FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Lindenhovious, ALC
Helmerhorts, GTT
Schnellen, AC
Vrahas, M
Ring, D
Kloen, P
AF Lindenhovious, Anneluuk L. C.
Helmerhorts, Gijs T. T.
Schnellen, Alexandra C.
Vrahas, Mark
Ring, David
Kloen, Peter
TI Differences in Prescription of Narcotic Pain Medication After Operative
Treatment of Hip and Ankle Fractures in the United States and the
Netherlands
SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE
LA English
DT Article
DE Narcotics; Pain medication; Hip; Ankle; Fractures
ID ADULT ATTACHMENT; ANALGESIA; SURGERY; DISABILITY; REPLACEMENT;
PREDICTORS; DICLOFENAC; INTENSITY; KETOROLAC; DISTRESS
AB Background: Interactions between American and Dutch surgeons suggested differences in prescription habits for pain medication after fracture treatment.
Methods: The percentages of 190 American [100 after hip open reduction and interal fixation (ORIF) and 90 after ankle ORIF] and 116 Dutch patients (69 after hip ORIF and 47 after ankle ORIF) receiving inpatient and outpatient prescriptions for narcotics were retrospectively compared between countries, to test the hypothesis that narcotics are prescribed more frequently in the United States as compared with the Netherlands after operative fracture treatment.
Results: Among patients with hip fractures, 85% of American and 58% of Dutch patients were prescribed narcotics during hospitalization (P < 0.001). After discharge, 77% of American and none of the Dutch patients were prescribed narcotics (p < 0.001). The multivariate model including country accounted for 11% of the variation in inpatient narcotic prescription (P < 0.001), and the model including country and surgeon accounted for 55% of the variation in outpatient narcotic prescription (p < 0.001). Among patients with ankle fracture, 98% of American and 64% of Dutch patients were prescribed narcotics during hospitalization (p < 0.001). After discharge, 82% of American patients and 6% of Dutch patients were prescribed narcotics (p < 0.001). Predictors included country and surgeon and they accounted for 20% of the variation in inpatient narcotics prescription (p < 0.001) and 49% of the variation in outpatient narcotic prescription (p < 0.001).
Conclusions: American patients are prescribed significantly more inpatient and outpatient narcotic pain medication than Dutch patients after operative treatment of hip and ankle fractures.
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands.
RP Ring, D (reprint author), Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA.
EM dring@partners.org
NR 30
TC 20
Z9 20
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 JUL
PY 2009
VL 67
IS 1
BP 160
EP 164
DI 10.1097/TA.0b013e31818c12ee
PG 5
WC Critical Care Medicine; Surgery
SC General & Internal Medicine; Surgery
GA 470CZ
UT WOS:000267953100029
PM 19590328
ER
PT J
AU Mimiaga, MJ
Reisner, SL
Cranston, K
Isenberg, D
Bright, D
Daffin, G
Bland, S
Driscoll, MA
VanDerwarker, R
Vega, B
Mayer, KH
AF Mimiaga, Matthew J.
Reisner, Sari L.
Cranston, Kevin
Isenberg, Deborah
Bright, Donna
Daffin, Gary
Bland, Sean
Driscoll, Maura A.
VanDerwarker, Rodney
Vega, Benny
Mayer, Kenneth H.
TI Sexual Mixing Patterns and Partner Characteristics of Black MSM in
Massachusetts at Increased Risk for HIV Infection and Transmission
SO JOURNAL OF URBAN HEALTH-BULLETIN OF THE NEW YORK ACADEMY OF MEDICINE
LA English
DT Article
DE HIV/AIDS; STD; African American/Black; MSM; Prevention
ID PERCEIVED SOCIAL SUPPORT; AFRICAN-AMERICAN MEN; UNITED-STATES; GAY MEN;
CAGE QUESTIONNAIRE; PSYCHOMETRIC EVALUATION; MULTIDIMENSIONAL SCALE;
TRANSMITTED-DISEASES; HIDDEN POPULATIONS; ANAL INTERCOURSE
AB Black men who have sex with men (MSM) are at increased risk for HIV infection in the United States compared to other MSM. The aim of this study was to investigate Black MSM's sexual mixing patterns and partner characteristics in relation to sexual risk taking, as a possible explanation for this observed increase in HIV incidence. Between January and July 2008, 197 Black MSM were recruited via modified respondent-driven sampling and completed optional pretest and post-test HIV serological testing, counseling, and a demographic, behavioral, and psychosocial assessment battery. Bivariate and multivariable logistic regression procedures were used to examine predictors of risky sex across partner types. Overall, 18% of the sample was HIV-infected; 50% reported unprotected intercourse with men, 30% with women, and 5% with transgender partners. Fifty-three percent identified as bisexual or straight, although all reported oral or anal sex with another man in the prior 12 months. Significant predictors of engaging in at least one episode of: (1) serodiscordant unprotected anal sex (UAS) with a male partner in the past 12 months: individuals at risk for social isolation (AOR = 4.23; p = 0.03), those with unstable housing (AOR = 4.19; p = 0.03), and those who used poppers at least weekly during sex (AOR = 5.90; p = 0.05); (2) UAS and/or unprotected vaginal intercourse with a female partner in the past 12 months: those with unstable housing (AOR = 4.85; p = 0.04), those who used cocaine at least weekly during sex (AOR = 16.78; p = 0.006), being HIV-infected (AOR = 0.07; p = 0.02), and feeling social norms favor condom use (AOR = 0.60; p = 0.05); (3) UAS with the participants' most recent nonmain male sex partner: use of alcohol and drugs during last sex by participant (AOR = 4.04; p = 0.01), having sex with a Hispanic/Latino male (AOR = 2.71; p = 0.04) or a Black male (AOR = 0.50; p = 0.05) compared to a White male, and lower education (AOR = 1.31; p = 0.02). Findings suggest that sexual risk behaviors of Black MSM differ across partner type and by the characteristics of their sexual networks and that this subpopulation of MSM are at high risk for HIV acquisition and transmission. Effective prevention strategies need to address the distinct sexual and behavioral risk patterns presented by different sexual partnerships reported by Black MSM.
C1 [Mimiaga, Matthew J.; Reisner, Sari L.; Bland, Sean; VanDerwarker, Rodney; Vega, Benny; Mayer, Kenneth H.] Fenway Community Hlth, Fenway Inst, Boston, MA 02215 USA.
[Mimiaga, Matthew J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Cranston, Kevin; Isenberg, Deborah; Driscoll, Maura A.] Massachusetts Dept Publ Hlth, Boston, MA USA.
[Bright, Donna] Justice Resource Inst, Boston, MA USA.
[Daffin, Gary] Multicultural AIDS Coalit, Boston, MA USA.
[Mayer, Kenneth H.] Miriam Hosp, Brown Med Sch, Providence, RI 02906 USA.
RP Mimiaga, MJ (reprint author), Fenway Community Hlth, Fenway Inst, 1340 Boylston St, Boston, MA 02215 USA.
EM mmimiaga@fenwayhealth.org
FU National Institute on Drug Abuse [R03DA023393]
FX This work was funded by the HIV/AIDS Bureau, Massachusetts Department of
Public Health. Some of the investigator time on this project was support
by grant number R03DA023393 from the National Institute on Drug Abuse
(PI: M. Mimiaga). The content is solely the responsibility of the
authors and does not necessarily represent the of. cial views of the
National Institutes of Health.
NR 70
TC 53
Z9 55
U1 3
U2 13
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1099-3460
J9 J URBAN HEALTH
JI J. Urban Health
PD JUL
PY 2009
VL 86
IS 4
BP 602
EP 623
DI 10.1007/s11524-009-9363-6
PG 22
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 465MW
UT WOS:000267592500009
PM 19466554
ER
PT J
AU Olumi, AF
AF Olumi, Aria F.
TI Predictive Value of Combined Immunohistochemical Markers in Patients
With pT1 Urothelial Carcinoma at Radical Cystectomy EDITORIAL COMMENT
SO JOURNAL OF UROLOGY
LA English
DT Editorial Material
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA.
RP Olumi, AF (reprint author), Harvard Univ, Massachusetts Gen Hosp, 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 0022-5347
J9 J UROLOGY
JI J. Urol.
PD JUL
PY 2009
VL 182
IS 1
BP 84
EP 84
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 457RI
UT WOS:000266949800025
ER
PT J
AU Rudolph, JL
Marcantonio, ER
Culley, DJ
Silverstein, JH
Rasmussen, LS
Crosby, GJ
Inouye, SK
AF Rudolph, J. L.
Marcantonio, E. R.
Culley, D. J.
Silverstein, J. H.
Rasmussen, L. S.
Crosby, G. J.
Inouye, S. K.
TI Delirium is Associated With Early Postoperative Cognitive Dysfunction
Editorial Comment
SO JOURNAL OF UROLOGY
LA English
DT Editorial Material
C1 [Rudolph, J. L.; Marcantonio, E. R.; Culley, D. J.; Silverstein, J. H.; Rasmussen, L. S.; Crosby, G. J.; Inouye, S. K.] Harvard Univ, Brigham & Womens Hosp, Div Aging,Med Sch, VA Boston Healthcare Syst,Geriatr Educ & Clin Ctr, Boston, MA 02115 USA.
RP Rudolph, JL (reprint author), Harvard Univ, Brigham & Womens Hosp, Div Aging,Med Sch, VA Boston Healthcare Syst,Geriatr Educ & Clin Ctr, 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 0022-5347
J9 J UROLOGY
JI J. Urol.
PD JUL
PY 2009
VL 182
IS 1
BP 187
EP 187
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 457RI
UT WOS:000266949800080
ER
PT J
AU Haynes, AB
Weiser, TG
Berry, WR
Lipsitz, SR
Breizat, AH
Dellinger, EP
Herbosa, T
Joseph, S
Kibatala, PL
Lapitan, MC
Merry, AF
Moorthy, K
Reznick, RK
Taylor, B
Gawande, AA
AF Haynes, A. B.
Weiser, T. G.
Berry, W. R.
Lipsitz, S. R.
Breizat, A. H.
Dellinger, E. P.
Herbosa, T.
Joseph, S.
Kibatala, P. L.
Lapitan, M. C.
Merry, A. F.
Moorthy, K.
Reznick, R. K.
Taylor, B.
Gawande, A. A.
CA Safe Surg Saves Lives Study Grp
TI A Surgical Safety Checklist to Reduce Morbidity and Mortality in a
Global Population Editorial Comment
SO JOURNAL OF UROLOGY
LA English
DT Editorial Material
C1 [Haynes, A. B.; Weiser, T. G.; Berry, W. R.; Lipsitz, S. R.; Breizat, A. H.; Dellinger, E. P.; Herbosa, T.; Joseph, S.; Kibatala, P. L.; Lapitan, M. C.; Merry, A. F.; Moorthy, K.; Reznick, R. K.; Taylor, B.; Gawande, A. A.; Safe Surg Saves Lives Study Grp] Harvard Univ, Sch Publ Hlth, Massachusetts Gen Hosp, Boston, MA 02115 USA.
RP Haynes, AB (reprint author), Harvard Univ, Sch Publ Hlth, Massachusetts Gen Hosp, 665 Huntington Ave, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 1
U2 10
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 JUL
PY 2009
VL 182
IS 1
BP 262
EP 262
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 457RI
UT WOS:000266949800111
ER
PT J
AU Malloy, PC
Grassi, CJ
Kundu, S
Gervais, DA
Miller, DL
Osnis, RB
Postoak, DW
Rajan, DK
Sacks, D
Schwartzberg, MS
Zuckerman, DA
Cardella, JF
AF Malloy, Patrick C.
Grassi, Clement J.
Kundu, Sanjoy
Gervais, Debra Ann
Miller, Donald L.
Osnis, Robert B.
Postoak, Darren W.
Rajan, Dheeraj K.
Sacks, David
Schwartzberg, Marc S.
Zuckerman, Darryl A.
Cardella, John F.
CA Stand Practice Committee
TI Consensus Guidelines for Periprocedural Management of Coagulation Status
and Hemostasis Risk in Percutaneous Image-guided Interventions
SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY
LA English
DT Article
ID CENTRAL VENOUS CATHETERS; LUMBAR PUNCTURE; LIVER-BIOPSY;
THROMBOCYTOPENIC PATIENTS; PLATELET TRANSFUSION; SUBCUTANEOUS
PHYTONADIONE; ANTITHROMBOTIC THERAPY; CANCER-PATIENT; ACUTE-LEUKEMIA;
REVERSAL
C1 [Malloy, Patrick C.] Hartford Hosp, Div Vasc & Intervent Radiol, Hartford, CT 06106 USA.
[Grassi, Clement J.] VAMC Boston, Boston Healthcare Syst, Dept Radiol, Boston, MA USA.
[Kundu, Sanjoy] Scarborough Gen Hosp, Dept Med Imaging, Richmond Hill, ON, Canada.
[Gervais, Debra Ann] Massachusetts Gen Hosp, GI GU Div, Dept Radiol, Boston, MA 02114 USA.
[Miller, Donald L.] Uniformed Serv Univ Hlth Sci, Dept Radiol & Radiol Sci, Bethesda, MD 20814 USA.
[Miller, Donald L.] Natl Naval Med Ctr, Dept Radiol, Bethesda, MD USA.
[Osnis, Robert B.] RADIA, Everett, WA USA.
[Postoak, Darren W.] Univ Florida, Dept Radiol, Gainesville, FL 32610 USA.
[Rajan, Dheeraj K.] Univ Toronto, Univ Hlth Network, Div Vasc & Intervent Radiol, Dept Med Imaging, Toronto, ON, Canada.
[Sacks, David] Reading Hosp Med Ctr, Dept Intervent Radiol, W Reading, PA USA.
[Schwartzberg, Marc S.] Radiol Associates Cent Florida, Mt Dora, FL USA.
[Zuckerman, Darryl A.] Edward Mallinckrodt Inst Radiol, St Louis, MO 63110 USA.
[Cardella, John F.] Geisinger Hlth Syst, Geisinger Syst Radiol, Danville, PA USA.
RP Malloy, PC (reprint author), Hartford Hosp, Div Vasc & Intervent Radiol, 85 Seymour St,Ste 200, Hartford, CT 06106 USA.
EM pmalloy@jeffersonradiology.com
NR 57
TC 55
Z9 57
U1 0
U2 3
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 JUL
PY 2009
VL 20
IS 7
BP S240
EP S249
DI 10.1016/j.jvir.2008.11.027
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular
Disease
SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System &
Cardiology
GA 465UK
UT WOS:000267613200007
PM 19394868
ER
PT J
AU Rose, SC
Dupuy, DE
Gervais, DA
Millward, SF
Brown, DB
Cardella, JF
Wallace, MJ
AF Rose, Steven C.
Dupuy, Damian E.
Gervais, Debra A.
Millward, Steven F.
Brown, Daniel B.
Cardella, John F.
Wallace, Michael J.
CA Technology Assessment Comm Soc Int
TI Research Reporting Standards for Percutaneous Thermal Ablation of Lung
Neoplasms
SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY
LA English
DT Article
ID GUIDED RADIOFREQUENCY ABLATION; PULMONARY MALIGNANT-TUMORS;
COLORECTAL-CARCINOMA; NONSURGICAL CANDIDATES; MICROWAVE ABLATION;
HELICAL CT; FOLLOW-UP; CANCER; METASTASES; PNEUMOTHORAX
C1 [Rose, Steven C.] Univ Calif San Diego, Med Ctr, Dept Radiol, Sect Intervent Oncol, San Diego, CA 92103 USA.
[Dupuy, Damian E.] Rhode Isl Hosp, Brown Med Sch, Dept Diagnost Imaging, Providence, RI USA.
[Gervais, Debra A.] Massachusetts Gen Hosp, Dept Radiol, Gastrointestinal Genitourinary Div, Boston, MA 02114 USA.
[Millward, Steven F.] Univ Western Ontario, Dept Radiol, London, ON, Canada.
[Millward, Steven F.] Peterborough Reg Hlth Ctr, Dept Radiol, Peterborough, ON, Canada.
[Brown, Daniel B.] Thomas Jefferson Univ Hosp, Dept Radiol, Div Intervent Radiol, Philadelphia, PA 19107 USA.
[Cardella, John F.] Geisinger Hlth Syst, Dept Radiol, Danville, PA USA.
[Wallace, Michael J.] Univ Texas MD Anderson Canc Ctr, Dept Intervent Radiol, Houston, TX 77030 USA.
RP Rose, SC (reprint author), Care of McClenny T, Soc Intervent Radiol, 3975 Fair Ridge Dr,Suite 400 N, Fairfax, VA 22033 USA.
EM mcclenny@sirweb.org
OI Dupuy, Damian/0000-0003-0524-5982
NR 56
TC 15
Z9 15
U1 1
U2 1
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 JUL
PY 2009
VL 20
IS 7
BP S474
EP S485
DI 10.1016/j.jvir.2009.01.016
PG 12
WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular
Disease
SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System &
Cardiology
GA 465UK
UT WOS:000267613200037
PM 19246213
ER
PT J
AU Patel, R
Conrad, MF
Paruchuri, V
Kwolek, CJ
Chung, TK
Cambria, RP
AF Patel, Rajendra
Conrad, Mark F.
Paruchuri, Vikram
Kwolek, Christopher J.
Chung, Thomas K.
Cambria, Richard P.
TI Thoracoabdominal aneurysm repair: Hybrid versus open repair
SO JOURNAL OF VASCULAR SURGERY
LA English
DT Article
ID THORACIC AORTIC-ANEURYSMS; OPEN-SURGICAL REPAIR; HIGH-RISK PATIENTS;
ENDOVASCULAR TREATMENT; STENT-GRAFT; TRIAL; OUTCOMES; IV;
REVASCULARIZATION; EXPERIENCE
AB Objective: Hybrid repair of thoracoabdominal aortic aneurysms (TAAA) may reduce morbidity and mortality in high-risk candidates for open repair. This study reviews the outcomes of hybrid TAAA repair for Crawford extent I-III TAAA in high-risk patients in comparison to patients who underwent concurrent open TAAA repair.
Methods. During the interval from June 2005 to December 2007, a total of 23 high-risk patients with TAAA (type 1: 9 [39%], 11: 5 [22%], and 111: 9 [39%]) underwent renal and/or mesenteric debranching (11 [48%] with four vessel debranching) with subsequent placement of a thoracic stent graft; 77 patients underwent open TAAA repair (type 1: 13 [17%], 11: 11 [14%], 111: 27 [35%], and IV: 26 [34%]) during the same interval. The primary high-risk criteria for hybrid TAAA included advanced age/poor functional status (n = 14), major pulmonary dysfunction (n = 8), and technical consideration (prior thoracic aortic aneurysm repair [n = 4] or prior thoracoabdominal aneurysm repair [n = 21 and obesity [n = 21) with 6 patients having overlapping high-risk criteria. Composite (30-day) mortality and/or permanent paraplegia (PP) were the major study endpoints.
Results: The hybrid and open TAAA groups had (respectively) no statistical difference in mean age (76.6 vs 72.7 years), aneurysm size (6.51 vs 6.52 cm), and non-elective operation (30.4% vs 26.0%). The hybrid group had a higher mean Society for Vascular Surgery (SVS) risk score (9.1 vs 6.0; P <= .001), incidence of oxygen-dependent chronic obstructive pulmonary disease (COPD) (34.8% vs 2.6%; P <= .001), and prior thoracic (n = 4) or thoracoabdominal (n = 2) repair (26.1% vs 1.3%; P <= .001). Composite mortality and/or PP was doubled in the hybrid group (21.7% vs 11.7%; P = .33). The rate of any type of reoperation was higher in hybrid TAAA repair (39.1% vs 20.8%; P = .03). One year actuarial survival for both groups was comparable (hybrid, 68 +/- 12%; open, 73 +/- 6%). A total of 5/23 (22%) hybrid TAAA patients developed an endoleak (type I: 3/23 and type II : 2/23) with 3 requiring endovascular re-intervention. A total of 7/70 (10%) visceral/renal bypass grafts were noted to be occluded during follow-up (I superior inesenteric artery, 1 celiac, and 5 renal). Examination of patients with an SVS risk score :58 (mean SVS risk score in hybrid 6.2 [n = 10] vs 5.5 [n = 68] in open; P = .27) revealed the hybrid group had a higher incidence of composite mortality and/or PP (40% vs 10.3%; P = .03).
Conclusion: Hybrid TAAA repair in high-risk patients has significant morbidity and mortality suggesting a non-interventional approach may be appropriate in many such patients. The morbidity and mortality of the hybrid TAAA repair was substantial even in lower risk patients (SVS risk score <= 8), albeit patient numbers were small. Prospective study in comparable patient risk cohorts is required to define the role of hybrid TAAA repair. (J Vasc Surg 2009;50: 15-22.)
C1 [Cambria, Richard P.] Massachusetts Gen Hosp, Dept Vasc & Endovasc Surg, Div Vasc & Endovasc Surg, Boston, MA 02114 USA.
RP Cambria, RP (reprint author), Massachusetts Gen Hosp, Dept Vasc & Endovasc Surg, Div Vasc & Endovasc Surg, 15 Parkman St,WAC 440, Boston, MA 02114 USA.
OI Chung, Thomas/0000-0001-6148-1184
NR 38
TC 56
Z9 58
U1 0
U2 1
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 JUL
PY 2009
VL 50
IS 1
BP 15
EP 22
DI 10.1016/j.jvs.2008.12.051
PG 8
WC Surgery; Peripheral Vascular Disease
SC Surgery; Cardiovascular System & Cardiology
GA 464IL
UT WOS:000267498500003
PM 19563950
ER
PT J
AU Alter, G
Rihn, S
Walter, K
Nolting, A
Martin, M
Rosenberg, ES
Miller, JS
Carrington, M
Altfeld, M
AF Alter, Galit
Rihn, Suzannah
Walter, Katharine
Nolting, Anne
Martin, Maureen
Rosenberg, Eric S.
Miller, Jeffrey S.
Carrington, Mary
Altfeld, Marcus
TI HLA Class I Subtype-Dependent Expansion of KIR3DS1(+) and KIR3DL1(+) NK
Cells during Acute Human Immunodeficiency Virus Type 1 Infection
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID NATURAL-KILLER-CELLS; IMMUNOGLOBULIN-LIKE RECEPTOR; ACUTE HIV-1
INFECTION; INHIBITORY RECEPTORS; PERIPHERAL-BLOOD; SELF-MHC; INNATE;
CYTOMEGALOVIRUS; ACTIVATION; RESISTANCE
AB NK cells are critical in the early containment of viral infections. Epidemiological and functional studies have shown an important role of NK cells expressing specific killer immunoglobulin-like receptors (KIRs) in the control of human immunodeficiency virus type 1 (HIV-1) infection, but little is known about the mechanisms that determine the expansion of these antiviral NK cell populations during acute HIV-1 infection. Here we demonstrate that NK cells expressing the activating receptor KIR3DS1(+) and, to a lesser extent, the inhibitory receptor KIR3DL1(+) specifically expand in acute HIV-1 infection in the presence of HLA-B Bw480I, the putative HLA class I ligand for KIR3DL1/3DS1. These data demonstrate for the first time the HLA class I subtype-dependent expansion of specific KIR+ NK cells during an acute viral infection in humans.
C1 [Alter, Galit; Rihn, Suzannah; Walter, Katharine; Nolting, Anne; Rosenberg, Eric S.; Altfeld, Marcus] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Infect Dis Unit, Boston, MA 02129 USA.
[Alter, Galit; Rihn, Suzannah; Walter, Katharine; Nolting, Anne; Rosenberg, Eric S.; Altfeld, Marcus] Harvard Univ, Ragon Inst MGH MIT & Harvard, Sch Med, Boston, MA 02129 USA.
[Alter, Galit; Rihn, Suzannah; Walter, Katharine; Nolting, Anne; Rosenberg, Eric S.; Altfeld, Marcus] Harvard Univ, Div AIDS, Sch Med, Boston, MA 02129 USA.
[Martin, Maureen; Carrington, Mary] SAIC Frederick Inc, Basic Res Program, Lab Genom Div, Frederick, MD USA.
[Miller, Jeffrey S.] Univ Minnesota, Ctr Canc, Div Hematol Oncol & Transplantat, Minneapolis, MN USA.
RP Alter, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Infect Dis Unit, Boston, MA 02129 USA.
EM galter@partners.org
OI Miller, Jeffrey S/0000-0002-0339-4944
FU NIH [R01-AI067031, PO1-AI074415]; National Cancer Institute, National
Institutes of Health [N01-C0-12400]; Susan Ragon Foundation
FX This work was supported by NIH grants R01-AI067031 and PO1-AI074415. The
project has been funded in part with federal funds from the National
Cancer Institute, National Institutes of Health, under contract
N01-C0-12400. CHAVI (Center for HIV/AIDS Vaccine Immunology) provided
support for the development of the quantitative RT-PCR. We thank the
Philip T. and Susan Ragon Foundation for support.
NR 37
TC 105
Z9 112
U1 0
U2 8
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 JUL
PY 2009
VL 83
IS 13
BP 6798
EP 6805
DI 10.1128/JVI.00256-09
PG 8
WC Virology
SC Virology
GA 462LM
UT WOS:000267354100046
PM 19386717
ER
PT J
AU Solberg, LI
Asche, SE
Anderson, LH
Sepucha, K
Thygeson, NM
Madden, JE
Morrissey, L
Kraemer, KK
AF Solberg, Leif I.
Asche, Stephen E.
Anderson, Louise H.
Sepucha, Karen
Thygeson, N. Marcus
Madden, Joan E.
Morrissey, Larry
Kraemer, Karen K.
TI Evaluating Preference-Sensitive Care for Uterine Fibroids: It's Not So
Simple
SO JOURNAL OF WOMENS HEALTH
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; DECISION-MAKING; REGIONAL-VARIATIONS;
PATIENT DECISION; HEALTH OUTCOMES; MEDICAL-CARE; NEW-HAVEN; QUALITY;
AIDS; SUPPORT
AB Background: Preference-sensitive care decisions should reflect an informed patient's preferences. This retrospective survey of women with fibroids, a benign condition with multiple treatment options, sought to evaluate the extent to which this was measurable and true.
Methods: All 260 women in one medical group with visit codes for uterine fibroids during a 9-month period in 2006 were mailed surveys constructed through focus groups with physicians and interviews with patients. Correlations tested associations among their preferences, knowledge, and treatment decisions.
Results: The adjusted response rate was 82%, but only 100 respondents fit all criteria for analysis. Nearly all wanted to either share or control the decision, and 86% felt informed, satisfied, and that the decision was consistent with their values. However, only 55% of patients could answer at least five of seven fibroid questions correctly. Hysterectomy use was significantly correlated with desire to relieve symptoms, have a permanent treatment, and do something right away (r = 0.36, 0.37, and 0.30, respectively). Those deciding not to treat were significantly less likely to have these preferences (r = -0.65, -0.40, and -0.58). These relationships were not affected by patient knowledge level, but patients with high knowledge scores were significantly more likely to believe their decision was concordant with their preferences (94.9% vs. 74.4%, p<0.01).
Conclusions: There were knowledge gaps but unclear associations between knowledge and decision-preference relationships for this condition, which has many different treatment alternatives. A prospective intervention trial is needed to determine if better information and counseling would produce stronger concordance between treatment selected and patient preferences.
C1 [Solberg, Leif I.; Asche, Stephen E.; Anderson, Louise H.; Thygeson, N. Marcus; Madden, Joan E.; Kraemer, Karen K.] HealthPartners Res Fdn, Minneapolis, MN 55440 USA.
[Solberg, Leif I.; Asche, Stephen E.; Anderson, Louise H.; Thygeson, N. Marcus; Madden, Joan E.; Kraemer, Karen K.] HealthPartners, HealthPartners Med Grp, Minneapolis, MN USA.
[Sepucha, Karen] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Morrissey, Larry] Stillwater Med Grp, Stillwater, MN USA.
RP Solberg, LI (reprint author), HealthPartners Res Fdn, POB 1524,MS 21111R, Minneapolis, MN 55440 USA.
EM leif.i.solberg@healthpartners.com
FU HealthPartners Research Foundation
FX We are very grateful to the obstetrics/gynecology physicians and
patients who helped so much in creating and modifying the questions used
to measure knowledge and decision quality. The physician collaboration
was greatly facilitated by the department chair (J.M.). This work was
supported by a Partnership grant from HealthPartners Research
Foundation.
NR 36
TC 4
Z9 4
U1 0
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-9996
J9 J WOMENS HEALTH
JI J. Womens Health
PD JUL
PY 2009
VL 18
IS 7
BP 1071
EP 1079
DI 10.1089/jwh.2008.0948
PG 9
WC Public, Environmental & Occupational Health; Medicine, General &
Internal; Obstetrics & Gynecology; Women's Studies
SC Public, Environmental & Occupational Health; General & Internal
Medicine; Obstetrics & Gynecology; Women's Studies
GA 469FS
UT WOS:000267881900018
PM 19580366
ER
PT J
AU Lu, TC
Wang, ZH
Feng, XB
Chuang, PY
Fang, W
Shen, YH
Levy, DE
Xiong, HB
Chen, N
He, JC
AF Lu, Ting-Chi
Wang, Zhao-Hui
Feng, Xiaobei
Chuang, Peter Y.
Fang, Wei
Shen, Yuhong
Levy, David E.
Xiong, Huabao
Chen, Nan
He, John Cijiang
TI Knockdown of Stat3 activity in vivo prevents diabetic glomerulopathy
SO KIDNEY INTERNATIONAL
LA English
DT Article
DE collagen IV; diabetic nephropathy; glomerulosclerosis; mesangial cells;
Stat3
ID JAK/STAT-SIGNALING PATHWAY; FACTOR-KAPPA-B; LOW-GRADE INFLAMMATION;
MESANGIAL CELLS; HIGH GLUCOSE; INDUCED ACTIVATION; KIDNEY GLOMERULI;
DB/DB MICE; NEPHROPATHY; GROWTH
AB Recent studies suggest that Stat3, a transcription factor that mediates cytokine signaling, plays a critical role in the pathogenesis of diabetic nephropathy. Complete Stat3 gene knockout is embryonic lethal; therefore, we crossed Stat3+/- mice with Stat3 mutant mice (SA/SA) that lack full Stat3 activity. This strategy generated Stat3SA/- mice (25% activity) and Stat3SA/+ mice (75% activity), which were made diabetic using streptozotocin in order to define the role of Stat3 in diabetic kidney disease. While the glomerular number was not different between these two groups of mice, the diabetic SA/- mice had significantly less proteinuria, mesangial expansion, glomerular cell proliferation, and macrophage infiltration than the diabetic SA/+ mice. The reduction in Stat3 activity did not affect glomerular hyperfiltration seen after the induction of diabetes, as it was increased to the same degree in both groups of mice. Phosphorylation of Stat3 was markedly increased in the glomeruli of diabetic SA/+ mice compared to diabetic SA/- mice. The expression of inflammatory markers, IL-6, MCP-1, and activated NF-kappa B; type IV collagen, TGF-beta, and ICAM-1 mRNA; or type IV collagen and TGF-beta protein, were all found to be significantly less in glomeruli isolated from diabetic SA/- mice, as compared with diabetic SA/+ mice. Our study shows that Stat3 plays a critical role in the regulation of inflammation and abnormal matrix synthesis at an early stage of DN.
C1 [He, John Cijiang] Mt Sinai Sch Med, Dept Med, Div Nephrol, New York, NY 10029 USA.
[Lu, Ting-Chi; He, John Cijiang] James J Peters VA Med Ctr, Bronx, NY USA.
[Wang, Zhao-Hui; Feng, Xiaobei; Chen, Nan] Shanghai Jiao Tong Univ, Sch Med, RuiJin Hosp, Dept Nephrol, Shanghai 200030, Peoples R China.
[Shen, Yuhong] Rockefeller Univ, Mol Cell Biol Lab, New York, NY 10021 USA.
[Levy, David E.] NYU, Dept Pathol, New York, NY 10016 USA.
[Xiong, Huabao] Mt Sinai Sch Med, Immunobiol Ctr, New York, NY USA.
[He, John Cijiang] Mt Sinai Sch Med, Dept Pharmacol & Syst Therapeut, New York, NY USA.
RP He, JC (reprint author), Mt Sinai Sch Med, Dept Med, Div Nephrol, Box 1243,1 Gustave L Levy Pl, New York, NY 10029 USA.
EM cijiang.he@mssm.edu
OI Levy, David/0000-0002-7320-7788
FU NIH [R01 DK078897, K08 KD082760]
FX JC He was supported by NIH R01 DK078897. PY Chuang was supported by NIH
K08 KD082760.
NR 43
TC 29
Z9 37
U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0085-2538
J9 KIDNEY INT
JI Kidney Int.
PD JUL
PY 2009
VL 76
IS 1
BP 63
EP 71
DI 10.1038/ki.2009.98
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 461KR
UT WOS:000267266200011
PM 19357722
ER
PT J
AU Eisner, BH
Tanrikut, C
Dahl, DM
AF Eisner, Brian H.
Tanrikut, Cigdem
Dahl, Douglas M.
TI Chyluria secondary to lymphorenal fistula
SO KIDNEY INTERNATIONAL
LA English
DT Editorial Material
C1 [Eisner, Brian H.; Tanrikut, Cigdem; Dahl, Douglas M.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA.
RP Eisner, BH (reprint author), Massachusetts Gen Hosp, Dept Urol, GRB 1102,55 Fruit St, Boston, MA 02114 USA.
EM beisner@partners.org
NR 0
TC 3
Z9 4
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0085-2538
J9 KIDNEY INT
JI Kidney Int.
PD JUL
PY 2009
VL 76
IS 1
BP 126
EP 126
DI 10.1038/ki.2009.64
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 461KR
UT WOS:000267266200020
PM 19528993
ER
PT J
AU Kiernan, TJ
Yan, BP
Gupta, V
Garasic, JM
AF Kiernan, Thomas J.
Yan, Bryan P.
Gupta, Vishal
Garasic, Joseph M.
TI Unusual case of recurrent renal artery stenosis: lessons to learn
SO KIDNEY INTERNATIONAL
LA English
DT Article
ID PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; PEDIATRIC RENOVASCULAR
HYPERTENSION; BALLOON ANGIOPLASTY; NEONATAL HYPERTENSION;
RANDOMIZED-TRIAL; STENT PLACEMENT; RISK-FACTORS; FOLLOW-UP; CHILDREN;
MANAGEMENT
AB A 39 year old male chef with previous right aorto-renal artery surgical reimplantation at age 8 for reported congenital renal artery stenosis presented to an outside hospital with gastroenteritis including symptoms of abdominal pain, nausea, diarrhea and vomiting. Past medical history apart from previous surgery for congenital renal artery stenosis was unremarkable. He was an active tobacco user of one pack per day for the previous 20 years. There was no family history of premature coronary disease. Examination revealed a blood pressure of 210/100 mmHg, heart rate of 88 beats per minute and respiratory rate of 16 per minute. Blood pressure recordings were equal in both upper limbs. The radial, brachial, femoral and distal lower limb pulses were symmetrical and of normal volume. No bruits were audible over the carotid, subclavian or femoral arteries. The remainders of the cardiac, respiratory and abdominal examinations were unremarkable apart from a surgical scar as a result of previous renal artery surgery. Medications included nifedipine 90 mg and enalapril 20 mg had been started one month earlier for worsening hypertension. Laboratory profile on admission is shown in (Table 1).
C1 [Kiernan, Thomas J.; Yan, Bryan P.; Gupta, Vishal; Garasic, Joseph M.] Massachusetts Gen Hosp, Dept Intervent Cardiol & Vasc Med, Boston, MA 02114 USA.
RP Kiernan, TJ (reprint author), Massachusetts Gen Hosp, Dept Intervent Cardiol & Vasc Med, 55 Fruit St, Boston, MA 02114 USA.
EM tom_kiernan@hotmail.com
RI Yan, Bryan/P-5928-2015
NR 41
TC 1
Z9 1
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0085-2538
J9 KIDNEY INT
JI Kidney Int.
PD JUL
PY 2009
VL 76
IS 2
BP 224
EP 228
DI 10.1038/ki.2008.353
PG 5
WC Urology & Nephrology
SC Urology & Nephrology
GA 464HV
UT WOS:000267496900015
PM 18633338
ER
PT J
AU Deschler, DG
Bunting, GW
Lin, DT
Emerick, K
Rocco, J
AF Deschler, Daniel G.
Bunting, Glenn W.
Lin, Derrick T.
Emerick, Kevin
Rocco, James
TI Evaluation of Voice Prosthesis Placement at the Time of Primary
Tracheoesophageal Puncture with Total Laryngectomy
SO LARYNGOSCOPE
LA English
DT Article
DE Tracheoesophageal voice restoration; total laryngectomy
ID VOCAL REHABILITATION; SPEAKING PROFICIENCY; BLOM-SINGER; RESTORATION;
EXPERIENCE; SPEECH
AB Objectives/Hypothesis: Primary tracheoesophageal puncture (TEP) is a well-described and accepted method of surgical voice restoration and is standardly completed with a catheter placement intraoperatively, which is replaced with a prosthesis at a later date. This study evaluates the intraoperative placement of the voice prosthesis at the time of the primary TEP in an effort to understand the potential advantages and disadvantages of voice prosthesis placement at the time of primary TEP completed in conjunction with total laryngectomy.
Study Design: Retrospective chart review within an academic medical center.
Methods: After approval by the institutional review board of the Massachusetts Eye and Ear Infirmary, a retrospective chart review was completed of all cases of primary tracheoesophageal prosthesis placement completed in conjunction with primary tracheoesophageal puncture performed at the time of total laryngectomy.
Results: Thirty patients were identified, 29 of whom underwent laryngectomy for advanced laryngeal carcinoma. Twenty-eight of 29 patients received preoperative full-dose radiation therapy. Twenty-nine of 30 patients had a 20F classic Indwelling Blom-Singer prosthesis (InHealth Technologies, Carpinteria, CA) placed. One had placement of 16F Indwelling Blom-Singer prosthesis. No complications were noted with intraoperative prosthesis placement. No prostheses were dislodged in the postoperative period. Twenty-nine of 30 subjects had initial success with tracheoesophageal voice production. At 1-year follow-up, 23/30 subjects (77%) had successful voice restoration. Five failed because of recurrent disease, one subject never achieved successful voice, and one subject wanted the prosthesis removed although successful voice was achieved. Twenty-three of 25 (92%) disease-free subjects had functional voice restoration at 1-year post-total laryngectomy and primary prosthesis placement.
Conclusions: This study demonstrates that the voice prosthesis can be safely and effectively placed intraoperatively at the time of primary TEP and laryngectomy. Initial voice acquisition rates were high and long-term success was well within the acceptable range.
C1 [Deschler, Daniel G.; Bunting, Glenn W.; Lin, Derrick T.; Emerick, Kevin; Rocco, James] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Div Head & Neck Surg,Dept Otol & Laryngol, Boston, MA USA.
RP Deschler, DG (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Div Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA.
EM daniel_deschler@meei.harvard.edu
NR 22
TC 15
Z9 15
U1 0
U2 3
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0023-852X
J9 LARYNGOSCOPE
JI Laryngoscope
PD JUL
PY 2009
VL 119
IS 7
BP 1353
EP 1357
DI 10.1002/lary.20490
PG 5
WC Medicine, Research & Experimental; Otorhinolaryngology
SC Research & Experimental Medicine; Otorhinolaryngology
GA 467KO
UT WOS:000267737800016
PM 19507224
ER
PT J
AU Lembo, AJ
Ganz, RA
Sheth, S
Cave, D
Kelly, C
Levin, P
Kazlas, PT
Baldwin, PC
Lindmark, WR
McGrath, JR
Hamblin, MR
AF Lembo, Anthony J.
Ganz, Robert A.
Sheth, Sunil
Cave, David
Kelly, Ciaran
Levin, Philip
Kazlas, Peter T.
Baldwin, Paul C., III
Lindmark, William R.
McGrath, Jonathan R.
Hamblin, Michael R.
TI Treatment of Helicobacter pylori Infection With Intra-Gastric Violet
Light Phototherapy: A Pilot Clinical Trial
SO LASERS IN SURGERY AND MEDICINE
LA English
DT Article
DE Helicobacter pylori; gastroenterology; laser phototherapy; porphyrins;
endoscopy
ID PHOTODYNAMIC THERAPY; PROPIONIBACTERIUM-ACNES; VISIBLE-LIGHT;
ERADICATION; PORPHYRINS; QUADRUPLE; BACTERIA
AB Background and Objective: Helicobacter pylori infects the mucus layer of the human stomach and causes peptic ulcers and adenocarcinoma. We have previously shown that H. pylori accumulates photoactive porphyrins making the organism susceptible to inactivation by light, and that small spot endoscopic illumination with violet light reduced bacterial load in human stomachs. This study assessed the feasibility and safety of whole-stomach intra-gastric violet phototherapy for the treatment of H. pylori infection. Study
Design/Materials and Methods: A controlled, prospective pilot trial was conducted using a novel light source consisting of laser diodes and diffusing fibers to deliver 408-nm illumination at escalating total fluences to the whole stomach. Eighteen adults (10 female) with H. pylori infection were treated at three U.S. academic endoscopy centers. Quantitative bacterial counts were obtained from biopsies taken from the antrum, body, and fundus, and serial urea breath tests.
Results: The largest reduction in bacterial load was in the antrum (>97%), followed by body (>95%) and fundus (>86%). There was a correlation between log reduction and initial bacterial load in the antrum. There was no dose-response seen with increasing illumination times. The urea breath test results indicated that the bacteria repopulated in days following illumination.
Conclusion: Intra-gastric violet light phototherapy is feasible and safe and may represent a novel approach to eradication of H. pylori, particularly in patients who have failed standard antibiotic treatment. This was a pilot study involving a small number of patients. Further research is needed to determine if phototherapy can be effective for eradicating H. pylori. Lasers Surg. Med. 41:337-344, 2009. (C) 2009 Wiley-Liss, Inc.
C1 [Baldwin, Paul C., III; Lindmark, William R.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Lembo, Anthony J.; Sheth, Sunil; Kelly, Ciaran] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Ganz, Robert A.] Abbott NW Hosp, Dept Gastroenterol, Minneapolis, MN 55407 USA.
[Cave, David] UMASS Med Ctr, Worcester, MA USA.
