behavior in healthy participants, and they are consistent with prior evidence suggesting that phasic DA signaling is required to reinforce actions leading to reward. The potential implications of the present findings to psychiatric conditions, including depression and impulse control disorders related to addiction, are discussed. C1 [Pizzagalli, Diego A.; Schetter, Erika Cowman; Pajtas, Petra E.; Santesso, Diane L.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Evins, A. Eden; Culhane, Melissa] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Frank, Michael J.] Univ Arizona, Dept Psychol, Tucson, AZ 85721 USA. RP Pizzagalli, DA (reprint author), Harvard Univ, Dept Psychol, 1220 William James Hall,33 Kirkland St, Cambridge, MA 02138 USA. EM dap@wjh.harvard.edu RI Frank, Michael/B-2979-2008 FU NIDA NIH HHS [R21 DA022630-01, K32 DA00510-01, DA022630, K23 DA000510, K23 DA000510-01, R21 DA022630]; NIMH NIH HHS [R01 MH068376, R01 MH68376, R01 MH068376-01A1] NR 74 TC 94 Z9 97 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD FEB PY 2008 VL 196 IS 2 BP 221 EP 232 DI 10.1007/s00213-007-0957-y PG 12 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 253UC UT WOS:000252542100006 PM 17909750 ER PT J AU Zhang, Y Zhou, JQ Held, KD Redmond, RW Prise, KM Liber, HL AF Zhang, Ying Zhou, Junqing Held, Kathryn D. Redmond, Robert W. Prise, Kevin M. Liber, Howard L. TI Deficiencies of double-strand break repair factors and effects on mutagenesis in directly gamma-irradiated and medium-mediated bystander human lymphoblastoid cells SO RADIATION RESEARCH LA English DT Article ID DEPENDENT PROTEIN-KINASE; SISTER-CHROMATID EXCHANGES; VERY-LOW FLUENCES; ALPHA-PARTICLES; HOMOLOGOUS RECOMBINATION; INTERCELLULAR COMMUNICATION; CHROMOSOMAL-ABERRATIONS; OXIDATIVE-METABOLISM; NONIRRADIATED CELLS; HUMAN FIBROBLASTS AB Using RNA interference techniques to knock down key proteins in two major double-strand break (DSB) repair pathways (DNA-PKcs for nonhomologous end joining, NHEJ, and Rad54 for homologous recombination, HR), we investigated the influence of DSB repair factors on radiation mutagenesis at the autosomal thymidine kinase (TK) locus both in directly irradiated cells and in unirradiated bystander cells. We also examined the role of p53 (TP53) in these processes by using cells of three human lymphoblastoid cell lines from the same donor but with differing p53 status (TK6 is p53 wild-type, NH32 is p53 null, and WTK1 is p53 mutant). Our results indicated that p53 status did not affect either the production of radiation bystander mutagenic signals or the response to these signals. In directly irradiated cells, knockdown of DNA-PKcs led to an increased mutant fraction in WTK1 cells and decreased mutant fractions in TK6 and NH32 cells. In contrast, knockdown of DNA-PKcs led to increased mutagenesis in bystander cells regardless of p53 status. In directly irradiated cells, knockdown of Rad54 led to increased induced mutant fractions in WTK1 and NH32 cells, but the knockdown did not affect mutagenesis in p53 wild-type TK6 cells. In all cell lines, Rad54 knockdown had no effect on the magnitude of bystander mutagenesis. Studies with extracellular catalase confirmed the involvement of H2O2 in bystander signaling. Our results demonstrate that DSB repair factors have different roles in mediating mutagenesis in irradiated and bystander cells. (C) 2008 by Radiation Research Society. C1 [Zhang, Ying; Zhou, Junqing; Liber, Howard L.] Colorado State Univ, Dept Environm & Radiol Hlth Sci, Ft Collins, CO 80523 USA. [Held, Kathryn D.] Massachusetts Gen Hosp, Harvard Med Sch, Dept Radiat Oncol, Boston, MA 02114 USA. [Held, Kathryn D.] Massachusetts Gen Hosp, Harvard Med Sch, Wellman Ctr Photomed, Boston, MA 02114 USA. [Prise, Kevin M.] Queens Univ Belfast, Ctr Canc Res & Cell Biol, Belfast BT9 7BL, Antrim, North Ireland. [Liber, Howard L.] Univ Colorado, Ctr Canc, Denver, CO 80262 USA. RP Zhang, Y (reprint author), Colorado State Univ, Dept Environm & Radiol Hlth Sci, Ft Collins, CO 80523 USA. EM ying.zhang@colostate.edu; howard.libcr@colostate.edu RI Prise, Kevin/N-7872-2015 OI Prise, Kevin/0000-0001-6134-7946 FU NCI NIH HHS [P01 CA095227] NR 51 TC 26 Z9 26 U1 1 U2 6 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD FEB PY 2008 VL 169 IS 2 BP 197 EP 206 DI 10.1667/RR1189.1 PG 10 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 255BZ UT WOS:000252633000008 PM 18220473 ER PT J AU Thrall, JH AF Thrall, James H. TI Changing relationships between radiologists and hospitals - Part II. Contracts and resolution of issues SO RADIOLOGY LA English DT Editorial Material C1 [Thrall, James H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Thrall, JH (reprint author), Massachusetts Gen Hosp, Dept Radiol, 14 Fruit St,MZ-FND 216,Box 9657, Boston, MA 02114 USA. EM jthrall@partners.org NR 6 TC 9 Z9 9 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD FEB PY 2008 VL 246 IS 2 BP 343 EP 347 DI 10.1148/radiol.2462071831 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 257JW UT WOS:000252796300002 PM 18227534 ER PT J AU Kopans, DB AF Kopans, Daniel B. TI Basic physics and doubts about