[Levin, Philip; Kazlas, Peter T.; Baldwin, Paul C., III; Lindmark, William R.; McGrath, Jonathan R.] LumeRx Inc, Marlborough, MA 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 Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed BAR414, 40 Blossom St, Boston, MA 02114 USA.
EM hamblin@helix.mgh.harvard.edu
OI Cave, David/0000-0003-3391-7299; Hamblin, Michael/0000-0001-6431-4605
FU LumeRx, Inc; NIH [R01AI050875]
FX Contract grant sponsor: LumeRx, Inc.; Contract grant sponsor: NIH;
Contract grant number: R01AI050875.
NR 22
TC 32
Z9 36
U1 1
U2 5
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 JUL
PY 2009
VL 41
IS 5
BP 337
EP 344
DI 10.1002/lsm.20770
PG 8
WC Dermatology; Surgery
SC Dermatology; Surgery
GA 464RS
UT WOS:000267524400002
PM 19533762
ER
PT J
AU Akilov, OE
Yousaf, W
Lukjan, SX
Verma, S
Hasan, T
AF Akilov, Oleg E.
Yousaf, Wajeeha
Lukjan, Sebastian X.
Verma, Sarika
Hasan, Tayyaba
TI Optimization of Topical Photodynamic Therapy With
3,7-bis(di-n-butylamino)Phenothiazin-5-ium Bromide for Cutaneous
Leishmaniasis
SO LASERS IN SURGERY AND MEDICINE
LA English
DT Article
DE Leishmania; topical application; light; antiparasitic therapy
ID VISCERAL LEISHMANIASIS; RESISTANCE; MILTEFOSINE; PROMASTIGOTES;
PAROMOMYCIN; PARASITES; EFFICACY; AGENTS
AB Background and Objective: Photodynamic therapy (PDT) has evolved as a promising therapeutic measure for the treatment of cutaneous leishmaniasis (CL). In particular, phenothiazine compounds have demonstrated efficacy for PDT of CL. The objective of our present study is to define the use of a new specific phenothiazine photosensitizer, 3,7-bis(di-n-butylamino)phenothiazin-5-ium bromide (PPA904) applied topically as a cream to treat CL.
Materials and Methods: To establish the optimal conditions for this treatment, we compared two different ways to improve current regimens of PDT with PPA904 cream (500 mu M of PPA904 in Unguentum M) by changing the duration of topical application, and by administration of several consecutive PDT procedures. An initial regimen recommended by the manufacturer (Photopharmica Co. Ltd., Leeds, UK) was maintained as a control: the cream was applied topically for 30 minutes at a final concentration of PPA904 at 500 mu M, and the designated treatment area was irradiated with a broad band light source of 665 +/- 15 nm at a fluence of 50 J/cm(2) (50 MW/cm(2)).
Results: The best curative PPA904-PDT regimen was achieved under the conditions of a longer duration of topical application time (90 minutes) and several (three) consecutive treatments with 4-day intervals between treatments. The mechanisms responsible for such improvements (kinetics of drug penetration, depth of necrosis of the CL lesions after PDT, and daily changes in the parasitic load after PDT) are discussed in the present study.
Conclusion: Topical PPA904-PDT, implemented as described above, is a promising treatment for CL, and clinical studies will be initiated to establish efficacy in humans. Lasers Surg. Med. 41:358-365, 2009. (C) 2009 Wiley-Liss, Inc.
C1 [Akilov, Oleg E.] Harvard Univ, Dept Dermatol, Sch Med, Massachusetts Gen Hosp,Wellman Ctr Photomed, Boston, MA 02114 USA.
[Yousaf, Wajeeha] Aga Khan Univ, Coll Med, Karachi, Pakistan.
[Akilov, Oleg E.; Verma, Sarika; Hasan, Tayyaba] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA.
[Lukjan, Sebastian X.] MIT, Cambridge, MA 02139 USA.
RP Hasan, T (reprint author), Harvard Univ, Dept Dermatol, Sch Med, Massachusetts Gen Hosp,Wellman Ctr Photomed, 40 Blossom St,BAR 314, Boston, MA 02114 USA.
EM thasan@partners.org
FU Department of Defense Medical Free Electron Laser Program
[FA9550-04-1-0079]
FX Biological Science, University of Notre Dame, Notre Dame, IN, USA) for
providing us with the L. major strain V1. We are appreciative of the
assistance of Carol Winkelman and Elizabeth Davis with the manuscript
preparation. This work was supported by the Department of Defense
Medical Free Electron Laser Program Grant No. FA9550-04-1-0079 (to T.
Hasan).
NR 34
TC 13
Z9 14
U1 0
U2 2
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 JUL
PY 2009
VL 41
IS 5
BP 358
EP 365
DI 10.1002/lsm.20775
PG 8
WC Dermatology; Surgery
SC Dermatology; Surgery
GA 464RS
UT WOS:000267524400005
PM 19533767
ER
PT J
AU Stegmaier, K
AF Stegmaier, K.
TI Genomic approaches to small molecule discovery
SO LEUKEMIA
LA English
DT Review
DE small molecule screening; gene expression; genomics; drug discovery
ID ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOGENOUS
LEUKEMIA; B-CELL LYMPHOMA; GENE-EXPRESSION SIGNATURE; TYROSINE KINASE
INHIBITOR; SET ENRICHMENT ANALYSIS; PROSTATE-CANCER; MYELODYSPLASTIC
SYNDROME; MEMORY DIFFERENTIATION
AB With the sequencing of the human genome and the development of new genomic technologies, biomedical discovery has been transformed. The applications of these new approaches are ever-expanding from disease classification, to identification of new targets, to outcome prediction. A logical next step is the integration of genomic approaches into small molecule discovery. This review will focus on the application of genomics to compound discovery, with an emphasis on the hematological malignancies. It will focus on the use of genomic tools to discover cancer targets and the development and application of both cell-based and in silico gene expression-based approaches to small molecule discovery. Leukemia (2009) 23, 1226-1235; doi: 10.1038/leu.2009.29; published online 5 March 2009
C1 [Stegmaier, K.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol,Childrens Hosp Boston, Boston, MA 02115 USA.
[Stegmaier, K.] Harvard Univ, Broad Inst, Cambridge, MA 02138 USA.
[Stegmaier, K.] MIT, Cambridge, MA 02139 USA.
RP Stegmaier, K (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol,Childrens Hosp Boston, D640C,44 Binney St, Boston, MA 02115 USA.
EM kimberly_stegmaier@dfci.harvard.edu
FU US National Institutes of Health; Howard Hughes Medical Institute
Physician Scientist Early Career Award; Leukemia and Lymphoma Society;
Sidney Kimmel Foundation for Cancer Research; Smith Family New
Investigator Awards Program (Richard Allan Barry Fund at the Boston
Foundation); SynCure Cancer Research Foundation; William Lawrence
Pediatric Foundation
FX The Stegmaier laboratory is supported by the US National Institutes of
Health, the Howard Hughes Medical Institute Physician Scientist Early
Career Award, the Leukemia and Lymphoma Society, the Sidney Kimmel
Foundation for Cancer Research, the Smith Family New Investigator Awards
Program (Richard Allan Barry Fund at the Boston Foundation), the SynCure
Cancer Research Foundation and the William Lawrence Pediatric
Foundation.
NR 70
TC 4
Z9 4
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
J9 LEUKEMIA
JI Leukemia
PD JUL
PY 2009
VL 23
IS 7
BP 1226
EP 1235
DI 10.1038/leu.2009.29
PG 10
WC Oncology; Hematology
SC Oncology; Hematology
GA 470KB
UT WOS:000267972500005
PM 19262600
ER
PT J
AU Neff, T
Armstrong, SA
AF Neff, T.
Armstrong, S. A.
TI Chromatin maps, histone modifications and leukemia
SO LEUKEMIA
LA English
DT Review
DE epigenetics; chromatin; histones; methyltransferases; methylation
ID EMBRYONIC STEM-CELLS; ACUTE MYELOID-LEUKEMIA; MIXED-LINEAGE LEUKEMIA;
GENOME-WIDE MAPS; DNA METHYLATION; GENE-EXPRESSION; GROUP PROTEINS;
SACCHAROMYCES-CEREVISIAE; SET DOMAIN; TRANSCRIPTIONAL ELONGATION
AB Recent years have seen great advances in the understanding of epigenetic gene regulation. Many of the molecular players involved have recently been identified and are rapidly being characterized in detail. Genome scale studies, using chromatin immunoprecipitation followed by expression arrays ('ChIP-Chip') or next generation sequencing ('ChIP-Seq'), have been applied to the study of transcription factor binding, DNA methylation, alternative histone use, and covalent histone modifications such as acetylation, ubiquitination and methylation. Initial studies focused on yeast, and embryonic stem cells. Genome-wide studies are now also being employed to characterize cancer and specifically leukemia genomes, with the prospect of improved diagnostic accuracy and discovery of novel therapeutic strategies. Here, we review some of the epigenetic modifications and their relevance for leukemia. Leukemia (2009) 23, 1243-1251; doi: 10.1038/leu.2009.40; published online 26 March 2009
C1 [Armstrong, S. A.] Childrens Hosp Boston, Div Hematol Oncol, Karp Family Res Labs, Boston, MA 02215 USA.
[Neff, T.; Armstrong, S. A.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Armstrong, S. A.] Harvard Stem Cell Inst, Boston, MA USA.
RP Armstrong, SA (reprint author), Childrens Hosp Boston, Div Hematol Oncol, Karp Family Res Labs, 1 Blackfan Circle, Boston, MA 02215 USA.
EM Scott.Armstrong@childrens.harvard.edu
OI Neff, Tobias/0000-0002-0188-8393
NR 126
TC 37
Z9 38
U1 2
U2 14
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
J9 LEUKEMIA
JI Leukemia
PD JUL
PY 2009
VL 23
IS 7
BP 1243
EP 1251
DI 10.1038/leu.2009.40
PG 9
WC Oncology; Hematology
SC Oncology; Hematology
GA 470KB
UT WOS:000267972500007
PM 19322211
ER
PT J
AU Stone, ME
AF Stone, Martha E.
TI Routine Miracles: Restoring Faith and Hope in Medicine.
SO LIBRARY JOURNAL
LA English
DT Book Review
C1 [Stone, Martha E.] Massachusetts Gen Hosp Lib, Boston, MA 02114 USA.
RP Stone, ME (reprint author), Massachusetts Gen Hosp Lib, Boston, MA 02114 USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU REED BUSINESS INFORMATION
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010 USA
SN 0363-0277
J9 LIBR J
JI Libr. J.
PD JUL
PY 2009
VL 134
IS 12
BP 117
EP 118
PG 2
WC Information Science & Library Science
SC Information Science & Library Science
GA 469AG
UT WOS:000267866400246
ER
PT J
AU Li, W
Meng, ZH
Liu, YL
Reyes, JD
Lang, JD
AF Li, Wei
Meng, Zihui
Liu, Yuliang
Reyes, Jorge D.
Lang, John D.
TI THE PROTECTIVE EFFECT OF NITRITE ON LIVER COLD ISCHEMIA REPERFUSION
INJURY
SO LIVER TRANSPLANTATION
LA English
DT Meeting Abstract
CT 15th Annual Congress of the International-Liver-Transplantation-Society
CY JUL 08-11, 2009
CL New York, NY
SP Int Liver Transplantat Soc
C1 [Li, Wei; Meng, Zihui; Liu, Yuliang; Reyes, Jorge D.; Lang, John D.] Univ Washington, Seattle, WA 98195 USA.
[Liu, Yuliang; Lang, John D.] VA Puget Sound Hlth Care Syst, Seattle, WA USA.
[Reyes, Jorge D.] Childrens Hosp & Reg Med Ctr, Seattle, WA USA.
NR 0
TC 1
Z9 1
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 JUL
PY 2009
VL 15
IS 7
BP S236
EP S236
PG 1
WC Gastroenterology & Hepatology; Surgery; Transplantation
SC Gastroenterology & Hepatology; Surgery; Transplantation
GA 468CV
UT WOS:000267792300547
ER
PT J
AU Rosen, AK
Loveland, SA
Romano, PS
Itani, KMF
Silber, JH
Even-Shoshan, OO
Halenar, MJ
Teng, Y
Zhu, JS
Volpp, KG
AF Rosen, Amy K.
Loveland, Susan A.
Romano, Patrick S.
Itani, Kamal M. F.
Silber, Jeffrey H.
Even-Shoshan, Orit O.
Halenar, Michael J.
Teng, Yun
Zhu, Jingsan
Volpp, Kevin G.
TI Effects of Resident Duty Hour Reform on Surgical and Procedural Patient
Safety Indicators Among Hospitalized Veterans Health Administration and
Medicare Patients
SO MEDICAL CARE
LA English
DT Article
DE patient safety; hospital quality; resident duty hour reform;
administrative data
ID WORK HOURS; ADVERSE EVENTS; CARE; MORTALITY; QUALITY; REGULATIONS;
PERFORMANCE; LIMITS; IMPACT; ERRORS
AB Objective: Improving patient safety was a strong motivation behind duty hour regulations implemented by Accreditation Council for Graduate Medical Education on July 1, 2003. We investigated whether rates of patient safety indicators (PSIs) changed after these reforms.
Research Design: Observational study of patients admitted to Veterans Health Administration (VA) (N = 826,047) and Medicare (N = 13,367,273) acute-care hospitals from July 1, 2000 to June 30, 2005. We examined changes in patient safety events in more versus less teaching-intensive hospitals before (2000-2003) and after (2003-2005) duty hour reform, using conditional logistic regression, adjusting for patient age, gender, comorbidities, secular trends, baseline severity, and hospital site.
Measures: Ten PSIs were aggregated into 3 composite measures based on factor analyses: "Continuity of Care," "Technical Care," and "Other" composites.
Results: Continuity of Care composite rates showed no significant changes postreform in hospitals of different teaching intensity in either VA or Medicare. In the VA, there were no significant changes postreform for the technical care composite. In Medicare, the odds of a Technical Care PSI event in more versus less teaching-intensive hospitals in postreform year 1 were 1.12 (95% CI; 1.01-1.25), there were no significant relative changes in postreform year 2. Other composite rates increased in VA in postreform year 2 in more versus less teaching-intensive hospitals (odds ratio, 1.63; 95% CI; 1.10-2.41), but not in Medicare in either postreform year.
Conclusions: Duty hour reform had no systematic impact on PSI rates. In the few cases where there were statistically significant increases in the relative odds of developing a PSI, the magnitude of the absolute increases were too small to be clinically meaningful.
C1 [Rosen, Amy K.; Loveland, Susan A.] VA Ctr Excellence, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA.
[Rosen, Amy K.; Loveland, Susan A.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA.
[Romano, Patrick S.] Univ Calif Davis, Sch Med, Div Gen Med, Sacramento, CA 95817 USA.
[Romano, Patrick S.] Univ Calif Davis, Sch Med, Ctr Healthcare Policy & Res, Sacramento, CA 95817 USA.
[Itani, Kamal M. F.] Boston VA Healthcare Syst, Dept Surg, Boston, MA USA.
[Itani, Kamal M. F.] Boston Univ, Dept Surg, Boston, MA 02215 USA.
[Silber, Jeffrey H.] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA.
[Silber, Jeffrey H.; Even-Shoshan, Orit O.; Halenar, Michael J.; Zhu, Jingsan; Volpp, Kevin G.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Silber, Jeffrey H.; Even-Shoshan, Orit O.; Teng, Yun; Volpp, Kevin G.] Childrens Hosp Philadelphia, Ctr Outcomes Res, Philadelphia, PA 19104 USA.
[Silber, Jeffrey H.; Volpp, Kevin G.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA.
[Halenar, Michael J.; Volpp, Kevin G.] VA Ctr Excellence, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA.
RP Rosen, AK (reprint author), VA Ctr Excellence, Ctr Hlth Qual Outcomes & Econ Res, 200 Springs Rd 152, Bedford, MA 01730 USA.
EM akrosen@bu.edu
RI Romano, Patrick/N-4225-2014
OI Romano, Patrick/0000-0001-6749-3979
FU VA [IIR 04.202.1]; NHLBI RO1 HL082637; National Science Foundation
[SES-06-0646002]
FX Supported by VA grant HSR&D IIR 04.202.1 and NHLBI RO1 HL082637, with
additional support from National Science Foundation grant
SES-06-0646002.
NR 47
TC 53
Z9 53
U1 1
U2 2
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 JUL
PY 2009
VL 47
IS 7
BP 723
EP 731
PG 9
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 463VZ
UT WOS:000267462400003
PM 19536029
ER
PT J
AU Keating, NL
Kouri, E
He, YL
Weeks, JC
Winer, EP
AF Keating, Nancy L.
Kouri, Elena
He, Yulei
Weeks, Jane C.
Winer, Eric P.
TI Racial Differences in Definitive Breast Cancer Therapy in Older Women
Are They Explained by the Hospitals where Patients Undergo Surgery?
SO MEDICAL CARE
LA English
DT Article
DE breast cancer; surgery; quality; racial disparities
ID ACUTE MYOCARDIAL-INFARCTION; HEALTH-SERVICES RESEARCH; BLACK-AND-WHITE;
COMORBIDITY INDEX; LINKED MEDICARE; LUNG-CANCER; DISPARITIES; VOLUME;
SURVIVAL; CARE
AB Background: Prior research has documented racial disparities in patterns of care and outcomes for women with breast cancer.
Objectives: To assess whether black women receive care from lower-quality or lower-volume hospitals and if such differences explain disparities in receipt of definitive primary breast cancer therapy.
Research Design: Observational study of a population-based sample of breast cancer patients included in the SEER-Medicare database.
Subjects: Fifty five thousand four hundred seventy white or black women aged >65 diagnosed with stage I/II breast cancer during 1992-2002.
Measures: Surgery at a high-quality hospital (top quartile rates of radiation after breast-conserving Surgery) or high volume (top quartile) hospital and receipt of definitive primary therapy (mastectomy or breast-conserving surgery with radiation).
Results: Black women were significantly less likely than white women to be treated at high-quality hospitals (adjusted odds ratio [OR] 0.60; 95% confidence interval [Cl]: 0.40-0.87) but not high-volume hospitals (adjusted OR 0.85; 95% Cl: 0.54-1.34). Black women were less likely than white women to receive definitive primary therapy, a finding partially explained by having surgery at a high-quality hospital but not by having surgery at a high-volume hospital.
Conclusions: Older black women were more likely than white women to undergo breast cancer surgery at hospitals with lower rates of radiation following breast-conserving surgery, and this explains some of the reported racial disparities previously observed in receipt of definitive therapy for early-stage breast cancer. Interventions to help hospitals treating large numbers of black women improve rates of radiation after breast-conserving surgery may help to decrease racial disparities in care.
C1 [Keating, Nancy L.] Brigham & Womens Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02115 USA.
[Keating, Nancy L.; Kouri, Elena; He, Yulei] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Weeks, Jane C.; Winer, Eric P.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA.
RP Keating, NL (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA.
EM keating@hcp.med.harvard.edu
FU Cure Foundation
FX Supported by the Susan G. Komen for the Cure Foundation.
NR 44
TC 43
Z9 43
U1 0
U2 2
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 JUL
PY 2009
VL 47
IS 7
BP 765
EP 773
PG 9
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 463VZ
UT WOS:000267462400008
PM 19536008
ER
PT J
AU Shugarman, LR
Mack, K
Sorbero, MES
Tian, HJ
Jain, AK
Ashwood, JS
Asch, SM
AF Shugarman, Lisa R.
Mack, Katherine
Sorbero, Melony E. S.
Tian, Haijun
Jain, Arvind K.
Ashwood, J. Scott
Asch, Steven M.
TI Race and Sex Differences in the Receipt of Timely and Appropriate Lung
Cancer Treatment
SO MEDICAL CARE
LA English
DT Article
DE Medicare; lung cancer; SEER program; treatment; sex differences; race
differences; disparities
ID AFRICAN-AMERICAN PATIENTS; SEER-MEDICARE DATA; LEUKEMIA GROUP-B;
QUALITY-OF-LIFE; SURGICAL RESECTION; SURVIVAL; DISPARITIES; GENDER;
CARE; CHEMOTHERAPY
AB Background: Previous research suggests that disparities in non-small-cell lung cancer (NSCLC) survival can be explained in part by disparities in the receipt of cancer treatment. Few studies, however, have considered race and sex disparities in the timing and appropriateness of treatment across stages of diagnosis.
Objective: To evaluate the relationship of sex and race with the receipt of timely and clinically appropriate NSCLC treatment for each stage of diagnosis.
Method: Surveillance Epidemiology and End Result data linked to Medicare claims for beneficiaries diagnosed with NSCLC between 1995 and 1999 were used to evaluate the relationship between race and sex with timely and appropriate NSCLC treatment while controlling for other demographic characteristics, comorbidities, socioeconomic status, and provider supply (N = 22,145).
Results: Overall adjusted rates of timely and appropriate treatment are 37.2%, 58.1%, and 29.2% for Medicare beneficiaries diagnosed with stage I or 11, 111, and IV NSCLC, respectively. Among stage I or 11 patients, women were 25% less likely to receive timely Surgical resection relative to men, and blacks were 66% less likely to receive timely and appropriate treatment than whites. Black men were least likely to receive resection (22.2% compared with 43.7% for white men). Blacks were 34% less likely to receive timely surgery, chemotherapy, or radiation for stage III disease and were 51% less likely to receive chemotherapy in a timely fashion for stage IV disease relative to whites.
Conclusion: Significant variations in appropriate timely treatment were found within and across stages of diagnosis, confirming that sex and race differences in NSCLC treatment exist.
C1 [Shugarman, Lisa R.; Mack, Katherine] RAND Corp, Santa Monica, CA 90407 USA.
[Sorbero, Melony E. S.; Ashwood, J. Scott] RAND Corp, Pittsburgh, PA USA.
[Tian, Haijun] MS Hlth, Woodland Hills, CA USA.
[Jain, Arvind K.] RAND Corp, Arlington, VA USA.
[Asch, Steven M.] Univ Calif Los Angeles, David Geffen Sch Med, RAND Corp, Vet Adm Greater Los Angeles Healthcare Syst, Santa Monica, CA USA.
RP Shugarman, LR (reprint author), RAND Corp, 1776 Main St,POB 2138, Santa Monica, CA 90407 USA.
EM lisas@rand.org
FU Health Resources and Services Administration (HRSA) Office of Rural
Health Policy [R04-RH03596-01-00]
FX Supported by the Health Resources and Services Administration (HRSA)
Office of Rural Health Policy (R04-RH03596-01-00).
NR 47
TC 41
Z9 41
U1 2
U2 2
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 JUL
PY 2009
VL 47
IS 7
BP 774
EP 781
PG 8
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 463VZ
UT WOS:000267462400009
PM 19536007
ER
PT J
AU Iwashyna, TJ
Christie, JD
Moody, J
Kahn, JM
Asch, DA
AF Iwashyna, Theodore J.
Christie, Jason D.
Moody, James
Kahn, Jeremy M.
Asch, David A.
TI The Structure of Critical Care Transfer Networks
SO MEDICAL CARE
LA English
DT Article
DE networks; critical care; regionalization; Medicare
ID ACUTE MYOCARDIAL-INFARCTION; PERCUTANEOUS CORONARY INTERVENTIONS;
UNITED-STATES; INTENSIVE-CARE; PRIMARY ANGIOPLASTY; HOSPITAL VOLUME;
SOCIAL NETWORK; OUTCOMES; MORTALITY; CENTRALITY
AB Rationale: Moving patients from low-performing hospitals to high-performing hospitals may improve patient outcomes. These transfers may be particularly important in critical care, where small relative improvements can yield substantial absolute changes in survival.
Objective: To characterize the existing critical care network in terms of the pattern of transfers.
Methods: In a retrospective cohort study, the nationwide 2005 Medicare fee-for-service claims were used to identify the interhospital transfer of critically ill patients, defined as instances where patients used critical care services in 2 temporally adjacent hospitalizations.
Measurements: We Measured the characteristics of the interhospital transfer network and the extent to which intensive care unit patients are referred to each hospital in that network-a continuous quantitative measure at the hospital-level known as centrality. We evaluated associations between hospital centrality and organizational, medical, surgical, and radiologic capabilities.
Results: There were 47,820 transfers of critically ill patients among 3308 hospitals. 4.5% of all critical care stays of any length involved an interhospital critical care transfer. Hospitals transferred out to a mean of 4.4 other hospitals. More central hospital positions were associated with multiple indicators of increased capability. Hospital characteristics explained 40.7% of the variance in hospitals' centrality.
Conclusions: Critical care transfers are common, and traverse an informal but structured network. The centrality of a hospital is associated with increased capability in delivery of services, suggesting that existing transfers generally direct patients toward better resourced hospitals. Studies of this network promise further improvements in patient outcomes and efficiency of care.
C1 [Iwashyna, Theodore J.] Univ Michigan, Dept Med, Div Pulm & Crit Care, Ann Arbor, MI 48109 USA.
[Iwashyna, Theodore J.; Kahn, Jeremy M.; Asch, David A.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA.
[Christie, Jason D.; Kahn, Jeremy M.] Hosp Univ Penn, Dept Med, Div Pulm Allergy & Crit Care, Philadelphia, PA 19104 USA.
[Christie, Jason D.; Kahn, Jeremy M.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Moody, James] Duke Univ, Dept Sociol, Durham, NC 27706 USA.
[Asch, David A.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA.
RP Iwashyna, TJ (reprint author), 3A23 300 NIB,SPC 5419,300 N Ingalls Bldg, Ann Arbor, MI 48109 USA.
EM tiwashyna@umich.edu
OI Iwashyna, Theodore/0000-0002-4226-9310
FU NIH [HL07891-09, K08 HL09 1249]; ATS Fellows Career Development Award
FX Supported in part by NIH grants HL07891-09 and K08 HL09 1249 and an ATS
Fellows Career Development Award.
NR 49
TC 64
Z9 64
U1 0
U2 4
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 JUL
PY 2009
VL 47
IS 7
BP 787
EP 793
PG 7
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 463VZ
UT WOS:000267462400011
PM 19536030
ER
PT J
AU Barnett, PG
AF Barnett, Paul G.
TI An Improved Set of Standards for Finding Cost for Cost-Effectiveness
Analysis
SO MEDICAL CARE
LA English
DT Article
DE cost-benefit analysis; costs and cost analysis/methods; hospital costs;
hospital charges; research design
ID ECONOMIC EVALUATIONS; HEALTH-CARE; METHODOLOGIC EVALUATION;
CLINICAL-TRIALS; TASK-FORCE; QUALITY; HOSPITALS; CHARGES
AB Background: Guidelines have helped standardize methods of cost-effectiveness analysis, allowing different interventions to be compared and enhancing the generalizability of study findings. There is agreement that all relevant services be valued from the societal perspective using a long-term time horizon and that more exact methods be used to cost services most affected by the Study intervention. Guidelines are not specific enough with respect to costing methods, however.
Method: The literature was reviewed to identify the problems associated with the 4 principal methods of cost determination.
Findings: Microcosting requires direct measurement and is ordinarily reserved to cost novel interventions. Analysts should include nonwage labor cost, person-level and institutional overhead, and the cost of development, set-up activities, supplies, space, and screening. Activity-based cost systems have promise of finding accurate costs of all services provided, but are not widely adopted. Quality must be evaluated and the generalizability of cost estimates to other settings must be considered. Administrative cost estimates, chiefly cost-adjusted charges, are widely used, but the analyst must consider items excluded from the available system. Gross costing methods determine quantity of services used and employ a unit cost. If the intervention will affect the characteristics of a service, the method should not assume that the service is homogeneous.
Conclusions: Questions are posed for future reviews of the quality of costing methods. The analyst must avoid inappropriate assumptions, especially those that bias the analysis by exclusion of costs that are affected by the intervention under study.
C1 [Barnett, Paul G.] US Dept Vet Affairs, Hlth Econ Resource Ctr, Stanford, CA USA.
[Barnett, Paul G.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA.
RP Barnett, PG (reprint author), Hlth Econ Resource Ctr, 795 Willow Rd 152,Menlo Pk, Menlo Pk, CA 94025 USA.
EM paul.barnett@va.gov
FU US Department of Veterans Affairs Health Services Research and
Development Service [ECN-99-017]; VA Cooperative Studies Program
FX Supported by the US Department of Veterans Affairs Health Services
Research and Development Service (ECN-99-017) and the VA Cooperative
Studies Program.
NR 41
TC 32
Z9 34
U1 3
U2 9
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 JUL
PY 2009
VL 47
IS 7
BP S82
EP S88
PG 7
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 463WA
UT WOS:000267462500014
PM 19536018
ER
PT J
AU Yabroff, KR
Warren, JL
Schrag, D
Mariotto, A
Meekins, A
Topor, M
Brown, ML
AF Yabroff, K. Robin
Warren, Joan L.
Schrag, Deborah
Mariotto, Angela
Meekins, Angela
Topor, Marie
Brown, Martin L.
TI Comparison of Approaches for Estimating Incidence Costs of Care for
Colorectal Cancer Patients
SO MEDICAL CARE
LA English
DT Article
DE health care costs; health services research; cost and cost analysis;
neoplasms; medicare; SEER program
ID STAGE BREAST-CANCER; SEER-MEDICARE DATA; UNITED-STATES; ENROLLEES;
DIAGNOSIS; WOMEN
AB Background: Estimates of the costs of medical care vary across patient populations, data sources, and methods. The objective of this study was to compare 3 approaches for estimating the incidence costs of colorectal cancer (CRC) care using similar patient populations, but different data sources and methods.
Methods: We used 2 data sources, linked SEER-Medicare and Medicare claims alone, to identify newly diagnosed CRC patients aged 65 and older and estimated their healthcare costs during the observation period, 1998 to 2002. Controls were matched by sex, age-group, and geographic location. We compared mean net costs, measured as the difference in total cost between cases and controls, for: (1) a SEER-Medicare cohort, (2) a Medicare claims alone cohort, and (3) a modeled phase of care approach using linked SEER-Medicare data. The SEER-Medicare cohort approach was considered the reference.
Results: We found considerable variability across approaches for estimating net costs of care in CRC patients. In the first year after diagnosis, mean net costs were $32,648 (95% CI: $31,826 and $33,470) in the SEER-Medicare cohort. The other approaches understated mean net costs in year 1 by about 16%. Mean net 5-year costs of care were $37,227 (95% CI: $35,711 and $38,744) in the SEER-Medicare cohort, and $30,310 (95% CI: $25,894 and $34,726) in the claims only approach, with the largest difference in the 65 to 69 age group. Mean net 5-year costs of care were more similar to the reference in the modeled phase of care approach ($37,701 [range: $36,972 and $38,4461]). Differences from the SEER-Medicare cohort estimates reflect misclassification of prevalent cancer patients as newly diagnosed patients in the Medicare claims only approach, and differences in years of data and assumptions about comparison groups in the modeled phase of care approach.
Conclusions: CRC incidence cost estimates vary substantially depending on the strategy and data source for identifying newly diagnosed cancer patients and methods for estimating longitudinal costs. Our findings may inform estimation of costs for other cancers as well as other diseases.
C1 [Yabroff, K. Robin] NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Schrag, Deborah] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA.
[Meekins, Angela; Topor, Marie] Informat Management Serv Inc, Rockville, MD USA.
RP Yabroff, KR (reprint author), NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Execut Plaza N,Room 4005,6130 Execut Blvd,MSC 734, Bethesda, MD 20892 USA.
EM yabroffr@mail.nih.gov
NR 27
TC 31
Z9 32
U1 2
U2 4
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 JUL
PY 2009
VL 47
IS 7
BP S56
EP S63
PG 8
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 463WA
UT WOS:000267462500010
PM 19536010
ER
PT J
AU Yabroff, KR
Warren, JL
Banthin, J
Schrag, D
Mariotto, A
Lawrence, W
Meekins, A
Topor, M
Brown, ML
AF Yabroff, K. Robin
Warren, Joan L.
Banthin, Jessica
Schrag, Deborah
Mariotto, Angela
Lawrence, William
Meekins, Angela
Topor, Marie
Brown, Martin L.
TI Comparison of Approaches for Estimating Prevalence Costs of Care for
Cancer Patients What Is the Impact of Data Source?
SO MEDICAL CARE
LA English
DT Article
DE health care costs; health services research; cost and cost analysis;
colorectal neoplasms; Medicare; SEER program; MEPS
ID SEER-MEDICARE DATA; UNITED-STATES; LIFE
AB Background: National prevalence costs of medical care can be key inputs in health policy decisions. Cost estimates vary across data sources, patient populations, and methods, however, the objective of this study was to compare 3 approaches for estimating the prevalence costs of colorectal cancer (CRC) care using different data sources, but similar patient populations and methods.
Methods: We identified prevalent CRC patients aged 65 and older from: (1) linked Surveillance Epidemiology and End Results (SEER) registry-Medicare data, (2) Medicare claims only, and (3) the Medical Expenditure Panel Survey (MEPS). Controls were matched by sex, age-group, and geographic location. Mean per person total and net costs, measured as the difference between patients and controls, were compared for each approach during a similar observation period. The SEER-Medicare approach was our reference, and we evaluated the impact of patient selection criteria with sensitivity analyses. Aggregate prevalence estimates were also compared.
Results: We found considerable variability across the different approaches to estimating prevalence costs of CRC. Mean net annual per person estimates in the SEER-Medicare reference were $5341 (95% CI: $5243, $5439), compared with $8736 (95% CI: $8203, $9269) for the Medicare claims only and $11,614 (95% CI: $7566, $15,663) for the MEPS. Aggregate national estimates of net prevalence costs of CRC in 2004 ranged from $4524 million, using the SEER-Medicare approach, to $9629 million, using the MEPS approach. Estimates varied by data source based on the payors included and identification of prevalent CRC patients.
Conclusions: CRC prevalence cost estimates vary substantially depending on the data sources. Our findings have implications for estimating prevalence costs for other cancers and other diseases without registry systems that can be used to identify newly diagnosed individuals as well as those diagnosed less recently.
C1 [Yabroff, K. Robin; Warren, Joan L.; Mariotto, Angela; Brown, Martin L.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Banthin, Jessica; Lawrence, William] Agcy Healthcare Res & Qual, Rockville, MD USA.
[Schrag, Deborah] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
[Schrag, Deborah] Harvard Univ, Sch Med, Boston, MA USA.
[Meekins, Angela; Topor, Marie] Informat Management Serv Inc, Rockville, MD USA.
RP Yabroff, KR (reprint author), Appl Res Program, Hlth Serv & Econ Branch, Execut Plaza N,Room 4005,6130 Execut Blvd,MSC 734, Bethesda, MD 20892 USA.
EM yabroffr@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 20
TC 35
Z9 36
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 JUL
PY 2009
VL 47
IS 7
BP S64
EP S69
PG 6
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 463WA
UT WOS:000267462500011
PM 19536016
ER
PT J
AU Sepucha, KR
Ozanne, EM
Partridge, AH
Moy, B
AF Sepucha, Karen R.
Ozanne, Elissa M.
Partridge, Ann H.
Moy, Beverly
TI Is There a Role for Decision Aids in Advanced Breast Cancer?
SO MEDICAL DECISION MAKING
LA English
DT Article; Proceedings Paper
CT 29th Annual Meeting of the Society-for-Medical-Decision-Making
CY OCT 20-24, 2007
CL Pittsburgh, PA
SP Soc Med Decis Making
DE decision making; metastatic breast cancer; decision aids
ID CELL LUNG-CANCER; TERM-FOLLOW-UP; 1ST-LINE CHEMOTHERAPY; MULTICENTER
TRIAL; PREFERENCES; DOXORUBICIN; CRITERIA; WOMEN; CARE; CYCLOPHOSPHAMIDE
AB Background. A diagnosis of metastatic breast cancer (BC) forces patients and providers to make difficult treatment decisions. Objective. To pilot test a decision aid (DA) for advanced BC. Design. Pretest, posttest study. Setting. Two academic cancer centers in Boston, Massachusetts. Patients. Fifty patients diagnosed with advanced BC. Intervention. A patient DA that consisted of a 30-minute DVD and booklet. Measurements. Patients were surveyed at baseline, after the intervention, and at 3 months. Measures included use and acceptability of DA, distress, treatment goals, and preference for and actual participation in decisions. Physicians were surveyed at baseline and 3 months. Measures included treatment goals, assessment of patients' experience with treatments, and patients' preference for and actual participation in decisions. Results. Thirty-two patients (64%) enrolled and completed the baseline survey, 30 completed the postvideo survey, and 25 completed the 3-month survey. The DA was acceptable and did not increase distress. The majority desired to share decision making with their doctor. Only 38% achieved their desired level of participation. At baseline, agreement between patients and providers on the main goal of treatment (lengthen life v. relieve symptoms) was 50% (kappa = -0.045, P = 0.71), and at 3 months it was 74% (kappa = 0.125, P = 0.48). Conclusions. It is feasible to perform a clinical trial of a DA with advanced BC patients. Most participants wanted to participate in decisions about their care and found the DA acceptable. This study highlights several issues in developing and implementing DAs in this vulnerable population facing complex decisions.
C1 [Sepucha, Karen R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hlth Decis Res Unit, Boston, MA 02114 USA.
[Ozanne, Elissa M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA 02114 USA.
[Partridge, Ann H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02114 USA.
[Moy, Beverly] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA.
RP Sepucha, KR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hlth Decis Res Unit, 50 Staniford St,Suite 936, Boston, MA 02114 USA.
EM ksepucha@partners.org
NR 38
TC 15
Z9 15
U1 0
U2 3
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0272-989X
J9 MED DECIS MAKING
JI Med. Decis. Mak.
PD JUL
PY 2009
VL 29
IS 4
BP 475
EP 482
DI 10.1177/0272989X09333124
PG 8
WC Health Care Sciences & Services; Medical Informatics
SC Health Care Sciences & Services; Medical Informatics
GA 474NP
UT WOS:000268291200008
PM 19329775
ER
PT J
AU Daartz, J
Engelsman, M
Paganetti, H
Bussiere, MR
AF Daartz, J.
Engelsman, M.
Paganetti, Harald
Bussiere, M. R.
TI Field size dependence of the output factor in passively scattered proton
therapy: Influence of range, modulation, air gap, and machine settings
SO MEDICAL PHYSICS
LA English
DT Article
DE biomedical measurement; dosimetry; phantoms; radiation therapy
ID COLLIMATOR SCATTER; BEAMS
AB At the Francis H. Burr Proton Therapy Center field specific output factors (i.e., dose per monitor unit) for patient treatments were modeled for all beamlines (two gantries, fixed stereotactic, and fixed eye beamline). The authors evaluated the accuracy of dose calculation and output model for small fields. Measurements in a water phantom were performed in three of our beamlines quantifying the dependency of the output factor on the field size for a variety of proton ranges. The influence of snout size, air gap, modulation, and second scatterer was investigated. The impact of field size on output depends strongly on the depth of interest. The air gap has a notable influence on small field outputs. A field size specific correction factor to the output is necessary if the latter was modeled or measured without the custom hardware in place. The output was shown to be field size dependent even for large fields, indicating an effect beyond charged particle disequilibrium caused by lateral scatter.
C1 [Daartz, J.; Engelsman, M.; Paganetti, Harald; Bussiere, M. R.] Massachusetts Gen Hosp, Dept Radiat Oncol, Francis H Burr Proton Therapy Ctr, Boston, MA 02114 USA.
[Daartz, J.] German Canc Res Ctr, Dept Med Phys Radiat Oncol, D-69120 Heidelberg, Germany.
RP Daartz, J (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Francis H Burr Proton Therapy Ctr, Boston, MA 02114 USA.
EM jdaartz@partners.org
NR 8
TC 15
Z9 15
U1 2
U2 8
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 JUL
PY 2009
VL 36
IS 7
BP 3205
EP 3210
DI 10.1118/1.3152111
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 463KW
UT WOS:000267431800037
PM 19673219
ER
PT J
AU Keane, MM
Martin, E
Verfaellie, M
AF Keane, Margaret M.
Martin, Elizabeth
Verfaellie, Mieke
TI Performance benefits and costs in forced choice perceptual
identification in amnesia: Effects of prior exposure and word frequency
SO MEMORY & COGNITION
LA English
DT Article
ID IMPLICIT MEMORY TASKS; COUNTER MODEL; ENHANCED DISCRIMINABILITY;
EXPLICIT MEMORY; BIAS; REPETITION; SYSTEMS
AB Accuracy in identifying a perceptually degraded word (e.g., stake) can be either enhanced by recent exposure to the same stimulus or reduced by recent exposure to a similar stimulus (e.g., stare). In the present study, we explored the mechanisms underlying these benefits and costs by examining the performance of amnesic and control groups in a forced choice perceptual identification (FCPI) task in which briefly flashed words (that were identical to studied words, similar to studied words, or new) had to be identified, and two response choices were provided that differed from each other by one letter. Control participants showed a performance benefit and cost in FCPI with both high- and low-frequency words. Amnesic participants showed a benefit (but no cost) with high-frequency words and a benefit and a cost with low-frequency words. The benefit/cost pattern with low-frequency words in amnesia was obtained even when the to-be-identified stimulus in the FCPI task was eliminated (Experiment 2), suggesting that this effect was driven by processes operating at the level of the response choices. Our findings suggest that implicit memory effects in FCPI reflect the operation of multiple mechanisms, the relative contributions of which may vary with the frequency of the test stimuli. The results also highlight the need for caution in interpreting results from normal participants in the FCPI task, since those findings may reflect a contribution of explicit memory processes.
C1 [Keane, Margaret M.] Wellesley Coll, Dept Psychol, Wellesley, MA 02481 USA.
[Keane, Margaret M.; Martin, Elizabeth; Verfaellie, Mieke] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Keane, Margaret M.; Martin, Elizabeth; Verfaellie, Mieke] Boston VA Healthcare Syst, Boston, MA USA.
RP Keane, MM (reprint author), Wellesley Coll, Dept Psychol, Wellesley, MA 02481 USA.
EM mkeane@wellesley.edu
OI Verfaellie, Mieke/0000-0001-5535-4584
FU NIMH NIH HHS [R01 MH057681, R01 MH070830, R01 MH070830-04, MH70830,
MH57681]
NR 33
TC 1
Z9 1
U1 0
U2 0
PU PSYCHONOMIC SOC INC
PI AUSTIN
PA 1710 FORTVIEW RD, AUSTIN, TX 78704 USA
SN 0090-502X
J9 MEM COGNITION
JI Mem. Cogn.