relationship between mammographically determined tissue density and breast cancer risk SO RADIOLOGY LA English DT Editorial Material ID PARENCHYMAL PATTERNS; WOMEN; POPULATION; INDICATOR; MODEL AB Numerous studies have suggested a link between breast tissue patterns, as defined with mammography, and risk for breast cancer. There may be a relationship, but the author believes all of these studies have methodological flaws. It is impossible; with the parameters used in these studies to accurately measure the percentage of tissues by, volume when two-dimensional x-ray mammographic images are used. Without exposure values, half-value layer information, and knowledge of the compressed thickness of the breast, an accurate volume of tissue cannot be calculated: The,great variability in positioning the breast for a mammogram is also an uncontrollable factor in mea- surfing tissue density. Computerized segmentation algo rithms can accurately assess the percentage of the x-ray image that is "dense," but this does not accurately mea sure the true volume of tissue. Since the percentage of dense tissue is ultimately measured in relation to the complete volume of the breast, defining the true bounds aries of the breast is also a problem. Studies that purport to show small percentage differences between groups are likely inaccurate. Future investigations need to use three-dimensional information. (C) RSNA 2008. C1 [Kopans, Daniel B.] Massachusetts Gen Hosp, Dept Radiol, Breast Imaging Div, Boston, MA 02114 USA. RP Kopans, DB (reprint author), Massachusetts Gen Hosp, Dept Radiol, Breast Imaging Div, Ambulatory Care Bldg,Suite 219,15 Parkman St, Boston, MA 02114 USA. NR 27 TC 98 Z9 100 U1 2 U2 12 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD FEB PY 2008 VL 246 IS 2 BP 348 EP 353 DI 10.1148/radiol.2461070309 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 257JW UT WOS:000252796300003 PM 18227535 ER PT J AU Taylor, SA Charman, SC Lefere, P McFarland, EG Paulson, EK Yee, J Aslam, R Barlow, JM Gupta, A Kim, DH Miller, CM Halligan, S AF Taylor, Stuart A. Charman, Susan C. Lefere, Philippe McFarland, Elizabeth G. Paulson, Erik K. Yee, Judy Aslam, Rizwan Barlow, John M. Gupta, Arun Kim, David H. Miller, Chad M. Halligan, Steve TI CT colonography: Investigation of the optimum reader paradigm by using computer-aided detection software SO RADIOLOGY LA English DT Article; Proceedings Paper CT 92nd Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America CY NOV 26-DEC 01, 2006 CL Chicago, IL SP Radiol Soc N Amer ID TOMOGRAPHIC COLONOGRAPHY; POLYP DETECTION; DIAGNOSIS SCHEME; COLONIC POLYPS; 1 CM; PERFORMANCE; COLONOSCOPY; SMALLER AB Purpose: To prospectively compare the diagnostic performance and time efficiency of both second and concurrent computer-aided detection (CAD) reading paradigms for retrospectively obtained computed tomographic (CT) colonography data sets by using consensus reading (three radiologists) of colonoscopic findings as a reference standard. Materials and Methods: Ethical permission, HIPAA compliance (for U.S. institutions), and patient consent were obtained from all institutions for use of CT colonography data sets in this study en radiologists each read 25 CT colonography data sets (12 men, 13 women; mean age, 61, years) containing 69 polyps (28 were 1-5 mm, 41 were >= 6 mm) by using workstations integrated with CAD software. Reading was randomized to either "second read" CAD (applied only after initial unassisted assessment) or "concurrent read" CAD (applied at. the start of assessment). Data sets were reread 6 weeks later by using the opposing paradigm. Polyp sensitivity and reading times were compared by using multilevel logistic and linear regression, respectively. Receiver operating characteristic (ROC) curves were generated. Results: Compared with the unassisted read, odds of improved polyp (>= 6 mm) detection were 1.5 (95 % confidence, interval [CI]: 1.0, 2.2) and 1.3 (95% CI: 0.9, 1.9) by using CAD as second and concurrent reader, respectively. Detection odds by using CAD concurrently were 0.87 (95% CI: 0.59, 1.3) 0.76 (95% CI: 0.57, 1.01) those of second read CAD excluding and including polyps 1-5 mm, respectively. The concurrent read took 2.9 minutes (95% CI: -3.8, -1.9 less than did second read. The mean areas under the ROC curve (95% CT) for the unassisted read, 1, second read CAD, and concurrent read CAD were 0.83 (95% CI: 0.78, 0.87), 0.86 (95% CI: 0.82, 0.90), and 0.88 (95% CI: 0.83, 0.92), respectively. Conclusion: CAD is more time efficient when used concurrently than when used as a second reader, with similar sensitivity for polyps 6 mm or larger. However, use of second read CAD maximizes sensitivity, particularly for smaller lesions. (C) RSNA, 2007. C1 [Taylor, Stuart A.; Halligan, Steve] UCL Hosp, Dept Specialist Xray, London NW1 2BU, England. [Charman, Susan C.] UCL Hosp, Med Stat Unit, London NW1 2BU, England. [Lefere, Philippe] Stedelijk Ziekenhuis, Dept Radiol, Roeselare, Belgium. [McFarland, Elizabeth G.] Edward Mallinckrodt Inst Radiol, Dept Radiol, St Louis, MO 63110 USA. [Paulson, Erik K.; Miller, Chad M.] Duke Univ, Med