PD JUL
PY 2009
VL 37
IS 5
BP 655
EP 666
DI 10.3758/MC.37.5.655
PG 12
WC Psychology, Experimental
SC Psychology
GA 457VO
UT WOS:000266962600012
PM 19487757
ER
PT J
AU Price, MD
Herndon, JH
AF Price, Mark D.
Herndon, James H.
TI Gender differences in osteoarthritis
SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY
LA English
DT Editorial Material
ID KNEE CARTILAGE DEFECTS; PATELLOFEMORAL JOINT; ARTICULAR-CARTILAGE; HIP
OSTEOARTHRITIS; RISK-FACTORS; PREVALENCE; WOMEN; PATTERNS; INJURY; MEN
C1 [Price, Mark D.; Herndon, James H.] Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA.
RP Price, MD (reprint author), Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA.
NR 23
TC 3
Z9 3
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1072-3714
J9 MENOPAUSE
JI Menopause-J. N. Am. Menopause Soc.
PD JUL-AUG
PY 2009
VL 16
IS 4
BP 624
EP 625
DI 10.1097/gme.0b013e3181a5c9e6
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 468RJ
UT WOS:000267837300003
PM 19384254
ER
PT J
AU Burnett-Bowie, SAM
AF Burnett-Bowie, Sherri-Ann M.
TI Vitamin D and fat: the chicken versus the egg
SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY
LA English
DT Editorial Material
ID D DEFICIENCY; 25-HYDROXYVITAMIN-D; POPULATION; COMPONENTS; WOMEN; RISK
C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
RP Burnett-Bowie, SAM (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
OI Burnett-Bowie, Sherri-Ann/0000-0002-0064-096X
NR 13
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1072-3714
J9 MENOPAUSE
JI Menopause-J. N. Am. Menopause Soc.
PD JUL-AUG
PY 2009
VL 16
IS 4
BP 637
EP 638
DI 10.1097/gme.0b013e3181aeebef
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 468RJ
UT WOS:000267837300008
PM 19546823
ER
PT J
AU Huang, AJ
Sawaya, GF
Vittinghoff, E
Lin, F
Grady, D
AF Huang, Alison J.
Sawaya, George F.
Vittinghoff, Eric
Lin, Feng
Grady, Deborah
TI Hot flushes, coronary heart disease, and hormone therapy in
postmenopausal women
SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY
LA English
DT Article
DE Hot flushes; Coronary heart disease; Hormone therapy; Menopause;
Estrogen
ID ESTROGEN PLUS PROGESTIN; CARDIOVASCULAR-DISEASE; MENOPAUSAL COMPLAINTS;
REPLACEMENT THERAPY; FLASHES; ASSOCIATION; HEALTH; RISK; POLYMORPHISMS;
SYMPTOMS
AB Objective: The aim of this study was to examine interactions between hot flushes, estrogen plus progestogen therapy (EPT), and coronary heart disease (CHD) events in postmenopausal women with CHD.
Methods: We analyzed data from the Heart and Estrogen/Progestin Replacement Study, a randomized, placebo-controlled trial of 0.625 mg conjugated equine estrogens plus 2.5 mg medroxyprogesterone acetate in 2,763 postmenopausal women with CHD. Hot flushes were assessed at baseline using self-administered questionnaires; women reporting bothersome hot flushes "some" to "all" of the time were considered to have clinically significant flushing. Cox regression models were used to examine the effect of EPT on risk of CHD events among women with and without significant flushing at baseline.
Results: The mean age of participants was 66.7 +/- 6.8 years, and 89% (n = 2,448) were white. Sixteen percent (n = 434) of participants reported clinically significant hot flushes at baseline. Among women with baseline flushing, EPT increased risk of CHD events nine-fold in the first year compared with placebo (hazard ratio = 9.01; 95% CI, 1.15-70.35); among women without baseline flushing, treatment did not significantly affect CHD event risk in the first year (hazard ratio = 1.32; 95% CI, 0.86-2.03; P = 0.07 for interaction of hot flushes with treatment). The trend toward differential effects of EPT on risk for CHD among women with and without baseline flushing did not persist after the first year of treatment.
Conclusions: Among older postmenopausal women with CHD, EPT may increase risk of CHD events substantially in the first year of treatment among women with clinically significant hot flushes but not among those without hot flushes.
C1 [Huang, Alison J.; Grady, Deborah] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Sawaya, George F.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA.
[Sawaya, George F.; Vittinghoff, Eric; Lin, Feng; Grady, Deborah] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Grady, Deborah] San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA USA.
RP Huang, AJ (reprint author), 1635 Divisadero St,Suite 600, San Francisco, CA 94115 USA.
EM ahuang@ucsfmed.org
FU Wyeth-Ayerst Research; National Institutes of Health (NIH); National
Center for Research Resources [KL2RR024130]
FX The Heart and Estrogen/Progestin Replacement Study was funded by
Wyeth-Ayerst Research, but Wyeth-Ayerst Research had no role in the
research described in this manuscript, including management, analysis,
or interpretation of the data, or preparation or revision of this
manuscript. This research was supported by National Institutes of Health
(NIH) and the National Center for Research Resources Grant KL2RR024130
to the University of California San Francisco Clinical and Translational
Science Institute.
NR 24
TC 46
Z9 46
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1072-3714
J9 MENOPAUSE
JI Menopause-J. N. Am. Menopause Soc.
PD JUL-AUG
PY 2009
VL 16
IS 4
BP 639
EP 643
DI 10.1097/gme.0b013e31819c11c4
PG 5
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 468RJ
UT WOS:000267837300009
PM 19325499
ER
PT J
AU Joffe, H
Soares, CN
Thurston, RC
White, DP
Cohen, LS
Hall, JE
AF Joffe, Hadine
Soares, Claudio N.
Thurston, Rebecca C.
White, David P.
Cohen, Lee S.
Hall, Janet E.
TI Depression is associated with worse objectively and subjectively
measured sleep, but not more frequent awakenings, in women with
vasomotor symptoms
SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY
LA English
DT Article
DE Vasomotor symptoms; Hot flashes; Sleep; Insomnia; Depression; Mood
ID MENOPAUSAL HOT FLASHES; DATA-ANALYSIS SOFTWARE; PERIMENOPAUSAL WOMEN;
POSTMENOPAUSAL WOMEN; WAKE ACTIVITY; PRIMARY-CARE; TRANSITION; INSOMNIA;
DISTURBANCE; ACTIGRAPHY
AB Objective: Depression occurs more commonly during the menopausal transition in women with vasomotor symptoms (VMS) than in those without, but most women with VMS do not develop depression. It has been hypothesized that VMS are associated with depression because VMS lead to repeated awakenings, which impair daytime well-being. We aimed to determine if objectively measured sleep and perceived sleep quality are worse in depressed women with VMS than in nondepressed women with VMS.
Methods: Objectively and subjectively measured sleep parameters were compared between 52 depressed women with VMS and 51 nondepressed controls with VMS. Actigraphic measures of objective sleep conducted in the home environment and subjective measures of sleep quality (Pittsburgh Sleep Questionnaire Index) were compared using linear regression models.
Results: On objective assessments, depressed women with VMS spent less time in bed (by 64.8 min; P < 0.001) and had shorter total sleep time (by 47.7 min; P = 0.008), longer sleep-onset latency (by 13.8 min; P = 0.03), and lower sleep efficiency (by 3.2 percentage points; P = 0.09), but did not awaken more or spend more time awake after sleep onset than nondepressed controls with VMS. Depressed women also reported worse sleep quality (mean Pittsburgh Sleep Questionnaire Index 12.0 vs 8.3; P < 0.001). Adjustment for VMS frequency and important demographic characteristics did not alter these associations.
Conclusions: Sleep quality and selected parameters of objectively measured sleep, but not sleep interruption, are worse in depressed than in nondepressed women with VMS. The type of sleep disturbance seen in depressed participants was not consistent with the etiology of depression secondary to VMS-associated awakenings.
C1 [Joffe, Hadine; Soares, Claudio N.; Cohen, Lee S.] Harvard Univ, Perinatal & Reprod Psychiat Program, Dept Psychiat, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA.
[Thurston, Rebecca C.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA.
[White, David P.] Brigham & Womens Hosp, Dept Med, Sleep Disorders Program, Boston, MA 02115 USA.
[Hall, Janet E.] Harvard Univ, Dept Med, Massachusetts Gen Hosp, Reprod Endocrine Unit,Med Sch, Boston, MA 02114 USA.
RP Joffe, H (reprint author), Harvard Univ, Perinatal & Reprod Psychiat Program, Dept Psychiat, Massachusetts Gen Hosp,Med Sch, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA.
EM hjoffe@partners.org
FU National Institute of Mental Health [K23 MH066978]; Susan G. Komen
Breast Cancer Foundation Award; GlaxoSmithKline
FX This work was supported in part by National Institute of Mental Health
grant K23 MH066978, a Susan G. Komen Breast Cancer Foundation Award, and
GlaxoSmithKline.
NR 55
TC 40
Z9 40
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1072-3714
J9 MENOPAUSE
JI Menopause-J. N. Am. Menopause Soc.
PD JUL-AUG
PY 2009
VL 16
IS 4
BP 671
EP 679
DI 10.1097/gme.0b013e3181957377
PG 9
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 468RJ
UT WOS:000267837300014
PM 19197217
ER
PT J
AU Nagrath, D
Xu, HZ
Tanimura, Y
Zuo, RJ
Berthiaume, F
Avila, M
Yarmush, R
Yarmush, ML
AF Nagrath, Deepak
Xu, Hongzhi
Tanimura, Yoko
Zuo, Rongjun
Berthiaume, Francois
Avila, Marco
Yarmush, Rubin
Yarmush, Martin L.
TI Metabolic preconditioning of donor organs: Defatting fatty livers by
normothermic perfusion ex vivo
SO METABOLIC ENGINEERING
LA English
DT Article
DE Nuclear receptors; Normothermic perfusion; Hepatocytes; Steatosis; Liver
transplantation
ID ISCHEMIA-REPERFUSION INJURY; PPAR-DELTA AGONIST; GENE-EXPRESSION;
RAT-LIVER; TRIACYLGLYCEROL HYDROLASE; LIPID-METABOLISM; WARM ISCHEMIA;
MUSCLE-CELLS; IN-VIVO; TRANSPLANTATION
AB Fatty liver is a significant risk factor for liver transplantation, and accounts for nearly half of the livers rejected from the donor pool. We hypothesized that metabolic preconditioning via ex vivo perfusion of the liver graft can reduce fat content and increase post-transplant survival to an acceptable range. We describe a perfusate medium containing agents that promote the defatting of hepatocytes and explanted livers. Defatting agents were screened on cultured hepatocytes made fatty by pre-incubation with fatty acids. The most effective agents were then used on fatty livers. Fatty livers were isolated from obese Zucker rats and normothermically perfused with medium containing a combination of defatting agents. This combination decreased the intracellular lipid content of cultured hepatocytes by 35% over 24h, and of perfused livers by 50% over 3h. Metabolite analysis suggests that the defatting cocktail upregulated both lipid oxidation and export. Furthermore, gene expression analysis for several enzymes and transcription factors involved in fatty acid oxidation and triglyceride clearance were elevated. We conclude that a cocktail of defatting agents can be used to rapidly clear excess lipid storage in fatty livers, thus providing a new means to recondition donor livers deemed unacceptable or marginally acceptable for transplantation. (C) 2009 Elsevier Inc. All rights reserved.
C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med Surg Serv, Boston, MA 02114 USA.
Shriners Hosp Children, Boston, MA 02114 USA.
RP Yarmush, ML (reprint author), Rice Univ, Houston, TX 77251 USA.
EM ireis@sbi.org
OI Nagrath, Deepak/0000-0002-8999-2282
FU National Institutes of Health [R01DK059766, R01DK43371, P41EB002503];
Shriners Hospitals for Children
FX Financial support: This work was partially supported by the National
Institutes of Health Grant nos. R01DK059766, R01DK43371, P41EB002503,
and the Shriners Hospitals for Children.
NR 52
TC 27
Z9 30
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 1096-7176
J9 METAB ENG
JI Metab. Eng.
PD JUL-SEP
PY 2009
VL 11
IS 4-5
BP 274
EP 283
DI 10.1016/j.ymben.2009.05.005
PG 10
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA 487JY
UT WOS:000269270700007
PM 19508897
ER
PT J
AU Nosho, K
Shima, K
Irahara, N
Kure, S
Firestein, R
Baba, Y
Toyoda, S
Chen, L
Hazra, A
Giovannucci, EL
Fuchs, CS
Ogino, S
AF Nosho, Katsuhiko
Shima, Kaori
Irahara, Natsumi
Kure, Shoko
Firestein, Ron
Baba, Yoshifumi
Toyoda, Saori
Chen, Li
Hazra, Aditi
Giovannucci, Edward L.
Fuchs, Charles S.
Ogino, Shuji
TI SIRT1 histone deacetylase expression is associated with microsatellite
instability and CpG island methylator phenotype in colorectal cancer
SO MODERN PATHOLOGY
LA English
DT Article
DE colon cancer; epigenetics; sir2; HDAC; sirtuin; acetylation
ID POPULATION-BASED SAMPLE; COLON-CANCER; LINE-1 HYPOMETHYLATION; CALORIE
RESTRICTION; REGULATES SIRT1; BRAF MUTATION; CELL-SURVIVAL; CIMP;
COHORT; P53
AB The class III histone deacetylase SIRT1 (sir2) is important in epigenetic gene silencing. Inhibition of SIRT1 reactivates silenced genes, suggesting a possible therapeutic approach of targeted reversal of aberrantly silenced genes. In addition, SIRT1 may be involved in the well-known link between obesity, cellular energy balance and cancer. However, a comprehensive study of SIRT1 using human cancer tissue with clinical outcome data is currently lacking, and its prognostic significance is uncertain. Using the database of 485 colorectal cancers in two independent prospective cohort studies, we detected SIRT1 overexpression in 180 (37%) tumors by immunohistochemistry. We examined its relationship to the CpG island methylator phenotype (CIMP), related molecular events, clinical features including body mass index, and patient survival. We quantified DNA methylation in eight CIMP-specific promoters (CACNA1G, CDKN2A, CRABP1, IGF2, MLH1, NEUROG1, RUNX3, and SOCS1) and eight other CpG islands (CHFR, HIC1, IGFBP3, MGMT, MINT1, MINT31, p14, and WRN) by MethyLight. SIRT1 overexpression was associated with CIMP-high (>= 6 of 8 methylated CIMP-specific promoters, P = 0.002) and microsatellite instability (MSI)-high phenotype (P<0.0001). In both univariate and multivariate analyses, SIRT1 overexpression was significantly associated with the CIMP-high MSI-high phenotype (multivariate odds ratio, 3.20; 95% confidence interval, 1.35-7.59; P = 0.008). In addition, mucinous component (P = 0.01), high tumor grade (P = 0.02), and fatty acid synthase overexpression (P = 0.04) were significantly associated with SIRT positivity in multivariate analysis. SIRT1 was not significantly related with age, sex, tumor location, stage, signet ring cells, cyclooxygenase-2 (COX-2), LINE-1 hypomethylation, KRAS, BRAF, BMI, PIK3CA, HDAC, p53, beta-catenin, COX-2, or patient prognosis. In conclusion, SIRT1 expression is associated with CIMP-high MSI-high colon cancer, suggesting involvement of SIRT1 in gene silencing in this unique tumor subtype. Modern Pathology (2009) 22, 922-932; doi: 10.1038/modpathol.2009.49; published online 8 May 2009
C1 [Ogino, Shuji] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol,Ctr Mol Oncol Pathol, Boston, MA 02115 USA.
[Nosho, Katsuhiko; Shima, Kaori; Irahara, Natsumi; Kure, Shoko; Firestein, Ron; Baba, Yoshifumi; Toyoda, Saori; Chen, Li; Hazra, Aditi; Giovannucci, Edward L.; Fuchs, Charles S.; Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Hazra, Aditi; Giovannucci, Edward L.; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Hazra, Aditi; Giovannucci, Edward L.; Ogino, Shuji] Harvard Univ, Sch Med, Dept Epidemiol, Boston, MA 02115 USA.
[Nosho, Katsuhiko; Shima, Kaori; Irahara, Natsumi; Kure, Shoko; Firestein, Ron; Baba, Yoshifumi; Toyoda, Saori; Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Ogino, S (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol,Ctr Mol Oncol Pathol, 75 Francis St,44 Binney St,Room JF-215C, Boston, MA 02115 USA.
EM shuji_ogino@dfci.harvard.edu
FU US National Institute of Health (NIH) [P01 CA87969, P01 CA55075, P50
CA127003, K07 CA122826]; Bennett Family Fund; Entertainment Industry
Foundation through the National Colorectal Cancer Research Alliance
(NCCRA); Japan Society for Promotion of Science
FX We thank the Nurses' Health Study and Health Professionals Follow-up
Study cohort participants who generously agreed to provide us with
biological specimens and information through responses to
questionnaires. We also thank Frank Speizer, Walter Willett, Susan
Hankinson, Graham Colditz, Meir Stampfer, and many other staff members
who implemented and have maintained the cohort studies. This work was
supported by US National Institute of Health (NIH) grants P01 CA87969,
P01 CA55075, P50 CA127003 (to CSF) and K07 CA122826 (to SO), and in part
by grants from the Bennett Family Fund and from the Entertainment
Industry Foundation through the National Colorectal Cancer Research
Alliance (NCCRA). KN was supported by a fellowship grant from the Japan
Society for Promotion of Science. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of NCI or NIH. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
paper.
NR 58
TC 59
Z9 61
U1 2
U2 11
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD JUL
PY 2009
VL 22
IS 7
BP 922
EP 932
DI 10.1038/modpathol.2009.49
PG 11
WC Pathology
SC Pathology
GA 465ID
UT WOS:000267575400009
PM 19430421
ER
PT J
AU Erickson, LA
Letts, GA
Shahy, SM
Shackelton, JB
Duncan, LM
AF Erickson, Lori A.
Letts, Gary A.
Shahy, Sonali M.
Shackelton, Jeffrey B.
Duncan, Lyn M.
TI TRPM1 (Melastatin-1/MLSN1) mRNA expression in Spitz nevi and nodular
melanomas
SO MODERN PATHOLOGY
LA English
DT Article
DE Spitz nevi; melanoma; TRPM1; melastatin; prognosis
ID CUTANEOUS MALIGNANT-MELANOMA; AMERICAN JOINT COMMITTEE; MELANOCYTIC
TUMORS; PROGNOSTIC MARKER; GENE; DIFFERENTIATION; MDA-7; PRODUCT; MART-1
AB The transient receptor potential cation channel, subfamily M, member 1 (TRPM1/Melastatin-1/MLSN-1) expression has been shown to have prognostic utility in the evaluation of primary cutaneous melanoma. We analyzed a series of spindled and epithelioid cell nevi (Spitz) and primary cutaneous nodular melanomas to determine whether the expression of TRPM1 mRNA may be useful in distinguishing between Spitz nevi and nodular melanomas and to further examine the patterns of TRPM1 mRNA expression in cutaneous melanocytic proliferations. Formalin-fixed, paraffin-embedded tissues from 95 Spitz nevi and 33 nodular melanomas were analyzed for the expression of TRPM1 mRNA by in situ hybridization using (35)S-labeled riboprobes. Ubiquitous melanocytic expression of TRPM1 mRNA was observed in 56 of 95 (59%) Spitz nevi and 4 of 33 (12%) nodular melanomas. Diffusely scattered loss of TRPM1 mRNA was identified in 38 of 95 (40%) Spitz nevi and 2 of 33 (6%) nodular melanomas. Regional loss of the TRPM1 mRNA expression by a significant subset of dermal tumor cells or a complete absence of TRPM1 expression by the dermal tumor was identified in 27 of 33 (82%) nodular melanomas, but only 1 of 95 (1%) Spitz nevi. These findings suggest that the pattern of TRPM1 mRNA expression may be helpful in the differentiation of Spitz nevi and nodular melanomas. Of the 16 patients who experienced metastasis, 15 (94%) had primary tumors that displayed reduced MLSN mRNA expression by all or a part of the dermal tumor. Modern Pathology (2009) 22, 969-976; doi: 10.1038/modpathol.2009.56; published online 24 April 2009
C1 [Duncan, Lyn M.] Massachusetts Gen Hosp, Dept Dermatopathol Unit, Dermatopathol Unit, Pathol Serv, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Duncan, LM (reprint author), Massachusetts Gen Hosp, Dept Dermatopathol Unit, Dermatopathol Unit, Pathol Serv, WRN827,55 Fruit St, Boston, MA 02114 USA.
EM duncan@helix.mgh.harvard.edu
NR 26
TC 13
Z9 13
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD JUL
PY 2009
VL 22
IS 7
BP 969
EP 976
DI 10.1038/modpathol.2009.56
PG 8
WC Pathology
SC Pathology
GA 465ID
UT WOS:000267575400014
PM 19396153
ER
PT J
AU Lisovsky, M
Dresser, K
Baker, S
Fisher, A
Woda, B
Banner, B
Lauwers, GY
AF Lisovsky, Mikhail
Dresser, Karen
Baker, Stephen
Fisher, Andrew
Woda, Bruce
Banner, Barbara
Lauwers, Gregory Y.
TI Cell polarity protein Lgl2 is lost or aberrantly localized in gastric
dysplasia and adenocarcinoma: an immunohistochemical study
SO MODERN PATHOLOGY
LA English
DT Article
DE gastric; dysplasia; Lgl2; cell polarity; adenocarcinoma
ID LETHAL GIANT LARVAE; EPITHELIAL DYSPLASIA; TUMOR SUPPRESSORS;
DROSOPHILA; CANCER; COMPLEX; APKC; CLASSIFICATION; ACTIVATION; HUGL-1
AB The diagnosis of gastric epithelial dysplasia, a precursor lesion of gastric adenocarcinoma, is hindered by interobserver variability and by its resemblance to regenerative changes. Loss of cell polarity, a histological feature of gastric epithelial dysplasia, may be difficult to ascertain, especially in the setting of inflammation or injury. A biomarker of cell polarity could be useful in diagnosis of dysplasia, but has not been reported. The Lethal giant larvae (lgl) gene controls apical-basal polarity of epithelial cells in Drosophila, and has properties of a tumor-suppressor gene. Two homologs, lgl1 and lgl2, are present in mammals and lgl2 mRNA is highly expressed in the stomach. The goal of our study was to test the hypothesis that Lgl2 protein expression and/or localization are disrupted in gastric epithelial dysplasia and adenocarcinoma. Routinely processed pathology specimens including 94 benign mucosae of digestive organs, in addition to 36 reactive gastropathy, 57 gastric epithelial dysplasia, and 77 gastric adenocarcinomas, were immunostained for Lgl2 protein. All normal, reactive, and chronically inflamed gastric epithelia showed basolateral Lgl2 staining. Normal esophageal, duodenal, colonic, biliary, and pancreatic duct mucosae, as well as gastric intestinal metaplasia, did not express Lgl2. All but one case each of gastric epithelial dysplasia and adenocarcinoma showed either complete loss of anti-Lgl2 immunoreactivity or diffuse, mostly weak, cytoplasmic staining. Complete loss of immunoreactivity was significantly more often observed in diffuse-type than in intestinal-type adenocarcinomas (79 vs 48%, respectively). Our data suggest that Lgl2 expression is either aberrantly localized or lost in gastric epithelial dysplasia and adenocarcinoma, whereas it is maintained in reactive gastric mucosa. We propose that Lgl2 may be a potential marker to rule out gastric epithelial dysplasia and adenocarcinoma in diagnostic specimens. However, the consistently negative anti-Lgl2 immunoreactivity seen in intestinal metaplasia does not allow differentiation of dysplasia from intestinal metaplasia with reactive change. Modern Pathology (2009) 22, 977-984; doi: 10.1038/modpathol.2009.68; published online 1 May 2009
C1 [Lisovsky, Mikhail; Lauwers, Gregory Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA.
[Lisovsky, Mikhail; Dresser, Karen; Fisher, Andrew; Woda, Bruce; Banner, Barbara] Univ Massachusetts, Sch Med, Dept Pathol, UMass Mem Med Ctr, Worcester, MA 01605 USA.
[Baker, Stephen] Univ Massachusetts, Sch Med, Biostat Unit, UMass Mem Med Ctr, Worcester, MA 01605 USA.
RP Lisovsky, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, 55 Fruit St,WRN 219, Boston, MA 02114 USA.
EM mlisovsky@partners.org
NR 28
TC 26
Z9 26
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD JUL
PY 2009
VL 22
IS 7
BP 977
EP 984
DI 10.1038/modpathol.2009.68
PG 8
WC Pathology
SC Pathology
GA 465ID
UT WOS:000267575400015
PM 19407852
ER
PT J
AU Dovey, M
Patton, EE
Bowman, T
North, T
Goessling, W
Zhou, Y
Zon, LI
AF Dovey, Michael
Patton, E. Elizabeth
Bowman, Teresa
North, Trista
Goessling, Wolfram
Zhou, Yi
Zon, Leonard I.
TI Topoisomerase II alpha Is Required for Embryonic Development and Liver
Regeneration in Zebrafish
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID RNA-POLYMERASE-II; CELL-CYCLE; CHROMATIN TEMPLATES; DNA TOPOISOMERASES;
NIH-3T3 CELLS; IN-VITRO; EXPRESSION; MUTANT; DECATENATION; INHIBITION
AB Topoisomerases solve the topological problems encountered by DNA throughout the lifetime of a cell. Topoisomerase II alpha, which is highly conserved among eukaryotes, untangles replicated chromosomes during mitosis and is absolutely required for cell viability. A homozygous lethal mutant, can4, was identified in a screen to identify genes important for cell proliferation in zebrafish by utilizing an antibody against a mitosis-specific marker, phospho-histone H3. Mutant embryos have a decrease in the number of proliferating cells and display increases in DNA content and apoptosis, as well as mitotic spindle defects. Positional cloning revealed that the genetic defect underlying these phenotypes was the result of a mutation in the zebrafish topoisomerase II alpha (top2a) gene. top2a was found to be required for decatenation but not for condensation in embryonic mitoses. In addition to being required for development, top2a was found to be a haploinsufficient regulator of adult liver regrowth in zebrafish. Regeneration analysis of other adult tissues, including fins, revealed no heterozygous phenotype. Our results confirm a conserved role for TOP2A in vertebrates as well as a dose-sensitive requirement for top2a in adults.
C1 [Zon, Leonard I.] Childrens Hosp Boston, Stem Cell Program & Hematol Oncol, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Harvard Stem Cell Inst, Howard Hughes Med Inst,Dana Farber Canc Inst, Boston, MA USA.
RP Zon, LI (reprint author), Childrens Hosp Boston, Stem Cell Program & Hematol Oncol, Karp Family Res Bldg Room 7211,1 Blackfan Circle, Boston, MA 02115 USA.
EM zon@enders.tch.harvard.edu
OI Goessling, Wolfram/0000-0001-9972-1569
FU NIH [5 R01 CA103846-04]; Howard Hughes Medical Institute
FX This work was supported by NIH 5 R01 CA103846-04. L.I.Z. is an
Investigator of the Howard Hughes Medical Institute.
NR 41
TC 16
Z9 17
U1 0
U2 1
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 JUL 1
PY 2009
VL 29
IS 13
BP 3746
EP 3753
DI 10.1128/MCB.01684-08
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 457ZK
UT WOS:000266978000025
PM 19380487
ER
PT J
AU Bodempudi, V
Yamoutpoor, F
Pan, WH
Dudek, AZ
Esfandyari, T
Piedra, M
Babovick-Vuksanovic, D
Woo, RA
Mautner, VF
Kluwe, L
Clapp, DW
DeVries, GH
Thomas, SL
Kurtz, A
Parada, LF
Farassati, F
AF Bodempudi, Vidya
Yamoutpoor, Farnaz
Pan, Weihong
Dudek, Arkadiusz Z.
Esfandyari, Tuba
Piedra, Mark
Babovick-Vuksanovic, Dusica
Woo, Richard A.
Mautner, Victor F.
Kluwe, Lan
Clapp, D. Wade
DeVries, George H.
Thomas, Stacey L.
Kurtz, Andreas
Parada, Luis F.
Farassati, Faris
TI Ral Overactivation in Malignant Peripheral Nerve Sheath Tumors
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID EPITHELIAL-MESENCHYMAL TRANSITION; GROWTH-FACTOR RECEPTOR;
NEUROFIBROMATOSIS TYPE-1; ONCOGENIC RAS; NF1 GENE; SIGNALING PATHWAY;
SCHWANN-CELLS; PROTEIN; CANCER; METASTASIS
AB Ras leads an important signaling pathway that is deregulated in neurofibromatosis type 1 and malignant peripheral nerve sheath tumor (MPNST). In this study, we show that overactivation of Ras and many of its downstream effectors occurred in only a fraction of MPNST cell lines. RalA, however, was overactivated in all MPNST cells and tumor samples compared to nontransformed Schwann cells. Silencing Ral or inhibiting it with a dominant-negative Ral (Ral S28N) caused a significant reduction in proliferation, invasiveness, and in vivo tumorigenicity of MPNST cells. Silencing Ral also reduced the expression of epithelial mesenchymal transition markers. Expression of the NF1-GTPase-related domain (NF1-GRD) diminished the levels of Ral activation, implicating a role for neurofibromin in regulating RalA activation. NF1-GRD treatment caused a significant decrease in proliferation, invasiveness, and cell cycle progression, but cell death increased. We propose Ral overactivation as a novel cell signaling abnormality in MPNST that leads to important biological outcomes with translational ramifications.
C1 [Esfandyari, Tuba; Farassati, Faris] Univ Kansas, Mol Med Lab, Sch Med, Dept Med, Kansas City, KS USA.
[Bodempudi, Vidya; Yamoutpoor, Farnaz; Pan, Weihong; Dudek, Arkadiusz Z.] Univ Minnesota, Minneapolis, MN USA.
[Piedra, Mark; Babovick-Vuksanovic, Dusica] Mayo Clin, Rochester, MN USA.
[Woo, Richard A.] So Illinois Univ, Springfield, IL USA.
[Mautner, Victor F.; Kluwe, Lan] Univ Hosp Eppendorf, Hamburg, Germany.
[Clapp, D. Wade] Indiana Univ, Sch Med, Indianapolis, IN USA.
[DeVries, George H.; Thomas, Stacey L.] VA Hosp, Res Serv, Hines, IL USA.
[Kurtz, Andreas] Massachusetts Gen Hosp, Charlestown, MA USA.
[Parada, Luis F.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
RP Farassati, F (reprint author), KUMC Mol Med Lab, 1000 Hixon,Mail Stop 4037,3901 Rainbow Blvd, Kansas City, KS 66160 USA.
EM ffarassati@kumc.edu
RI Parada, luis/B-9400-2014
FU Department of Defense-NF [NF050014]
FX This study was supported in part by Department of Defense-NF research
program grant NF050014 to F. F. We acknowledge the thoughtful advice and
analysis by R. L. Martuza and S. D. Rabkin. We appreciate the editorial
assistance of Michael J. Franklin, Martha Montello, and Amanda Wise.
NR 72
TC 22
Z9 23
U1 0
U2 0
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 JUL
PY 2009
VL 29
IS 14
BP 3964
EP 3974
DI 10.1128/MCB.01153-08
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 469ZA
UT WOS:000267939300013
PM 19414599
ER
PT J
AU Hoang, B
Benavides, A
Shi, YJ
Frost, P
Lichtenstein, A
AF Hoang, Bao
Benavides, Angelica
Shi, Yijiang
Frost, Patrick
Lichtenstein, Alan
TI Effect of autophagy on multiple myeloma cell viability
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Article
ID UNFOLDED PROTEIN RESPONSE; ENDOPLASMIC-RETICULUM STRESS; PROTEASOME
INHIBITOR PS-341; OVERCOMES DRUG-RESISTANCE; ISOLATED RAT HEPATOCYTES;
MOLECULAR-MECHANISMS; ANTIMYELOMA ACTIVITY; MAMMALIAN TARGET;
DEGRADATION; BORTEZOMIB
AB Because accumulation of potentially toxic malfolded protein may be extensive in immunoglobulin-producing multiple myeloma (MM) cells, we investigated the phenomenon of autophagy in myeloma, a physiologic process that can protect against malfolded protein under some circumstances. Autophagy in MM cell lines that express and secrete immunoglobulin and primary specimens was significantly increased by treatment with the endoplasmic reticulum stress-inducing agent thapsigargin, the mammalian target of rapamycin inhibitor rapamycin, and the proteasome inhibitor bortezomib. Inhibition of basal autophagy in these cell lines and primary cells by use of the inhibitors 3-methyladenine and chloroquine resulted in a cytotoxic effect that was associated with enhanced apoptosis. Use of small interfering RNA to knock down expression of beclin-1, a key protein required for autophagy, also inhibited viable recovery of MM cells. Because the data suggested that autophagy protected MM cell viability, we predicted that autophagy inhibitors would synergize with bortezomib for enhanced antimyeloma effects. However, the combination of these drugs resulted in an antagonistic response. In contrast, the autophagy inhibitor 3-methyladenine did synergize with thapsigargin for an enhanced cytotoxic response. These data suggest that autophagy inhibitors have therapeutic potential in myeloma but caution against combining such drugs with bortezomib. [Mol Cancer Ther 2009;8(7):1974-84]
C1 Univ Calif Los Angeles, Sch Med, Div Hematol Oncol, Dept Med,Greater Los Angeles Vet Affairs Healthca, Los Angeles, CA 90024 USA.
Jonsson Comprehens Canc Ctr, Los Angeles, CA 90034 USA.
RP Lichtenstein, A (reprint author), W Los Angeles Vet Affairs Hosp, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
EM alan.lichtenstein@med.va.gov
OI Frost, Patrick/0000-0003-3348-5983
FU NIH [RO1CA111448, KO1CA111623]; Multiple Myeloma Research Foundation;
Veteran's Administration
FX NIH grants RO1CA111448 and KO1CA111623, Multiple Myeloma Research
Foundation, and research funds of the Veteran's Administration.
NR 46
TC 67
Z9 70
U1 0
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1535-7163
J9 MOL CANCER THER
JI Mol. Cancer Ther.
PD JUL
PY 2009
VL 8
IS 7
BP 1974
EP 1984
DI 10.1158/1535-7163.MCT-08-1177
PG 11
WC Oncology
SC Oncology
GA 470UG
UT WOS:000268005700026
PM 19509276
ER
PT J
AU Sleat, DE
Ding, L
Wang, S
Zhao, CF
Wang, YH
Xin, WN
Zheng, HY
Moore, DF
Sims, KB
Lobel, P
AF Sleat, David E.
Ding, Lin
Wang, Shudan
Zhao, Caifeng
Wang, Yanhong
Xin, Winnie
Zheng, Haiyan
Moore, Dirk F.
Sims, Katherine B.
Lobel, Peter
TI Mass Spectrometry-based Protein Profiling to Determine the Cause of
Lysosomal Storage Diseases of Unknown Etiology
SO MOLECULAR & CELLULAR PROTEOMICS
LA English
DT Article
ID NEURONAL CEROID-LIPOFUSCINOSIS; SANFILIPPO-A-SYNDROME; SULFAMIDASE GENE;
SHOTGUN PROTEOMICS; MOLECULAR DEFECTS; IIIA SANFILIPPO; CLN5 MUTATION;
IDENTIFICATION; ONSET; GLYCOPROTEINS
AB Diagnosis of lysosomal storage diseases (LSDs) can be problematic in atypical cases where clinical phenotype may overlap with other genetically distinct disorders. In addition, LSDs may result from mutations in genes not yet implicated in disease. Thus, there are individuals that are diagnosed with apparent LSD based upon clinical criteria where the gene defect remains elusive. The objective of this study was to determine whether comparative proteomics approaches could provide useful insights into such cases. Most LSDs arise from mutations in genes encoding lysosomal proteins that contain mannose 6-phosphate, a carbohydrate modification that acts as a signal for intracellular targeting to the lysosome. We purified mannose 6-phosphorylated proteins by affinity chromatography and estimated relative abundance of individual proteins in the mixture by spectral counting of peptides detected by tandem mass spectrometry. Our rationale was that proteins that are decreased or absent in patients compared with controls could represent candidates for the primary defect, directing biochemical or genetics studies. On a survey of brain autopsy specimens from 23 patients with either confirmed or possible lysosomal disease, this approach identified or validated the genetic basis for disease in eight cases. These results indicate that this protein expression approach is useful for identifying defects in cases of undiagnosed lysosomal disease, and we demonstrated that it can be used with more accessible patient samples, e. g. cultured cells. Furthermore this approach was instrumental in the identification or validation of mutations in two lysosomal proteins, CLN5 and sulfamidase, in the adult form of neuronal ceroid lipofuscinosis. Molecular & Cellular Proteomics 8: 1708-1718, 2009.
C1 [Sleat, David E.; Ding, Lin; Zhao, Caifeng; Wang, Yanhong; Zheng, Haiyan; Lobel, Peter] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA.
[Sleat, David E.; Ding, Lin; Lobel, Peter] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Pharmacol, Piscataway, NJ 08854 USA.
[Moore, Dirk F.] Univ Med & Dent New Jersey, Sch Publ Hlth, Dept Biostat, Piscataway, NJ 08854 USA.
[Wang, Shudan] McGill Univ, Montreal, PQ H3A 2T5, Canada.
[Xin, Winnie; Sims, Katherine B.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
RP Sleat, DE (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Ctr Adv Biotechnol & Med, 679 Hoes Lane, Piscataway, NJ 08854 USA.
EM sleat@cabm.rutgers.edu
FU National Institutes of Health [DK054317, S10RR017992]; Batten Disease
Support and Research Association
FX This work was supported, in whole or in part, by National Institutes of
Health Grants DK054317 and S10RR017992 (to P. L.). This work was also
supported by a grant from the Batten Disease Support and Research
Association (to D. E. S.).
NR 39
TC 24
Z9 25
U1 1
U2 7
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 1535-9476
EI 1535-9484
J9 MOL CELL PROTEOMICS
JI Mol. Cell. Proteomics
PD JUL
PY 2009
VL 8
IS 7
BP 1708
EP 1718
DI 10.1074/mcp.M900122-MCP200
PG 11
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 470FJ
UT WOS:000267960300020
PM 19383612
ER
PT J
AU Tilly, JL
Telfer, EE
AF Tilly, Jonathan L.
Telfer, Evelyn E.
TI Purification of germline stem cells from adult mammalian ovaries: a step
closer towards control of the female biological clock?
SO MOLECULAR HUMAN REPRODUCTION
LA English
DT Editorial Material
DE germline stem cell; oogenesis; oocyte; ovary; menopause
ID BONE-MARROW; MENOPAUSAL TRANSITION; POSTNATAL OOGENESIS; MICE;
CHEMOTHERAPY; FERTILITY; FOLLICLES; OOCYTES; PROTEIN; EXPRESSION
AB For decades it was believed that a non-renewable pool of oocyte-containing follicles is established in female mammals at birth. This cornerstone of reproductive biology was challenged 5 years ago by a study reporting on the presence of mitotically-active germ cells in juvenile and adult mouse ovaries. Additional findings presented in this study and others that followed further suggested that mammals retain the capacity to generate oocytes during adulthood; however, isolation of oocyte-producing germline stem cells (GSC) as unequivocal proof of their existence remained elusive. This piece of information now appears to have been provided by Ji Wu and colleagues. In addition to showing that proliferative germ cells resembling male spermatogonial stem cells can be purified from neonatal or adult mouse ovaries and maintained in vitro for months, transplantation studies demonstrated that these cells generate oocytes in ovaries of chemotherapy-sterilized recipients that fertilize and produce viable offspring. Although these findings do not establish that oogenesis occurs in adult females under physiological conditions, they strongly support the existence of GSC in adult mouse ovaries. If equivalent cells can be found in human ovaries, stem cell-based rejuvenation of the oocyte reserve in ovaries on the verge of failure may one day be realized.
C1 [Tilly, Jonathan L.] Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Vincent Ctr Reprod Biol, Boston, MA 02114 USA.
[Tilly, Jonathan L.] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02114 USA.
[Telfer, Evelyn E.] Univ Edinburgh, Inst Cell Biol, Edinburgh EH9 3JR, Midlothian, Scotland.
RP Tilly, JL (reprint author), Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Vincent Ctr Reprod Biol, Boston, MA 02114 USA.
EM jtilly@partners.org; evelyn.telfer@ed.ac.uk
FU NIA NIH HHS [R01-AG024999, R37-AG012279]
NR 54
TC 43
Z9 44
U1 1
U2 18
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1360-9947
J9 MOL HUM REPROD
JI Mol. Hum. Reprod.
PD JUL
PY 2009
VL 15
IS 7
BP 393
EP 398
DI 10.1093/molehr/gap036
PG 6
WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
GA 460XM
UT WOS:000267225600001
PM 19509111
ER
PT J
AU Warren, HS
Elson, CM
Hayden, DL
Schoenfeld, DA
Cobb, JP
Maier, RV
Moldawer, LL
Moore, EE
Harbrecht, BG
Pelak, K
Cuschieri, J
Herndon, DN
Jeschke, MG
Finnerty, CC
Brownstein, BH
Hennessy, L
Mason, PH
Tompkins, RG
AF Warren, H. Shaw
Elson, Constance M.
Hayden, Douglas L.
Schoenfeld, David A.
Cobb, J. Perren
Maier, Ronald V.
Moldawer, Lyle L.
Moore, Ernest E.
Harbrecht, Brian G.
Pelak, Kimberly
Cuschieri, Joseph
Herndon, David N.
Jeschke, Marc G.
Finnerty, Celeste C.
Brownstein, Bernard H.
Hennessy, Laura
Mason, Philip H.
Tompkins, Ronald G.
CA Inflammation Host Response Injury
TI A Genomic Score Prognostic of Outcome in Trauma Patients
SO MOLECULAR MEDICINE
LA English
DT Article
ID MULTIPLE ORGAN FAILURE; INJURY SEVERITY SCORE; APACHE-II; VARIABILITY;
PREDICTORS; DISEASE; SYSTEM; CARE
AB Traumatic injuries frequently lead to infection, organ failure, and death. Health care providers rely on several injury scoring systems to quantify the extent of injury and to help predict clinical outcome. Physiological, anatomical, and clinical laboratory analytic scoring systems (Acute Physiology and Chronic Health Evaluation (APACHE), Injury Severity Score (ISS)) are utilized, with limited success, to predict outcome following injury. The recent development of techniques for measuring the expression level of all of a person's genes simultaneously may make it possible to develop an injury scoring system based on the degree of gene activation. We hypothesized that a peripheral blood leukocyte gene expression score could predict outcome, including multiple organ failure, following severe blunt trauma. To test such a scoring system, we measured gene expression of peripheral blood leukocytes from patients within 12 h of traumatic injury. cRNA derived from whole blood leukocytes obtained within 12 h of injury provided gene expression data for the entire genome that were used to create a composite gene expression score for each patient. Total blood leukocytes were chosen because they are active during inflammation, which is reflective of poor outcome. The gene expression score combines the activation levels of all the genes into a single number which compares the patient's gene expression to the average gene expression in uninjured volunteers. Expression profiles from healthy volunteers were averaged to create a reference gene expression profile which was used to compute a difference from reference (DFR) score for each patient. This score described the overall genomic response of patients within the first 12 h following severe blunt trauma. Regression models were used to compare the association of the DFR, APACHE, and ISS scores with outcome. We hypothesized that patients with a total gene response more different from uninjured volunteers would tend to have poorer outcome than those more similar. Our data show that for measures of poor outcome, such as infections, organ failures, and length of hospital stay, this is correct. DFR scores were associated significantly with adverse outcome, including multiple organ failure, duration of ventilation, length of hospital stay, and infection rate. The association remained significant after adjustment for injury severity as measured by APACHE or ISS. A single score representing changes in gene expression in peripheral blood leukocytes within hours of severe blunt injury is associated with adverse clinical outcomes that develop later in the hospital course. Assessment of genome-wide gene expression provides useful clinical information that is different from that provided by currently utilized anatomic or physiologic scores. (C) 2009 The Feinstein Institute for Medical Research, www.feinsteininstitute.org Online address: http://www.molmed.org doi: 10.2119/molmed.2009.00027
C1 [Warren, H. Shaw] Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA USA.
[Elson, Constance M.; Hayden, Douglas L.; Schoenfeld, David A.; Pelak, Kimberly] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA.
[Cobb, J. Perren; Brownstein, Bernard H.] Washington Univ, Dept Surg, St Louis, MO USA.
[Maier, Ronald V.; Cuschieri, Joseph; Hennessy, Laura] Univ Washington, Harborview Med Ctr, Dept Surg, Seattle, WA 98104 USA.
[Moldawer, Lyle L.] Univ Florida, Coll Med, Dept Surg, Gainesville, FL USA.
[Moore, Ernest E.] Univ Colorado, Dept Surg, Denver Hlth Med Ctr, Denver, CO 80202 USA.
[Harbrecht, Brian G.] Univ Louisville, Dept Surg, Louisville, KY 40292 USA.
[Mason, Philip H.; Tompkins, Ronald G.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Herndon, David N.; Jeschke, Marc G.; Finnerty, Celeste C.] Univ Texas Med Branch, Shriners Burn Hosp, Dept Surg, Galveston, TX USA.
RP Hayden, DL (reprint author), MGH Biostat Ctr, 50 Staniford St 560, Boston, MA 02114 USA.
EM swarren1@partners.org; dhayden@partners.org
FU NIGMS NIH HHS [2 U54 GM062119, U54 GM062119]
NR 25
TC 38
Z9 39
U1 0
U2 3
PU FEINSTEIN INST MED RES
PI MANHASSET
PA 350 COMMUNITY DR, MANHASSET, NY 11030 USA
SN 1076-1551
J9 MOL MED
JI Mol. Med.
PD JUL-AUG
PY 2009
VL 15
IS 7-8
BP 220
EP 227
DI 10.2119/molmed.2009.00027
PG 8
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 575CV
UT WOS:000276043800003
PM 19593405
ER
PT J
AU Benoff, S
Hauser, R
Marmar, JL
Hurley, IR
Napolitano, B
Centola, GM
AF Benoff, Susan
Hauser, Russ
Marmar, Joel L.
Hurley, Ian R.
Napolitano, Barbara
Centola, Grace M.
TI Cadmium Concentrations in Blood and Seminal Plasma: Correlations with
Sperm Number and Motility in Three Male Populations (Infertility
Patients, Artificial Insemination Donors, and Unselected Volunteers)
SO MOLECULAR MEDICINE
LA English
DT Article
ID REPRODUCTIVE ENDOCRINE FUNCTION; INDUCED TESTICULAR DAMAGE; RESISTANT
MURINE STRAINS; IN-VITRO FERTILIZATION; SEMEN QUALITY;
GENERAL-POPULATION; RAT TESTIS; INTRAUTERINE INSEMINATION;
GENDER-DIFFERENCES; ACROSOME-REACTION
AB To investigate a possible common environmental exposure that may partially explain the observed decrease in human semen quality, we correlated seminal plasma and blood cadmium levels with sperm concentration and sperm motility. We studied three separate human populations: group 1, infertility patients (Long Island, NY, USA); group 2, artificial insemination donors (AID) (Rochester, NY, USA); and group 3, general population volunteers (Rochester, NY, USA). Information about confounding factors was collected by questionnaire. Seminal plasma cadmium did not correlate with blood cadmium (Spearman correlation, n = 91, r = -0.092, P = 0.386, NS). Both blood and seminal plasma cadmium were significantly higher among infertility patients than the other subjects studied (for example, median seminal plasma cadmium was 0.282 mu g/L in infertility patients versus 0.091 mu g/L in AID and 0.092 mu g/L in general population volunteers; Kruskal-Wallis test, P < 0.001). The percentage of motile sperm and sperm concentration correlated inversely with seminal plasma cadmium among the infertility patients (r = -0.201, P < 0.036 and r = -0.189, Pc 0.05, respectively), but not in the other two groups. Age (among infertility patients) was the only positive confounder correlating with seminal plasma cadmium. To validate our human findings in an animal model, we chronically exposed adolescent male Wistar rats to low-moderate cadmium in drinking water. Though otherwise healthy the rats exhibited decreases in epididymal sperm count and sperm motility associated with cadmium dose and time of exposure. Our human and rat study results are consistent with the hypothesis that environmental cadmium exposures may contribute significantly to reduced human male sperm concentration and sperm motility. (C) 2009 The Feinstein Institute for Medical Research, www.feinsteininstitute.org Online address: http://www.moimed.org doi: 10.2119/molmed.2008.00104
C1 [Benoff, Susan; Hurley, Ian R.] Feinstein Inst Med Res, Fertil Res Labs, Manhasset, NY 11030 USA.
[Benoff, Susan] N Shore Univ Hosp, Dept Obstet & Gynecol, Manhasset, NY USA.
[Benoff, Susan] NYU, Dept Obstet & Gynecol, Sch Med, New York, NY 10016 USA.
[Benoff, Susan] NYU, Sch Med, Dept Cell Biol, New York, NY 10016 USA.
[Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA.
[Hauser, Russ] Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Androl Lab, Boston, MA 02114 USA.
[Hauser, Russ] Massachusetts Gen Hosp, In Vitro Fertilizat Unit, Boston, MA 02114 USA.
[Marmar, Joel L.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Surg, Div Urol, Camden, NJ 08103 USA.
[Napolitano, Barbara] Feinstein Inst Med Res, Biostat Unit, Manhasset, NY 11030 USA.
[Centola, Grace M.] Univ Rochester, Med Ctr, Dept Obstet & Gynecol, Rochester, NY 14642 USA.
[Centola, Grace M.] New England Cryogen Ctr, Newton, MA USA.
RP Benoff, S (reprint author), Feinstein Inst Med Res, Fertil Res Labs, 350 Community Dr, Manhasset, NY 11030 USA.
EM Sbenoff@optonline.net
FU NIEHS NIH HHS [ES06100, R01 ES010496, ES10496, R01 ES006100]; NIOSH CDC
HHS [R21 OH007330, OH07330]
NR 145
TC 49
Z9 52
U1 2
U2 11
PU FEINSTEIN INST MED RES
PI MANHASSET
PA 350 COMMUNITY DR, MANHASSET, NY 11030 USA
SN 1076-1551
J9 MOL MED
JI Mol. Med.
PD JUL-AUG
PY 2009
VL 15
IS 7-8
BP 248
EP 262
DI 10.2119/molmed.2008.00104
PG 15
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 575CV
UT WOS:000276043800007
PM 19593409
ER
PT J
AU Ginsburg, G
Forde, R
Martyn, JAJ
Eikermann, M
AF Ginsburg, Greg
Forde, Ryan
Martyn, Jeevendra A. J.
Eikermann, Matthias
TI INCREASED SENSITIVITY TO A NONDEPOLARIZING MUSCLE RELAXANT IN A PATIENT
WITH ACQUIRED NEUROMYOTONIA
SO MUSCLE & NERVE
LA English
DT Article
DE acquired neuromyotonia; Isaacs syndrome; voltage-gated
potassium-channels; nondepolarizing muscle relaxants; rocuronium
sensitivity
ID ISAACS SYNDROME; VECURONIUM
AB Neuromyotonia is a disorder of hyperexcitability of the peripheral nerve. It has electromyographic features of spontaneous, continuous, irregularly occurring doublets, or multiplets of motor unit potential discharges. Neuromyotonia is characterized by both myokymic and neuromyotonic discharges. To our knowledge, this is the first report in the literature to assess the sensitivity of skeletal muscle to a nondepolarizing muscle relaxant drug, rocuronium, in a woman with acquired neuromyotonia. She had a past medical history notable for prolonged postoperative paralysis following anesthesia. The patient showed increased sensitivity to the neuromuscular effects of rocuronium. This increase in sensitivity may be explained by downregulation of acetylcholine receptors in response to chronic high agonist (acetylcholine) concentrations. If patients with neuromyotonia receive anesthesia, we recommend that smaller doses of a nondepolarizing muscle relaxant be administered, accompanied by monitoring of neuromuscular function, so as to provide optimal muscle relaxation while avoiding overdose and prolonged postoperative recovery. Muscle Nerve 40: 139-142, 2009
C1 [Eikermann, Matthias] Massachusetts Gen Hosp, Shriners Hosp Children, Dept Anesthesia & Crit Care, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Eikermann, M (reprint author), Massachusetts Gen Hosp, Shriners Hosp Children, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA.
EM meikermann@partners.org
FU NIGMS NIH HHS [R01 GM055082]
NR 23
TC 2
Z9 2
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0148-639X
J9 MUSCLE NERVE
JI Muscle Nerve
PD JUL
PY 2009
VL 40
IS 1
BP 139
EP 142
DI 10.1002/mus.21322
PG 4
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 494WD
UT WOS:000269849200024
PM 19533664
ER
PT J
AU Addona, TA
Abbatiello, SE
Schilling, B
Skates, SJ
Mani, DR
Bunk, DM
Spiegelman, CH
Zimmerman, LJ
Ham, AJL
Keshishian, H
Hall, SC
Allen, S
Blackman, RK
Borchers, CH
Buck, C
Cardasis, HL
Cusack, MP
Dodder, NG
Gibson, BW
Held, JM
Hiltke, T
Jackson, A
Johansen, EB
Kinsinger, CR
Li, J
Mesri, M
Neubert, TA
Niles, RK
Pulsipher, TC
Ransohoff, D
Rodriguez, H
Rudnick, PA
Smith, D
Tabb, DL
Tegeler, TJ
Variyath, AM
Vega-Montoto, LJ
Wahlander, A
Waldemarson, S
Wang, M
Whiteaker, JR
Zhao, L
Anderson, NL
Fisher, SJ
Liebler, DC
Paulovich, AG
Regnier, FE
Tempst, P
Carr, SA
AF Addona, Terri A.
Abbatiello, Susan E.
Schilling, Birgit
Skates, Steven J.
Mani, D. R.
Bunk, David M.
Spiegelman, Clifford H.
Zimmerman, Lisa J.
Ham, Amy-Joan L.
Keshishian, Hasmik
Hall, Steven C.
Allen, Simon
Blackman, Ronald K.
Borchers, Christoph H.
Buck, Charles
Cardasis, Helene L.
Cusack, Michael P.
Dodder, Nathan G.
Gibson, Bradford W.
Held, Jason M.
Hiltke, Tara
Jackson, Angela
Johansen, Eric B.
Kinsinger, Christopher R.
Li, Jing
Mesri, Mehdi
Neubert, Thomas A.
Niles, Richard K.
Pulsipher, Trenton C.
Ransohoff, David
Rodriguez, Henry
Rudnick, Paul A.
Smith, Derek
Tabb, David L.
Tegeler, Tony J.
Variyath, Asokan M.
Vega-Montoto, Lorenzo J.
Wahlander, Asa
Waldemarson, Sofia
Wang, Mu
Whiteaker, Jeffrey R.
Zhao, Lei
Anderson, N. Leigh
Fisher, Susan J.
Liebler, Daniel C.
Paulovich, Amanda G.
Regnier, Fred E.
Tempst, Paul
Carr, Steven A.
TI Multi-site assessment of the precision and reproducibility of multiple
reaction monitoring-based measurements of proteins in plasma
SO NATURE BIOTECHNOLOGY
LA English
DT Article
ID MASS-SPECTROMETRIC QUANTITATION; ABSOLUTE QUANTIFICATION;
ISOTOPE-DILUTION; BIOMARKER DISCOVERY; PEPTIDE STANDARDS; SERUM; ASSAYS;
LC/MS/MS; PROTEOME; LIMITS
AB Verification of candidate biomarkers relies upon specific, quantitative assays optimized for selective detection of target proteins, and is increasingly viewed as a critical step in the discovery pipeline that bridges unbiased biomarker discovery to preclinical validation. Although individual laboratories have demonstrated that multiple reaction monitoring (MRM) coupled with isotope dilution mass spectrometry can quantify candidate protein biomarkers in plasma, reproducibility and transferability of these assays between laboratories have not been demonstrated. We describe a multilaboratory study to assess reproducibility, recovery, linear dynamic range and limits of detection and quantification of multiplexed, MRM-based assays, conducted by NCI-CPTAC. Using common materials and standardized protocols, we demonstrate that these assays can be highly reproducible within and across laboratories and instrument platforms, and are sensitive to low lg/ml protein concentrations in unfractionated plasma. We provide data and benchmarks against which individual laboratories can compare their performance and evaluate new technologies for biomarker verification in plasma.
C1 [Addona, Terri A.; Abbatiello, Susan E.; Mani, D. R.; Keshishian, Hasmik; Blackman, Ronald K.; Carr, Steven A.] Broad Inst MIT & Harvard, Cambridge, MA USA.
[Schilling, Birgit; Cusack, Michael P.; Gibson, Bradford W.; Held, Jason M.] Buck Inst Age Res, Novato, CA USA.
[Skates, Steven J.; Pulsipher, Trenton C.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA.
[Bunk, David M.; Dodder, Nathan G.; Rudnick, Paul A.] Natl Inst Stand & Technol, Chem Sci & Technol Lab, Gaithersburg, MD 20899 USA.
[Spiegelman, Clifford H.; Variyath, Asokan M.; Vega-Montoto, Lorenzo J.] Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA.
[Zimmerman, Lisa J.; Ham, Amy-Joan L.; Li, Jing; Tabb, David L.; Liebler, Daniel C.] Vanderbilt Univ, Nashville, TN USA.
[Hall, Steven C.; Allen, Simon; Johansen, Eric B.; Niles, Richard K.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA.
[Borchers, Christoph H.; Jackson, Angela; Smith, Derek] Univ Victoria, Genome BC Prote Ctr, Victoria, BC, Canada.
[Buck, Charles; Regnier, Fred E.] Purdue Univ, W Lafayette, IN 47907 USA.
[Cardasis, Helene L.; Neubert, Thomas A.; Wahlander, Asa] NYU, Sch Med, Kimmel Ctr Biol & Med, Skirball Inst, New York, NY USA.
[Cardasis, Helene L.; Neubert, Thomas A.; Wahlander, Asa] NYU, Sch Med, Dept Pharmacol, New York, NY USA.
[Hiltke, Tara; Kinsinger, Christopher R.; Mesri, Mehdi; Rodriguez, Henry] NCI, NIH, Bethesda, MD 20892 USA.
[Ransohoff, David] Univ N Carolina, Chapel Hill, NC USA.
[Tegeler, Tony J.; Wang, Mu] Monarch Life Sci, Indianapolis, IN USA.
[Wang, Mu] Indiana Univ, Sch Med, Indianapolis, IN USA.
[Whiteaker, Jeffrey R.; Zhao, Lei; Paulovich, Amanda G.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Anderson, N. Leigh] Plasma Proteome Inst, Washington, DC USA.
[Tempst, Paul] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
RP Carr, SA (reprint author), Broad Inst MIT & Harvard, Cambridge, MA USA.
EM scarr@broad.mit.edu
RI Held, Jason/B-1319-2010; Waldemarson, Sofia/C-6377-2012; Dodder,
Nathan/C-7971-2015; Vega-Montoto, Lorenzo/B-9035-2017;
OI Dodder, Nathan/0000-0001-5913-1767; Vega-Montoto,
Lorenzo/0000-0002-4096-1100; Tempst, Paul/0000-0002-6680-3987; Held,
Jason/0000-0001-8024-2736; Liebler, Daniel/0000-0002-7873-3031
FU NCI NIH HHS [U24 CA126480-01, U24 CA126476, U24 CA126476-03, U24
CA126480, U24 CA126485]; PHS HHS [U24 126477, U24 126479, U24 126480]
NR 38
TC 588
Z9 595
U1 9
U2 102
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1087-0156
J9 NAT BIOTECHNOL
JI Nat. Biotechnol.
PD JUL
PY 2009
VL 27
IS 7
BP 633
EP U85
DI 10.1038/nbt.1546
PG 12
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA 469OF
UT WOS:000267908500020
PM 19561596
ER
PT J
AU De Jager, PL
Jia, XM
Wang, J
de Bakker, PIW
Ottoboni, L
Aggarwal, NT
Piccio, L
Raychaudhuri, S
Tran, D
Aubin, C
Briskin, R
Romano, S
Baranzini, SE
McCauley, JL
Pericak-Vance, MA
Haines, JL
Gibson, RA
Naeglin, Y
Uitdehaag, B
Matthews, PM
Kappos, L
Polman, C
McArdle, WL
Strachan, DP
Evans, D
Cross, AH
Daly, MJ
Compston, A
Sawcer, SJ
Weiner, HL
Hauser, SL
Hafler, DA
Oksenberg, JR
AF De Jager, Philip L.
Jia, Xiaoming
Wang, Joanne
de Bakker, Paul I. W.
Ottoboni, Linda
Aggarwal, Neelum T.
Piccio, Laura
Raychaudhuri, Soumya
Tran, Dong
Aubin, Cristin
Briskin, Rebeccah
Romano, Susan
Baranzini, Sergio E.
McCauley, Jacob L.
Pericak-Vance, Margaret A.
Haines, Jonathan L.
Gibson, Rachel A.
Naeglin, Yvonne
Uitdehaag, Bernard
Matthews, Paul M.
Kappos, Ludwig
Polman, Chris
McArdle, Wendy L.
Strachan, David P.
Evans, Denis
Cross, Anne H.
Daly, Mark J.
Compston, Alastair
Sawcer, Stephen J.
Weiner, Howard L.
Hauser, Stephen L.
Hafler, David A.
Oksenberg, Jorge R.
CA Int MS Genetics Consortium
TI Meta-analysis of genome scans and replication identify CD6, IRF8 and
TNFRSF1A as new multiple sclerosis susceptibility loci
SO NATURE GENETICS
LA English
DT Article
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; PERIPHERAL-BLOOD CELLS; WIDE ASSOCIATION;
PERIODIC-SYNDROME; R92Q MUTATION; RHEUMATOID-ARTHRITIS; HAPLOTYPE MAP;
INTERFERON; DISEASE; RISK
AB We report the results of a meta-analysis of genome-wide association scans for multiple sclerosis (MS) susceptibility that includes 2,624 subjects with MS and 7,220 control subjects. Replication in an independent set of 2,215 subjects with MS and 2,116 control subjects validates new MS susceptibility loci at TNFRSF1A (combined P = 1.59 x 10(-11)), IRF8 (P = 3.73 x 10(-9)) and CD6 (P = 3.79 x 10(-9)). TNFRSF1A harbors two independent susceptibility alleles: rs1800693 is a common variant with modest effect (odds ratio 1.2), whereas rs4149584 is a nonsynonymous coding polymorphism of low frequency but with stronger effect (allele frequency 0.02; odds ratio 1.6). We also report that the susceptibility allele near IRF8, which encodes a transcription factor known to function in type I interferon signaling, is associated with higher mRNA expression of interferon-response pathway genes in subjects with MS.
C1 [De Jager, Philip L.; Ottoboni, Linda; Romano, Susan; Weiner, Howard L.; Hafler, David A.] Brigham & Womens Hosp, Div Mol Immunol, Ctr Neurol Dis, Dept Neurol, Boston, MA 02115 USA.
[De Jager, Philip L.; Ottoboni, Linda; Briskin, Rebeccah] Partners Ctr Personalized Genet Med, Boston, MA USA.
[De Jager, Philip L.; de Bakker, Paul I. W.; Ottoboni, Linda; Raychaudhuri, Soumya; Tran, Dong; Aubin, Cristin; Daly, Mark J.; Hafler, David A.] Harvard Univ, Program Med & Populat Genet, Broad Inst, Cambridge, MA 02138 USA.
[De Jager, Philip L.; de Bakker, Paul I. W.; Ottoboni, Linda; Raychaudhuri, Soumya; Tran, Dong; Aubin, Cristin; Daly, Mark J.; Hafler, David A.] MIT, Cambridge, MA 02139 USA.
[Jia, Xiaoming; de Bakker, Paul I. W.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet,Dept Med, Boston, MA 02115 USA.
[Wang, Joanne; Baranzini, Sergio E.; Hauser, Stephen L.; Oksenberg, Jorge R.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
[Wang, Joanne; Hauser, Stephen L.; Oksenberg, Jorge R.] Univ Calif San Francisco, Inst Human Genet, Sch Med, San Francisco, CA 94143 USA.
[Aggarwal, Neelum T.; Evans, Denis] Rush Univ, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA.
[Aggarwal, Neelum T.; Evans, Denis] Rush Univ, Dept Neurol Sci, Chicago, IL 60612 USA.
[Piccio, Laura; Cross, Anne H.] Washington Univ, Dept Neurol, St Louis, MO USA.
[Raychaudhuri, Soumya] Brigham & Womens Hosp, Dept Med, Div Immunol Allergy & Rheumatol, Boston, MA 02115 USA.
[McCauley, Jacob L.; Pericak-Vance, Margaret A.] Univ Miami, Miller Sch Med, Miami Inst Human Genom, Miami, FL 33136 USA.
[Haines, Jonathan L.] Vanderbilt Univ, Med Ctr, Ctr Human Genet Res, Nashville, TN USA.
[Gibson, Rachel A.; Matthews, Paul M.] Univ London Imperial Coll Sci Technol & Med, Dept Clin Neurosci, London SW7 2AZ, England.
[Gibson, Rachel A.; Matthews, Paul M.] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, GlaxoSmithKline Clin Imaging Ctr, London SW7 2AZ, England.
[Naeglin, Yvonne; Kappos, Ludwig] Univ Basel Hosp, Dept Neurol, CH-4031 Basel, Switzerland.
[Uitdehaag, Bernard; Polman, Chris] Vrije Univ Amsterdam, Med Ctr, Dept Neurol, Amsterdam, Netherlands.
[McArdle, Wendy L.] Univ Bristol, Dept Social Med, Bristol, Avon, England.
[Strachan, David P.] Univ London, Div Community Hlth Sci, London, England.
[Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Compston, Alastair; Sawcer, Stephen J.] Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Cambridge CB2 2QQ, England.
RP De Jager, PL (reprint author), Brigham & Womens Hosp, Div Mol Immunol, Ctr Neurol Dis, Dept Neurol, 75 Francis St, Boston, MA 02115 USA.
EM pdejager@rics.bwh.harvard.edu
RI Haines, Jonathan/C-3374-2012; Baranzini, Sergio/A-9422-2013; Fuller,
Stephen/C-1200-2009; de Bakker, Paul/B-8730-2009; Hauser,
Stephen/J-2978-2016;
OI Baranzini, Sergio/0000-0003-0067-194X; de Bakker,
Paul/0000-0001-7735-7858; OTTOBONI, LINDA/0000-0001-5412-7785; Matthews,
Paul M/0000-0002-1619-8328
FU Medical Research Council [G0000934, MC_QA137934]; NIAID NIH HHS [P01
AI039671]; NIAMS NIH HHS [K08 AR055688, K08 AR055688-01A1]; NINDS NIH
HHS [K08 NS046341, K08 NS46341, R01 NS046630, R01 NS049477]; Wellcome
Trust [068545/Z/02]
NR 48
TC 400
Z9 402
U1 2
U2 17
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD JUL
PY 2009
VL 41
IS 7
BP 776
EP U26
DI 10.1038/ng.401
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 468AS
UT WOS:000267786200006
PM 19525953
ER
PT J
AU Viswanathan, SR
Powers, JT
Einhorn, W
Hoshida, Y
Ng, TL
Toffanin, S
O'Sullivan, M
Lu, J
Phillips, LA
Lockhart, VL
Shah, SP
Tanwar, PS
Mermel, CH
Beroukhim, R
Azam, M
Teixeira, J
Meyerson, M
Hughes, TP
Llovet, JM
Radich, J
Mullighan, CG
Golub, TR
Sorensen, PH
Daley, GQ
AF Viswanathan, Srinivas R.
Powers, John T.
Einhorn, William
Hoshida, Yujin
Ng, Tony L.
Toffanin, Sara
O'Sullivan, Maureen
Lu, Jun
Phillips, Letha A.
Lockhart, Victoria L.
Shah, Samar P.
Tanwar, Pradeep S.
Mermel, Craig H.
Beroukhim, Rameen
Azam, Mohammad
Teixeira, Jose
Meyerson, Matthew
Hughes, Timothy P.
Llovet, Josep M.
Radich, Jerald
Mullighan, Charles G.
Golub, Todd R.
Sorensen, Poul H.
Daley, George Q.
TI Lin28 promotes transformation and is associated with advanced human
malignancies
SO NATURE GENETICS
LA English
DT Article
ID HUMAN HEPATOCELLULAR-CARCINOMA; EPITHELIAL OVARIAN-CANCER; LUNG-CANCER;
WILMS-TUMOR; MICRORNA EXPRESSION; GENE-EXPRESSION; CELL-DIFFERENTIATION;
STEM-CELLS; LET-7; METASTASIS
AB Multiple members of the let-7 family of miRNAs are often repressed in human cancers(1,2), thereby promoting oncogenesis by derepressing targets such as HMGA2, K-Ras and c-Myc(3,4). However, the mechanism by which let-7 miRNAs are coordinately repressed is unclear. The RNA-binding proteins LIN28 and LIN28B block let-7 precursors from being processed to mature nmiRNAs(5-8), suggesting that their overexpression might promote malignancy through repression of let-7. Here we show that LIN28 and LIN28B are overexpressed in primary human tumors and human cancer cell lines (overall frequency B15%), and that overexpression is linked to repression of let-7 family miRNAs and derepression of let-7 targets. LIN28 and LIN28b facilitate cellular transformation in vitro, and overexpression is associated with advanced disease across multiple tumor types. Our work provides a mechanism for the coordinate repression of let-7 miRNAs observed in a subset of human cancers, and associates activation of LIN28 and LIN28B with poor clinical prognosis.
C1 [Viswanathan, Srinivas R.; Powers, John T.; Einhorn, William; Shah, Samar P.; Azam, Mohammad; Daley, George Q.] Harvard Univ, Childrens Hosp, Dept Biol Chem & Mol Pharmacol, Med Sch,Harvard Stem Cell Inst, Boston, MA 02115 USA.
[Hoshida, Yujin; Golub, Todd R.; Daley, George Q.] Childrens Hosp Boston, Div Pediat Hematol Oncol, Cambridge, MA USA.
[Hoshida, Yujin; Golub, Todd R.; Daley, George Q.] Dana Farber Canc Inst, Cambridge, MA USA.
[Hoshida, Yujin; Lu, Jun; Mermel, Craig H.; Beroukhim, Rameen; Meyerson, Matthew; Golub, Todd R.] MIT & Harvard, Broad Inst, Canc Program, Cambridge, MA USA.
[Hoshida, Yujin; Lu, Jun; Mermel, Craig H.; Beroukhim, Rameen; Meyerson, Matthew; Golub, Todd R.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Hoshida, Yujin; Lu, Jun; Mermel, Craig H.; Beroukhim, Rameen; Meyerson, Matthew; Golub, Todd R.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA.
[Ng, Tony L.; Sorensen, Poul H.] Univ British Columbia, Dept Pathol, Vancouver, BC V5Z 1M9, Canada.
[Ng, Tony L.; Sorensen, Poul H.] BC Canc Res Ctr, Dept Mol Oncol, Vancouver, BC, Canada.
[Toffanin, Sara; Llovet, Josep M.] Mt Sinai Sch Med, Div Liver Dis, Mt Sinai Liver Canc Program, New York, NY USA.
[Toffanin, Sara] IRCSS Fdn, Natl Canc Inst, Gastrointestinal Surg & Liver Transplantat Unit, Milan, Italy.
[O'Sullivan, Maureen] Our Ladys Childrens Hosp, Dept Pathol, Dublin, Ireland.
[O'Sullivan, Maureen] Trinity Coll Dublin, Dept Pathol, Dublin, Ireland.
[Phillips, Letha A.; Mullighan, Charles G.] St Jude Childrens Hosp, Dept Pathol, Memphis, TN 38105 USA.
[Lockhart, Victoria L.; Radich, Jerald] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA.
[Tanwar, Pradeep S.; Teixeira, Jose] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA.
[Hughes, Timothy P.] Inst Med & Vet Sci, Div Haematol, Adelaide, SA 5000, Australia.
[Llovet, Josep M.] Hosp Clin Barcelona, HCC Translat Res Lab, Barcelona Clin Liver Canc Grp,CIBERehd, Liver Unit,Inst Invest Biomed August Pi & Sunyer, Catalonia, Spain.
[Llovet, Josep M.] Inst Catalana Recerca & Estudis Avancats, Catalonia, Spain.
[Golub, Todd R.; Daley, George Q.] Howard Hughes Med Inst, Boston, MA 02115 USA.
[Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA.
[Daley, George Q.] Manton Ctr Orphan Dis Res, Boston, MA USA.
RP Daley, GQ (reprint author), Harvard Univ, Childrens Hosp, Dept Biol Chem & Mol Pharmacol, Med Sch,Harvard Stem Cell Inst, Boston, MA 02115 USA.
EM george.daley@childrens.harvard.edu
RI Meyerson, Matthew/E-7123-2012; Llovet, Josep M /D-4340-2014;
OI Llovet, Josep M /0000-0003-0547-2667; Teixeira,
Jose/0000-0002-6438-5064; Mullighan, Charles/0000-0002-1871-1850
FU Howard Hughes Medical Institute; NHLBI NIH HHS [T32-HL 66987]; NICHD NIH
HHS [R01 HD052701, R01 HD052701-02]; NIDDK NIH HHS [1 R01 DK076986-01,
R01 DK076986]; NIGMS NIH HHS [T32 GM007753]; NIH HHS [DP1 OD000256, DP1
OD000256-01]
NR 55
TC 415
Z9 430
U1 2
U2 32
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD JUL
PY 2009
VL 41
IS 7
BP 843
EP U109
DI 10.1038/ng.392
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 468AS
UT WOS:000267786200018
PM 19483683
ER
PT J
AU Perrigoue, JG
Saenz, SA
Siracusa, MC
Allenspach, EJ
Taylor, BC
Giacomin, PR
Nair, MG
Du, YR
Zaph, C
van Rooijen, N
Comeau, MR
Pearce, EJ
Laufer, TM
Artis, D
AF Perrigoue, Jacqueline G.
Saenz, Steven A.
Siracusa, Mark C.
Allenspach, Eric J.
Taylor, Betsy C.
Giacomin, Paul R.
Nair, Meera G.
Du, Yurong
Zaph, Colby
van Rooijen, Nico
Comeau, Michael R.
Pearce, Edward J.
Laufer, Terri M.
Artis, David
TI MHC class II-dependent basophil-CD4(+) T cell interactions promote T(H)2
cytokine-dependent immunity
SO NATURE IMMUNOLOGY
LA English
DT Article
ID THYMIC STROMAL LYMPHOPOIETIN; ANTIGEN-PRESENTING CELLS; DENDRITIC CELLS;
IN-VIVO; HELMINTH INFECTION; TYPE-2 IMMUNITY; CUTTING EDGE; MAST-CELLS;
GASTROINTESTINAL-TRACT; EFFECTOR MECHANISMS
AB Dendritic cells can prime naive CD4(+) T cells; however, here we demonstrate that dendritic cell-mediated priming was insufficient for the development of T helper type 2 cell-dependent immunity. We identify basophils as a dominant cell population that coexpressed major histocompatibility complex class II and interleukin 4 message after helminth infection. Basophilia was promoted by thymic stromal lymphopoietin, and depletion of basophils impaired immunity to helminth infection. Basophils promoted antigen-specific CD4(+) T cell proliferation and interleukin 4 production in vitro, and transfer of basophils augmented the population expansion of helminth-responsive CD4(+) T cells in vivo. Collectively, our studies suggest that major histocompatibility complex class II-dependent interactions between basophils and CD4(+) T cells promote T helper type 2 cytokine responses and immunity to helminth infection.
C1 [Perrigoue, Jacqueline G.; Saenz, Steven A.; Siracusa, Mark C.; Taylor, Betsy C.; Giacomin, Paul R.; Nair, Meera G.; Du, Yurong; Pearce, Edward J.; Artis, David] Univ Penn, Dept Pathobiol, Philadelphia, PA 19104 USA.
[Allenspach, Eric J.; Laufer, Terri M.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
[Zaph, Colby] Univ British Columbia, Biomed Res Ctr, Dept Pathol & Lab Med, Vancouver, BC, Canada.
[van Rooijen, Nico] Vrije Univ Amsterdam, Dept Mol Cell Biol, Amsterdam, Netherlands.
[Comeau, Michael R.] Amgen Inc, Inflammat Res, Seattle, WA USA.
[Laufer, Terri M.] Univ Penn, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA.
RP Artis, D (reprint author), Univ Penn, Dept Pathobiol, Philadelphia, PA 19104 USA.
EM dartis@vet.upenn.edu
OI Zaph, Colby/0000-0002-9889-9848
FU NCI NIH HHS [T32 CA09140-30, T32 CA009140]; NIAID NIH HHS [AI074878,
AI32573, AI53825, AI61570, R01 AI032573, R01 AI053825, R01 AI061570, R01
AI061570-05, R01 AI074878, R01 AI074878-02, R56 AI032573, T32 AI007532,
T32 AI007532-08]; NIDDK NIH HHS [DK50306, P30 DK050306]; NIGMS NIH HHS
[F31 GM082187]
NR 59
TC 347
Z9 356
U1 3
U2 22
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
J9 NAT IMMUNOL
JI Nat. Immunol.
PD JUL
PY 2009
VL 10
IS 7
BP 697
EP U45
DI 10.1038/ni.1740
PG 10
WC Immunology
SC Immunology
GA 459WF
UT WOS:000267142600008
PM 19465906
ER
PT J
AU Schmitz, AM
Morrison, MF
Agunwamba, AO
Nibert, ML
Lesser, CF
AF Schmitz, Alexa M.
Morrison, Monica F.
Agunwamba, Akochi O.
Nibert, Max L.
Lesser, Cammie F.
TI Protein interaction platforms: visualization of interacting proteins in
yeast
SO NATURE METHODS
LA English
DT Article
ID III SECRETION APPARATUS; SHIGELLA-FLEXNERI; SACCHAROMYCES-CEREVISIAE;
CHAPERONE; INVASION; LOCALIZATION; SYSTEM; ASSAYS; SPA15
AB Here we describe the protein interaction platform assay, a method for identifying interacting proteins in Saccharomyces cerevisiae. This assay relies on the reovirus scaffolding protein mu NS, which forms large focal inclusions in living cells. When a query protein is fused to mu NS and potential interaction partners are fused to a fluorescent reporter, interactors can be identified by screening for yeast that display fluorescent foci.
C1 [Schmitz, Alexa M.; Morrison, Monica F.; Agunwamba, Akochi O.; Lesser, Cammie F.] Massachusetts Gen Hosp, Div Infect Dis, Dept Med Microbiol & Mol Genet, Cambridge, MA USA.
[Schmitz, Alexa M.; Morrison, Monica F.; Agunwamba, Akochi O.; Lesser, Cammie F.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Nibert, Max L.; Lesser, Cammie F.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA.
RP Lesser, CF (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Dept Med Microbiol & Mol Genet, Cambridge, MA USA.
EM clesser@partners.org
FU US National Institutes of Health [R56 AI067445, R01 AI064285];
Rockefeller Brothers Fund; Goldman Philanthropic
FX We thank S. Alberti and S. Lindquist (Whitehead Institute, Massachusetts
Institute of Technology) for providing the pAG destination clones; A.
Gray, K. Fixen and M. Goldberg ( Massachusetts General Hospital, Harvard
Medical School) for providing plasmids pNG162 and pDSW206 and antibodies
to IcsA and isocitrate dehydrogenase; J. Heindl (Massachusetts General
Hospital, Harvard Medical School) for providing the IpgB2 W62A
construct; T. Hao, D. Hill and M. Vidal (Dana Farber Cancer Institute,
Harvard Medical School) for assistance in designing primers to create
the S. flexneri Gateway entry clones and for providing the
Gateway-compatible Y2H vectors; and R. Levy and C. Koser (Massachusetts
General Hospital, Harvard Medical School) for cloning and expressing S.
typhimurium effectors in yeast. We also thank the US National Institute
of Allergy and Infectious Diseases and the J. Craig Venter Institute for
supplying the S. typhimurium Gateway entry clones. Partial support for
this work was provided by US National Institutes of Health grants R56
AI067445 to M.L.N. and R01 AI064285 to C. F. L., and by a Charles E.
Culpeper Medical Scholarship from the Rockefeller Brothers Fund and
Goldman Philanthropic Partnerships to C. F. L.
NR 24
TC 18
Z9 18
U1 0
U2 1
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 JUL
PY 2009
VL 6
IS 7
BP 500
EP U43
DI 10.1038/nmeth.1337
PG 5
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 463PA
UT WOS:000267442900016
PM 19483691
ER
PT J
AU Razansky, D
Distel, M
Vinegoni, C
Ma, R
Perrimon, N
Koster, RW
Ntziachristos, V
AF Razansky, Daniel
Distel, Martin
Vinegoni, Claudio
Ma, Rui
Perrimon, Norbert
Koester, Reinhard W.
Ntziachristos, Vasilis
TI Multispectral opto-acoustic tomography of deep-seated fluorescent
proteins in vivo
SO NATURE PHOTONICS
LA English
DT Article
ID HIGH-RESOLUTION; MICROSCOPY; BRAIN
AB Fluorescent proteins have become essential reporter molecules for studying life at the cellular and sub-cellular level, re-defining the ways in which we investigate biology. However, because of intense light scattering, most organisms and tissues remain inaccessible to current fluorescence microscopy techniques at depths beyond several hundred micrometres. We describe a multispectral opto-acoustic tomography technique capable of high-resolution visualization of fluorescent proteins deep within highly light-scattering living organisms. The method uses multiwavelength illumination over multiple projections combined with selective-plane opto-acoustic detection for artifact-free data collection. Accurate image reconstruction is enabled by making use of wavelength-dependent light propagation models in tissue. By performing whole-body imaging of two biologically important and optically diffuse model organisms, Drosophila melanogaster pupae and adult zebrafish, we demonstrate the facility to resolve tissue-specific expression of eGFP and mCherrry fluorescent proteins for precise morphological and functional observations in vivo.
C1 [Razansky, Daniel; Ma, Rui; Ntziachristos, Vasilis] Tech Univ Munich, Inst Biol & Med Imaging, D-85764 Neuherberg, Germany.
[Distel, Martin; Koester, Reinhard W.] Helmholtz Ctr Munich, Inst Dev Genet, D-85764 Neuherberg, Germany.
[Vinegoni, Claudio] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[Vinegoni, Claudio] Harvard Univ, Sch Med, Richard B Simches Res Ctr, Boston, MA 02114 USA.
[Perrimon, Norbert] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Perrimon, Norbert] Howard Hughes Med Inst, Boston, MA 02115 USA.
RP Razansky, D (reprint author), Tech Univ Munich, Inst Biol & Med Imaging, Landstr 1, D-85764 Neuherberg, Germany.
EM dr@tum.de; v.ntziachristos@tum.de
FU Deutsche Forschungsgemeinschaft (DFG) [RA 1848/1-1]; Studienstiftung des
deutschen Volkes; German Ministry for Education and Research (BMBF)
[0311889]
FX D. R. acknowledges financial support by the Deutsche
Forschungsgemeinschaft (DFG) research grant RA 1848/1-1. M. D. is a
fellow of the Studienstiftung des deutschen Volkes. R. W. K. is
supported by a BioFuture Award Grant (0311889) of the German Ministry
for Education and Research (BMBF). We thank R. Jagasia for providing
Hela mitodsRed cells.
NR 31
TC 331
Z9 334
U1 3
U2 47
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1749-4885
J9 NAT PHOTONICS
JI Nat. Photonics
PD JUL
PY 2009
VL 3
IS 7
BP 412
EP 417
DI 10.1038/NPHOTON.2009.98
PG 6
WC Optics; Physics, Applied
SC Optics; Physics
GA 471OL
UT WOS:000268067700018
ER
PT J
AU Brown, JR
Freedman, AS
AF Brown, Jennifer R.
Freedman, Arnold S.
TI ASCT in follicular lymphoma
SO NATURE REVIEWS CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; HIGH-DOSE
THERAPY; PROGRESSION-FREE SURVIVAL; NON-HODGKINS-LYMPHOMA; 1ST
REMISSION; TRIAL; CHEMOTHERAPY; MULTICENTER; TIME
C1 [Brown, Jennifer R.; Freedman, Arnold S.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Brown, JR (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA.