Ctr, Abdominal Imaging Sect, Durham, NC USA. [Yee, Judy; Aslam, Rizwan] Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Radiol, San Francisco, CA USA. [Barlow, John M.] Mayo Clin, Coll Med, Dept Radiol, Rochester, MN USA. [Gupta, Arun] St Marks Hosp, Dept Intestinal Imaging, Harrow, Middx, England. [Kim, David H.] Univ Wisconsin, Sch Med, Dept Radiol, Madison, WI USA. RP Taylor, SA (reprint author), UCL Hosp, Dept Specialist Xray, 235 Euston Rd,2F Podium, London NW1 2BU, England. EM csytaylor@yahoo.co.uk RI Halligan, Steve /C-5875-2009 NR 20 TC 41 Z9 42 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD FEB PY 2008 VL 246 IS 2 BP 463 EP 471 DI 10.1148/radio1.2461070190 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 257JW UT WOS:000252796300016 PM 18094263 ER PT J AU Kalva, SP Jagannathan, JP Hahn, PF Wicky, ST AF Kalva, Sanjeeva P. Jagannathan, Jyothi P. Hahn, Peter F. Wicky, Stephan T. TI Venous thromboembolism: Indirect CT venography during CT pulmonary angiography - Should the pelvis be imaged? SO RADIOLOGY LA English DT Article; Proceedings Paper CT 92nd Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America CY NOV 26-DEC 01, 2006 CL Chicago, IL SP Radiol Soc N Amer ID DEEP-VEIN THROMBOSIS; LOWER-EXTREMITY; HELICAL CT; COMPRESSION ULTRASOUND; COMPUTED-TOMOGRAPHY; EMBOLISM; DIAGNOSIS; DISEASE; SONOGRAPHY; US AB Purpose: To retrospectively determine the relative contribution of pelvic and lower-extremity indirect computed tomographic (CT) venography to the diagnosis of venous thromboembolism (VTE) in patients undergoing CT for pulmonary embolism (PE). Materials and Methods: This HIPAA-compliant study was approved by the institutional review board, and informed consent was waived. The records or 2074 consecutive patients (890 men, 1184 women; mean age, 59 years; age range, 15-97 years) suspected of having RE. who underwent combined CT pulmonary angiography and CT venography between May 2005 and March 2006 were reviewed. CT venograms from the iliac crests to the popliteal fossae were, reviewed for presence and location of thrombi. Radiology reports were reviewed for CT pulmonary angiographic results. Thrombus detection rates with and without pelvic CT venography were compared by Using the chi(2) test. Separate effective radiation doses for CT venography of pelvis and lower extremities were calculated. Results: On CT images of the 2074 patients, WE was detected in 283 (13.6%) patients; PE, in 237 (11.4%); and deep vein thrombosis (DVT), in 121 (5.8%). Forty-six patients had DVT but no PE. Addition of CT venography to CT pulmonary angiography increased the detection of VTE by 19.4% (46 of 237). Isolated pelvic DVT was seen in two (0, 1%) patients. There was no difference in the detection of WE whether or not the pelvis was included (P = .92). Effective radiation dose for CT venography was 5.2 mSv +/- 0.5 (standard deviation) for the pelvis and 0.6 mSv +/- 0.2 for the lower extremities. Conclusion: CT venography of the pelvis during CT pulmonary angiography does not significantly improve the detection of WE CT venography may be limited to the lower extremities, thus reducing radiation dose. (C) RSNA, 2008. C1 [Kalva, Sanjeeva P.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Kalva, SP (reprint author), Massachusetts Gen Hosp, Dept Radiol, GRB-290,55 Fruit St, Boston, MA 02114 USA. EM skalva@partners.org NR 47 TC 36 Z9 39 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD FEB PY 2008 VL 246 IS 2 BP 605 EP 611 DI 10.1148/radio1.2462070319 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 257JW UT WOS:000252796300032 PM 18227548 ER PT J AU Suit, H Kooy, H Trofimov, A Farr, J Munzenrider, J DeLaney, T Loeffler, J Clasie, B Safai, S Paganetti, H AF Suit, Herman Kooy, Hanne Trofimov, Alexei Farr, Jonathan Munzenrider, John DeLaney, Thomas Loeffler, Jay Clasie, Benjamin Safai, Sairos Paganetti, Harald TI Should positive phase III clinical trial data be required before proton beam therapy is more widely adopted? No SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE proton therapy; clinical trial; ethical ID RANDOMIZED CONTROLLED-TRIAL; RADIATION-THERAPY; PHOTON BEAMS; CANCER; RADIOTHERAPY; MORTALITY; PROSTATE AB Purpose: Evaluate the rationale for the proposals that prior to a wider use of proton radiation therapy there must be supporting data from phase III clinical trials. That is, would less dose to normal tissues be an advantage to the patient? Methods: Assess the basis for the assertion that proton dose distributions are superior to those of photons for most situations. Consider the requirements for determining the risks of normal tissue injury, acute and remote, in the examination of the data from a trial. Analyze the probable cost differential between high technology photon and proton therapy. Evaluate the rationale for phase III clinical trials of proton vs photon radiation therapy when the only difference in dose delivered is a difference in distribution of low LET radiation. Results: The distributions of biological effective dose by protons are superior to those by X-rays for most clinical situations, viz. for a defined dose and dose distribution to the target by protons there is a lower dose to non-target tissues. This superiority is due to these physical properties of protons: (1) protons have a finite range and that range is exclusively dependent on the initial energy and the density distribution along the beam path; (2) the Bragg peak; (3) the proton energy distribution may be designed to provide a spread out Bragg peak that yields a uniform dose across the target volume and virtually zero dose deep to the target. Importantly, proton and photon treatment plans can employ beams in the same number and directions (coplanar, non-co-planar), utilize intensity modulation and employ 4D image guided techniques. Thus, the only difference between protons and photons is the distribution of biologically effective dose and this difference can be readily evaluated and quantified. Additionally, this dose distribution advantage should increase the tolerance of certain chemotherapeutic agents and thus permit higher drug doses. The cost of service (not developmental) proton therapy performed in 3-5 gantry centers operating 14-16 h/day and 6 days/week is likely to be equal to or less than twice that of high technology X-ray therapy. Conclusions: Proton therapy provides superior distributions of low LET radiation dose relative to that by photon therapy for treatment of a large proportion of tumor/normal tissue situations. Our assessment is that there is no medical rationale for clinical trials of protons as they deliver lower biologically effective doses to non-target tissue than do photons for a specified dose and dose distribution to the target. Based on present knowledge, there will be some gain for patients treated by proton beam techniques. This is so even though quantitation of the clinical gain is less secure than the quantitation of reduction in physical dose. Were proton therapy less expensive than X-ray therapy, there would be no interest in conducting phase III trails. The talent, effort and funds required to conduct phase III clinical trials of protons vs photons would surely be more productive in the advancement of radiation oncology if employed to investigate real problems, e.g. the most effective total dose, dose fractionation, definition of CTV and GTV, means for reduction of PTV and the gains and risks of combined modality therapy. (c) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Suit, Herman; Kooy, Hanne; Trofimov, Alexei; Munzenrider, John; DeLaney, Thomas; Loeffler, Jay; Clasie, Benjamin; Safai, Sairos; Paganetti, Harald] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Suit, Herman; Kooy, Hanne; Trofimov, Alexei; Munzenrider, John; DeLaney, Thomas; Loeffler, Jay; Clasie, Benjamin; Safai, Sairos; Paganetti, Harald] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Farr, Jonathan] Midw Proton Radiotherapy Inst, Bloomington, IN USA. RP Suit, H (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Fruit St, Boston, MA 02114 USA. EM hsuit@partners.org NR 23 TC 63 Z9 63 U1 2 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD FEB PY 2008 VL 86 IS 2 BP 148 EP 153 DI 10.1016/j.radonc.2007.12.024 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 268XO UT WOS:000253613800003 PM 18237800 ER PT J AU Phelps, LF Williams, RM Raichle, KA Turner, AP Ehde, DM AF Phelps, Lori F. Williams, Rhonda M. Raichle, Katherine A. Turner, Aaron P. Ehde, Dawn M. TI The importance of cognitive processing to adjustment in the 1st year following amputation SO REHABILITATION PSYCHOLOGY LA English DT Article DE amputees; posttraumatic stress disorder; trauma; adjustment; depression ID POSTTRAUMATIC-STRESS-DISORDER; LOWER-LIMB AMPUTATION; BREAST-CANCER; PRIMARY-CARE; RISK-FACTORS; HAND INJURY; PSYCHOSOCIAL ADAPTATION; PSYCHOMETRIC PROPERTIES; DEPRESSIVE SYMPTOMS; INTRUSIVE THOUGHTS AB Objective: To describe depressive symptoms, posttraumatic stress disorder (PTSD), and posttraumatic growth at 6 and 12 months following amputation and to explore differences by demographic variables and cognitive processing of trauma. Participants: 83 adults with newly acquired limb loss. Setting: Two large metropolitan hospitals. Main Outcome Measures: The Patient Health Questionnaire depression module, PTSD Checklist, and Posttraumatic Growth Inventory. Results: Significant depressive and PTSD symptoms were reported by 15%-25% of participants. Relatively low levels of posttraumatic growth were reported. Negative cognitive processing predicted depressive and PTSD symptoms at 6 months. Positive cognitive processing predicted posttraumatic growth at 12 months. Conclusion: Cognitive processing appears to be integral to positive and negative psychosocial outcomes following amputation and should be targeted by clinical interventions. C1 [Phelps, Lori F.; Williams, Rhonda M.; Turner, Aaron P.] VA Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA USA. [Williams, Rhonda M.; Turner, Aaron P.; Ehde, Dawn M.] Univ Washington, Sch Med, Dept Rehabil Med, Seattle, WA 98195 USA. [Raichle, Katherine A.] Seattle Univ, Dept Psychol, Seattle, WA USA. RP Phelps, LF (reprint author), William S Middleton Mem Vet Adm