EM jbrown2@partners.org
NR 10
TC 1
Z9 1
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-4774
J9 NAT REV CLIN ONCOL
JI Nat. Rev. Clin. Oncol.
PD JUL
PY 2009
VL 6
IS 7
BP 380
EP 382
DI 10.1038/nrclinonc.2009.87
PG 4
WC Oncology
SC Oncology
GA 463OK
UT WOS:000267441300004
PM 19561632
ER
PT J
AU Rupnik, M
Wilcox, MH
Gerding, DN
AF Rupnik, Maja
Wilcox, Mark H.
Gerding, Dale N.
TI Clostridium difficile infection: new developments in epidemiology and
pathogenesis
SO NATURE REVIEWS MICROBIOLOGY
LA English
DT Review
ID HUMAN GUT MODEL; SURFACE-LAYER PROTEINS; TERM-CARE FACILITY; TOXIN-B;
BINARY TOXIN; ANTIBODY-RESPONSE; PCR RIBOTYPES; ADP-RIBOSYLTRANSFERASE;
HYPERVIRULENT STRAIN; PATHOGENICITY LOCUS
AB Clostridium difficile is now considered to be one of the most important causes of health care-associated infections. C. difficile infections are also emerging in the community and in animals used for food, and are no longer viewed simply as unpleasant complications that follow antibiotic therapy. Since 2001, the prevalence and severity of C. difficile infection has increased significantly, which has led to increased research interest and the discovery of new virulence factors, and has expanded and focused the development of new treatment and prevention regimens. This Review summarizes the recent epidemiological changes in C. difficile infection, our current knowledge of C. difficile virulence factors and the clinical outcomes of C. difficile infection.
C1 [Rupnik, Maja] Inst Publ Hlth Maribor, Ctr Microbiol, Maribor 2000, Slovenia.
[Rupnik, Maja] Univ Maribor, Fac Med, Maribor 2000, Slovenia.
[Wilcox, Mark H.] Leeds Gen Infirm, Leeds LS1 3EX, W Yorkshire, England.
[Gerding, Dale N.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA.
[Gerding, Dale N.] Loyola Univ Chicago, Stritch Sch Med, ACOS Res & Dev, Hines, IL 60141 USA.
RP Rupnik, M (reprint author), Inst Publ Hlth Maribor, Ctr Microbiol, Prvomajska 1, Maribor 2000, Slovenia.
EM maja.rupnik@uni-mb.si; mark.wilcox@leedsth.nhs.uk;
dale.gerding2@med.va.gov
FU EU [223585]; ERA NET PathoGenoMics; ARRS [J3-0194-0377-08]
FX M. R. was supported by EU grant 223585, ERA NET PathoGenoMics grant and
ARRS grant J3-0194-0377-08.
NR 129
TC 580
Z9 608
U1 28
U2 202
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 JUL
PY 2009
VL 7
IS 7
BP 526
EP 536
DI 10.1038/nrmicro2164
PG 11
WC Microbiology
SC Microbiology
GA 458KF
UT WOS:000267016700013
PM 19528959
ER
PT J
AU Chen, Z
Vijayan, S
Barbieri, R
Wilson, MA
Brown, EN
AF Chen, Zhe
Vijayan, Sujith
Barbieri, Riccardo
Wilson, Matthew A.
Brown, Emery N.
TI Discrete- and Continuous-Time Probabilistic Models and Algorithms for
Inferring Neuronal UP and DOWN States
SO NEURAL COMPUTATION
LA English
DT Article
ID CHAIN MONTE-CARLO; HIDDEN MARKOV-MODELS; ACTIVITY IN-VIVO;
MAXIMUM-LIKELIHOOD-ESTIMATION; SINGLE-CHANNEL RECORDINGS; NEURAL SPIKING
ACTIVITY; TRAIN DATA-ANALYSIS; EM ALGORITHM; BAYESIAN-INFERENCE; SEIZURE
COUNTS
AB UP and DOWN states, the periodic fluctuations between increased and decreased spiking activity of a neuronal population, are a fundamental feature of cortical circuits. Understanding UP-DOWN state dynamics is important for understanding how these circuits represent and transmit information in the brain. To date, limited work has been done on characterizing the stochastic properties of UP-DOWN state dynamics. We present a set of Markov and semi-Markov discrete-and continuous-time probability models for estimating UP and DOWN states from multiunit neural spiking activity. We model multiunit neural spiking activity as a stochastic point process, modulated by the hidden (UP and DOWN) states and the ensemble spiking history. We estimate jointly the hidden states and the model parameters by maximum likelihood using an expectation-maximization (EM) algorithm and a Monte Carlo EM algorithm that uses reversible-jump Markov chain Monte Carlo sampling in the E-step. We apply our models and algorithms in the analysis of both simulated multiunit spiking activity and actual multiunit spiking activity recorded from primary somatosensory cortex in a behaving rat during slow-wave sleep. Our approach provides a statistical characterization of UP-DOWN state dynamics that can serve as a basis for verifying and refining mechanistic descriptions of this process.
C1 [Chen, Zhe; Barbieri, Riccardo; Brown, Emery N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab,Dept Anesthesia & Crit Care, Boston, MA 02114 USA.
[Brown, Emery N.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Vijayan, Sujith] Harvard Univ, Program Neurosci, Cambridge, MA 02139 USA.
[Wilson, Matthew A.] MIT, Dept Biol, Cambridge, MA 02139 USA.
[Wilson, Matthew A.] MIT, Picower Inst Learning & Memory, RIKEN MIT Neurosci Res Ctr, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
RP Chen, Z (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab,Dept Anesthesia & Crit Care, Boston, MA 02114 USA.
EM zhechen@mit.edu; vijayan@post.harvard.edu; barbieri@neurostat.mit.edu;
mwilson@mit.edu; enb@neurostat.mit.edu
OI Barbieri, Riccardo/0000-0001-9381-3833; Chen, Zhe/0000-0002-6483-6056
FU NHLBI NIH HHS [T32 HL07901, R01 HL084502-03, T32 HL007901, R01-HL084502,
R01 HL084502]; NIDA NIH HHS [R01-DA015644, R01 DA015644]; NIH HHS [DP1
OD003646, DP1 OD003646-03, DP1-OD003646]
NR 78
TC 14
Z9 14
U1 0
U2 4
PU MIT PRESS
PI CAMBRIDGE
PA ONE ROGERS ST, CAMBRIDGE, MA 02142-1209 USA
SN 0899-7667
EI 1530-888X
J9 NEURAL COMPUT
JI Neural Comput.
PD JUL
PY 2009
VL 21
IS 7
BP 1797
EP 1862
DI 10.1162/neco.2009.06-08-799
PG 66
WC Computer Science, Artificial Intelligence; Neurosciences
SC Computer Science; Neurosciences & Neurology
GA 457UK
UT WOS:000266959100001
PM 19323637
ER
PT J
AU Strozyk, D
Launer, LJ
Adlard, PA
Cherny, RA
Tsatsanis, A
Volitakis, I
Blennow, K
Petrovitch, H
White, LR
Bush, AI
AF Strozyk, Dorothea
Launer, Lenore J.
Adlard, Paul A.
Cherny, Robert A.
Tsatsanis, Andrew
Volitakis, Irene
Blennow, Kai
Petrovitch, Helen
White, Lon R.
Bush, Ashley I.
TI Zinc and copper modulate Alzheimer A beta levels in human cerebrospinal
fluid
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Amyloid; Alzheimer's disease; Metalloproteinase; Cerebrospinal fluid;
Zinc; Copper; Iron; Manganese; Chromium
ID AMYLOID-BETA; HYDROGEN-PEROXIDE; DISEASE; PROTEIN; CLIOQUINOL; PEPTIDE;
AGGREGATION; MICE; IRON; DEGRADATION
AB Abnormal interaction of beta-amyloid 42 (A beta 42) with copper, zinc and iron induce peptide aggregation and oxidation in Alzheimer's disease (AD). However, in health, A beta degradation is mediated by extracellular metalloproteinases, neprilysin, insulin degrading enzyme (IDE) and matrix metalloproteinases. We investigated the relationship between levels of A beta and biological metals in CSF. We assayed CSF copper, zinc, other metals and A beta 42 in ventricular autopsy samples of Japanese American men (N=131) from the population-based Honolulu Asia Aging Study. There was a significant inverse correlation of CSF A beta 42 with copper, zinc, iron, manganese and chromium. The association was particularly strong in the subgroup with high levels of both zinc and copper. Selenium and aluminum levels were not associated to CSF A beta 42. In vitro, the degradation of synthetic A beta substrate added to CSF was markedly accelerated by low levels (2 mu M) of exogenous zinc and copper. While excessive interaction with copper and zinc may induce neocortical A beta precipitation in AD, soluble A beta degradation is normally promoted by physiological copper and zinc concentrations. (C) 2007 Elsevier Inc. All rights reserved.
C1 [Strozyk, Dorothea; Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Neuroepidemiol Sect, NIH, Bethesda, MD 20892 USA.
[Strozyk, Dorothea] Albert Einstein Coll Med, Dept Neurol, Bronx, NY 10467 USA.
[Adlard, Paul A.; Cherny, Robert A.; Tsatsanis, Andrew; Volitakis, Irene; Bush, Ashley I.] Univ Melbourne, Dept Pathol, Mental Hlth Res Inst Victoria, Melbourne, Vic 3010, Australia.
[Blennow, Kai] Sahlgrens Univ Hosp, Dept Clin Neurosci, Molndal, Sweden.
[Petrovitch, Helen; White, Lon R.] Kuakini Med Ctr, Pacific Hlth Res Inst, Honolulu, HI USA.
[Bush, Ashley I.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA.
RP Launer, LJ (reprint author), NIA, Lab Epidemiol Demog & Biometry, Neuroepidemiol Sect, NIH, Bethesda, MD 20892 USA.
EM launerl@nia.nih.gov; abush@mhri.edu.au
RI Bush, Ashley/A-1186-2007;
OI Bush, Ashley/0000-0001-8259-9069; Volitakis, Irene/0000-0003-0766-817X
FU NIH (National Institute on Aging) [1RO1 AG12686, 1 U01 AG19349-01, 5 R01
AG017155-04]; Intramural Research Program of the NIH; National Institute
on Aging; Australian Research Council Federation Fellowship; National
health and Medical Research Council of Australia; American Health
Assistance Foundation; University of Melbourne; Mental Health Research
Institute of Victoria, Victorian Forensic Institute of Medicine;
Neurosciences Australia and the National Health & Medical Research
Council
FX This study was supported by NIH (National Institute on Aging); Grant
Numbers 1RO1 AG12686 (to AIB), 1 U01 AG19349-01, 5 R01 AG017155-04, and
in part by the Intramural Research Program of the NIH, National
Institute on Aging, as well as (to AIB) the Australian Research Council
Federation Fellowship, the National health and Medical Research Council
of Australia, the Alzheimer Association Zenith Award and the American
Health Assistance Foundation. The Victorian Brain Bank Network is
supported by The University of Melbourne, The Mental Health Research
Institute of Victoria, Victorian Forensic Institute of Medicine and
funded by Neurosciences Australia and the National Health & Medical
Research Council.
NR 43
TC 68
Z9 71
U1 6
U2 20
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD JUL
PY 2009
VL 30
IS 7
BP 1069
EP 1077
DI 10.1016/j.neurobiolaging.2007.10.012
PG 9
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 453OI
UT WOS:000266619800007
PM 18068270
ER
PT J
AU Huang, SN
Liu, C
Dai, GP
Kim, YR
Rosen, BR
AF Huang, Shuning
Liu, Christina
Dai, Guangping
Kim, Young Ro
Rosen, Bruce R.
TI Manipulation of tissue contrast using contrast agents for enhanced MR
microscopy in ex vivo mouse brain
SO NEUROIMAGE
LA English
DT Article
ID MAGNETIC-RESONANCE MICROSCOPY; PROTON RELAXATION; HIGH-RESOLUTION;
MANGANESE IONS; RAT MYOCARDIUM; IN-VIVO; ATLAS; SUSCEPTIBILITY;
ACTIVATION; TRANSPORT
AB Detailed 3D mouse brain images may promote better understanding of phenotypical differences between normal and transgenic/mutant Mouse models. Previously, a number of magnetic resonance microscopy (MRM) studies have successfully established brain atlases, revealing genotypic traits of several commonly used mouse strains. In such Studies, MR contrast agents, mainly gadolinium (Gd) based, were often used to reduce acquisition time and improve signal-to-noise ratio (SNR). In this paper, we intended to extend the utility of contrast agents for MRM applications. Using Gd-DTPA and MnCl(2), we exploited the potential use of MR Contrast agents to manipulate image contrast by drawing upon the multiple relaxation mechanisms and tissue-dependent staining properties characteristic of each contrast agent. We quantified r(1) and r(2) of GdDTPA and MnCl(2) in both aqueous solution and brain tissue and demonstrated the presence of divergent relaxation mechanisms between solution and tissue for each contrast agent. Further analyses using nuclear magnetic resonance dispersion (NMRD) of Mn(2+) in ex vivo tissue strongly suggested macromolecule binding of Mn(2+), leading to increased T(1) relaxation. Moreover, inductively coupled plasma (ICP) mass spectroscopy revealed that MnCl(2) had higher tissue affinity than Gd-DTPA. As a result, multiple regions of the brain stained by the two agents exhibited different image contrasts. Our results show that differential MRM staining can be achieved using multiple MR contrast agents, revealing detailed cytoarchitecture, and may ultimately offer a window for investigating new techniques by which to understand biophysical MR relaxation mechanisms and perhaps to Visualize tissue anomalies even at the molecular level. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Kim, Young Ro] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Huang, Shuning; Rosen, Bruce R.] MIT, Cambridge, MA 02139 USA.
RP Kim, YR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, E Bldg 149,13th St, Charlestown, MA 02129 USA.
EM shuning@mit.edu; chliu@nmr.mgh.harvard.edu; dai@nmr.mgh.harvard.edu;
spmn@nmr.mgh.harvard.edu; bruce@nmr.mgh.harvard.edu
OI Liu, Christina/0000-0002-5723-177X
FU NCRR [P41RR14075]; NIBIB [8R01EB002066-14]; MIND Institute; Athinoula A.
Martincis Center for Biomedical Imaging
FX This project is supported by NCRR (P41RR14075), NIBIB (8R01EB002066-14),
the MIND Institute, and the Athinoula A. Martincis Center for Biomedical
Imaging. The authors would also like to thank Dr. Peter Caravan and Dr.
Ritika Uppal for their help and discussion on ICP analysis. We would
also like to thank Dr. Philip Liu for his technical support on brain
preparation.
NR 39
TC 20
Z9 21
U1 0
U2 3
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 JUL 1
PY 2009
VL 46
IS 3
BP 589
EP 599
DI 10.1016/j.neuroimage.2009.02.027
PG 11
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 443VK
UT WOS:000265938700005
PM 19264139
ER
PT J
AU Ou, WM
Nissila, I
Radhakrishnan, H
Boas, DA
Hamalainen, MS
Franceschini, MA
AF Ou, Wanmei
Nissila, Ilkka
Radhakrishnan, Harsha
Boas, David A.
Hamalainen, Matti S.
Franceschini, Maria Angela
TI Study of neurovascular coupling in humans via simultaneous
magnetoencephalography and diffuse optical imaging acquisition
SO NEUROIMAGE
LA English
DT Article
DE Magnetoencephalography (MEG); Diffuse optical imaging (DOI); Near
infrared spectroscopy (NIRS); Neurovascular coupling; Somatosensory
response; Primary sensory area (SI)
ID NEAR-INFRARED SPECTROSCOPY; RAT SOMATOSENSORY CORTEX;
CEREBRAL-BLOOD-FLOW; TOTAL-HEMOGLOBIN CONCENTRATION; ACTIVITY-DEPENDENT
INCREASES; MEDIAN NERVE-STIMULATION; LASER-DOPPLER FLOWMETRY; EVOKED
MAGNETIC-FIELDS; SURFACE-BASED ANALYSIS; RODENT BARREL CORTEX
AB By combining diffuse optical imaging (DOI) and magnetoencephalography (MEG) we investigate neurovascular coupling non-invasively in human subjects using median-nerve stimulation. Previous fMRI studies have shown a habituation effect in the hemodynamic blood oxygen level-dependent (BOLD) response for stimulation periods longer than 2 s. With DOI and MEG we can test whether this effect in hemodynamic response can be accounted for by a habituation effect in the neural response. Our experimental results show that the habituation effect in the hemodynamic response is stronger than that in the earliest cortical neural response (N20). Using a linear convolution model to predict hemodynamic responses we found that including late neural components (>= 30 ms) improves the prediction of the hemoglobin response. This finding suggests that in addition to the initial evoked-response deflections related to the talamic afferent input, later cortical activity is needed to predict the hemodynamic response. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Ou, Wanmei] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA.
[Nissila, Ilkka; Radhakrishnan, Harsha; Boas, David A.; Hamalainen, Matti S.; Franceschini, Maria Angela] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging,Dept Radiol, Boston, MA USA.
RP Ou, WM (reprint author), MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA.
EM wanmei@mit.edu; ilkka.nissila@hut.fi; harsha@nmr.mgh.harvard.edu;
dboas@nmr.mgh.harvard.edu; msh@nmr.mgh.harvard.edu;
mari@nmr.mgh.harvard.edu
RI Nissila, Ilkka/G-6879-2012; Radhakrishnan, Harsha/K-5557-2012;
Hamalainen, Matti/C-8507-2013
OI Nissila, Ilkka/0000-0001-6534-8436;
FU US National Institutes of Health (NIH) [R01-EB001954, P41-RR14075,
R01-EB006385]; NSF; PHS [DA022759-03]
FX We thank Dr. Solomon Diamond and Dr. Ted Huppert for helping with probe
design and Deirdre Foxe and Natsuko Mori for helping with MEG
measurements. This research is supported by the US National Institutes
of Health (NIH) grants R01-EB001954, P41-RR14075 and R01-EB006385.
Wanmei Ou is partially supported by the NSF graduate fellowship and the
PHS training grant DA022759-03.
NR 70
TC 30
Z9 31
U1 1
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 JUL 1
PY 2009
VL 46
IS 3
BP 624
EP 632
DI 10.1016/j.neuroimage.2009.03.008
PG 9
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 443VK
UT WOS:000265938700009
PM 19286463
ER
PT J
AU Neema, M
Goldberg-Zimring, D
Guss, ZD
Healy, BC
Guttmann, CRG
Houtchens, MK
Weiner, HL
Horsfield, MA
Hackney, DB
Alsop, DC
Bakshi, R
AF Neema, Mohit
Goldberg-Zimring, Daniel
Guss, Zachary D.
Healy, Brian C.
Guttmann, Charles R. G.
Houtchens, Maria K.
Weiner, Howard L.
Horsfield, Mark A.
Hackney, David B.
Alsop, David C.
Bakshi, Rohit
TI 3 T MRI relaxometry detects T2 prolongation in the cerebral
normal-appearing white matter in multiple sclerosis
SO NEUROIMAGE
LA English
DT Article
ID CLINICALLY ISOLATED SYNDROMES; T-2 RELAXATION; GRAY-MATTER; BRAIN
ATROPHY; SPINAL-CORD; HIGH-FIELD; 3.0 TESLA; IN-VIVO; TIME; LESIONS
AB MRI at 3 T has increased sensitivity in detecting overt multiple sclerosis (MS) brain lesions; a growing body of data suggests clinically relevant damage occurs in the normal-appearing white matter (NAWM). We tested a novel pulse sequence to determine whether 3 T MRI spin-spin relaxometry detected damage in NAWM of MS patients (n = 13) vs. age-matched normal controls [(NL) (n = 11)]. Baseline characteristics of the MS group were: age (mean +/- SD) 42.5 +/- 5.4 (range 33-51 years), disease duration 9.0 +/- 6.4 (range 1-22 years), Expanded Disability Status Scale score 2.5 +/- 1.7 (range 1-6.5). Brain MRI measures, obtained at 3 T, included global and regional NAWM transverse relaxation rate [R2 (=1/T2)], derived from 3D fast spin-echo T2 prepared images, and global white matter volume fraction derived from SPGR images. The regional NAWM areas investigated were the frontal lobe, parietal lobe, and the genu and splenium of the corpus callosum. Mean NAWM R2 was lower (indicating T2 prolongation) in MS than NL, in the whole brain (p = 0.00047). frontal NAWM (p = 0.00015), parietal NAWM (p = 0.0069) and callosal genu (p = 0.0019). Similarly, R2 histogram peak position was lower in NAWM in MS than NL in the whole brain (p = 0.019). However, the normalized WM Volume fractions were similar in both MS and NL (p > 0.1). This pilot study suggests that a novel 3D fast spin-echo pulse sequence at 3 T, used to derive R2 relaxation maps, can detect tissue damage in the global and regional cerebral NAWM of MS patients that is missed by conventional lesion and atrophy measures. Such findings may represent demyelination, inflammation, glial proliferation and axonal loss. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Neema, Mohit; Goldberg-Zimring, Daniel; Guss, Zachary D.; Healy, Brian C.; Guttmann, Charles R. G.; Houtchens, Maria K.; Weiner, Howard L.; Bakshi, Rohit] Harvard Univ, Sch Med, Dept Neurol,Partners MS Ctr, Brigham & Womens Hosp,Lab Neuroimaging Res, Boston, MA 02115 USA.
[Goldberg-Zimring, Daniel; Guttmann, Charles R. G.; Bakshi, Rohit] Harvard Univ, Sch Med, Dept Radiol,Partners MS Ctr, Brigham & Womens Hosp,Lab Neuroimaging Res, Boston, MA 02115 USA.
[Healy, Brian C.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA.
[Horsfield, Mark A.] Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England.
[Hackney, David B.; Alsop, David C.] Harvard Univ, Sch Med, Dept Radiol, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA.
RP Neema, M (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Lab Neuroimaging Res, 1 Brookline Pl,Suite 602, Brookline, MA 02445 USA.
EM mneema@bwh.harvard.edu
RI Horsfield, Mark/C-6569-2013; Alsop, David/J-5764-2013; Hackney,
David/A-5337-2010
OI Horsfield, Mark/0000-0002-0815-6697; Alsop, David/0000-0002-8206-1995;
FU National Institutes of Health [K23 NS42379-01, 1101 NS055083-01];
National Multiple Sclerosis Society [RG3705A1, RG3798A2, RG4032A1/1]
FX This work was Supported by research grants from the National Institutes
of Health (NIH-NINDS K23 NS42379-01 and 1101 NS055083-01) and National
Multiple Sclerosis Society (RG3705A1; RG3798A2; RG4032A1/1). We thank
Ms. Sophie Tamm for her assistance with manuscript preparations.
NR 56
TC 44
Z9 44
U1 0
U2 5
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 JUL 1
PY 2009
VL 46
IS 3
BP 633
EP 641
DI 10.1016/j.neuroimage.2009.03.001
PG 9
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 443VK
UT WOS:000265938700010
PM 19281850
ER
PT J
AU Latorre, JGS
Greer, DM
AF Latorre, Julius Gene S.
Greer, David M.
TI Management of Acute Intracranial Hypertension A Review
SO NEUROLOGIST
LA English
DT Review
DE intracranial pressure; intracranial hypertension; acute brain injury;
neurocritical care
ID TRAUMATIC BRAIN-INJURY; SEVERE HEAD-INJURY; CEREBRAL-BLOOD-FLOW;
INTENSIVE INSULIN THERAPY; ARTERY TERRITORY INFARCTION; INTRA-CRANICAL
PRESSURE; ACUTE ISCHEMIC STROKE; SPONTANEOUS INTRACEREBRAL HEMORRHAGE;
FRAMELESS STEREOTACTIC ASPIRATION; PROLONGED PROPOFOL INFUSION
AB Background: Patients with acute brain injury from various etiologies commonly develop increased intracranial pressure. Acute intracranial hypertension resulting from elevation of intracranial pressure is a medical emergency requiring prompt diagnosis and management. Appropriate and timely management strategies result in better patient outcome in an otherwise severely debilitating or fatal disease process.
Review Summary: The clinical manifestation and principles of management of acute intracranial hypertension are discussed and reviewed. Acute treatment protocols are presented in an algorithm-based format aimed at utilizing the current available management strategies and suggested therapeutic goals. Individualization of specific therapeutic modalities is emphasized to optimize the clinical outcome.
Conclusions: Clinicians treating patients with acute brain injury should be familiar with the principles of management of increased intracranial pressure. Since acute intracranial hypertension is a potentially reversible condition, high index of suspicion, and low threshold for diagnostic and therapeutic strategies will improve patient care.
C1 [Latorre, Julius Gene S.] SUNY Upstate Med Univ, Dept Neurol, Syracuse, NY 13210 USA.
[Greer, David M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA.
RP Latorre, JGS (reprint author), SUNY Upstate Med Univ, Dept Neurol, 7134UH,750 E Adams St, Syracuse, NY 13210 USA.
EM latorrej@upstate.edu
NR 275
TC 12
Z9 15
U1 2
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1074-7931
J9 NEUROLOGIST
JI Neurologist
PD JUL
PY 2009
VL 15
IS 4
BP 193
EP 207
DI 10.1097/NRL.0b013e31819f956a
PG 15
WC Clinical Neurology
SC Neurosciences & Neurology
GA 469PC
UT WOS:000267911000004
PM 19590379
ER
PT J
AU Stella, SL
Hu, WD
Brecha, NC
AF Stella, Salvatore L., Jr.
Hu, Wanda D.
Brecha, Nicholas C.
TI Adenosine suppresses exocytosis from cone terminals of the salamander
retina
SO NEUROREPORT
LA English
DT Article
DE activity-dependent dye; ATP; Ca(2+) channel; L-glutamate; purines;
Synaptored-C2
ID CALCIUM-CHANNELS; RECEPTORS; PHOTORECEPTORS; RODS; CA2+; SYNAPSES;
SLICES; FM1-43; INFLUX; RAT
AB In the retina, adenosine is released in the dark and has been shown to inhibit Ca(2+) influx through voltage-gated Ca(2+) channels in cones. Therefore, we tested whether adenosine can inhibit exocytosis from isolated cone photoreceptors. Simultaneous measurements of membrane exocytosis and Ca(2+) were made from cones using the activity-dependent dye, Synaptored-C2, and the Ca(2+) indicator dye, Fluo-4. Adenosine suppressed exocytosis in cones, indicating that transmitter release is also reduced from cone terminals, and further supports an inhibitory mechanism for modulating transmitter release onto second-order neurons. Furthermore, this raises the possibility that adenosine might be neuroprotective for photoreceptors and second-order neurons by suppressing Ca(2+) levels in cones and reducing exocytosis of L-glutamate, respectively. NeuroReport 20:923-929 (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins.
C1 [Stella, Salvatore L., Jr.; Hu, Wanda D.; Brecha, Nicholas C.] Univ Calif Los Angeles, Dept Neurobiol, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Brecha, Nicholas C.] Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Brecha, Nicholas C.] Univ Calif Los Angeles, Jules Stein Eye Inst, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Brecha, Nicholas C.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
RP Stella, SL (reprint author), Univ Calif Los Angeles, Dept Neurobiol, David Geffen Sch Med, 10833 Conte Blvd,Box 951763,CHS 73-323, Los Angeles, CA 90095 USA.
EM sstella@mednet.ucla.edu
OI Stella Jr., Salvatore/0000-0003-1971-2537
FU NIH [04067, 41301]; VA Senior Career Scientist; Fight-For-Sight Student
Fellowship; Jeanette Duval Scholarship; UCLA Undergraduate Research
Scholars Program
FX The authors thank Alejandro Vila and Uyenchi Huynh for providing
technical support, and Arlene Hirano for critically reading earlier
versions of this manuscript and providing insightful comments. This
research was supported by NIH grants EY 04067, and DK 41301 and a VA
Senior Career Scientist to N.C.B., Fight-For-Sight, Grant-in-Aid to
S.L.S., and Fight-For-Sight Student Fellowship, Jeanette Duval
Scholarship, and UCLA Undergraduate Research Scholars Program to W.D.H.
NR 23
TC 3
Z9 3
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 JUL 1
PY 2009
VL 20
IS 10
BP 923
EP 929
DI 10.1097/WNR.0b013e32832ca4b0
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA 466AW
UT WOS:000267633600006
PM 19491713
ER
PT J
AU Reed, CL
Hagler, DJ
Marinkovic, K
Dale, A
Halgren, E
AF Reed, Catherine L.
Hagler, Donald J., Jr.
Marinkovic, Ksenija
Dale, Anders
Halgren, Eric
TI Sequences of cortical activation for tactile pattern discrimination
using magnetoencephalography
SO NEUROREPORT
LA English
DT Article
DE magnetoencephalography; neuroimaging; object recognition; pattern
recognition; somatosensory; spatiotemporal maps; tactile; touch
ID OBJECT RECOGNITION; SURFACE RECONSTRUCTION; FMRI; MEG; LOCALIZATION;
SYSTEM; FIELDS; CORTEX; TOUCH; SHAPE
AB To observe sequential stages in tactile pattern discrimination and their modification with and without attention, we used whole-head anatomically constrained magnetoencephalography to spatiotemporally map brain responses. Eight, normal, right-handed participants discriminated between two patterns presented on the palm. Latencies of neural activity were determined from stimulus contact with the palm. Early cortical activation moved from sensorimotor cortex (SM1) to secondary somatosensory cortex (SII), Broca's area (BA), and superior parietal cortex by 65 ms. It continued bilaterally to temporal and frontal poles by 290 ms. Subtraction of nonattended from attended conditions removed primarily the early contralateral sensory components. There was some indication of a preferred order of sensory processing that may express and optimize hemispheric computational specializations. Results indicate similar functional organizations for tactile and visual pattern recognition. NeuroReport 20:941-945 (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins.
C1 [Reed, Catherine L.] Claremont Mckenna Coll, Dept Psychol, Claremont, CA 91711 USA.
[Reed, Catherine L.] Univ Denver, Dept Psychol, Denver, CO 80208 USA.
[Hagler, Donald J., Jr.] Univ Calif San Diego, Dept Cognit Sci, La Jolla, CA 92093 USA.
[Dale, Anders; Halgren, Eric] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA.
[Dale, Anders; Halgren, Eric] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
[Marinkovic, Ksenija; Halgren, Eric] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA.
[Marinkovic, Ksenija] Massachusetts Gen Hosp, Martinos Ctr, Boston, MA 02114 USA.
RP Reed, CL (reprint author), Claremont Mckenna Coll, Dept Psychol, 850 Columbia Ave, Claremont, CA 91711 USA.
EM cathy.reed@cmc.edu
RI Dale, Anders/A-5180-2010
NR 25
TC 3
Z9 3
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 JUL 1
PY 2009
VL 20
IS 10
BP 941
EP 945
DI 10.1097/WNR.0b013e32832c5f65
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 466AW
UT WOS:000267633600009
PM 19525880
ER
PT J
AU Hu, R
Eskandar, E
Williams, Z
AF Hu, Rollin
Eskandar, Emad
Williams, Ziv
TI Role of deep brain stimulation in modulating memory formation and recall
SO NEUROSURGICAL FOCUS
LA English
DT Article
DE deep brain stimulation; learning; memory
ID 3 MOTOR AREAS; BASAL GANGLIA; NEURONAL-ACTIVITY; STRIATUM; CORTEX;
MONKEY; MOVEMENT; ENHANCEMENT; HIPPOCAMPAL; EXPECTATION
AB Deep brain stimulation (DBS) has become an increasingly popular tool for treating a variety of medically refractory neurological and psychiatric disorders such as Parkinson disease, essential tremor, depression, and obsessive-compulsive disorder. Several targets have been identified for ablation or stimulation based on their anatomical location and presumed function. Areas such as the subthalamic nucleus, globus pallidus, and thalamus, for example, are believed to play a key role in motor control and execution, and they are commonly used in the treatment of motor disorders. Limbic structures such as the cingulate cortex and ventral striatum, believed to be important in motivation, emotion, and higher cognition, have also been targeted for treatment of a number of psychiatric disorders. In all of these settings, DBS is largely aimed at addressing the deleterious aspects of these diseases. In Parkinson disease, for example, DBS has been used to reduce rigidity and tremor, whereas in obsessive-compulsive disorder it has been used to limit compulsive behavior. More recently, however, attention has also turned to the potential use of DBS for enhancing or improving otherwise nonpathological aspects of cognitive function. This review explores the potential role of DBS in augmenting memory formation and recall, and the authors discuss recent studies and future trends in this emerging field. (DOI:10.3171/2009.4.FOCUS0975)
C1 [Hu, Rollin; Eskandar, Emad; Williams, Ziv] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
RP Williams, Z (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St,WAC 745K, Boston, MA 02114 USA.
EM zwilliams@partners.org
FU NEI NIH HHS [R01 EY017658-03, R01 EY017658, R01 EY017658-01A1, R01
EY017658-02]; NIDA NIH HHS [R01 DA026297-02, R01 DA026297-01, R01
DA026297]
NR 41
TC 9
Z9 9
U1 0
U2 3
PU AMER ASSOC NEUROLOGICAL SURGEONS
PI ROLLING MEADOWS
PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA
SN 1092-0684
J9 NEUROSURG FOCUS
JI Neurosurg. Focus
PD JUL
PY 2009
VL 27
IS 1
AR E3
DI 10.3171/2009.4.FOCUS0975
PG 5
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 478JI
UT WOS:000268583300003
PM 19569891
ER
PT J
AU Pezaris, JS
Eskandar, EN
AF Pezaris, John S.
Eskandar, Emad N.
TI Getting signals into the brain: visual prosthetics through thalamic
microstimulation
SO NEUROSURGICAL FOCUS
LA English
DT Article
DE visual prosthesis; deep brain stimulation; visual function
ID LATERAL GENICULATE-NUCLEUS; HUMAN OCCIPITAL CORTEX;
ELECTRICAL-STIMULATION; OPTIC-NERVE; PARKINSONS-DISEASE; INTRACORTICAL
MICROSTIMULATION; MAGNETIC STIMULATION; RETINITIS-PIGMENTOSA; RETINAL
PROSTHESIS; ARTIFICIAL VISION
AB Common causes of blindness are diseases that affect the ocular structures, such as glaucoma, retinitis pigmentosa, and macular degeneration, rendering the eyes no longer sensitive to light. The visual pathway, however, as a predominantly central structure, is largely spared in these cases. It is thus widely thought that a device-based prosthetic approach to restoration of visual function will be effective and will enjoy similar success as cochlear implants have for restoration of auditory function. In this article the authors review the potential locations for stimulation electrode placement for visual prostheses, assessing the anatomical and functional advantages and disadvantages of each. Of particular interest to the neurosurgical community is placement of deep brain stimulating electrodes in thalamic structures that has shown substantial promise in an animal model. The theory of operation of visual prostheses is discussed, along with a review of the current state of knowledge. Finally, the visual prosthesis is proposed as a model for a general high-fidelity machine-brain interface. (DOI:10.3171/2009.4.FOCUS0986)
C1 [Pezaris, John S.; Eskandar, Emad N.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
RP Pezaris, JS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St,THR 425, Boston, MA 02114 USA.
EM pezaris.john@mgh.harvard.edu
FU NEI NIH HHS [R01 EY017658-01A1, R01 EY017658, R01 EY017658-02, R01
EY017658-03, R01 EY019679]; NIDA NIH HHS [R01 DA026297, R01 DA026297-01,
R01 DA026297-02]
NR 92
TC 27
Z9 30
U1 3
U2 12
PU AMER ASSOC NEUROLOGICAL SURGEONS
PI ROLLING MEADOWS
PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA
SN 1092-0684
J9 NEUROSURG FOCUS
JI Neurosurg. Focus
PD JUL
PY 2009
VL 27
IS 1
AR E6
DI 10.3171/2009.4.FOCUS0986
PG 11
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 478JI
UT WOS:000268583300006
PM 19569894
ER
PT J
AU Oh, MC
Lim, DA
AF Oh, Michael C.
Lim, Daniel A.
TI Novel Treatment Strategies for Malignant Gliomas Using Neural Stem Cells
SO NEUROTHERAPEUTICS
LA English
DT Review
DE Neural stem cells; brain tumor stem cells; glioma; gene therapy
ID APOPTOSIS-INDUCING LIGAND; TUMOR-INITIATING CELLS; GENE-THERAPY;
PROGENITOR CELLS; PRECURSOR CELLS; BRAIN-TUMORS;
GLIOBLASTOMA-MULTIFORME; SUBVENTRICULAR ZONE; ADULT BRAIN; IN-VIVO
AB Recent studies in stem cell biology have refined our understanding of the origin and progression of cancer. Identification and characterization of endogenous neural stem cells (NSCs), especially those in the adult human brain, have inspired new ideas for selectively targeting and destroying malignant gliomas. Gliomas consist of a heterogeneous population of cells, and some of these cells have characteristics of cancer stem cells. These brain tumor stem cells (BTSCs) share certain characteristics with normal NSCs. It is still unclear, however, whether malignant gliomas in human patients originate from these aberrant BTSCs. Nonetheless, the cellular and molecular similarities between BTSCs and normal NSCs suggest a common research landscape underlying both normal and cancer stem cell biology, wherein findings of one field are relevant to the other. Furthermore, the natural tropism of NSCs to gliomas has generated the idea that modified NSCs can deliver modified genes to selectively destroy malignant brain tumor cells, and even BTSCs, while leaving healthy surrounding neurons intact. These studies and others on the basic biology of both BTSCs and NSCs will be crucial to expanding our treatment strategies for malignant gliomas.
C1 [Oh, Michael C.; Lim, Daniel A.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA.
[Lim, Daniel A.] San Francisco VA Med Ctr, Surg Serv, Neurosurg Sect, Dept Vet Affairs, San Francisco, CA 94121 USA.
RP Oh, MC (reprint author), Univ Calif San Francisco, Dept Neurol Surg, 505 Parnassus Ave, San Francisco, CA 94143 USA.
EM ohmc@neurosurg.ucsf.edu
NR 66
TC 10
Z9 10
U1 0
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1933-7213
J9 NEUROTHERAPEUTICS
JI Neurotherapeutics
PD JUL
PY 2009
VL 6
IS 3
BP 458
EP 464
PG 7
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 465KE
UT WOS:000267581800005
PM 19560736
ER
PT J
AU Chi, AS
Norden, AD
Wen, PY
AF Chi, Andrew S.
Norden, Andrew D.
Wen, Patrick Y.
TI Antiangiogenic Strategies for Treatment of Malignant Gliomas
SO NEUROTHERAPEUTICS
LA English
DT Review
DE Malignant glioma; glioblastoma; angiogenesis; vascular endothelial
growth factor; edema; biomarker
ID ENDOTHELIAL-GROWTH-FACTOR; PHASE-II TRIAL; HIGH-GRADE GLIOMAS;
NEWLY-DIAGNOSED GLIOBLASTOMA; BEVACIZUMAB PLUS IRINOTECAN; LOW-DOSE
CHEMOTHERAPY; ANTI-ANGIOGENIC THERAPY; RENAL-CELL CARCINOMA; RECURRENT
GLIOBLASTOMA; TUMOR ANGIOGENESIS
AB Numerous antiangiogenic agents with diverse mechanisms of action are currently under investigation for the treatment of patients with glioblastoma (GBM), a diagnosis that continues to carry a poor prognosis despite maximal conventional therapy. Early clinical trials suggest that antiangiogenic drugs, which target the blood vessels of these highly angiogenic tumors, may have clinical benefit in GBM patients. Antiangiogenic agents have potent antiedema and steroid-sparing effects in patients, and emerging data suggest that these drugs may modestly improve progression-free survival. Although these early results are encouraging, several issues arise regarding the use and efficacy of these agents. Interpretation of the radiographic changes that occur after treatment with antiangiogenic agents presents a major challenge. Still lacking are reliable radiographic and biologic markers that can predict which patients will benefit from treatment and that accurately indicate response and progression during therapy. In addition, most patients treated with antiangiogenic drugs eventually progress, and the mechanisms by which tumors escape from therapy are only beginning to be understood. Larger prospective trials that incorporate correlative biomarker studies will be required to address these challenges. Here, we summarize the clinical experience with antiangiogenic therapy in patients with malignant gliomas (MG), review the major issues concerning the use and development of these agents, and discuss strategies that may build upon the initial gains observed with antiangiogenic agents.
C1 [Norden, Andrew D.; Wen, Patrick Y.] Dana Farber Brigham & Womans Canc Ctr, Ctr Neurooncol, Dept Med Oncol, Boston, MA 02115 USA.
[Norden, Andrew D.; Wen, Patrick Y.] Brigham & Womens Hosp, Dept Neurol, Div Neurooncol, Boston, MA 02115 USA.
[Chi, Andrew S.; Norden, Andrew D.; Wen, Patrick Y.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Chi, Andrew S.; Norden, Andrew D.; Wen, Patrick Y.] Dana Farber Harvard Canc Ctr, Boston, MA 02115 USA.
[Chi, Andrew S.] Massachusetts Gen Hosp, Ctr Canc,Dept Neurol, Stephen E & Catherine Pappas Ctr Neurooncol, Div Hematol & Oncol, Boston, MA 02115 USA.
RP Wen, PY (reprint author), Dana Farber Brigham & Womans Canc Ctr, Ctr Neurooncol, Dept Med Oncol, SW430 D,44 Binney St, Boston, MA 02115 USA.
EM patrick_wen@dfci.harvard.edu
FU Melinda Wanatick Brain Tumor Research Fund
FX We gratefully acknowledge the support of the Melinda Wanatick Brain
Tumor Research Fund.
NR 127
TC 23
Z9 23
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1933-7213
J9 NEUROTHERAPEUTICS
JI Neurotherapeutics
PD JUL
PY 2009
VL 6
IS 3
BP 513
EP 526
PG 14
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 465KE
UT WOS:000267581800010
PM 19560741
ER
PT J
AU Janulewicz, P
Walsh, J
Nixon, T
Olson, S
Holmes, L
Adams, J
AF Janulewicz, Patricia
Walsh, Jessica
Nixon, Tanya
Olson, Sam
Holmes, Lewis
Adams, Jane
TI Attention and working memory in children exposed prenatally to
anticonvulsant monotherapy
SO NEUROTOXICOLOGY AND TERATOLOGY
LA English
DT Meeting Abstract
CT 33rd Annual Meeting of the Neurobehavioral-Teratology-Society/49th
Annual Meeting of the Teratology-Society/22nd Annual Meeting of the
Organization-of-Teratology-Information-Specialists
CY JUN 28-JUL 01, 2009
CL Rio Grande, PR
SP Neurobehav Teratol Soc, Teratol Soc, Org Teratol Informat Specialists
C1 [Janulewicz, Patricia; Walsh, Jessica; Nixon, Tanya; Olson, Sam; Adams, Jane] Univ Massachusetts, Boston, MA 02125 USA.