Med Ctr, 2500 Overlook Terrace, Madison, WI 53705 USA. EM Lori.Phelps2@va.gov OI Turner, Aaron/0000-0001-6897-8003 NR 89 TC 36 Z9 37 U1 6 U2 15 PU EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0090-5550 J9 REHABIL PSYCHOL JI Rehabil. Psychol. PD FEB PY 2008 VL 53 IS 1 BP 28 EP 37 DI 10.1037/0090-5550.53.1.28 PG 10 WC Psychology, Clinical; Rehabilitation SC Psychology; Rehabilitation GA 266JR UT WOS:000253431900004 ER PT J AU Siegel, SD Turner, AP Haselkorn, JK AF Siegel, Scott D. Turner, Aaron P. Haselkorn, Jodie K. TI Adherence to disease-modifying therapies in multiple sclerosis: Does caregiver social support matter? SO REHABILITATION PSYCHOLOGY LA English DT Article DE multiple sclerosis; medication adherence; social support; caregiver ID ANTIRETROVIRAL THERAPY; PATIENT ADHERENCE; MEDICATION; IMPAIRMENT; DISABILITY; MS AB Objective: To evaluate the relationship between caregiver-specific social support and adherence to disease-modifying therapies (DMT) for multiple sclerosis (MS). Design: Telephone survey with 6 monthly follow-up assessments. Setting: Veterans Health Administration. Participants: 54 veterans with MS who identified a primary caregiver and who were currently prescribed DMT. Measures: Demographic information. Caregiver supportive and conflictual qualities were assessed with the Quality of Relationships Inventory-Short Form. Medication-specific support was assessed with 4 items developed from qualitative focus groups. DMT adherence was assessed with a single item that requested missed doses in the past month. Results: Adherence in this population of ongoing DMT users was relatively high, with 85.1% (95% confidence interval = 75.6%-94.8%) reporting adherence >= 80% of prescribed doses. Using logistic regression adjusting for disability, type of DMT, and length of time on current DMT, the authors predicted longitudinal adherence by supportive qualities of the caregiver-care recipient relationship but not by conflictual qualities or medication-specific support. Conclusion: Supportive qualities of the caregiver-care recipient relationship represent an important predictor of DMT adherence and a potential target in adherence-based interventions. C1 [Siegel, Scott D.; Turner, Aaron P.; Haselkorn, Jodie K.] Vet Affairs Puget Sound Hlth Care Syst, Rehabil Care Serv, Seattle, WA 98108 USA. [Turner, Aaron P.; Haselkorn, Jodie K.] Univ Washington, Dept Rehabil Med, Seattle, WA 98108 USA. [Haselkorn, Jodie K.] Univ Washington, Dept Epidemiol, Seattle, WA 98108 USA. [Siegel, Scott D.] Helen F Graham Canc Ctr, Newark, DE USA. RP Turner, AP (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Rehabil Care Serv, S-117-RCS,1660 S Columbian Way, Seattle, WA 98108 USA. EM Aaron.Turner@med.va.gov OI Turner, Aaron/0000-0001-6897-8003 NR 28 TC 7 Z9 7 U1 3 U2 6 PU EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0090-5550 J9 REHABIL PSYCHOL JI Rehabil. Psychol. PD FEB PY 2008 VL 53 IS 1 BP 73 EP 79 DI 10.1037/0090-5550.53.1.73 PG 7 WC Psychology, Clinical; Rehabilitation SC Psychology; Rehabilitation GA 266JR UT WOS:000253431900009 ER PT J AU Menon, R Merialdi, M Betran, AP Allen, T Lin, B Eckardt, J Khoury, M Ioannidis, JP Bertram, L Hollegaard, M Velez, DR Dolan, S AF Menon, Ramkumar Merialdi, Mario Betran, Ana Pilar Allen, Tomas Lin, Bruce Eckardt, Judith Khoury, Mont Ioannidis, John P. Bertram, Lars Hollegaard, Mads Velez, Digna R. Dolan, Siobhan TI Systematic review and meta-analyses of preterm birth genetic association studies SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 55th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 26-29, 2008 CL San Diego, CA SP Soc Gynecol Invest C1 [Menon, Ramkumar; Velez, Digna R.] Perinatal Res Ctr, Nashville, TN USA. [Merialdi, Mario; Betran, Ana Pilar; Allen, Tomas] WHO, Geneva, NY USA. [Lin, Bruce] March Dimes, New York, NY USA. [Khoury, Mont] Ctr Dis Control, Atlanta, GA 30333 USA. [Ioannidis, John P.] Univ Ioannina, Sch Med, GR-45110 Ioannina, Greece. [Bertram, Lars] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hollegaard, Mads] NANEA, Aarhus, Denmark. [Dolan, Siobhan] Albert Einstein Coll Med, New York, NY USA. RI Betran, Ana Pilar/G-2023-2010; Ioannidis, John/G-9836-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD FEB PY 2008 VL 15 IS 2 SU S MA 142 BP 101A EP 101A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 268LP UT WOS:000253581600144 ER PT J AU Selesniemi, K Lee, HJ Tilly, JL AF Selesniemi, Kaisa Lee, Ho-Joon Tilly, Jonathan L. TI Extension of fertile lifespan in female mice by adult-onset caloric restriction. SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 55th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 26-29, 2008 CL San Diego, CA SP Soc Gynecol Invest C1 [Selesniemi, Kaisa; Lee, Ho-Joon; Tilly, Jonathan L.] Massachusetts Gen Hosp, Harvard Med Sch, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD FEB PY 2008 VL 15 IS 2 SU S MA 245 BP 158A EP 158A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 268LP UT WOS:000253581600347 ER PT J AU Smith, LP Deiorio-Haggar, K Reindollar, J Penzias, AS Usheva-Simidjiyska, A AF Smith, Laura P. Deiorio-Haggar, Kaila