[Holmes, Lewis] MassGen Hosp Children, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0892-0362
J9 NEUROTOXICOL TERATOL
JI Neurotoxicol. Teratol.
PD JUL-SEP
PY 2009
VL 31
IS 4
MA NBTS51
BP 249
EP 250
DI 10.1016/j.ntt.2009.04.055
PG 2
WC Neurosciences; Toxicology
SC Neurosciences & Neurology; Toxicology
GA 461GY
UT WOS:000267253900058
ER
PT J
AU Naamati, G
Askenazi, M
Linial, M
AF Naamati, Guy
Askenazi, Manor
Linial, Michal
TI ClanTox: a classifier of short animal toxins
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID 3-FINGER TOXINS; EVOLUTION; DATABASE; PREDICTION; SEQUENCES; PEPTIDES;
PROTEINS; SERVER
AB Toxins are detected in sporadic species along the evolutionary tree of the animal kingdom. Venomous animals include scorpions, snakes, bees, wasps, frogs and numerous animals living in the sea such as the stonefish, snail, jellyfish, hydra and more. Interestingly, proteins that share a common scaffold with animal toxins also exist in non-venomous species. However, due to their short length and primary sequence diversity, these, toxin-like proteins remain undetected by classical search engines and genome annotation tools. We construct a toxin classification machine and web server called ClanTox (Classifier of Animal Toxins) that is based on the extraction of sequence-driven features from the primary protein sequence followed by the application of a classification system trained on known animal toxins. For a given input list of sequences, from venomous or non-venomous settings, the ClanTox system predicts whether each sequence is toxin-like. ClanTox provides a ranked list of positively predicted candidates according to statistical confidence. For each protein, additional information is presented including the presence of a signal peptide, the number of cysteine residues and the associated functional annotations. ClanTox is a discovery-prediction tool for a relatively overlooked niche of toxin-like cell modulators, many of which are therapeutic agent candidates. The ClanTox web server is freely accessible at http://www.clantox.cs.huji.ac.il.
C1 [Askenazi, Manor; Linial, Michal] Hebrew Univ Jerusalem, Sudarsky Ctr Computat Biol, Inst Life Sci, Dept Biol Chem, IL-91905 Jerusalem, Israel.
[Askenazi, Manor] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02115 USA.
RP Linial, M (reprint author), Hebrew Univ Jerusalem, Sudarsky Ctr Computat Biol, Inst Life Sci, Dept Biol Chem, IL-91905 Jerusalem, Israel.
EM michall@cc.huji.ac.il
OI Naamati, Guy/0000-0002-0523-4071
FU Israel Science Foundation (ISF); US-Israel Binational Science Foundation
(BSF); Sudarsky Center for Computational Biology (SCCB)
FX Israel Science Foundation (ISF) and the US-Israel Binational Science
Foundation (BSF); Sudarsky Center for Computational Biology (SCCB) (to
G. N.).
NR 23
TC 19
Z9 19
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JUL 1
PY 2009
VL 37
BP W363
EP W368
DI 10.1093/nar/gkp299
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 469IG
UT WOS:000267889100064
PM 19429697
ER
PT J
AU Oeffinger, KC
Ford, JS
Moskowitz, CS
Diller, LR
Hudson, MM
Chou, JF
Smith, SM
Mertens, AC
Henderson, TO
Friedman, DL
Leisenring, WM
Robison, LL
AF Oeffinger, Kevin C.
Ford, Jennifer S.
Moskowitz, Chaya S.
Diller, Lisa R.
Hudson, Melissa M.
Chou, Joanne F.
Smith, Stephanie M.
Mertens, Ann C.
Henderson, Tara O.
Friedman, Debra L.
Leisenring, Wendy M.
Robison, Leslie L.
TI Breast Cancer Surveillance Practices Among Women Previously Treated With
Chest Radiation for a Childhood Cancer EDITORIAL COMMENT
SO OBSTETRICAL & GYNECOLOGICAL SURVEY
LA English
DT Editorial Material
C1 [Oeffinger, Kevin C.] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA.
Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA.
Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY 10021 USA.
Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
St Jude Childrens Hosp, Memphis, TN 38105 USA.
Emory Univ, Atlanta, GA 30322 USA.
Univ Chicago, Chicago, IL 60637 USA.
Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA.
Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
RP Oeffinger, KC (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pediat, 1275 York Ave, New York, NY 10021 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7828
J9 OBSTET GYNECOL SURV
JI Obstet. Gynecol. Surv.
PD JUL
PY 2009
VL 64
IS 7
BP 466
EP 467
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 463AQ
UT WOS:000267401100020
ER
PT J
AU Winkfield, KM
Harris, JR
AF Winkfield, Karen M.
Harris, Jay R.
TI Effective Local Therapy and Long-Term Survival in Breast Cancer
SO ONCOLOGY-NEW YORK
LA English
DT Article
AB The causal link between local control and long-term survival in breast cancer has become clearer over the past few years. Although the prevalence of breast cancer is high, there has been a steady decline in breast cancer mortality since the early 1990s. Improvements in breast cancer-specific mortality are the result of greater emphasis on cancer screening and improved treatment modalities, principally the development of effective adjuvant systemic therapy. Adjuvant radiation therapy (RT) substantially reduces local recurrence rates, and this reduction is even greater when combined with systemic therapy. Randomized controlled trials and meta-analyses have shown that reducing local recurrence improves overall long-term survival following both mastectomy and breast-conserving therapy. Clinical and translational research has begun to shed light on new prognostic and predictive markers that can assist in the assessment of an individual patient's risk of local recurrence without RT and the likelihood of a survival benefit with RT. The ability to appropriately tailor therapy to reduce local recurrence rates is vital toward continuing the decline in breast cancer mortality.
C1 [Harris, Jay R.] Harvard Univ, Dana Farber Canc Inst, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Harris, Jay R.] Harvard Univ, Dept Radiat Oncol, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Winkfield, Karen M.] Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA 02115 USA.
RP Harris, JR (reprint author), Harvard Univ, Dana Farber Canc Inst, Brigham & Womens Hosp, Sch Med, 44 Binney St,Dana 1622, Boston, MA 02115 USA.
EM JHarris@LROC.Harvard.edu
NR 31
TC 3
Z9 3
U1 0
U2 1
PU UBM MEDICA
PI NORWALK
PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA
SN 0890-9091
J9 ONCOLOGY-NY
JI Oncology-NY
PD JUL
PY 2009
VL 23
IS 8
BP 669
EP 675
PG 7
WC Oncology
SC Oncology
GA V18PR
UT WOS:000208017200001
PM 19711579
ER
PT J
AU Jakobiec, FA
Mehta, M
Sutula, F
AF Jakobiec, Frederick A.
Mehta, Manisha
Sutula, Francis
TI Keratinous Cyst of the Palpebral Conjunctiva
SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY
LA English
DT Article
AB A whitish-opalescent, mildly elevated superior tarsal conjunctival lesion measuring 3.0 mm in diameter caused a refractory corneal abrasion in a 54-year-old man. Complete local excision without entering the tarsus produced relief of symptoms. There has been no recurrence during 9 months of follow-up. Histopathologically, a unique keratinous cyst was delimited mostly by basaloid cells resembling the matrical cells in pilomatrixoma. There were no keratohyalin granules in the lining cells, which focally transformed in ghost cells. These histopathologic features are characteristic of trichilemmal keratinization, a heretofore undescribed metaplasia of the conjunctival epithelium.
C1 [Jakobiec, Frederick A.; Mehta, Manisha] Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA.
[Mehta, Manisha; Sutula, Francis] Massachusetts Eye & Ear Infirm, Oculoplast Serv, Dept Ophthalmol, Boston, MA 02114 USA.
RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, 243 Charles St,Room 321, Boston, MA 02114 USA.
NR 9
TC 5
Z9 5
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0740-9303
J9 OPHTHAL PLAST RECONS
JI Ophthalmic Plast. Reconstr. Surg.
PD JUL-AUG
PY 2009
VL 25
IS 4
BP 337
EP 339
DI 10.1097/IOP.0b013e3181aada9a
PG 3
WC Ophthalmology; Surgery
SC Ophthalmology; Surgery
GA 474MQ
UT WOS:000268288600028
PM 19617807
ER
PT J
AU Salti, HI
Nasrallah, M
Haddad, S
Khairallah, W
Salti, IS
AF Salti, Haytham I.
Nasrallah, Mona
Haddad, Sandra
Khairallah, Walid
Salti, I. S.
TI Enhancing Nonmydriatic Color Photographs of the Retina With
Monochromatic Views and a Stereo Pair to Detect Diabetic Retinopathy
SO OPHTHALMIC SURGERY LASERS & IMAGING
LA English
DT Article
ID OPHTHALMOSCOPY; CAMERA; SPECIFICITY; SENSITIVITY; IMAGES
AB BACKGROUND AND OBJECTIVE: Nonmydriatic digital color imaging is rapidly gaining an important role in screening for diabetic retinopathy. However, it has yet to equal a dilated fundus examination or seven Early Treatment Diabetic Retinopathy Study field 35-mm photography. The authors therefore attempted to enhance efficacy and validity by adding two low-cost steps to the nonmydriatic digital image evaluation.
PATIENTS AND METHODS: The fundi of 145 consecutive patients with diabetes mellitus were evaluated for diabetic retinopathy using two different nonmydriatic reading techniques: creating a red-free view (using digital filters) and looking at a stereo pair of each field taken. These methods were each compared to a mydriatic fundus examination.
RESULTS: although the first technique yielded views with sensitivities and specificities similar to what exists in the literature using this same technique, enhancing these photographs (second technique) yielded a statistically significant increase in sensitivity and specificity (P < .005).
CONCLUSION: The authors recommend using both low-cost steps when screening for diabetic retinopathy through nonmydriatic digital color imaging.
C1 [Salti, Haytham I.; Haddad, Sandra] Amer Univ Beirut, Med Ctr, Dept Ophthalmol, Beirut 11072020, Lebanon.
[Nasrallah, Mona; Salti, I. S.] Amer Univ Beirut, Med Ctr, Div Endocrinol & Metab, Beirut 11072020, Lebanon.
[Khairallah, Walid] Joslin Diabet Ctr, Manama, Bahrain.
RP Salti, HI (reprint author), Amer Univ Beirut, Med Ctr, Dept Ophthalmol, POB 110236, Beirut 11072020, Lebanon.
NR 19
TC 1
Z9 2
U1 0
U2 1
PU SLACK INC
PI THOROFARE
PA 6900 GROVE RD, THOROFARE, NJ 08086 USA
SN 1542-8877
J9 OPHTHAL SURG LAS IM
JI Ophthalmic Surg. Lasers Imaging
PD JUL-AUG
PY 2009
VL 40
IS 4
BP 373
EP 378
DI 10.3928/15428877-2006030-04
PG 6
WC Ophthalmology; Surgery
SC Ophthalmology; Surgery
GA 472JV
UT WOS:000268127800004
PM 19634741
ER
PT J
AU Savar, A
Vavvas, D
AF Savar, Aaron
Vavvas, Demetrios
TI Optical Coherence Tomography Appearance of a Retinal Artery
Macroaneurysm
SO OPHTHALMIC SURGERY LASERS & IMAGING
LA English
DT Article
AB Macroaneuysms are saccular dilatations of the retinal arterioles commonly seen in systemic hypertension. The authors present the first report of the high-resoultion optical coherence tomography appearance of all unruptured retinal artery macroaneurysm. [Ophthalmic Surg Lasers Imaging 2009;40:403-404.]
C1 [Savar, Aaron; Vavvas, Demetrios] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
RP Savar, A (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA.
OI Vavvas, Demetrios/0000-0002-8622-6478
NR 7
TC 3
Z9 3
U1 0
U2 0
PU SLACK INC
PI THOROFARE
PA 6900 GROVE RD, THOROFARE, NJ 08086 USA
SN 1542-8877
J9 OPHTHAL SURG LAS IM
JI Ophthalmic Surg. Lasers Imaging
PD JUL-AUG
PY 2009
VL 40
IS 4
BP 403
EP 404
DI 10.3928/15428877-20096030-09
PG 2
WC Ophthalmology; Surgery
SC Ophthalmology; Surgery
GA 472JV
UT WOS:000268127800009
PM 19634746
ER
PT J
AU Kumar, ATN
Chung, E
Raymond, SB
van de Water, JAJM
Shah, K
Fukumura, D
Jain, RK
Bacskai, BJ
Boas, DA
AF Kumar, Anand T. N.
Chung, Euiheon
Raymond, Scott B.
van de Water, Jeroen A. J. M.
Shah, Khalid
Fukumura, Dai
Jain, Rakesh K.
Bacskai, Brian J.
Boas, David A.
TI Feasibility of in vivo imaging of fluorescent proteins using lifetime
contrast
SO OPTICS LETTERS
LA English
DT Article
ID TOMOGRAPHY; MICROSCOPY; DOMAIN; CELLS
AB We show that fluorescence lifetime is a powerful contrast mechanism that can enhance the whole-body imaging of fluorescent proteins (FPs), in the presence of background tissue autofluorescence (AF). The nonexponential AF decay is characterized from time-domain (TD) measurements on multiple nude mice and separated from the FP fluorescence using a linear fit to a priori basis functions. We illustrate this approach using an orthotopic mouse tumor model of breast adenocarcinoma. We also report that four commonly used FPs show distinct lifetimes, indicating their suitability for in vivo lifetime multiplexing. These results suggest the potential for exploiting fluorescence lifetime for imaging Fps for a variety of whole-body small-animal imaging applications. (C) 2009 Optical Society of America
C1 [Kumar, Anand T. N.; Boas, David A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Chung, Euiheon; Fukumura, Dai; Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02129 USA.
[Raymond, Scott B.] Harvard Mit Div Hlth Sci & Technol, Boston, MA 02115 USA.
[van de Water, Jeroen A. J. M.; Shah, Khalid] Massachusetts Gen Hosp, Dept Radiol & Neurol, Mol Neurotherapy & Imaging Lab, Charlestown, MA 02129 USA.
[Bacskai, Brian J.] Massachusetts Gen Hosp, Dept Neurol, Alzheimers Dis Res Unit, Charlestown, MA 02129 USA.
RP Kumar, ATN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
EM ankumar@nmr.mgh.harvard.edu
RI van de Water, Jeroen/F-1302-2011;
OI van de Water, Jeroen/0000-0001-6974-2270; Raymond,
Scott/0000-0001-7008-8974
FU National Institutes of Health (NIH) [AG026240, CA80124, CA85140,
CA96915, CA115767, CA126642]; Federal Share/NCI Proton Beam Program
FX This study was supported by the National Institutes of Health (NIH)
grants AG026240, CA80124, CA85140, CA96915, CA115767, and CA126642 and
Federal Share/NCI Proton Beam Program Income grant(s).
NR 11
TC 16
Z9 16
U1 0
U2 4
PU OPTICAL SOC AMER
PI WASHINGTON
PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA
SN 0146-9592
J9 OPT LETT
JI Opt. Lett.
PD JUL 1
PY 2009
VL 34
IS 13
BP 2066
EP 2068
PG 3
WC Optics
SC Optics
GA 475QV
UT WOS:000268376200052
PM 19572001
ER
PT J
AU Haddad, R
Braschayko, P
Sonis, S
Posner, M
Wirth, L
Tishler, R
AF Haddad, R.
Braschayko, P.
Sonis, S.
Posner, M.
Wirth, L.
Tishler, R.
TI Randomized phase II study of concomitant chemoradiation using weekly
carboplatin/paclitaxel/concomitant boost radiation with or without daily
subcutaneous amifostine in patients with newly diagnosed locally
advanced head and neck cancer
SO ORAL ONCOLOGY
LA English
DT Meeting Abstract
CT 2nd World Congress of the International-Academy-of-Oral-Oncology
CY JUL 08-11, 2009
CL Toronto, CANADA
SP Int Acad Oral Oncol
C1 [Haddad, R.; Braschayko, P.; Sonis, S.; Posner, M.; Wirth, L.; Tishler, R.] Dana Farber Canc Inst, Boston, MA USA.
[Haddad, R.; Sonis, S.; Posner, M.; Tishler, R.] Brigham & Womens Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1368-8375
J9 ORAL ONCOL
JI Oral Oncol.
PD JUL
PY 2009
BP 65
EP 65
DI 10.1016/j.oos.2009.06.113
PG 1
WC Oncology; Dentistry, Oral Surgery & Medicine
SC Oncology; Dentistry, Oral Surgery & Medicine
GA 509KJ
UT WOS:000271015100069
ER
PT J
AU Xu, L
Polur, I
Lim, C
Servais, JM
Dobeck, J
Li, Y
Olsen, BR
AF Xu, L.
Polur, I.
Lim, C.
Servais, J. M.
Dobeck, J.
Li, Y.
Olsen, B. R.
TI Early-onset osteoarthritis of mouse temporomandibular joint induced by
partial discectomy
SO OSTEOARTHRITIS AND CARTILAGE
LA English
DT Article
DE Temporomandibular joint; Articular cartilage; Discectomy; Osteoarthritis
ID DISCOIDIN DOMAIN RECEPTOR-2; MATRIX-METALLOPROTEINASE;
ARTICULAR-CARTILAGE; DEFICIENT MICE; IN-VITRO; EXPRESSION; COLLAGEN;
DEGRADATION; CLONING; DDR2
AB Objective: The objective of this study is to characterize mouse temporomandibular joint (TMJ) following partial discectomy, since there is no documentation of whether or not partial discectomy can induce early-onset osteoarthritis (OA) in mouse TMJ.
Methods: Partial discs of TMJ in mice were removed by microsurgery. Histology was performed to characterize articular cartilages from the TMJ of mice. The morphology of the articular cartilages was evaluated using a modified Mankin scoring system. Immunohistostaining was carried out to examine the expression of discoidin domain receptor 2 (Ddr2), a type II collagen receptor, matrix metalloproteinase-13 (Mmp-13), and Mmp-derived type II collagen fragments in the articular cartilage of condyles from the mouse TMJ.
Results: Articular cartilage degeneration was seen in the mouse TMJ post-discectomy, including increased proteoglycan staining in the extracellular matrix at 4 weeks, the appearance of chondrocyte clusters at 8 weeks, reduced proteoglycan staining and fibrillation at 12 weeks and the loss of articular cartilage at 16 weeks. Increased immunostaining for Ddr2, Mmp-13, and Mmp-derived type 11 collagen fragments was detected.
Conclusion: Results indicate that partial discectomy induces early-onset OA in mouse TMJ and that increased expression of Mmp-13, likely due to the elevated expression of Ddr2, may be one of the factors responsible for the early-onset OA in mouse TMJ. (C) 2009 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
C1 [Xu, L.] Forsyth Inst, Boston, MA 02115 USA.
[Xu, L.; Polur, I.; Lim, C.; Servais, J. M.; Dobeck, J.; Li, Y.; Olsen, B. R.] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA.
[Olsen, B. R.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
RP Xu, L (reprint author), Forsyth Inst, 140 Fenway, Boston, MA 02115 USA.
EM lin_xu@hms.harvard.edu
FU Jaw Joints & Allied Musculo-Skeletal Disorders Foundation [JJAMD]; NIH
[R01-AR-051989, R01-AR-36819]
FX This work was supported by Renee and Milton Glass TMJD Fellowship from
Jaw Joints & Allied Musculo-Skeletal Disorders Foundation [JJAMD] (to
Xu) and by NIH grants R01-AR-051989 (to Xu and Li) and R01-AR-36819 (to
Olsen).
NR 29
TC 20
Z9 20
U1 0
U2 1
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 JUL
PY 2009
VL 17
IS 7
BP 917
EP 922
DI 10.1016/j.joca.2009.01.002
PG 6
WC Orthopedics; Rheumatology
SC Orthopedics; Rheumatology
GA 474DN
UT WOS:000268262800013
PM 19230720
ER
PT J
AU Roditi, RE
Eppsteiner, RW
Sauter, TB
Lee, DJ
AF Roditi, Rachel E.
Eppsteiner, Robert W.
Sauter, Todd B.
Lee, Daniel J.
TI Cervical vestibular evoked myogenic potentials (cVEMPs) in patients with
superior canal dehiscence syndrome (SCDS)
SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY
LA English
DT Article; Proceedings Paper
CT 112th Annual Meeting of the
American-Academy-of-Otolaryngology-Head-and-Neck-Surgery
CY SEP 21-24, 2008
CL Chicago, IL
SP Amer Acad Otolaryngol Head & Neck Surg
ID SOUND; VERTIGO
AB OBJECTIVE: To determine the usefulness of both amplitude and threshold data from tone-burst cervical vestibular evoked myogenic potential (cVEMP) testing for the evaluation of superior canal dehiscence syndrome (SCDS).
STUDY DESIGN: Case series with chart review.
SUBJECTS AND METHODS: Sixty-seven patients underwent cVEMP testing. We correlated mean tone burst cVEMP amplitude and threshold data with temporal bone CT findings. Patients were excluded for Meniere's disease, middle ear disease. or otologic surgery.
RESULTS: Superior canal dehiscence patients had higher mean cVEMP amplitudes (SCDS 173.8 mu V vs non-SCDS 69.7 mu V, P = 0.031) and lower mean thresholds (SCDS 72.8 dB nHL vs non-SCDS 80.9 dB nHL) at 500 Hz.
CONCLUSION: Patients with SCDS have larger amplitudes and lower thresholds on cVEMP testing at 500 Hz. This study supports the utility of tone burst cVEMPs for the evaluation of SCDS and is one of few large single-center studies to establish normative data. (C) 2009 American Academy of Otolaryngology-Head and Neck Surgery Foundation. All rights reserved.
C1 [Lee, Daniel J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
[Lee, Daniel J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA.
[Sauter, Todd B.] UMass Mem Med Ctr, Dept Audiol, Worcester, MA USA.
[Roditi, Rachel E.; Eppsteiner, Robert W.; Sauter, Todd B.] Univ Massachusetts, Sch Med, Dept Otolaryngol, Worcester, MA USA.
RP Lee, DJ (reprint author), Harvard Univ, Sch Med, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA.
EM daniel_lee@meei.harvard.edu
NR 18
TC 11
Z9 11
U1 0
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0194-5998
J9 OTOLARYNG HEAD NECK
JI Otolaryngol. Head Neck Surg.
PD JUL
PY 2009
VL 141
IS 1
BP 24
EP 28
DI 10.1016/j.otohns.2009.03.012
PG 5
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA 463CB
UT WOS:000267404900008
PM 19559953
ER
PT J
AU Leung, MK
Platt, MP
Metson, R
AF Leung, Man-Kit
Platt, Michael P.
Metson, Ralph
TI Revision endoscopic orbital decompression in the management of Graves'
orbitopathy
SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY
LA English
DT Article
ID OPTIC-NERVE DECOMPRESSION; OPHTHALMOPATHY; REACTIVATION
AB OBJECTIVE: Endoscopic orbital decompression has proved to be an effective treatment for Graves' orbitopathy. In select patients, however, persistent or recurrent orbital symptoms necessitate additional therapy. The objective of this study is to determine the safety and effectiveness of revision endoscopic orbital decompression in patients with refractory Graves' orbitopathy.
STUDY DESIGN: Case-control series.
SETTING: Academic medical center.
METHODS: The study population consisted of 10 patients with Graves' orbitopathy who underwent 13 revision endoscopic orbital decompressions (three bilateral cases) between 1991 and 2008. Outcome measures, including reduction in proptosis, improvement in visual acuity, and complication rates, were compared with a control cohort of 10 consecutive patients (16 orbits) who underwent primary endoscopic decompression during the same time period.
RESULTS: Indications for revision decompression included exposure keratopathy (n = 8, 62%), optic neuropathy (n = 3, 23%), and gaze restriction (n = 2, 15%). There were no intraoperative complications. Mean reduction in proptosis was 1.4 mm less for patients who underwent revision decompression compared with primary cases (mean decompression 3.6 +/- 1.0 mm vs 5.0 +/- 2.1 mm, respectively), although this difference was not statistically significant (P = 0.13). Visual acuity improved in 62 percent of revision cases, compared with 20 percent of primary cases (P = 0.09). Rates for postoperative complications, which included sinusitis and frontal mucocele formation, were also similar between revision and primary decompression groups (38% vs 13% respectively, P = 0.17).
CONCLUSIONS: This report is the first to describe the endoscopic technique for revision orbital decompression. It appears to be a safe and effective procedure for the treatment of refractory orbitopathy in patients with Graves' disease. (C) 2009 American Academy of Otolaryngology-Head and Neck Surgery Foundation. All rights reserved.
C1 [Leung, Man-Kit; Metson, Ralph] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
[Platt, Michael P.] Boston Univ, Dept Otolaryngol Head & Neck Surg, Boston, MA 02215 USA.
[Leung, Man-Kit; Metson, Ralph] Boston Univ, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02215 USA.
RP Leung, MK (reprint author), 0 Emerson Pl, Boston, MA 02114 USA.
EM Man-Kit_Leung@meei.harvard.edu
NR 11
TC 4
Z9 4
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0194-5998
J9 OTOLARYNG HEAD NECK
JI Otolaryngol. Head Neck Surg.
PD JUL
PY 2009
VL 141
IS 1
BP 46
EP 51
DI 10.1016/j.otohns.2009.04.007
PG 6
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA 463CB
UT WOS:000267404900012
PM 19559957
ER
PT J
AU Lindsay, RW
Hadlock, TA
Cheney, ML
AF Lindsay, Robin W.
Hadlock, Tessa A.
Cheney, Mack L.
TI Bilateral simultaneous free gracilis muscle transfer: A realistic option
in management of bilateral facial paralysis
SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY
LA English
DT Article
AB OBJECTIVES: Bilateral facial paralysis patients have oral incompetence, poor articulation, and dental caries. This problem is frequently addressed by performing staged gracilis transplants without specific oral sphincter reconstruction. The purpose of this study is to describe the technique of bilateral simultaneous free gracilis muscle transfer with oral sphincter reconstruction, for one-stage facial reanimation in patients with bilateral facial paralysis.
STUDY DESIGN: Case series.
METHODS/RESULTS: One-stage bilateral gracilis transfer was performed in three patients with bilateral facial paralysis. Muscle transplants produced a meaningful smile in all transferred muscles. All patients reported improved speech and decreased drooling.
CONCLUSIONS: Bilateral gracilis transplants with reconstruction of the oral commissure is a realistic option in management of the bilaterally paralyzed face. In this small series, it appears to improve oral competence, restore smiling, and contribute favorably to lower lip support. This technique has been made more feasible because the operative time for free tissue transfer has continuously declined with the use of two-team surgery, improved microsurgical techniques, and the advent of venous coupling devices. (C) 2009 American Academy of Otolaryngology-l-lead and Neck Surgery Foundation. All rights reserved.
C1 [Lindsay, Robin W.] Massachusetts Eye & Ear Infirm, Div Facial Plast & Reconstruct Surg, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Lindsay, RW (reprint author), Massachusetts Eye & Ear Infirm, Div Facial Plast & Reconstruct Surg, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA.
EM robin_lindsay@meei.harvard.edu
NR 5
TC 9
Z9 9
U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0194-5998
J9 OTOLARYNG HEAD NECK
JI Otolaryngol. Head Neck Surg.
PD JUL
PY 2009
VL 141
IS 1
BP 139
EP 141
DI 10.1016/j.otohns.2009.03.005
PG 3
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA 463CB
UT WOS:000267404900029
PM 19559974
ER
PT J
AU Hansen, LK
Brown, M
Johnson, D
Palme, DF
Love, C
Darouiche, R
AF Hansen, Linda K.
Brown, Mary
Johnson, David
Palme, Donald F., II
Love, Charles
Darouiche, Rabih
TI In Vivo Model of Human Pathogen Infection and Demonstration of Efficacy
by an Antimicrobial Pouch for Pacing Devices
SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY
LA English
DT Article
DE device infection; pacemaker
ID CENTRAL VENOUS CATHETERS; PACEMAKER IMPLANTATION; PERMANENT PACEMAKER;
COLONIZATION; PREVENTION; GUIDELINES; MANAGEMENT; TRIAL
AB Objective: The purpose of this study was to determine the efficacy of the AIGIS(RX)(TM) antibacterial envelope (TyRx Pharma, Inc., Monmouth Junction, NJ, USA) designed to reduce device-related infections by incorporating minocycline and rifampin in a controlled release polymer.
Methods: An infection was established in a rabbit model by creating bilateral subcutaneous implant pockets, into which a pacing device with or without AIGIS(RX)(TM) was placed. The incisions were closed, and a defined dose of bacteria was infused into each implant pocket. After 7 days, devices were explanted and sampled for viable bacteria by swabbing and sonication.
Results: Initial studies evaluated the ability of the AIGIS(RX) pouch to reduce Staphylococcus epidermidis (S. epi) infection in this model using clinical and quantitative microbial endpoints. Results demonstrate S. epi infection in all control samples, while no pathogens were recovered from samples with the AIGIS(RX)(TM) pouch. Systemic antibiotic levels were undetectable. Additional studies tested the efficacy of the AIGIS(RX)(TM) pouch with additional bacterial strains, Staphylococcus capitis, Escherichia coli, and Acinetobacter Baumannii. In each case, the device and implant pocket with the AIGIS(RX)(TM) pouch was free of any signs of infection. An assessment of biofilm produced by Acinetobacter demonstrated the elimination of biofilm formation on the implanted device.
Conclusion: These results demonstrate that in this animal model, the AIGIS(RX)(TM) device reduces the risk for infection of viable pathogens within implant pockets.
(PACE 2009; 32:898-907).
C1 [Hansen, Linda K.; Brown, Mary; Johnson, David; Palme, Donald F., II] WuXi AppTec Inc, St Paul, MN 55120 USA.
[Love, Charles] Ohio State Univ, Med Ctr, Dept Internal Med, Div Cardiovasc Med, Columbus, OH 43210 USA.
[Darouiche, Rabih] Michael E Debakey Vet Affairs Med Ctr, Houston, TX USA.
RP Hansen, LK (reprint author), WuXi AppTec Inc, St Paul, MN 55120 USA.
EM linda.hansen@wuxiapptec.com
FU TyRx Pharma, Inc.
FX The testing presented in this manuscript was sponsored by TyRx Pharma,
Inc., manufacturer of the AIGISRX(TM) product.
NR 18
TC 19
Z9 19
U1 0
U2 6
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0147-8389
J9 PACE
JI PACE-Pacing Clin. Electrophysiol.
PD JUL
PY 2009
VL 32
IS 7
BP 898
EP 907
PG 10
WC Cardiac & Cardiovascular Systems; Engineering, Biomedical
SC Cardiovascular System & Cardiology; Engineering
GA 462CD
UT WOS:000267322500011
PM 19572866
ER
PT J
AU Kabra, R
Gopinathannair, R
Sandesara, C
Messinger, C
Olshansky, B
AF Kabra, Rajesh
Gopinathannair, Rakesh
Sandesara, Chirag
Messinger, Catherine
Olshansky, Brian
TI The Dual Role of Implantable Loop Recorder in Patients with Potentially
Arrhythmic Symptoms: A Retrospective Single-Center Study
SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY
LA English
DT Article
DE implantable loop recorders; syncope; palpitations
ID UNEXPLAINED SYNCOPE; MONITORING STRATEGY
AB Methods: This large single-center retrospective study sought to assess the role of ILR in the evaluation of potentially arrhythmic symptoms, both in terms of diagnosis of an arrhythmia as well as to rule out an arrhythmic cause. Clinical data, indications for ILR, interrogation reports, and further management strategies were collected in all 86 patients who received ILR from June 1999 to April 2008 at the University of Iowa Hospitals and Clinics. The indications for ILR were unexplained syncope (76%), palpitations (14%), and presyncope or dizziness (10%).
Results: During a mean follow-up period of 10 +/- 7 months, 53 patients (62%) had recurrent symptoms after ILR placement with the mean time to recurrence of 12 +/- 17 weeks. Of these, an arrhythmic diagnosis was established in 12 patients (14%). Forty-one patients (48%) did not have any arrhythmia during their symptoms. These patients were discharged from the electrophysiology clinic. Thirty-three patients (38%) did not have any symptoms following ILR placement. Out of these, device was explanted in 10 patients, while the rest are still being followed.
Conclusions: In patients with potentially arrhythmic symptoms, ILR plays an important role not only in diagnosing an arrhythmia, but also to rule out an arrhythmic cause.
(PACE 2009; 32:908-912).
C1 [Kabra, Rajesh] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
[Gopinathannair, Rakesh; Sandesara, Chirag; Messinger, Catherine; Olshansky, Brian] Univ Iowa Hosp & Clin, Dept Internal Med, Iowa City, IA 52242 USA.
RP Kabra, R (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St, Boston, MA 02114 USA.
EM rkabra@partners.org
NR 14
TC 8
Z9 8
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0147-8389
J9 PACE
JI PACE-Pacing Clin. Electrophysiol.
PD JUL
PY 2009
VL 32
IS 7
BP 908
EP 912
PG 5
WC Cardiac & Cardiovascular Systems; Engineering, Biomedical
SC Cardiovascular System & Cardiology; Engineering
GA 462CD
UT WOS:000267322500012
PM 19572867
ER
PT J
AU Gallagher, RM
AF Gallagher, Rollin M.
TI AAPM and Health Care Reform: Your Voice Is Needed
SO PAIN MEDICINE
LA English
DT Editorial Material
C1 [Gallagher, Rollin M.] Univ Penn, Amer Acad Pain Med, Philadelphia, PA 19104 USA.
[Gallagher, Rollin M.] Philadelphia VA Med Ctr, Philadelphia, PA USA.
RP Gallagher, RM (reprint author), Univ Penn, Amer Acad Pain Med, Philadelphia, PA 19104 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1526-2375
J9 PAIN MED
JI Pain Med.
PD JUL-AUG
PY 2009
VL 10
IS 5
BP 781
EP 783
DI 10.1111/j.1526-4637.2009.00674.x
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 476ZI
UT WOS:000268485000003
PM 19682271
ER
PT J
AU Meghani, SH
Wiedemer, NL
Becker, WC
Gracely, EJ
Gallagher, RM
AF Meghani, Salimah H.
Wiedemer, Nancy L.
Becker, William C.
Gracely, Ed J.
Gallagher, Rollin M.
TI Predictors of Resolution of Aberrant Drug Behavior in Chronic Pain
Patients Treated in a Structured Opioid Risk Management Program
SO PAIN MEDICINE
LA English
DT Article
DE Opioids; Chronic Pain; Aberrant Drug Behavior; Substance Abuse; Primary
Care; Opioid Renewal Clinic
ID PRIMARY-CARE PHYSICIANS; CHRONIC NONCANCER PAIN; SOCIAL SUPPORT; ABUSE;
THERAPY; MISUSE; ADJUSTMENT; DEPENDENCE; ADDICTION; NETWORK
AB Objective.
To identify demographic and clinical predictors of the resolution of aberrant drug-related behaviors (ADRBs) in a group of patients referred to the Opioid Renewal Clinic (ORC) by their primary care providers (PCPs). ORC is a program supporting PCPs' use of opioids for chronic pain in patients perceived as at risk for opioid abuse or those with demonstrated ADRBs.
Methods.
A retrospective chart review was conducted for 195 consecutive subjects referred to the ORC from January 17, 2002 to August 27, 2004, for ADRBs. Binary logistic regression was employed to identify independent predictors of aberrant behavior outcome at 1 year.
Results.
Of the 195 referred, 45.6% (N = 89) resolved their ADRB at 1 year. Other outcomes, classified as nonresolution of ADRB, self-discharged or discharged by the ORC for inability to adhere to the opioid treatment agreement (N = 86, 44.1%) and acceptance of referral for addiction treatment (N = 20, 10.2%). A history of cocaine abuse increased the odds of failing the program by five times (odds ratio [OR] = 4.97, P = 0.001). Each additional pain diagnosis reduced the odds of failure by 16% (OR = 0.837, P = 0.008). When compared with singles, married individuals were 62% less likely to fail the ORC program (OR = 0.38, P = 0.028).
Conclusions.
Nearly half of the patients resolved their aberrant behavior within the ORC. Patients with cocaine abuse were at higher risk for failure, suggesting a need for further research into safe and effective ways to manage pain in this complex subset of patients. Aberrant behaviors tended to resolve in patients with multiple pain locations, possibly because of their desire for relief.
C1 [Wiedemer, Nancy L.; Becker, William C.; Gallagher, Rollin M.] Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA.
[Meghani, Salimah H.] Univ Penn, Sch Nursing, NewCourtland Ctr Transit & Hlth, Philadelphia, PA 19104 USA.
[Gracely, Ed J.] Drexel Univ, Coll Med, Philadelphia, PA USA.
[Gallagher, Rollin M.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
RP Wiedemer, NL (reprint author), Philadelphia VA Med Ctr, 3900 Woodland Ave, Philadelphia, PA 19104 USA.
EM Nancy.Wiedemer@va.gov
OI Becker, William/0000-0002-0788-1467
NR 25
TC 9
Z9 9
U1 1
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1526-2375
J9 PAIN MED
JI Pain Med.
PD JUL-AUG
PY 2009
VL 10
IS 5
BP 858
EP 865
DI 10.1111/j.1526-4637.2009.00643.x
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 476ZI
UT WOS:000268485000015
PM 19523029
ER
PT J
AU Manchikanti, L
Boswell, MV
Singh, V
Benyamin, RM
Fellows, B
Abdi, S
Buenaventura, RM
Conn, A
Datta, S
Derby, R
Falco, FJE
Erhart, S
Diwan, S
Hayek, SM
Helm, S
Parr, AT
Schultz, DM
Smith, HS
Wolfer, LR
Hirsch, JA
AF Manchikanti, Laxmaiah
Boswell, Mark V.
Singh, Vijay
Benyamin, Ramsin M.
Fellows, Bert
Abdi, Salahadin
Buenaventura, Ricardo M.
Conn, Ann
Datta, Sukdeb
Derby, Richard
Falco, Frank J. E.
Erhart, Stephanie
Diwan, Sudhir
Hayek, Salim M.
Helm, Standiford, II
Parr, Allan T.
Schultz, David M.
Smith, Howard S.
Wolfer, Lee R.
Hirsch, Joshua A.
TI Comprehensive Evidence-Based Guidelines for Interventional Techniques in
the Management of Chronic Spinal Pain
SO PAIN PHYSICIAN
LA English
DT Review
DE Interventional techniques; chronic spinal pain; diagnostic blocks;
therapeutic interventions; facet joint interventions; epidural
injections; epidural adhesiolysis; discography; radiofrequency; disc
decompression; spinal cord stimulation; intrathecal implantable systems
ID LOW-BACK-PAIN; EPIDURAL STEROID INJECTION; INTRADISCAL ELECTROTHERMAL
THERAPY; LUMBAR FACET JOINT; 2000-2010 TASK-FORCE; HIGH-INTENSITY ZONE;
OF-THE-LITERATURE; 5-YEAR FOLLOW-UP; LASER DISC DECOMPRESSION;
DORSAL-ROOT GANGLION
AB Background: Comprehensive, evidence-based guidelines for interventional techniques in the management of chronic spinal pain are described here to provide recommendations for clinicians.
Objective: To develop evidence-based clinical practice guidelines for interventional techniques in the diagnosis and treatment of chronic spinal pain.
Design: Systematic assessment of the literature.
Methods: Strength of evidence was assessed by the U.S. Preventive Services Task Force (USPSTF) criteria utilizing 5 levels of evidence ranging from Level I to III with 3 subcategories in Level II.
Outcomes: Short-term pain relief was defined as relief lasting at least 6 months and long-term relief was defined as longer than 6 months, except for intradiscal therapies, mechanical disc decompression, spinal cord stimulation and intrathecal infusion systems, wherein up to one year relief was considered as short-term.
Results: The indicated evidence for accuracy of diagnostic facet joint nerve blocks is Level I or 111 in the diagnosis of lumbar, thoracic, and cervical facet joint pain. The evidence for lumbar and cervical provocation discography and sacroiliac joint injections is Level II-2, whereas it is Level II-3 for thoracic provocation discography
The indicated evidence for therapeutic interventions is Level I for caudal epidural steroid injections in managing disc herniation or radiculitis, and discogenic pain without disc herniation or radiculitis. The evidence is Level I or II-1 for percutaneous adhesiolysis in management of pain secondary to post-lumbar surgery syndrome. The evidence is Level II-1 or II-2 for therapeutic cervical, thoracic, and lumbar facet joint nerve blocks; for caudal epidural injections in managing pain of post-lumbar surgery syndrome, and lumbar spinal stenosis, for cervical interlaminar epidural injections in managing cervical pain (Level II-1); for lumbar transforaminal epidural injections; and spinal cord stimulation for post-lumbar surgery syndrome.
The indicated evidence for intradiscal electrothermal therapy (IDET), mechanical disc decompression with automated percutaneous lumbar discectomy (APLD), and percutaneous lumbar laser discectomy (PLDD) is Level II-2.
Limitations: The limitations of these guidelines include a continued paucity of the literature, lack of updates, and conflicts in preparation of systematic reviews and guidelines by various organizations.
Conclusion: The indicated evidence for diagnostic and therapeutic interventions is variable from Level I to III. These guidelines include the evaluation of evidence for diagnostic and therapeutic procedures in managing chronic spinal pain and recommendations for managing spinal pain, However, these guidelines do not constitute inflexible treatment recommendations. Further, these guidelines also do not represent "standard of care."
C1 [Manchikanti, Laxmaiah; Fellows, Bert] Pain Management Ctr Paducah, Paducah, KY USA.
[Boswell, Mark V.] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA.
[Singh, Vijay] Pain Diagnost Associates, Niagara, WI USA.
[Benyamin, Ramsin M.] Millennium Pain Ctr, Bloomington, IL USA.
[Abdi, Salahadin] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
[Buenaventura, Ricardo M.] Pain Relief Dayton, Centerville, OH USA.
[Conn, Ann; Parr, Allan T.] Premier Pain Ctr, Covington, LA USA.
[Datta, Sukdeb] Vanderbilt Univ, Med Ctr, Nashville, TN USA.
[Derby, Richard; Wolfer, Lee R.] Spinal Diagnost & Treatment Ctr, Daly City, CA USA.
[Falco, Frank J. E.; Erhart, Stephanie] Mid Atlantic Spine & Pain Specialists, Newark, DE USA.
[Diwan, Sudhir] Univ Hosp Cleveland, Cleveland, OH 44106 USA.
[Hayek, Salim M.] Weill Cornell Med Coll, New York Presbyterian Hosp, New York, NY USA.
[Helm, Standiford, II] Pacific Coast Pain Management Ctr, Laguna Hills, CA USA.
[Schultz, David M.] Med Adv Pain Specialists, Minneapolis, MN USA.
[Smith, Howard S.] Albany Med Coll, Albany, NY 12208 USA.
[Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA.
[Hayek, Salim M.] Outcomes Res Consortium, Cleveland, OH USA.
RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA.
EM drlm@thepainmd.com
OI Roth, Stephanie/0000-0001-5415-1718
NR 1072
TC 224
Z9 230
U1 6
U2 39
PU AM SOC INTERVENTIONAL PAIN PHYSICIANS
PI PADUCAH
PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA
SN 1533-3159
J9 PAIN PHYSICIAN
JI Pain Physician
PD JUL-AUG
PY 2009
VL 12
IS 4
BP 699
EP 802
PG 104
WC Anesthesiology; Clinical Neurology
SC Anesthesiology; Neurosciences & Neurology
GA 485RG
UT WOS:000269140800001
PM 19644537
ER
PT J
AU Manchikanti, L
Singh, V
Datta, S
Cohen, SP
Hirsch, JA
AF Manchikanti, Laxmaiah
Singh, Vijay
Datta, Sukdeb
Cohen, Steven P.
Hirsch, Joshua A.
TI Comprehensive Review of Epidemiology, Scope, and Impact of Spinal Pain
SO PAIN PHYSICIAN
LA English
DT Article
DE Chronic pain; chronic spinal pain; chronic low back pain; chronic neck
pain; chronic thoracic pain; prevalence; health care utilization; loss
of productivity; interventional techniques; surgery; comorbid factors;
socioeconomic effects; health care impact
ID LOW-BACK-PAIN; 2000-2010 TASK-FORCE; CHRONIC WIDESPREAD PAIN;
ZYGAPOPHYSIAL JOINT PAIN; QUALITY-OF-LIFE; LUMBAR INTERVERTEBRAL-DISK;
LOCAL-ANESTHETIC BLOCKS; CHRONIC NECK PAIN; 5-YEAR FOLLOW-UP;
PREDOMINANTLY NEUROPATHIC ORIGIN
AB Persistent pain interfering with daily activities is common. Chronic pain has been defined in many ways. Chronic pain syndrome is a separate entity from chronic pain. Chronic pain is defined as, "pain that persists 6 months after an injury and beyond the usual course of an acute disease or a reasonable time for a comparable injury to heal, that is associated with chronic pathologic processes that cause continuous or intermittent pain for months or years, that may continue in the presence or absence of demonstrable pathologies; may not be amenable to routine pain control methods; and healing may never occur." In contrast, chronic pain syndrome has been defined as a complex condition with physical, psychological, emotional, and social components.
The prevalence of chronic pain in the adult population ranges from 2% to 40%, with a median point prevalence of 15%. Among chronic pain disorders, pain arising from various structures of the spine constitutes the majority of the problems. The lifetime prevalence of spinal pain has been reported as 54% to 80%. Studies of the prevalence of low back pain and neck pain and its impact in general have shown 23% of patients reporting Grade II to IV low back pain (high pain intensity with disability) versus 15% with neck pain. Further, age related prevalence of persistent pain appears to be much more common in the elderly associated with functional limitations and difficulty in performing daily life activities. Chronic persistent low back and neck pain is seen in 25% to 60% of patients, one-year or longer after the initial episode.
Spinal pain is associated with significant economic, societal, and health impact. Estimates and patterns of productivity losses and direct health care expenditures among individuals with back and neck pain in the United States continue to escalate. Recent studies have shown significant increases in the prevalence of various pain problems including low back pain.
Frequent use of opioids in managing chronic non-cancer pain has been a major issue for health care in the United States placing a significant strain on the economy with the majority of patients receiving opioids for chronic pain necessitating an increased production of opioids, and escalating costs of opioid use, even with normal intake. The additional costs of misuse, abuse, and addiction are enormous. Comorbidities including psychological and physical conditions and numerous other risk factors are common in spinal pain and add significant complexities to the interventionalist's clinical task.
This section of the American Society of Interventional Pain Physicians (ASIPP)/Evidence-Based Medicine (EBM) guidelines evaluates the epidemiology, scope, and impact of spinal pain and its relevance to health care interventions.
C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, NY USA.
[Singh, Vijay] Pain Diagnost Associates, Niagara, WI USA.
Vanderbilt Univ, Med Ctr, Nashville, TN USA.
[Cohen, Steven P.] Johns Hopkins Sch Med, Baltimore, MD USA.
[Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA.
RP Manchikanti, L (reprint author), Pain Management Ctr Paducah, Paducah, NY USA.
NR 557
TC 163
Z9 172
U1 11
U2 32
PU AM SOC INTERVENTIONAL PAIN PHYSICIANS
PI PADUCAH
PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA
SN 1533-3159
J9 PAIN PHYSICIAN
JI Pain Physician
PD JUL-AUG
PY 2009
VL 12
IS 4
BP E35
EP E70
PG 36
WC Anesthesiology; Clinical Neurology
SC Anesthesiology; Neurosciences & Neurology
GA V20HC
UT WOS:000208130100002
PM 19668291
ER
PT J
AU Manchikanti, L
Singh, V
Pampati, V
Boswell, MV
Benyamin, RM
Hirsch, JA
AF Manchikanti, Laxmaiah
Singh, Vijay
Pampati, Vidyasagar
Boswell, Mark V.
Benyamin, Ramsin M.
Hirsch, Joshua A.
TI Description of Documentation in the Management of Chronic Spinal Pain
SO PAIN PHYSICIAN
LA English
DT Article
DE Documentation; billing; coding; compliance; fraud and abuse;
interventional techniques; evaluation and management services; office
visit; consultation; new patient; established patient
AB Documentation assists health care professionals in providing appropriate services to patients by documenting indications and medical necessity, and reflects the competency and character of the physician. Documentation is considered a cornerstone of the quality of patient care. This is nowhere more true than in interventional pain management. Thus, documentation in physicians' offices, hospital settings, ambulatory surgery centers, rehabilitation centers, and other settings must be accurate, complete, and reflect all of the services provided during each encounter.
The Centers for Medicare and Medicaid Services (CMS) defines medical necessity in these terms: "no payment may be made under Part A or Part B for any expense incurred for items or services which are not reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a participant." The American Medical Association (AMA) defines medical necessity as, "health care services or procedures that a prudent physician would provide to a patient for the purpose of preventing, diagnosing, or treating an illness, injury, disease, or its symptoms in a manner that is in accordance with generally accepted standards of medical practice, clinically appropriate in terms of type, frequency, extent, site, and duration, and not primarily for the convenience of the patient, physician, or other health care provider."
Documentation requirements include an appropriate medical record utilizing recognized and acceptable standards of documentation and an established process. However, the evolution of electronic medical records (EMRs) or electronic health records (EHRs) nullifies many of the issues faced in handwritten documentation.
Multiple types of documentation include evaluation and management services and documentations in ambulatory surgery centers, hospital outpatient departments, and in office settings, specifically while performing interventional procedures. Evaluation and management services incorporate 5 levels of service for consultations and visits, with multiple key elements of service including history, physical examination, and medical decision making.
Documentation of interventional procedures in general requires a history and physical, indication and medical necessity, intra-operative procedural description, post-operative monitoring and ambulation, discharge, and disposition. With minor variations, these requirements are similar for an in-office setting, hospital out patient department, and ambulatory surgery centers.
C1 [Manchikanti, Laxmaiah; Pampati, Vidyasagar] Pain Management Ctr Paducah, Paducah, KY USA.
[Singh, Vijay] Pain Diagnost Associates, Niagara, WI USA.
[Boswell, Mark V.] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA.
[Benyamin, Ramsin M.] Millennium Pain Ctr, Bloomington, IL USA.
[Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA.
RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA.
EM drlm@thepainmd.com
NR 73
TC 17
Z9 17
U1 1
U2 4
PU AM SOC INTERVENTIONAL PAIN PHYSICIANS
PI PADUCAH
PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA
SN 1533-3159
J9 PAIN PHYSICIAN
JI Pain Physician
PD JUL-AUG
PY 2009
VL 12
IS 4
BP E199
EP E224
PG 26
WC Anesthesiology; Clinical Neurology
SC Anesthesiology; Neurosciences & Neurology
GA V20HC
UT WOS:000208130100005
PM 19668282
ER
PT J
AU Manchikanti, L
Boswell, MV
Singh, V
Derby, R
Fellows, B
Falco, FJE
Datta, S
Smith, HS
Hirsch, JA
AF Manchikanti, Laxmaiah
Boswell, Mark V.
Singh, Vijay
Derby, Richard
Fellows, Bert
Falco, Frank J. E.
Datta, Sukdeb
Smith, Howard S.
Hirsch, Joshua A.
TI Comprehensive Review of Neurophysiologic Basis and Diagnostic
Interventions in Managing Chronic Spinal Pain
SO PAIN PHYSICIAN
LA English
DT Review
DE Diagnostic interventional techniques; chronic spinal pain; facet joint
interventions; epidural procedures; provocation discography; sacroiliac
joint blocks; post lumbar surgery syndrome; spinal stenosis; provocation
discography
AB Background: Understanding the neurophysiological basis of chronic spinal pain and diagnostic interventional techniques is crucial in the proper diagnosis and management of chronic spinal pain.Central to the understanding of the structural basis of chronic spinal pain is the provision of physical diagnosis and validation of patient symptomatology. It has been shown that history, physical examination, imaging, and nerve conduction studies in non-radicular or discogenic pain are unable to diagnose the precise cause in 85% of the patients. In contrast, controlled diagnostic blocks have been shown to determine the cause of pain in as many as 85% of the patients.
Objective: To provide evidence-based clinical practice guidelines for diagnostic interventional techniques.
Design: Best evidence synthesis.
Methods: Strength of evidence was assessed by the U.S. Preventive Services Task Force (USPSTF) criteria utilizing 5 levels of evidence ranging from Level I to III with 3 subcategories in Level II.
Diagnostic Criteria: Diagnostic criteria established by systematic reviews were utilized with controlled diagnostic blocks. Diagnostic criteria included at least 80% pain relief with controlled local anesthetic blocks with the ability to perform multiple maneuvers which were painful prior to the diagnostic blocks for facet joint and sacroiliac joint blocks, whereas for provocation discography, the criteria included concordant pain upon stimulation of the target disc with 2 adjacent discs producing no pain at all.
Results: The indicated level of evidence for diagnostic lumbar, cervical, and thoracic facet joint nerve blocks is Level I or II-1. The indicated evidence is Level II-2 for lumbar and cervical discography, whereas it is Level II-3 for thoracic provocation discography. The evidence for diagnostic sacroiliac joint nerve blocks is Level II-2. Level of evidence for selective nerve root blocks for diagnostic purposes is Level II-3.
Limitations: Limitations of this guideline preparation include a continued paucity of literature and conflicts in preparation of systematic reviews and guidelines.
Conclusion: These guidelines include the evaluation of evidence for diagnostic interventional procedures in managing chronic spinal pain and recommendations. However, these guidelines do not constitute inflexible treatment recommendations. These guidelines also do not represent a "standard of care."
C1 [Manchikanti, Laxmaiah; Fellows, Bert] Pain Management Ctr Paducah, Paducah, KY USA.
[Boswell, Mark V.] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA.
[Singh, Vijay] Pain Diagnost Associates, Niagara, WI USA.
[Derby, Richard] Spinal Diagnost & Treatment Ctr, Daly City, CA USA.
[Falco, Frank J. E.] Spinal Diagnost & Treatment Ctr, Daly City, CA USA.
[Datta, Sukdeb] Vanderbilt Univ, Med Ctr, Nashville, TN USA.
[Smith, Howard S.] Albany Med Coll, Albany, NY 12208 USA.
[Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA.
RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA.
EM drlm@thepainmd.com
FU Sucampo Pharmaceuticals
FX Dr. Hirsch is a consultant for Cardinal Healthcare and Medtronic, he has
previously served as a consultant for Arthrocare, he serves on the
Steering Committee for KAVIAR trial (volunteer position), and on the
Data and Safety Monitoring Board (DSMB): CEEP trial (volunteer
position).Dr. Datta receives research support from Sucampo
Pharmaceuticals and an honorarium from Smith and Nephew. Dr. Derby has
stock options of less than $10,000 with Laurimed and Kyphon.
NR 783
TC 75
Z9 78
U1 1
U2 4
PU AM SOC INTERVENTIONAL PAIN PHYSICIANS
PI PADUCAH
PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA
SN 1533-3159
J9 PAIN PHYSICIAN
JI Pain Physician
PD JUL-AUG
PY 2009
VL 12
IS 4
BP E71
EP E121
PG 51
WC Anesthesiology; Clinical Neurology
SC Anesthesiology; Neurosciences & Neurology
GA V20HC
UT WOS:000208130100003
PM 19668292
ER
PT J
AU Manchikanti, L
Singh, V
Helm, S
Schultz, DM
Datta, S
Hirsch, J
AF Manchikanti, Laxmaiah
Singh, Vijay
Helm, Standiford, II
Schultz, David M.
Datta, Sukdeb
Hirsch, Joshua
TI An Introduction to an Evidence-Based Approach to Interventional
Techniques in the Management of Chronic Spinal Pain
SO PAIN PHYSICIAN
LA English
DT Article
DE Evidence-based medicine; clinical practice guidelines; critical
appraisal; guideline development; interventional pain management;
interventional techniques; evidence synthesis; clinical relevance;
grading recommendations; systematic reviews
ID LOW-BACK-PAIN; CLINICAL-PRACTICE GUIDELINES; EVIDENCE-BASED MEDICINE;
RANDOMIZED CONTROLLED-TRIALS; CHRONIC NONCANCER PAIN; FACET JOINT
INTERVENTIONS; LUMBAR SURGERY SYNDROME; SYSTEMATIC REVIEWS; HEALTH-CARE;
CORD STIMULATION
AB Practice guidelines are systematically developed statements to assist practitioners and patients in making decisions about appropriate health care for specific clinical circumstances. Clinical practice guidelines present statements of best practice based on a thorough evaluation of the evidence from published studies on the outcomes of treatment. In November 1989, Congress mandated the creation of the Agency for Healthcare Policy and Research (AHCPR). AHCPR was given broad responsibility for supporting research, data development, and related activities. Associated with this mandate, the National Academy of Sciences published a document indicating that guidelines are expected to enhance the quality, appropriateness, and effectiveness of health care services.
Guidelines as a whole have been characterized by multiple conflicts in terminology and technique. These conflicts are notable for the confusion they create and for what they reflect about differences in values, experiences, and interest among different parties. Despite this confusion, public and private development of guidelines is growing exponentially. There are only limited means to coordinate these guidelines in order to resolve inconsistencies, fill in gaps, track applications and results, and assess the soundness of individual guidelines. Significant diversity exists in clinical practice guidelines. The inconsistency amongst guidelines arises from variations in values, tolerance for risks, preferences, expertise, and conflicts of interest.
In 2000, the American Society of Interventional Pain Physicians (ASIPP) first created treatment guidelines to help practitioners. There have been 4 subsequent updates. These guidelines address the issues of systematic: evaluation and ongoing care of chronic or persistent pain, and provide information about the scientific basis of recommended procedures. These guidelines are expected to increase patient compliance, dispel misconceptions among providers and patients, manage patient expectations reasonably, and form the basis of a therapeutic partnership between the patient, the provider, and payors.
The ASIPP guidelines are based on evidence-based medicine (EBM). EBM is in turn based on 4 basic contingencies: the recognition of the patient's problem and the construction of a structured clinical question; the ability to efficiently and effectively search the medical literature to retrieve the best available evidence to answer the clinical question; clinical appraisal of the evidence; and integration of the evidence with all aspects of the individual patient's decision-making to determine the best clinical care of the patient. Evidence synthesis for guidelines includes the review of all relevant systematic reviews and individual articles, grading them for relevance, methodologic quality, consistency, and recommendations.
C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA.
[Singh, Vijay] Pain Diagnost Associates, Niagara, WI USA.
[Helm, Standiford, II] Pacific Coast Pain Management Ctr, Laguna Hills, CA USA.
[Schultz, David M.] Med Adv Pain Specialists, Minneapolis, MN USA.
[Datta, Sukdeb] Vanderbilt Univ, Med Ctr, Nashville, TN USA.
[Hirsch, Joshua] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Hirsch, Joshua] Harvard Univ, Sch Med, Boston, MA USA.
RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA.
EM drlm@thepainmd.com
FU Medtronic
FX There was no external funding in the preparation of this manuscript. No
statement on this article should be construed as an official position of
ASIPP. Dr. Hirsch is a consultant for Cardinal Healthcare and Medtronic,
he has previously served as a consultant for Arthrocare, he serves on
the Steering Committee for KAVIAR trial (volunteer position), and on the
Data and Safety Monitoring Board (DSMB): CEEP trial (volunteer
position). Dr. Schultz receives funding from Medtronic.
NR 265
TC 34
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U1 2
U2 3
PU AM SOC INTERVENTIONAL PAIN PHYSICIANS
PI PADUCAH
PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA
SN 1533-3159
J9 PAIN PHYSICIAN
JI Pain Physician
PD JUL-AUG
PY 2009
VL 12
IS 4
BP E1
EP E33
PG 33
WC Anesthesiology; Clinical Neurology
SC Anesthesiology; Neurosciences & Neurology
GA V20HC
UT WOS:000208130100001
PM 19668280
ER
PT J
AU Larochelle, MR
Rodriguez, KL
Arnold, RM
Barnato, AE
AF Larochelle, M. R.
Rodriguez, K. L.
Arnold, R. M.
Barnato, A. E.
TI Hospital staff attributions of the causes of physician variation in
end-of-life treatment intensity
SO PALLIATIVE MEDICINE
LA English
DT Article
DE decision making; practice variation; qualitative research; terminal care
ID CARE-UNIT; ADVANCE DIRECTIVES; PREFERENCES; DECISIONS; COMMUNICATION;
PROGNOSES; SUPPORT; PATIENT; DEATH; TRIAL
AB Discrepancies between patient wishes and end-of-life treatment decisions have been documented, and the determinants of end-of-life treatment decisions are not well understood. Our objective was to understand hospital staff perceptions of the role of acute care hospital medical doctors in end-of-life treatment intensity. In 11 purposively sampled Pennsylvania hospitals, we completed 108 audiotaped semistructured interviews with key informants involved in decision making or discharge planning. Using grounded theory, we qualitatively analysed transcripts using constant comparison to identify factors affecting end-of-life treatment decisions. A predominant theme identified was that end-of-life treatment intensity depends on the doctor. Communication with patients and families and collaboration with other care team members also were reported to vary, contributing to treatment variation. Informants attributed physician variation to individual beliefs and attitudes regarding the end-of-life (religion and culture, determination of when a patient is dying, quality-of-life determination and fear of failing) and to socialization by and interaction with the healthcare system (training, role perception, experience and response to incentives). When end-of-life treatment depends on the doctor, patient and family preferences may be neglected. Targeted interventions may reduce variability and align end-of-life treatment with patient wishes. Palliative Medicine (2009); 23: 460-470
C1 [Barnato, A. E.] Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA 15213 USA.
[Larochelle, M. R.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA.
[Rodriguez, K. L.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA.
[Arnold, R. M.] Univ Pittsburgh, Dept Med, Div Gen Internal Med, Sect Palliat Care & Med Eth, Pittsburgh, PA 15213 USA.
RP Barnato, AE (reprint author), Univ Pittsburgh, Ctr Res Hlth Care, 200 Meyran St,Suite 200, Pittsburgh, PA 15213 USA.
EM aeb2@pitt.edu
FU National Institute on Aging [K08 AG021921, P01 AG19783]
FX Financial support for this research was from National Institute on Aging
grants K08 AG021921 and P01 AG19783. Amber Barnato would like to thank
research mentors Derek Angus and Judith Lave for their intellectual and
personal contributions.
NR 30
TC 30
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U1 2
U2 3
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0269-2163
J9 PALLIATIVE MED
JI Palliat. Med.
PD JUL
PY 2009
VL 23
IS 5
BP 460
EP 470
DI 10.1177/0269216309103664
PG 11
WC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Medicine, General & Internal
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; General & Internal Medicine
GA 457ON
UT WOS:000266941500011
PM 19324922
ER
PT J
AU Jenner, P
Mori, A
Hauser, R
Morelli, M
Fredholm, BB
Chen, JF
AF Jenner, P.
Mori, A.
Hauser, R.
Morelli, M.
Fredholm, B. B.
Chen, J. F.
TI Adenosine, adenosine A(2A) antagonists, and Parkinson's disease
SO PARKINSONISM & RELATED DISORDERS
LA English
DT Review
DE Parkinson's disease; Adenosine; Adenosine antagonists
ID RECEPTOR MESSENGER-RNA; INDUCED MOTOR COMPLICATIONS; DEEP
BRAIN-STIMULATION; MPTP-TREATED MONKEYS; L-DOPA; GLOBUS-PALLIDUS;
6-HYDROXYDOPAMINE-LESIONED RATS; MEDIATED MODULATION; POSSIBLE
RELEVANCE; A-2A RECEPTORS
AB Adenosine derived from the degradation of ATP/AMP functions as a signalling molecule in the nervous system through the occupation of A1, A2, and A3 adenosine receptors. Adenosine A(2A) receptors have a selective localization to the basal ganglia and specifically to the indirect output pathway, and as a consequence offer a unique opportunity to modulate the output from the striatum that is believed critical to the occurrence of motor components of PD. Indeed, the ability of A(2A) antagonists to modulate basal ganglia neurotransmission has been shown to be associated with improved motor function in experimental models of PD. This suggests that A(2A) antagonists would be effective as a symptomatic treatment in humans without provoking marked dyskinesia. Indeed, the A(2A) antagonist istradefylline reduces OFF time in moderate- to late-stage patients with PD already receiving dopaminergic therapy, with an increase in non-troublesome dyskinesia. Adenosine and adenosine receptors also exert actions relevant to pathogenesis in PD, raising the possibility of their use as neuroprotective agents. Both epidemiologic evidence and the current preclinical data strongly support a role for A(2A) antagonists in protecting dopaminergic neurons and influencing the onset and progression of PD. Crown Copyright (C) 2009 Published by Elsevier Ltd. All rights reserved.
C1 [Jenner, P.] Kings Coll London, Neurodegenerat Dis Res Ctr, Sch Hlth & Biomed Sci, London SE1 1UL, England.
[Mori, A.] Kyowa Hakko Kogyo Co Ltd, Div Pharmaceut Res & Dev, Tokyo, Japan.
[Hauser, R.] Univ S Florida, Dept Neurol, Tampa, FL 33620 USA.
[Hauser, R.] Univ S Florida, Dept Pharmacol & Expt Therapeut, Tampa, FL 33620 USA.
[Hauser, R.] Natl Parkinson Fdn Ctr Excellence, Tampa, FL USA.
[Morelli, M.] Univ Cagliari, Dept Toxicol, Cagliari, Italy.
[Fredholm, B. B.] Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
[Chen, J. F.] Massachusetts Gen Hosp, Mol Neurobiol Lab, Dept Neurol, Charlestown, MA USA.
RP Jenner, P (reprint author), Kings Coll London, Neurodegenerat Dis Res Ctr, Sch Hlth & Biomed Sci, London SE1 1UL, England.
EM peter.jenner@kcl.ac.uk
OI morelli, micaela/0000-0003-0394-5782
NR 99
TC 114
Z9 116
U1 2
U2 11
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1353-8020
J9 PARKINSONISM RELAT D
JI Parkinsonism Relat. Disord.
PD JUL
PY 2009
VL 15
IS 6
BP 406
EP 413
DI 10.1016/j.parkreldis.2008.12.006
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 473MH
UT WOS:000268210500002
PM 19446490
ER
PT J
AU Ross, OA
Spanaki, C
Griffith, A
Lin, CH
Kachergus, J
Haugarvoll, K
Latsoudis, H
Plaitakis, A
Ferreira, JJ
Sampaio, C
Bonifati, V
Wu, RM
Zabetian, CP
Farrer, MJ
AF Ross, Owen A.
Spanaki, Cleanthe
Griffith, Alida
Lin, Chin-Hsien
Kachergus, Jennifer
Haugarvoll, Kristoffer
Latsoudis, Helen
Plaitakis, Andreas
Ferreira, Joaquim J.
Sampaio, Cristina
Bonifati, Vincenzo
Wu, Ruey-Meei
Zabetian, Cyrus P.
Farrer, Matthew J.
TI Haplotype analysis of Lrrk2 R1441H carriers with parkinsonism
SO PARKINSONISM & RELATED DISORDERS
LA English
DT Article
DE Parkinson's disease; Leucine-rich repeat kinase 2; R1441H
ID DISEASE; MUTATIONS; RISK; GENE
AB The Roc domain of the Lrrk2 protein harbors two pathogenic mutations which cause autosomal dominant parkinsonism (R1441C and R1441G). A third putatively pathogenic variant (R1441H) has been identified in four probands of diverse ethnicity with parkinsonism. Herein we show that the R1441H substitutions lie on different haplotypes within our patients, confirming this codon as a mutational hotspot. The absence of this variant in control subjects and the presence of two other pathogenic variants at this amino acid position collectively support the contention that 81441 H is a pathogenic substitution. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Ross, Owen A.] Mayo Clin, Morris K Udall Parkinsons Dis Res Ctr Excellence, Dept Neurosci, Jacksonville, FL 32224 USA.
[Spanaki, Cleanthe; Latsoudis, Helen; Plaitakis, Andreas] Univ Crete, Dept Neurol, Sch Med, Iraklion, Crete, Greece.
[Griffith, Alida] Evergreen Hosp, Med Ctr, Booth Gardner Parkinsons Care Ctr, Kirkland, WA USA.
[Lin, Chin-Hsien; Wu, Ruey-Meei] Natl Taiwan Univ, Natl Taiwan Univ Hosp, Coll Med, Dept Neurol, Taipei 10764, Taiwan.
[Ferreira, Joaquim J.; Sampaio, Cristina] Lisbon Sch Med, Inst Mol Med, Neurol Clin, Res Unit, Lisbon, Portugal.
[Bonifati, Vincenzo] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands.
[Zabetian, Cyrus P.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA.
[Zabetian, Cyrus P.] VA Puget Sound Hlth Care Syst, Geriatr Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA USA.
[Zabetian, Cyrus P.] VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA.
RP Ross, OA (reprint author), Mayo Clin, Morris K Udall Parkinsons Dis Res Ctr Excellence, Dept Neurosci, 4500 San Pablo Rd, Jacksonville, FL 32224 USA.
EM ross.owen@mayo.edu
RI Ross, Owen/D-7573-2013; Haugarvoll, Kristoffer/L-1486-2015;
OI Haugarvoll, Kristoffer/0000-0001-9381-1109; Wu,
Ruey-Meei/0000-0002-4947-5467; Lin, Chin-Hsien/0000-0001-8566-7573;
Zabetian, Cyrus/0000-0002-7739-4306; Ferreira, Joaquim
J/0000-0003-3950-5113
FU Morris K. Udall Parkinson's Disease Research Center of Excellence
[NS40256]; Department of Veterans Affairs; Taiwan National Science
Council [96-2628-B-002-103-MY2]; Internationaal Parkinson Fonds, The
Netherlands; Parkinson Disease Foundation
FX We would like to thank all those who have contributed to our research.
This work is supported by a Morris K. Udall Parkinson's Disease Research
Center of Excellence (NINDS P50 #NS40256), the Department of Veterans
Affairs (Merit Review Award), the Taiwan National Science Council
(96-2628-B-002-103-MY2), by a grant from the "Internationaal Parkinson
Fonds" (The Netherlands) to VB, and by a research grant from the
"Parkinson Disease Foundation" to CS.
NR 10
TC 20
Z9 21
U1 0
U2 2
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1353-8020
J9 PARKINSONISM RELAT D
JI Parkinsonism Relat. Disord.
PD JUL
PY 2009
VL 15
IS 6
BP 466
EP 467
DI 10.1016/j.parkreldis.2008.09.001
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA 473MH
UT WOS:000268210500014
PM 18952485
ER
PT J
AU Kennifer, SL
Alexander, SC
Pollak, KI
Jeffreys, AS
Olsen, MK
Rodriguez, KL
Arnold, RM
Tulsky, JA
AF Kennifer, Sarah L.
Alexander, Stewart C.
Pollak, Kathryn I.
Jeffreys, Amy S.
Olsen, Maren K.
Rodriguez, Keri L.
Arnold, Robert M.
Tulsky, James A.
TI Negative emotions in cancer care: Do oncologists' responses depend on
severity and type of emotion?
SO PATIENT EDUCATION AND COUNSELING
LA English
DT Article
DE Doctor-patient relations; Communication; Cancer; Emotion
ID COMMUNICATION; DOCTOR; NEWS
AB Objective: To examine how type and severity of patients' negative emotions influence oncologists' responses and subsequent conversations.
Methods: We analyzed 264 audio-recorded conversations between advanced cancer patients and their oncologists. Conversations were coded for patients' expressions of negative emotion, which were categorized by type of emotion and severity. Oncologists' responses were coded as using either empathic language or blocking and distancing approaches.
Results: Patients presented fear more often than anger or sadness; severity of disclosures was most often moderate. Oncologists responded to 35% of these negative emotional disclosures with empathic language. They were most empathic when patients presented intense emotions. Responding empathically to patients' emotional disclosures lengthened discussions by an average of only 21 s.
Conclusion: Greater response rates to severe emotions suggest oncologists may recognize negative emotions better when patients express them more intensely. Oncologists were least responsive to patient fear and responded with greatest empathy to sadness.
Practice implications: Oncologists may benefit from additional training to recognize negative emotions, even when displayed without intensity. Teaching cancer patients to better articulate their emotional concerns may also enhance patient-oncologist communication. (c) 2008 Elsevier Ireland Ltd. All rights reserved.
C1 [Kennifer, Sarah L.; Alexander, Stewart C.; Tulsky, James A.] Duke Univ, Med Ctr, Ctr Palliat Care, Durham, NC 27705 USA.
[Alexander, Stewart C.; Jeffreys, Amy S.; Olsen, Maren K.; Tulsky, James A.] Durham VA Med Ctr, Hlth Serv Res & Dev, Durham, NC USA.
[Pollak, Kathryn I.; Tulsky, James A.] Duke Univ, Med Ctr, Duke Canc Prevent Detect & Control Res Program, Durham, NC 27705 USA.
[Rodriguez, Keri L.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA.
[Rodriguez, Keri L.; Arnold, Robert M.] Univ Pittsburgh, Sch Med, Dept Gen Internal Med, Pittsburgh, PA 15260 USA.
RP Kennifer, SL (reprint author), Duke Univ, Med Ctr, Ctr Palliat Care, Hock Plaza,Suite 1105,Box 2720,2424 Erwin Rd, Durham, NC 27705 USA.
EM sarah.kennifer@duke.edu
FU National Cancer Institute [R01-CA100387]
FX This work has been funded by a grant from the National Cancer Institute
(R01-CA100387).
NR 24
TC 29
Z9 32
U1 2
U2 13
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0738-3991
J9 PATIENT EDUC COUNS
JI Patient Educ. Couns.
PD JUL
PY 2009
VL 76
IS 1
BP 51
EP 56
DI 10.1016/j.pec.2008.10.003
PG 6
WC Public, Environmental & Occupational Health; Social Sciences,
Interdisciplinary
SC Public, Environmental & Occupational Health; Social Sciences - Other
Topics
GA 467HO
UT WOS:000267729500010
PM 19041211
ER
PT J
AU Cote, CJ
Hartnick, CJ
AF Cote, Charles J.
Hartnick, Christopher J.
TI Pediatric transtracheal and cricothyrotomy airway devices for emergency
use: which are appropriate for infants and children?
SO PEDIATRIC ANESTHESIA
LA English
DT Review
DE cricothyrotomy; tracheostomy; transtracheal; emergency; airway; airway
obstruction; pediatric
ID PERCUTANEOUS DILATATIONAL TRACHEOSTOMY; TRANS-TRACHEAL VENTILATION;
LARYNGEAL MASK AIRWAY; FIBEROPTIC INTUBATION; NEEDLE TRACHEOSTOMY;
SURGICAL CRICOTHYROIDOTOMY; LARYNGOTRACHEAL TRAUMA; RANDOMIZED
CROSSOVER; DIFFICULT-AIRWAY; JET VENTILATION
AB P>Cricothyrotomy or insertion of a transtracheal device is a life-saving maneuver that may be performed on an emergent or semi-elective basis as a means of bypassing an obstructed upper airway. A surgeon is trained to perform this life-saving procedure whereas most anesthesiologists are not facile with the scalpel. It is for this reason that many percutaneous devices have been developed for use by surgeons and nonsurgeons alike. Unfortunately, the majority of such devices are designed for use in adults and/or teenagers but are not appropriate for neonates and infants. The unique anatomy of the infant larynx, the small size of the cricothyroid membrane, and the technical difficulty of locating the correct anatomical structures make the use of most of these devices impractical if not outright dangerous in neonates and infants. This paper will review many (but not all) of the available devices, associated literature, pitfalls and dangers. It is emphasized that each clinician should become familiar with the advantages and disadvantages of these devices and obtain training with simulators or animal models. A strategy for management of the 'cannot ventilate, cannot oxygenate, cannot intubate' situation should be developed with age and size appropriate equipment.
C1 [Cote, Charles J.] Harvard Univ, Massachusetts Gen Hosp,Sch Med, Div Pediat Anesthesia,Dept Anesthesia & Crit Care, MassGen Hosp Children, Boston, MA 02115 USA.
[Hartnick, Christopher J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA.
RP Cote, CJ (reprint author), Harvard Univ, Massachusetts Gen Hosp,Sch Med, Div Pediat Anesthesia,Dept Anesthesia & Crit Care, MassGen Hosp Children, 55 Fruit St, Boston, MA 02115 USA.
EM cjcole@partners.org
NR 73
TC 26
Z9 26
U1 0
U2 2
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1155-5645
J9 PEDIATR ANESTH
JI Pediatr. Anesth.
PD JUL
PY 2009
VL 19
SU 1
BP 66
EP 76
DI 10.1111/j.1460-9592.2009.02996.x
PG 11
WC Anesthesiology; Pediatrics
SC Anesthesiology; Pediatrics
GA 463JI
UT WOS:000267427800009
PM 19572846
ER
PT J
AU Fidkowski, CW
Fuzaylov, G
Sheridan, RL
Cote, CJ
AF Fidkowski, Christina W.
Fuzaylov, Gennadiy
Sheridan, Robert L.
Cote, Charles J.
TI Inhalation burn injury in children
SO PEDIATRIC ANESTHESIA
LA English
DT Review
DE inhalation injury; burn injury; pediatric
ID ACUTE LUNG INJURY; INHALED NITRIC-OXIDE; SMOKE-INHALATION;
CARBON-MONOXIDE; PULSE OXIMETRY; EMERGENCY-DEPARTMENT; SODIUM
NITROPRUSSIDE; PEDIATRIC-PATIENTS; CYANIDE TOXICITY; MORTALITY
AB P>With advances in burn care, many children are surviving severe burn injuries. Inhalation injury remains a predictor of morbidity and mortality in burn injury. Inhalation of smoke and toxic gases leads to pulmonary complications, including airway obstruction from bronchial casts, pulmonary edema, decreased pulmonary compliance, and ventilation-perfusion mismatch, as well as systemic toxicity from carbon monoxide poisoning and cyanide toxicity. The diagnosis of inhalation injury is suggested by the history and physical exam and can be confirmed by bronchoscopy. Management consists of supportive measures, pulmonary toilet, treatment of pulmonary infection and ventilatory support as needed. This review details the pathophysiology, diagnosis, and management options for inhalation injury.
C1 [Fuzaylov, Gennadiy; Cote, Charles J.] Harvard Univ, Massachusetts Gen Hosp,Mass Gen Hosp Children, Pediat Anesthesia Serv,Sch Med, Dept Anesthesia & Crit Care,Div Pediat Anesthesia, Boston, MA 02155 USA.
[Sheridan, Robert L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02155 USA.
RP Fuzaylov, G (reprint author), Harvard Univ, Massachusetts Gen Hosp,Mass Gen Hosp Children, Pediat Anesthesia Serv,Sch Med, Dept Anesthesia & Crit Care,Div Pediat Anesthesia, 55 Fruit St,Clin 309, Boston, MA 02155 USA.
EM gfuzaylov@partners.org
NR 67
TC 10
Z9 10
U1 0
U2 4
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1155-5645
J9 PEDIATR ANESTH
JI Pediatr. Anesth.
PD JUL
PY 2009
VL 19
SU 1
BP 147
EP 154
DI 10.1111/j.1460-9592.2008.02884.x
PG 8
WC Anesthesiology; Pediatrics
SC Anesthesiology; Pediatrics
GA 463JI
UT WOS:000267427800016
PM 19143954
ER
PT J
AU Janeway, KA
Albritton, KH
Van Den Abbeele, AD
D'Amato, GZ
Pedrazzoli, P
Siena, S
Picus, J
Butrynski, JE
Schlemmer, M
Heinrich, MC
Demetri, GD
AF Janeway, Katherine A.
Albritton, Karen H.
Van Den Abbeele, Annick D.
D'Amato, Gina Z.
Pedrazzoli, Paolo
Siena, Salvatore
Picus, Joel
Butrynski, James E.
Schlemmer, Marcus
Heinrich, Michael C.
Demetri, George D.
TI Sunitinib Treatment in Pediatric Patients With Advanced GIST Following
Failure of Imatinib
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE clinical trials; drug resistance; new agents; pediatric oncology; soft
tissue sarcoma
ID GASTROINTESTINAL STROMAL TUMORS; TYROSINE KINASE INHIBITOR;
OF-THE-LITERATURE; POSITRON-EMISSION-TOMOGRAPHY; GROWTH-FACTOR; IN-VIVO;
MESYLATE; SU11248; KIT; MUTATIONS
AB Background. Sunitinib inhibits KIT and other members of the split-kirase-domain family of receptor tyrosine kinases. Sunitinib prolong; survival in adult patients with imatinib-resistant gastrointestinal stroinal tumor (GIST). We report the experience with sunitinib in pediatric patients with advanced GIST following failure of imatinib. Procedure. Sunitinib therapy was provided through a treatment-use protocol. Patients were 10-17 years old at enrollment. All patients had GIST resistant to imatinib therapy. Sunitinib was administered daily for 4 weeks in 6-week treatment cycles. KIT and platelet-derived growth factor receptor alpha (PDGFRA) genotyping of tumor tissue were performed. Results. One patient achieved a partial response, five patients had stable disease and one patient had progressive disease on sunitinib. The duration of disease stabilization was between 7 and 21 + months, with a mean of 15 months. Time to tumor progression was longer on sunitinib than on prior imatinib treatment for five of six patients. Two patients experienced grade 3 adverse events. All other adverse events were grade 1-2. None of the five patients tested had mutations in KIT or PDGFRA. Conclusion. Sunitinib treatment was associated with substantial initial antitumor activity and acceptable tolerability in this group of pediatric patients with imatinib-resistant GIST. Pediatr Blood Cancer 2009;52:767-771. (C) 2009 Wiley-Liss, Inc.
C1 [Demetri, George D.] Dana Farber Canc Inst, Ludwig Ctr Dana Farber, Harvard Canc Ctr, Boston, MA 02115 USA.
[Janeway, Katherine A.; Albritton, Karen H.] Childrens Hosp, Dept Med, Boston, MA 02115 USA.
[Van Den Abbeele, Annick D.] Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA.
[D'Amato, Gina Z.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
[Pedrazzoli, Paolo; Siena, Salvatore] Osped Niguarda Ca Granda, Div Oncol Med Falck, Milan, Italy.
[Picus, Joel] Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO USA.
[Butrynski, James E.; Demetri, George D.] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA.
[Butrynski, James E.; Demetri, George D.] Harvard Univ, Sch Med, Boston, MA USA.
[Butrynski, James E.] Univ Washington, Seattle, WA 98195 USA.
[Butrynski, James E.] Seattle Canc Care Alliance, Seattle, WA USA.
[Schlemmer, Marcus] Univ Munich, Klinikum Grosshadern, Med Ctr, Dept Internal Med 3, D-8000 Munich, Germany.
[Heinrich, Michael C.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA.
[Heinrich, Michael C.] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA.
RP Demetri, GD (reprint author), Dana Farber Canc Inst, Ludwig Ctr Dana Farber, Harvard Canc Ctr, D1212,44 Binney St, Boston, MA 02115 USA.
EM gdemetri@partners.org
OI SIENA, SALVATORE/0000-0002-2681-2846
FU Pfizer Inc
FX We greatly appreciate the assistance of the following additional
contributors: Christopher Corless, Travis Quigley, Samuel Agresta, Chris
Garrett, and Dana Matthews. The manuscript was written by Katherine
Janeway with substantive input frorn all authors. Logistical and
editorial assistance were provided by ACUMED (Tytherington, UK), with
funding from Pfizer Inc.
NR 29
TC 65
Z9 70
U1 0
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 JUL 1
PY 2009
VL 52
IS 7
BP 767
EP 771
DI 10.1002/pbc.21909
PG 5
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 435LT
UT WOS:000265346100006
PM 19326424
ER
PT J
AU Grace, RF
Mednick, RE
Neufeld, EJ
AF Grace, Rachael F.
Mednick, Rachel E.
Neufeld, Ellis J.