Reindollar, Jason Penzias, Alan S. Usheva-Simidjiyska, Army TI Bile acids in human ovarian follicular fluid. SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 55th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 26-29, 2008 CL San Diego, CA SP Soc Gynecol Invest C1 [Smith, Laura P.; Deiorio-Haggar, Kaila; Reindollar, Jason; Penzias, Alan S.; Usheva-Simidjiyska, Army] BIDMC, Boston, MA USA. [Smith, Laura P.; Penzias, Alan S.] Boston IVF, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD FEB PY 2008 VL 15 IS 2 SU S MA 246 BP 158A EP 159A PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 268LP UT WOS:000253581600348 ER PT J AU Rana, S Rauh-Hain, A Karumanchi, A Thadhani, R AF Rana, Sarosh Rauh-Hain, Alejandro Karumanchi, Ananth Thadhani, Ravi TI Alterations in levels of angiogenic proteins in first trimester and subsequent risk of developing abruption. SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 55th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 26-29, 2008 CL San Diego, CA SP Soc Gynecol Invest C1 [Rana, Sarosh] Women & Infants Hosp Rhode Isl, Providence, RI USA. [Rauh-Hain, Alejandro; Thadhani, Ravi] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Karumanchi, Ananth] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Karumanchi, Ananth] Beth Israel Deaconess Med Ctr, Dept OB Gyn, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD FEB PY 2008 VL 15 IS 2 SU S MA 550 BP 215A EP 215A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 268LP UT WOS:000253581600552 ER PT J AU Curley, MD Cummings, CL Sergent, PA Batra, SK Davis, JS Scadden, DT Rueda, BR Foster, R AF Curley, Michael D. Cummings, Christine L. Sergent, Petra A. Batra, Surinder K. Davis, John S. Scadden, David T. Rueda, Bo R. Foster, Rosemary TI Defining the gene signature of ovarian tumor-initiating cells SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 55th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 26-29, 2008 CL San Diego, CA SP Soc Gynecol Invest C1 [Cummings, Christine L.; Sergent, Petra A.; Rueda, Bo R.] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. [Cummings, Christine L.; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Batra, Surinder K.] Univ Nebraska Med Ctr, Dept Biochem & Mol Biol, Omaha, NE USA. [Davis, John S.] Univ Nebraska Med Ctr, Dept Obstet & Gynecol, Omaha, NE USA. [Foster, Rosemary] Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD FEB PY 2008 VL 15 IS 2 SU S MA 866 BP 304A EP 304A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 268LP UT WOS:000253581600868 ER PT J AU Friel, AM Sergent, PA Cummings, CL Foster, R Scadden, DT Rueda, BR AF Friel, Anne M. Sergent, Petra A. Cummings, Christine L. Foster, Rosemary Scadden, David T. Rueda, Bo R. TI Defining the tumor initiating capacity of CD133(+) human endometrial cancer cells. SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 55th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 26-29, 2008 CL San Diego, CA SP Soc Gynecol Invest C1 [Friel, Anne M.; Sergent, Petra A.; Rueda, Bo R.] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. [Cummings, Christine L.; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Foster, Rosemary] Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD FEB PY 2008 VL 15 IS 2 SU S MA 876 BP 306A EP 306A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 268LP UT WOS:000253581600878 ER PT J AU Meeker, JD Ravi, SR Barr, DB Hauser, R AF Meeker, John D. Ravi, Sarena R. Barr, Dana B. Hauser, Russ TI Circulating estradiol in men is inversely related to urinary metabolites of nonpersistent insecticides SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE carbaryl; chlorpyrifos; endocrine disruption; estradiol; hormone; male reproduction; pesticides; prolactin ID FOLLICLE-STIMULATING-HORMONE; MALE REPRODUCTIVE HORMONES; PROSTATE-CANCER RISK; PESTICIDE APPLICATORS; AGRICULTURAL HEALTH; SWEDISH AGRICULTURE; MASS-SPECTROMETRY; ELDERLY-MEN; IN-VITRO; EXPOSURE AB Background: Estradiol plays an important role in male reproductive health as a germ cell survival factor. Chlorpyrifos and carbaryl, nonpersistent insecticides to which the general population are commonly exposed, were recently shown to inhibit estradiol metabolism in vitro which could lead to altered hormone balance. Methods: Subjects (N = 322) were the male partners in couples presenting to a Massachusetts infertility clinic from years 2000-2003. 3,5,6-Trichloro-2-pyridinol (TCPY), the major urinary metabolite of chlorpyrifos and chlorpyrifos-methyl, and 1- and 2-naphthol (1N and 2N), urinary metabolites of carbaryl and naphthalene, were measured in a spot urine sample from each subject. Estradiol, sex hormone binding globulin (SHBG), and prolactin were measured in serum collected from subjects during the same clinic visit. Results: Using multiple linear regression, an interquartile range (IQR) increase in TCPY was associated with a 1.36 pg/mL decline (95% confidence interval = -2.91 to -0.22) in estradiol concentration. When estradiol and TCPY were divided into quintiles, there was a dose-dependent increase in the odds of being in the lowest estradiol quintile with increasing TCPY quintiles. Conclusion: On a population level, these reductions in estradiol levels are of potential public health importance because of widespread exposure to TCPY and its parent insecticides. (C) 2008 Elsevier Inc. All rights reserved. C1 [Meeker, John D.; Ravi, Sarena R.] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA. [Barr, Dana B.] Ctr Dis & Control & Prevent, Atlanta, GA USA. [Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Hauser, Russ] Massachusetts Gen Hosp, Fertil Ctr, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. RP Meeker, JD (reprint author), Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, 6635 SPH Tower,109 S Observ St, Ann Arbor, MI 48109 USA. EM meekerj@umich.edu RI Perez , Claudio Alejandro/F-8310-2010; Barr, Dana/E-6369-2011; Barr, Dana/E-2276-2013; OI Perez , Claudio Alejandro/0000-0001-9688-184X; Meeker, John/0000-0001-8357-5085 FU NIEHS NIH HHS [ES09718, R01 ES009718, R01 ES009718-09] NR 55 TC 13 Z9 14 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD FEB PY 2008 VL 25 IS 2 BP 184 EP 191 DI 10.1016/j.reprotox.2007.12.005 PG 8 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 284RL UT WOS:000254723400006 PM 18249523 ER PT J AU Alam, HB Shults, C Ahuja, N Ayuste, EC Chen, HZ Koustova, E Sailhamer, EA Li, YQ Liu, BL de Moya, M Velmahos, GC AF Alam, Hasan B. Shults, Christian Ahuja, Naresh Ayuste, Eduardo C. Chen, Huazhen Koustova, Elena Sailhamer, Elizabeth A. Li, Yongqing Liu, Baoling de Moya, Marc Velmahos, George C. TI Impact of resuscitation strategies on the acetylation status of cardiac histones in a swine model of hemorrhage SO RESUSCITATION LA English DT Article DE histone; acetylation; hemorrhagic shock; resuscitation; Ringer's; ketone; gene transcription; post-transtational modification; epigenetics; immediate-early response genes; histone deacetylase ID OPERATION-IRAQI-FREEDOM; PULMONARY APOPTOSIS; FLUID RESUSCITATION; SHOCK; CODE; CHROMATIN; EXPRESSION; GENE; EXPERIENCE; KETONE AB Background: Chromatin remodeling through histone acetylation is a key control mechanism in gene transcription. We have shown previously that fluid resuscitation in rodents is coupled with highly structured post-translational modifications of cardiac histones. The current experiment was performed to validate this concept in a clinically relevant large animal model of hemorrhage and resuscitation, and to correlate the changes in histone acetylation with altered expression of immediate-early response genes. Study design: Yorkshire swine (n=49, 7/group, weight=40-58kg) were subjected to combined uncontrolled and controlled hemorrhage (40% of estimated blood volume) and randomly assigned to the following resuscitation groups: (1) 0.9% saline (NS), (2) racemic lactated Ringer's (DL-LR), (3) L-isomer lactated Ringer's (L-LR), (4) Ketone Ringer's (KR), (5) 6% hetastarch in saline (Hespan). KR contained an equimolar substitution of lactate with beta-hydroxybutyrate. No hemorrhage (NH) and no resuscitation (NR) groups were included as controls. Cardiac protein was used in Western blotting to analyze total protein acetylation and histone acetylation specifically. Lysine residue-specific acetylation of histone subunits H3 and H4 was further evaluated. In addition, Chromatin Immunoprecipitation (ChIP) technique was used to separate the DNA bound to acetylated histones (H3 and H4 subunits), followed by measurement of genes that are altered by hemorrhage/resuscitation, including immediate-early response genes (c-fos and c-myc), and heat shock protein (HSP) 70. Results: The type of fluid used for resuscitation influenced the patterns of cardiac histone acetylation. Resuscitation with DL-LR and KR induced hyperacetylation on H3K9. KR resuscitation was also associated with increased acetylation on H3K14 and H4K5, and hypoacetylation on H3K18. The expression of genes was also fluid specific, with the largest number of changes following KR resuscitation (increased c-fos and c-myc, HSP 70 linked with H3; and increased c-myc Linked with H4). Among the histone subunits studied, altered H3 acetylations were associated with the majority of changes in immediate-early gene expression. Conclusions: Acetylation status of cardiac histones, affected by hemorrhage, is further modulated by resuscitation producing a fluid-specific code that is preserved in different species. Resuscitation with KR causes histone acetylation at the largest number of Lysine sites (predominately H3 subunit), and has the most pronounced impact on the transcriptional regulation of selected (immediate-early response) genes. (c) 2007 Elsevier Ireland Ltd. ALL rights reserved. C1 [Alam, Hasan B.; Ahuja, Naresh; Ayuste, Eduardo C.; Chen, Huazhen; Koustova, Elena] Uniformed Serv Univ Hlth Sci, Trauma Res & Readiness Inst Surg, Bethesda, MD 20814 USA. [Shults, Christian; Ahuja, Naresh] Washington Hosp Ctr, Dept Surg, Washington, DC 20010 USA. [Alam, Hasan B.; Sailhamer, Elizabeth A.; Li, Yongqing; Liu, Baoling; de Moya, Marc; Velmahos, George C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Alam, HB (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM hbalam@partners.org NR 34 TC 21 Z9 23 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-9572 J9 RESUSCITATION JI Resuscitation PD FEB PY 2008 VL 76 IS 2 BP 299 EP 310 DI 10.1016/j.resuscitation.2007.07.030 PG 12 WC Critical Care Medicine; Emergency Medicine SC General & Internal Medicine; Emergency Medicine GA 270RQ UT WOS:000253738300023 PM 17822827 ER PT J AU Weiss, AP Goff, DC Duff, M Roffman, JL Schacter, DL AF Weiss, Anthony P. Goff, Donald C. Duff, Margaret Roffman, Joshua L. Schacter, Daniel L. TI Distinguishing familiarity-based from source-based memory performance in patients with schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE schizophrenia; memory; source memory; episodic memory; novelty detection; response time ID SOURCE-MONITORING DEFICITS; RECOGNITION MEMORY; ANTIPSYCHOTIC MEDICATIONS; RECOLLECTION; RETRIEVAL; IMPAIRMENT; HALLUCINATIONS; DISCRIMINATION; METAANALYSIS; CONFIDENCE AB Background: There is substantial current interest in the cognitive deficits associated with schizophrenia, particularly those in the realm of memory. Yet the exact nature of these deficits remains a matter of some debate. This study sought to examine performance on two distinct aspects of memory performance: familiarity-based and source-based memory processes. Methods: Eighteen medicated outpatients with schizophrenia and eighteen healthy adult control subjects performed an external source memory task. Key measures included the ability to distinguish old (previously experienced) items from new items, the ability to correctly identify the source (male voice or female voice) of previously experienced items, and the reaction time associated with these responses. Results: Patients with schizophrenia showed an impaired ability to distinguish old from new items, but intact performance in correctly identifying the source of items recognized as old. Whereas control subjects showed a rapid response to items deemed unfamiliar, particularly in rejecting novel items, these responses were slowed in patients with schizophrenia. This was not attributable to a generalized diminution in processing speed, as reaction times to correctly recognized old items (regardless of source accuracy) did not differ between the two groups. Conclusions: Patients with schizophrenia demonstrated impaired familiarity-based and intact source-based memory performance. In addition, the reaction time for novelty detection, an important component of familiarity-based memory, was significantly delayed in patients compared to controls, while the response times for source-based decisions were completely overlapping. Considered together, these findings suggest a deficit in the familiarity-based aspect of episodic memory in at least some patients with schizophrenia. (C) 2007 Elsevier B.V. All rights reserved. C1 [Weiss, Anthony P.; Goff, Donald C.; Duff, Margaret; Roffman, Joshua L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Schacter, Daniel L.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. RP Weiss, AP (reprint author), Massachusetts Gen Hosp E, Dept Psychiat, CNY 2606,13th St, Charlestown, MA 02129 USA. EM aweiss@partners.org OI Schacter, Daniel/0000-0002-2460-6061 FU NIMH NIH HHS [K23-MH06019, K23 MH067019-05] NR 52 TC 17 Z9 18 U1 2 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD FEB PY 2008 VL 99 IS 1-3 BP 208 EP 217 DI 10.1016/j.schres.2007.05.028 PG 10 WC Psychiatry SC Psychiatry GA 278SM UT WOS:000254306600026 PM 17629463 ER PT J AU Bartzokis, G Lu, PH Nuechterlein, KH Gitlin, M Doi, C Edwards, N Lieu, C Altshuler, LL Mintz, J AF Bartzokis, George Lu, Po H. Nuechterlein, Keith H. Gitlin, Michael Doi, Clarissa Edwards, Nancy Lieu, Christopher Altshuler, Lori L. Mintz, Jim TI Differential effects of typical and atypical antipsychotics on brain myelination in schizophrenia (vol 93, pg 13, 2007) SO SCHIZOPHRENIA RESEARCH LA English DT Correction C1 [Bartzokis, George; Lu, Po H.; Doi, Clarissa; Edwards, Nancy; Lieu, Christopher] Univ Calif Los Angeles, Alzheimers Dis Ctr, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Bartzokis, George] Univ Calif Los Angeles, Dept Neurol, David Geffen Sch Med, Div Brain Mapping,Lab Neuroimaging, Los Angeles, CA 90095 USA. [Bartzokis, George; Lu, Po H.; Doi, Clarissa; Edwards, Nancy; Lieu, Christopher] Greater Los Angeles VA Hlthcare Syst, Los Angeles, CA 90073 USA. [Bartzokis, George] Univ Calif Los Angeles, Inst Brain Res, Los Angeles, CA 90095 USA. [Nuechterlein, Keith H.; Gitlin, Michael; Altshuler, Lori L.; Mintz, Jim] Univ Calif Los Angeles, Dept Psychiat & Behav Sci, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Nuechterlein, Keith H.; Altshuler, Lori L.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. RP Bartzokis, G (reprint author), Univ Calif Los Angeles, Alzheimers Dis Ctr, David Geffen Sch Med, Dept Neurol, 710 Westwood Pl,Room 2-238, Los Angeles, CA 90095 USA. EM gbar@ucla.edu RI Bartzokis, George/K-2409-2013 NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD FEB PY 2008 VL 99 IS 1-3 BP 379 EP 379 DI 10.1016/j.schres.2007.09.023 PG 1 WC Psychiatry SC Psychiatry GA 278SM UT WOS:000254306600049 ER EF