TI Compliance With Immunizations in Splenectomized Individuals With
Hereditary Spherocytosis
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE hereditary spherocytosis; immunizations; splenectomy
ID OVERWHELMING POSTSPLENECTOMY INFECTION; SEPSIS; RISK; CHILDHOOD; ADULTS
AB Overwhelming infection by encapsulated bacteria is a significant risk of splenectomy. Strict adherence to immunizations against encapsulated organisms is recommended. We performed a cross-sectional study to determine immunization Status after splenectomy in the hereditary spherocytosis (HS) Population. As HS is most often autosomal dominant, we used a strategy of ascertaining older affected individuals by expanding pedigrees from patients in Our pediatric hematology center. Only 26% of asplenic patients reported receiving all recommended post-splenectomy vaccines. This study demonstrates that pediatric hematology clinics have a unique opportunity to provide or recommend catch-Up and booster vaccinations to splenectomized adult relatives of their patients. Pediatr Blood Cancer 2009;52:865-867. (C) 2009 Wiley-Liss, Inc.
C1 [Grace, Rachael F.; Mednick, Rachel E.; Neufeld, Ellis J.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
[Grace, Rachael F.; Neufeld, Ellis J.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Grace, Rachael F.; Neufeld, Ellis J.] Harvard Univ, Sch Med, Boston, MA USA.
RP Neufeld, EJ (reprint author), Childrens Hosp, Div Hematol Oncol, 300 Longwood Ave,Karp 8, Boston, MA 02115 USA.
EM ellis.neufeld@tch.harvard.edu
RI Neufeld, Ellis/F-9331-2011;
OI Grace, Fergal/0000-0002-3144-5999
NR 20
TC 6
Z9 7
U1 0
U2 0
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 JUL 1
PY 2009
VL 52
IS 7
BP 865
EP 867
DI 10.1002/pbc.21961
PG 3
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 435LT
UT WOS:000265346100024
PM 19214975
ER
PT J
AU Langman, CB
Alon, U
Ingelfinger, J
Englund, M
Saland, J
Somers, MJG
Stapleton, FB
Sibu, NO
Cochat, P
Wong, W
Eke, FU
Satlin, L
Salusky, I
AF Langman, Craig B.
Alon, Uri
Ingelfinger, Julie
Englund, Marta
Saland, Jeffrey M.
Somers, Michael J. G.
Stapleton, F. Bruder
Orta Sibu, Nelson
Cochat, Pierre
Wong, William
Eke, Felicia U.
Satlin, Lisa
Salusky, Isidro
TI A position statement on kidney disease from powdered infant
formula-based melamine exposure in Chinese infants
SO PEDIATRIC NEPHROLOGY
LA English
DT Editorial Material
DE Acute kidney failure; Infant nutrition; Nephrolithiasis; Poisoning
ID CARCINOGENICITY; DOGS
AB Melamine, a man-made non-nutritive substance containing nitrogen, can falsely elevate measures of protein content in foodstuffs. Several manufacturers of powdered infant formula in China apparently added melamine to raise the measured protein content and thereby exposed thousands of infants and young children to very high levels of melamine. Such exposure resulted in cases of acute kidney failure and nephrolithiasis. This Editorial from members of the world-wide Pediatric Nephrology community provides a common-sense approach to the care of infants who may have been exposed to powdered infant formula in 2007-2008.
C1 [Langman, Craig B.] Northwestern Univ, Childrens Mem Hosp, Feinberg Sch Med, Chicago, IL 60614 USA.
[Alon, Uri] Childrens Mercy Hosp, Kansas City, MO 64108 USA.
[Ingelfinger, Julie] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Englund, Marta] Karolinska Inst, Sachs Childrens Hosp, Stockholm, Sweden.
[Saland, Jeffrey M.; Satlin, Lisa] Mt Sinai Med Ctr, Dept Pediat, New York, NY 10029 USA.
[Somers, Michael J. G.] Harvard Univ, Sch Med, Boston, MA USA.
[Stapleton, F. Bruder] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA.
[Orta Sibu, Nelson] Univ Carabobo, Hosp Ninos Insalud, Valencia, Venezuela.
[Cochat, Pierre] Hop Edouard Herriot, INSERM, U820, Ctr Reference Malad Renales Hereditaires, Lyon, France.
[Wong, William] Starship Childrens Hosp, Dept Nephrol, Auckland, New Zealand.
[Eke, Felicia U.] Univ Port Harcourt, Port Harcourt, Nigeria.
[Salusky, Isidro] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Los Angeles, CA 90095 USA.
[Stapleton, F. Bruder] Seattle Childrens Hosp, Seattle, WA USA.
[Somers, Michael J. G.] Childrens Hosp Boston, Boston, MA USA.
[Englund, Marta] Soder Sjukhuset, Dept Clin Sci & Educ, S-10064 Stockholm, Sweden.
[Cochat, Pierre] Univ Lyon 1, F-69365 Lyon, France.
RP Langman, CB (reprint author), Northwestern Univ, Childrens Mem Hosp, Feinberg Sch Med, 2300 Childrens Plaza 37, Chicago, IL 60614 USA.
EM c-langman@northwestern.edu
NR 10
TC 25
Z9 26
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0931-041X
J9 PEDIATR NEPHROL
JI Pediatr. Nephrol.
PD JUL
PY 2009
VL 24
IS 7
BP 1263
EP 1266
DI 10.1007/s00467-009-1129-6
PG 4
WC Pediatrics; Urology & Nephrology
SC Pediatrics; Urology & Nephrology
GA 451XN
UT WOS:000266504300001
PM 19198884
ER
PT J
AU Wesseling-Perry, K
Harkins, GC
Wang, HJ
Sahney, S
Gales, B
Elashoff, RM
Juppner, H
Salusky, IB
AF Wesseling-Perry, Katherine
Harkins, G. Chris
Wang, He-Jing
Sahney, Shobha
Gales, Barbara
Elashoff, Robert M.
Juppner, Harald
Salusky, Isidro B.
TI Response of different PTH assays to therapy with sevelamer or CaCO3 and
active vitamin D sterols
SO PEDIATRIC NEPHROLOGY
LA English
DT Article
DE Calcium carbonate; Parathyroid hormone; Secondary hyperparathyroidism;
Sevelamer; Vitamin D
ID INTACT PARATHYROID-HORMONE; SECONDARY HYPERPARATHYROIDISM;
HEMODIALYSIS-PATIENTS; PEDIATRIC-PATIENTS; RENAL-FAILURE; BONE-DISEASE;
CALCIFICATION; FRAGMENTS; CALCIUM; CORONARY
AB Amino-terminally truncated parathyroid hormone (PTH) fragments are detected to differing degrees by first- and second-generation immunometric PTH assays (PTH-IMAs), and acute changes in serum calcium affect the proportion of these fragments in circulation. However, the effect of chronic calcium changes and different vitamin D doses on these PTH measurements remains to be defined. In this study, 60 pediatric dialysis patients, aged 13.9 +/- 0.7 years, with secondary hyperparathyroidism were randomized to 8 months of therapy with oral vitamin D combined with either calcium carbonate (CaCO3) or sevelamer. Serum phosphorus levels did not differ between groups. Serum calcium levels rose from 9.3 +/- 0.1 to 9.7 +/- 0.1 mg/dl during CaCO3 therapy (p < 0.01 from baseline) but remained unchanged during sevelamer therapy. In the CaCO3 and sevelamer groups, baseline serum PTH levels (1st PTH-IMA; Nichols Institute Diagnostics, San Clemente, CA) were 964 +/- 75 and 932 +/- 89 pg/ml, and levels declined to 491 +/- 55 and 543 +/- 59 pg/ml, respectively (nonsignificant between groups). Patients treated with sevelamer received higher doses of vitamin D than those treated with CaCO3. The PTH values obtained by first- and second-generation PTH-IMAs correlated closely throughout therapy and the response of PTH was similar to both PTH-IMAs, despite differences in serum calcium levels.
C1 [Wesseling-Perry, Katherine] Univ Calif Los Angeles, Div Pediat Nephrol, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Harkins, G. Chris] Immutop Int, San Clemente, CA USA.
[Wang, He-Jing; Elashoff, Robert M.] Univ Calif Los Angeles, Dept Biomath, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Sahney, Shobha] Loma Linda Med Ctr, Dept Pediat, Loma Linda, CA USA.
[Juppner, Harald] Harvard Univ, Sch Med, Mass Gen Hosp, Dept Pediat, Boston, MA USA.
[Wesseling-Perry, Katherine; Gales, Barbara; Salusky, Isidro B.] Univ Calif Los Angeles, Dept Pediat, David Geffen Sch Med, Los Angeles, CA 90095 USA.
RP Wesseling-Perry, K (reprint author), Univ Calif Los Angeles, Div Pediat Nephrol, David Geffen Sch Med, A2-383 MDCC,10833 LeConte Ave, Los Angeles, CA 90095 USA.
EM kwesseling@mednet.ucla.edu
FU USPHS [DK-35423, DK-67563, RR-00865]; Casey Lee Ball Foundation;
National Kidney Foundation
FX This work was supported in part by USPHS grants DK-35423, DK-67563 and
RR-00865 and funds from the Casey Lee Ball Foundation. Dr. Katherine
Wesseling-Perry was a recipient of a fellowship award from the National
Kidney Foundation. PTH-IMA (Immutopics) values were kindly provided by
Immutopics International.
NR 27
TC 12
Z9 12
U1 1
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0931-041X
EI 1432-198X
J9 PEDIATR NEPHROL
JI Pediatr. Nephrol.
PD JUL
PY 2009
VL 24
IS 7
BP 1355
EP 1361
DI 10.1007/s00467-009-1143-8
PG 7
WC Pediatrics; Urology & Nephrology
SC Pediatrics; Urology & Nephrology
GA 451XN
UT WOS:000266504300012
PM 19301038
ER
PT J
AU Biederman, J
Monuteaux, MC
Spencer, T
Wilens, TE
Faraone, SV
AF Biederman, Joseph
Monuteaux, Michael C.
Spencer, Thomas
Wilens, Timothy E.
Faraone, Stephen V.
TI Do Stimulants Protect Against Psychiatric Disorders in Youth With ADHD?
A 10-Year Follow-up Study
SO PEDIATRICS
LA English
DT Article
DE ADHD; psychopharmacology; stimulants; comorbidity
ID ATTENTION-DEFICIT HYPERACTIVITY; DEFICIT/HYPERACTIVITY DISORDER; BIPOLAR
DISORDER; PHARMACOLOGICAL-TREATMENT; CONDUCT DISORDER; SUBSTANCE USE;
METHYLPHENIDATE; CHILDREN; DEPRESSION; ADOLESCENTS
AB OBJECTIVE: Little is known about the effect of stimulant treatment in youth with attention-deficit/hyperactivity disorder (ADHD) on the subsequent development of comorbid psychiatric disorders. We tested the association between stimulant treatment and the subsequent development of psychiatric comorbidity in a longitudinal sample of patients with ADHD.
METHODS: We conducted a case-control, 10-year prospective follow-up study into young-adult years of youth with ADHD. At baseline, we assessed consecutively referred white male children with (n = 140) and without (n = 120) ADHD, aged 6 to 18 years. At the 10-year follow-up, 112 (80%) and 105 (88%) of the children in the ADHD and control groups, respectively, were reassessed (mean age: 22 years). We examined the association between stimulant treatment in childhood and adolescence and subsequent comorbid disorders and grade retention by using proportional hazards survival models.
RESULTS: Of the 112 participants with ADHD, 82 (73%) were previously treated with stimulants. Participants with ADHD who were treated with stimulants were significantly less likely to subsequently develop depressive and anxiety disorders and disruptive behavior and less likely to repeat a grade compared with participants with ADHD who were not treated.
CONCLUSIONS: We found evidence that stimulant treatment decreases the risk for subsequent comorbid psychiatric disorders and academic failure in youth with ADHD. Pediatrics 2009;124:71-78
C1 [Biederman, Joseph] Massachusetts Gen Hosp, Dept Psychiat, Clin & Res Program Pediat Psychopharmacol, Pediat Psychopharmacol Unit ACC 725, Boston, MA 02114 USA.
[Biederman, Joseph; Monuteaux, Michael C.; Spencer, Thomas; Wilens, Timothy E.] Massachusetts Gen Hosp, Dept Psychiat, Clin & Res Program Adult ADHD, Boston, MA 02114 USA.
[Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA.
[Faraone, Stephen V.] SUNY Genet Res Program, Syracuse, NY USA.
RP Biederman, J (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Clin & Res Program Pediat Psychopharmacol, Pediat Psychopharmacol Unit ACC 725, Fruit St, Boston, MA 02114 USA.
EM jbiederman@partners.org
OI Faraone, Stephen/0000-0002-9217-3982
FU US Department of Health and Human Services; National Institutes of
Health: Eunice Kennedy Shriver National Institute of Child Health and
Human Development [5RO1 HD36317]; National Institute on Drug Abuse [K24
DA016264]
FX This work was supported in part by the following grants awarded by the
US Department of Health and Human Services, National Institutes of
Health: Eunice Kennedy Shriver National Institute of Child Health and
Human Development grant 5RO1 HD36317 (to Dr Biederman) and National
Institute on Drug Abuse grant K24 DA016264 (to Dr Wilens).
NR 41
TC 86
Z9 87
U1 3
U2 20
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
J9 PEDIATRICS
JI Pediatrics
PD JUL
PY 2009
VL 124
IS 1
BP 71
EP 78
DI 10.1542/peds.2008-3347
PG 8
WC Pediatrics
SC Pediatrics
GA 463QY
UT WOS:000267448100010
PM 19564285
ER
PT J
AU Sittig, DF
Teich, JM
Osheroff, JA
Singh, H
AF Sittig, Dean F.
Teich, Jonathan M.
Osheroff, Jerome A.
Singh, Hardeep
TI Improving Clinical Quality Indicators Through Electronic Health Records:
It Takes More Than Just a Reminder
SO PEDIATRICS
LA English
DT Editorial Material
ID PHYSICIAN ORDER ENTRY; DECISION-SUPPORT; SYSTEM; CARE; OUTCOMES
C1 [Sittig, Dean F.] Univ Texas Houston, Sch Hlth Informat Sci, Houston, TX USA.
[Sittig, Dean F.] UT Mem Hermann Ctr Healthcare Qual & Safety, Houston, TX USA.
[Teich, Jonathan M.] Elsevier Hlth Sci, Philadelphia, PA USA.
[Teich, Jonathan M.] Harvard Univ, Dept Med, Boston, MA 02115 USA.
[Osheroff, Jerome A.] Thomson Reuters, Ann Arbor, MI USA.
[Osheroff, Jerome A.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
[Singh, Hardeep] Baylor Coll Med, Dept Med, Hlth Policy & Qual Program, Houston Vet Affairs Hlth Serv Res & Dev Ctr Excel, Houston, TX 77030 USA.
[Singh, Hardeep] Baylor Coll Med, Dept Med, Ctr Inquiry Improve Outpatient Safety Effect Elec, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA.
[Singh, Hardeep] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA.
RP Sittig, DF (reprint author), Univ Texas Hlth Sci Ctr Houston, Sch Hlth Informat Sci, 6410 Fannin St, Houston, TX 77030 USA.
EM dean.f.sittig@uth.tmc.edu
FU NCI NIH HHS [K23 CA125585, K23 CA125585-04]
NR 16
TC 19
Z9 19
U1 2
U2 4
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
J9 PEDIATRICS
JI Pediatrics
PD JUL
PY 2009
VL 124
IS 1
BP 375
EP 377
DI 10.1542/peds.2009-0339
PG 3
WC Pediatrics
SC Pediatrics
GA 463QY
UT WOS:000267448100046
PM 19564321
ER
PT J
AU Joshi, VA
Duffy, E
Funke, BH
Farwell, LM
Mancini-Dinardo, D
Kucherlapati, R
AF Joshi, Victoria A.
Duffy, Elizabeth
Funke, Birgit H.
Farwell, Lisa M.
Mancini-Dinardo, Debora
Kucherlapati, Raju
TI Platform evaluation for rapid genotyping of CYP2C9 and VKORC1 alleles
SO PERSONALIZED MEDICINE
LA English
DT Article
DE CYP2C9; genotyping; VKORC1; warfarin
ID WARFARIN; PROBES; ASSAY; DNA
AB Aims: Warfarin is a commonly prescribed drug with a narrow therapeutic index. Adverse drug reactions owing to over- or under-dosing are common. It is now established that genetic differences between individuals play a major role in warfarin metabolism. In particular, common variants in CYP2C9 ((star)2 and (star)3) and VKORC1 (-1639G>A) have been associated with a reduced drug-dosage requirement. Materials & methods: We have evaluated the performance of five platforms that can be used to genotype individuals for these variants. These include Third Wave Technologies Invader (R), Applied Biosystems TaqMan (R), AutoGenomics INFINITI (TM) 2C9-VKORC1 assay, Osmetech eSensor (R) XT-8 warfarin sensitivity test and the Idaho Technologies LightScanner (R). Results & conclusions: Excluding failures, all of these technologies had 100% concordance rates with either Sanger sequencing or another validated technology. All of these platforms had high sensitivity and specificity and are therefore appropriate for clinical molecular diagnostics. Therefore, platform choice is likely to be driven by clinical laboratories interested in performing this service taking other factors into account, including turnaround time, capacity, cost and ease of use.
C1 [Joshi, Victoria A.; Duffy, Elizabeth; Funke, Birgit H.; Farwell, Lisa M.; Kucherlapati, Raju] Partners HealthCare, Ctr Personalized Genet Med, Cambridge, MA 02139 USA.
[Joshi, Victoria A.; Funke, Birgit H.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Joshi, VA (reprint author), Partners HealthCare, Ctr Personalized Genet Med, 65 Landsdowne St, Cambridge, MA 02139 USA.
EM vjoshi@partners.org
NR 16
TC 1
Z9 1
U1 0
U2 1
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1741-0541
J9 PERS MED
JI Pers. Med.
PD JUL
PY 2009
VL 6
IS 4
BP 449
EP 457
DI 10.2217/PME.09.8
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 481BC
UT WOS:000268780500017
ER
PT J
AU Barrett, LF
AF Barrett, Lisa Feldman
TI The Future of Psychology: Connecting Mind to Brain
SO PERSPECTIVES ON PSYCHOLOGICAL SCIENCE
LA English
DT Article
ID NEUROIMAGING TELL; COGNITION; EMOTION; CORTEX; COMMUNICATION;
ASSOCIATION; INFORMATION; PREDICTIONS; EXPERIENCE; NEOCORTEX
AB Psychological states such as thoughts and feelings are real. Brain states are real. The problem is that the two are not real in the same way, creating the mind-brain correspondence problem. In this article, I present a possible solution to this problem that involves two suggestions. First, complex psychological states such as emotion and cognition can be thought of as constructed events that can be causally reduced to a set of more basic, psychologically primitive ingredients that are more clearly respected by the brain. Second, complex psychological categories like emotion and cognition are the phenomena that require explanation in psychology, and, therefore, they cannot be abandoned by science. Describing the content and structure of these categories is a necessary and valuable scientific activity.
C1 [Barrett, Lisa Feldman] Massachusetts Gen Hosp, Dept Psychol, Boston Coll, Chestnut Hill, MA 02467 USA.
[Barrett, Lisa Feldman] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
RP Barrett, LF (reprint author), Massachusetts Gen Hosp, Dept Psychol, Boston Coll, Chestnut Hill, MA 02467 USA.
EM barretli@bc.edu
FU NIA NIH HHS [R01 AG030311]; NIH HHS [DP1 OD003312, DP1 OD003312-01];
NIMH NIH HHS [K02 MH001981]
NR 74
TC 97
Z9 98
U1 5
U2 19
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1745-6916
J9 PERSPECT PSYCHOL SCI
JI Perspect. Psychol. Sci.
PD JUL
PY 2009
VL 4
IS 4
BP 326
EP 339
PG 14
WC Psychology, Multidisciplinary
SC Psychology
GA 467QB
UT WOS:000267755400002
PM 19844601
ER
PT J
AU Zeman, RJ
Zhao, JB
Zhang, YF
Zhao, WD
Wen, XL
Wu, Y
Pan, JP
Bauman, WA
Cardozo, C
AF Zeman, Richard J.
Zhao, Jingbo
Zhang, Yuangfei
Zhao, Weidong
Wen, Xialing
Wu, Yong
Pan, Jiangping
Bauman, William A.
Cardozo, Christopher
TI Differential skeletal muscle gene expression after upper or lower motor
neuron transection
SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
LA English
DT Article
DE Ubiquitin ligases; Atrogin-1; Paralysis; Muscle atrophy
ID SPINAL-CORD-INJURY; GROWTH-FACTOR-I; FOXO TRANSCRIPTION FACTORS;
NF-KAPPA-B; DENERVATION ATROPHY; UBIQUITIN LIGASES; RAT; TESTOSTERONE;
PROTEIN; SLOW
AB Causes of disuse atrophy include loss of upper motor neurons, which occurs in spinal cord injury (SCI) or lower motor neurons (denervation). Whereas denervation quickly results in muscle fibrillations, SCI causes delayed onset of muscle spasticity. To compare the influence of denervation or SCI on muscle atrophy and atrophy-related gene expression, male rats had transection of either the spinal cord or sciatic nerve and were sacrificed 3, 7, or 14 days later. Rates of atrophy increased gradually over the first week after denervation and then were constant. In contrast, atrophy after SCI peaked at 1 week, then declined sharply. The greater atrophy after SCI compared to denervation was preceded by high levels of ubiquitin ligase genes, MAFbx and MuRF1, which then also markedly declined. After denervation, however, expression of these genes remained elevated at lower levels throughout the 2-week time course. Interestingly, expression of the muscle growth factor, IGF-1 was increased at 3 days after denervation when fibrillation also peaks compared to SCI. Expression of IGF-1R, GADD45, myogenin, and Runx1 were also initially increased after denervation or SCI, with later declines in expression levels which correlated less well with rates of atrophy. Thus, there were significant time-dependent differences in muscle atrophy and MAFbx, MuRF1, and IGF-1 expression following SCI or denervation which may result from distinct temporal patterns of spontaneous muscle contractile activity due to injury to upper versus lower motor neurons.
C1 [Zhao, Jingbo; Zhang, Yuangfei; Zhao, Weidong; Wu, Yong; Pan, Jiangping; Bauman, William A.; Cardozo, Christopher] James J Peters VA Med Ctr, Ctr Excellence Med Consequences SCI, Dept Vet Affairs, Bronx, NY 10468 USA.
[Zhao, Jingbo; Bauman, William A.; Cardozo, Christopher] Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA.
[Bauman, William A.; Cardozo, Christopher] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY 10029 USA.
[Zeman, Richard J.; Wen, Xialing] New York Med Coll, Dept Cell Biol & Anat, Valhalla, NY 10595 USA.
RP Zeman, RJ (reprint author), New York Med Coll, Dept Cell Biol & Anat, Valhalla, NY 10595 USA.
EM Zeman@nymc.edu
FU Veterans Health Administration, Rehabilitation Research and Development
Service [B4162C, B3347K]; United Spinal Association
FX This work was supported by Veterans Health Administration,
Rehabilitation Research and Development Service (B4162C to WAB, B3347K
to CC), and United Spinal Association (to WAB).
NR 66
TC 28
Z9 30
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0031-6768
EI 1432-2013
J9 PFLUG ARCH EUR J PHY
JI Pflugers Arch.
PD JUL
PY 2009
VL 458
IS 3
BP 525
EP 535
DI 10.1007/s00424-009-0643-5
PG 11
WC Physiology
SC Physiology
GA 455TP
UT WOS:000266789000008
PM 19214561
ER
PT J
AU Vincent, DF
Yan, KP
Treilleux, I
Gay, F
Arfi, V
Kaniewsky, B
Marie, JC
Lepinasse, F
Martel, S
Goddard-Leon, S
Iovanna, JL
Dubus, P
Garcia, S
Puisieux, A
Rimokh, R
Bardeesy, N
Scoazec, JY
Losson, R
Bartholin, L
AF Vincent, David F.
Yan, Kai-Ping
Treilleux, Isabelle
Gay, Fabien
Arfi, Vanessa
Kaniewsky, Bastien
Marie, Julien C.
Lepinasse, Florian
Martel, Sylvie
Goddard-Leon, Sophie
Iovanna, Juan L.
Dubus, Pierre
Garcia, Stephane
Puisieux, Alain
Rimokh, Ruth
Bardeesy, Nabeel
Scoazec, Jean-Yves
Losson, Regine
Bartholin, Laurent
TI Inactivation of TIF1 gamma Cooperates with Kras(G12D) to Induce Cystic
Tumors of the Pancreas
SO PLOS GENETICS
LA English
DT Article
ID TGF-BETA; DUCTAL ADENOCARCINOMA; K-RAS; INTRAEPITHELIAL NEOPLASIA;
CANCER; MICE; MOUSE; TRANSCRIPTION; GROWTH; SMAD4
AB Inactivation of the Transforming Growth Factor Beta (TGF beta) tumor suppressor pathway contributes to the progression of Pancreatic Ductal AdenoCarcinoma (PDAC) since it is inactivated in virtually all cases of this malignancy. Genetic lesions inactivating this pathway contribute to pancreatic tumor progression in mouse models. Transcriptional Intermediary Factor 1 gamma (TIF1 gamma) has recently been proposed to be involved in TGF beta signaling, functioning as either a positive or negative regulator of the pathway. Here, we addressed the role of TIF1 gamma in pancreatic carcinogenesis. Using conditional Tif1 gamma knockout mice (Tif1 gamma(lox/lox)), we selectively abrogated Tif1 gamma expression in the pancreas of Pdx1-Cre;Tif1 gamma(lox/lox) mice. We also generated Pdx1-Cre;LSL-Kras(G12D);Tif1 gamma(lox/lox) mice to address the effect of Tif1 gamma loss-of-function in precancerous lesions induced by oncogenic Kras(G12D). Finally, we analyzed TIF1 gamma expression in human pancreatic tumors. In our mouse model, we showed that Tif1 gamma was dispensable for normal pancreatic development but cooperated with Kras activation to induce pancreatic tumors reminiscent of human Intraductal Papillary Mucinous Neoplasms (IPMNs). Interestingly, these cystic lesions resemble those observed in Pdx1-Cre;LSL-Kras(G12D);Smad4(lox/lox) mice described by others. However, distinctive characteristics, such as the systematic presence of endocrine pseudo-islets within the papillary projections, suggest that SMAD4 and TIF1 gamma don't have strictly redundant functions. Finally, we report that TIF1 gamma expression is markedly down-regulated in human pancreatic tumors by quantitative RT-PCR and immunohistochemistry supporting the relevance of these findings to human malignancy. This study suggests that TIF1 gamma is critical for tumor suppression in the pancreas, brings new insight into the genetics of pancreatic cancer, and constitutes a promising model to decipher the respective roles of SMAD4 and TIF1 gamma in the multifaceted functions of TGF beta in carcinogenesis and development.
C1 [Vincent, David F.; Arfi, Vanessa; Kaniewsky, Bastien; Martel, Sylvie; Puisieux, Alain; Rimokh, Ruth; Bartholin, Laurent] INSERM, U590, IFR62, F-69008 Lyon, France.
[Vincent, David F.; Arfi, Vanessa; Kaniewsky, Bastien; Lepinasse, Florian; Puisieux, Alain; Rimokh, Ruth; Scoazec, Jean-Yves; Bartholin, Laurent] Univ Lyon, Lyon, France.
[Vincent, David F.; Arfi, Vanessa; Kaniewsky, Bastien; Martel, Sylvie; Bartholin, Laurent] INSERM, Avenir Grp, F-69008 Lyon, France.
[Yan, Kai-Ping; Losson, Regine] IGBMC, Illkirch Graffenstaden, France.
[Vincent, David F.; Treilleux, Isabelle; Arfi, Vanessa; Kaniewsky, Bastien; Martel, Sylvie; Goddard-Leon, Sophie; Puisieux, Alain; Bartholin, Laurent] Ctr Leon Berard, F-69373 Lyon, France.
[Gay, Fabien; Lepinasse, Florian; Scoazec, Jean-Yves] INSERM, U865, Fac Laennec, F-69008 Lyon, France.
[Marie, Julien C.] INSERM, U758, F-69008 Lyon, France.
[Lepinasse, Florian; Scoazec, Jean-Yves] Hop Edouard Herriot, Hosp Civils Lyon, Lyon, France.
[Iovanna, Juan L.; Garcia, Stephane] INSERM, U624, F-13258 Marseille, France.
[Dubus, Pierre] Univ Bordeaux, EA 2406, Bordeaux, France.
[Bardeesy, Nabeel] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA.
RP Vincent, DF (reprint author), INSERM, U590, IFR62, F-69008 Lyon, France.
EM bartholi@lyon.fnclcc.fr
RI Rimokh, Ruth/G-7506-2014; Marie, Julien/I-5084-2016;
OI Vincent, David/0000-0001-6482-8040
FU ARC [3891]; INSERM; INCA; Ligue Contre le Cancer
FX This work was supported by grants from, ARC 3891 (LB), INSERM "Avenir''
program (LB), INCA "libre'' (RR/LB, JYS, and JCM), INCA "plateforme''
(LB and JCM), and Ligue Contre le Cancer (LB). DFV is a MENRT doctoral
fellow. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 48
TC 59
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U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7390
J9 PLOS GENET
JI PLoS Genet.
PD JUL
PY 2009
VL 5
IS 7
AR e1000575
DI 10.1371/journal.pgen.1000575
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 486SZ
UT WOS:000269219500016
PM 19629168
ER
PT J
AU Ranjbar, S
Boshoff, HI
Mulder, A
Siddiqi, N
Rubin, EJ
Goldfeld, AE
AF Ranjbar, Shahin
Boshoff, Helena I.
Mulder, Amara
Siddiqi, Noman
Rubin, Eric J.
Goldfeld, Anne E.
TI HIV-1 Replication Is Differentially Regulated by Distinct Clinical
Strains of Mycobacterium tuberculosis
SO PLOS ONE
LA English
DT Article
AB Background: Tuberculosis ( TB) is the largest cause of death in human immunodeficiency virus type 1 (HIV-1) infection, having claimed an estimated one third to one half of the 30 million AIDS deaths that have occurred worldwide. Different strains of Mycobacterium tuberculosis (MTb), the causative agent of TB, are known to modify the host immune response in a strain-specific manner. However, a MTb strain-specific impact upon the regulation of HIV-1 replication has not previously been established.
Methology/Principal Findings: We isolated normal human peripheral blood mononuclear cells (PBMC) and co-infected them with HIV-1 and with either the well characterized CDC1551 or HN878 MTb clinical isolate. We show that HIV-1 co-infection with the CDC1551 MTb strain results in higher levels of virus replication relative to co-infection with the HN878 MTb strain ex vivo. Furthermore, we show that the distinct pattern of CDC1551 or HN878 induced HIV-1 replication is associated with significantly increased levels of TNF and IL-6, and of the transcription and nuclear translocation of the p65 subunit of the transcription factor NF-kappa B, by CDC1551 relative to HN878.
Conclusions/Significance: These results provide a precedent for TB strain-specific effects upon HIV-1 replication and thus for TB strain-specific pathogenesis in the outcome of HIV-1/TB co-infection. MTb strain-specific factors and mechanisms involved in the regulation of HIV-1 during co-infection will be of importance in understanding the basic pathogenesis of HIV-1/TB co-infection.
RP Ranjbar, S (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
EM ranjbar@idi.harvard.edu; goldfeld@idi.harvard.edu
OI Rubin, Eric/0000-0001-5120-962X
FU Intramural NIH HHS; NHLBI NIH HHS [HL 059838]; NIAID NIH HHS [P30 AI
060354, AI 065285, P30 AI060354, R01 AI065285, R56 AI065285]
NR 66
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U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 1
PY 2009
VL 4
IS 7
AR e6116
DI 10.1371/journal.pone.0006116
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 465HA
UT WOS:000267572200015
PM 19568431
ER
PT J
AU Hare, S
Di Nunzio, F
Labeja, A
Wang, JM
Engelman, A
Cherepanov, P
AF Hare, Stephen
Di Nunzio, Francesca
Labeja, Alfred
Wang, Jimin
Engelman, Alan
Cherepanov, Peter
TI Structural Basis for Functional Tetramerization of Lentiviral Integrase
SO PLOS PATHOGENS
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; VIRAL-DNA BINDING; CARBOXYL-TERMINAL
DOMAINS; TARGET SITE SELECTION; AMINO-ACID-RESIDUES; HIV-1 INTEGRASE;
IN-VITRO; CRYSTAL-STRUCTURE; CATALYTIC DOMAIN; COACTIVATOR P75
AB Experimental evidence suggests that a tetramer of integrase ( IN) is the protagonist of the concerted strand transfer reaction, whereby both ends of retroviral DNA are inserted into a host cell chromosome. Herein we present two crystal structures containing the N-terminal and the catalytic core domains of maedi-visna virus IN in complex with the IN binding domain of the common lentiviral integration co-factor LEDGF. The structures reveal that the dimer-of-dimers architecture of the IN tetramer is stabilized by swapping N-terminal domains between the inner pair of monomers poised to execute catalytic function. Comparison of four independent IN tetramers in our crystal structures elucidate the basis for the closure of the highly flexible dimer-dimer interface, allowing us to model how a pair of active sites become situated for concerted integration. Using a range of complementary approaches, we demonstrate that the dimer-dimer interface is essential for HIV-1 IN tetramerization, concerted integration in vitro, and virus infectivity. Our structures moreover highlight adaptable changes at the interfaces of individual IN dimers that allow divergent lentiviruses to utilize a highly-conserved, common integration co-factor.
C1 [Hare, Stephen; Labeja, Alfred; Cherepanov, Peter] Univ London Imperial Coll Sci Technol & Med, Div Med, London, England.
[Di Nunzio, Francesca; Engelman, Alan] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[Wang, Jimin] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT USA.
RP Hare, S (reprint author), Univ London Imperial Coll Sci Technol & Med, Div Med, St Marys Campus, London, England.
EM alan_engelman@dfci.harvard.edu; p.cherepanov@imperial.ac.uk
RI Di Nunzio, Francesca/A-6153-2014; Cherepanov, Peter/F-6859-2010;
OI Di Nunzio, Francesca/0000-0003-2879-3164; Cherepanov,
Peter/0000-0002-0634-538X; Hare, Stephen/0000-0003-2951-1595
FU NIH [AI070042]; UK Medical Research Council [G0600009]
FX This work was funded by NIH Grant AI070042 ( A. E.) and UK Medical
Research Council grant G0600009 ( P. C.). The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 72
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U1 0
U2 2
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 JUL
PY 2009
VL 5
IS 7
AR e1000515
DI 10.1371/journal.ppat.1000515
PG 15
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 486UJ
UT WOS:000269224500018
PM 19609359
ER
PT J
AU Lin, AE
O'Brien, B
Demmer, LA
Almeda, KK
Blanco, CL
Glasow, PF
Berul, CI
Hamilton, R
Innes, AM
Lauzon, JL
Sol-Church, K
Gripp, KW
AF Lin, Angela E.
O'Brien, Barbara
Demmer, Laurie A.
Almeda, Kristina K.
Blanco, Cynthia L.
Glasow, Patrick F.
Berul, Charles I.
Hamilton, Robert
Innes, A. Micheil
Lauzon, Julie L.
Sol-Church, Katia
Gripp, Karen W.
TI Prenatal features of Costello syndrome: ultrasonographic findings and
atrial tachycardia
SO PRENATAL DIAGNOSIS
LA English
DT Article
DE chaotic atrial rhythm; chaotic atrial tachycardia; Costello syndrome;
fetal arrhythmia; HRAS gene; polyhydramnios; prenatal ultrasound;
supraventricular tachycardia
ID FACIO-CUTANEOUS SYNDROME; GROWTH RETARDATION SYNDROME; TUMOR SCREENING
PROTOCOL; HRAS MUTATION ANALYSIS; NATURAL-HISTORY; SKELETAL SYNDROME;
EMBRYONAL RHABDOMYOSARCOMA; DIFFERENTIAL-DIAGNOSIS; PHENOTYPE
CORRELATION; HORMONE DEFICIENCY
AB Objective Delineate prenatal features of Costello syndrome (caused by HRAS mutations), which consists of mental retardation. facial. cardiovascular, skin. and musculoskeletal anomalies. and tumor predisposition.
Methods Literature and new cases classified as Group I (pre-HRAS), Group II (HRAS confirmed). and Group III (HRAS confirmed ill natural history study. Plus three contributed cases).
Results Polyhydramnios Occurred in most (mean 79%) pregnancies of cases in Groups 1 (98) 11 (107), and III (17); advanced paternal age and prematurity were noted in approximately half. Less frequent were nuchal thickening. ascites, shortened long, bones. abnormal hand posture. ventriculomegaly, macrosomia, and macrocephaly. Fetal arrhythmia Occurred in nine cases (six supraventricular or unspecified tachycardia, one Unspecified arrhythmia. and two premature atrial contractions. PACs); excluding three new cases and two with PACs, the estimated prenatal frequency is 4/222 (2%).
Conclusion Costello syndrome can be suspected prenatally when polyhydramnios is accompanied by nuchal thickening, hydrops, shortened long bones, abnormal hand Posture. ventriculomegaly, large size, and macrocephaly, and especially fetal atrial tachycardia. Consideration should be given for timely prenatal diagnostic Studies for continuative HRAS gene mutations and for maternal treatment of serious fetal arrhythmia. Copyright (C) 22009 John Wiley & Sons. Ltd.
C1 [Lin, Angela E.] MassGen Hosp Children, Genet Unit, Dept Pediat, Boston, MA USA.
[O'Brien, Barbara; Demmer, Laurie A.] Tufts Med Ctr, Div Genet, Boston, MA USA.
[O'Brien, Barbara] Brown Univ, Women & Infants Hosp, Dept Obstet & Gynecol, Providence, RI USA.
[Almeda, Kristina K.; Blanco, Cynthia L.] Univ Texas Hlth Sci Ctr San Antonio, Div Neonatol, San Antonio, TX 78229 USA.
[Glasow, Patrick F.] Univ Texas Hlth Sci Ctr San Antonio, Div Pediat Cardiol, San Antonio, TX 78229 USA.
[Berul, Charles I.] Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA.
[Hamilton, Robert] Hosp Sick Children, Dept Cardiol, Toronto, ON M5G 1X8, Canada.
[Innes, A. Micheil; Lauzon, Julie L.] Alberta Childrens Prov Gen Hosp, Dept Med Genet, Calgary, AB, Canada.
[Sol-Church, Katia] Nemours Childrens Clin, Wilmington, DE USA.
[Gripp, Karen W.] Alfred I DuPont Hosp Children, Div Med Genet, Wilmington, DE USA.
RP Lin, AE (reprint author), MassGen Hosp Children, Genet Unit, Dept Pediat, 185 Cambridge St,Simches 2222, Boston, MA USA.
EM lin.angela@mgh.harvard.edu
RI innes, allan micheil/A-9955-2017;
OI Innes, Micheil/0000-0001-9881-5467
FU NCRR NIH HHS [P20 RR020173, P20-RR020173]
NR 89
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Z9 26
U1 0
U2 2
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 0197-3851
J9 PRENATAL DIAG
JI Prenat. Diagn.
PD JUL
PY 2009
VL 29
IS 7
BP 682
EP 690
DI 10.1002/pd.2276
PG 9
WC Genetics & Heredity; Obstetrics & Gynecology
SC Genetics & Heredity; Obstetrics & Gynecology
GA 472UF
UT WOS:000268157000007
PM 19382114
ER
PT J
AU Anstead, GM
Zhang, Q
Melby, PC
AF Anstead, G. M.
Zhang, Q.
Melby, P. C.
TI Malnutrition promotes prostaglandin over leukotriene production and
dysregulates eicosanoid-cytokine crosstalk in activated resident
macrophages
SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS
LA English
DT Article
DE Prostaglandin; Leukotriene; Malnutrition; Cytokine; Macrophage; Nitric
oxide; Tumor necrosis factor-alpha; Interleukin-10; Granulocyte
macrophage colony stimulating factor
ID COLONY-STIMULATING FACTOR; PROTEIN-CALORIE MALNUTRITION;
ARACHIDONIC-ACID METABOLITES; RAT ALVEOLAR MACROPHAGES; NITRIC-OXIDE
SYNTHASE; NECROSIS-FACTOR-ALPHA; KAPPA-B ACTIVATION; CELL-LINE J774;
ACUTE-INFLAMMATION; CYCLIC-AMP
AB We previously described a murine model of malnutrition that mimicked features of moderate human malnutrition, and led to increased dissemination of Leishmania donovani. In this study, we investigated the effect of malnutrition on macrophage production of cytokines, prostaglandins (PCs), and leukotrienes (LTs). Using either LPS or calcium ionophore A23187 as a stimulus, macrophages from the malnourished mice produced a 3-fold higher PG/LT ((PGE(2)+6-keto-PGF(1 alpha))/(LTB(4)+cysteinyl leukotrienes)) ratio than macrophages from well-nourished mice. LPS-stimulated macrophages from the malnourished mice produced decreased levels of TNF-alpha, GM-CSF, and IL-10, but similar levels of IL-6 and NO compared to well-nourished mice. A complex crosstalk between the eicosanoids and cytokines in the LPS-stimulated macrophages from the malnourished mice was evident by the following: ( I) high levels of PC secretion despite low levels of TNF-alpha; (2) Supplemental IL-10 modulated the excessive PC production; (3) GM-CSF rectified the PG/LT ratio, but did not correct the abnormal cytokine profile: and (4) inhibitors of cyclooxygenase decreased the PG/LT ratio, but did not affect TNF-alpha. Thus, in this model of malnutrition, there is a relative increase in anti-inflammatory PCs compared to pro-inflammatory LTs, which may contribute to immunodeficiency. Published by Elsevier Ltd.
C1 [Anstead, G. M.; Zhang, Q.; Melby, P. C.] Univ Texas Hlth Sci Ctr San Antonio, Div Infect Dis, Dept Med, San Antonio, TX 78229 USA.
[Anstead, G. M.; Melby, P. C.] Audie L Murphy Mem Vet Adm Med Ctr, Res Serv, San Antonio, TX 78284 USA.
RP Anstead, GM (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Infect Dis, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
EM anstead@uthscsa.edu
FU US Department of Veterans Affairs (GMA, PCM); San Antonio Area
Foundation; University of Texas Health Science Center at San Antonio
FX The work was supported by funding from the US Department of Veterans
Affairs (GMA, PCM), the San Antonio Area Foundation, and the University
of Texas Health Science Center at San Antonio (institutional Research
Grant to GMA).
NR 74
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U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0952-3278
J9 PROSTAG LEUKOTR ESS
JI Prostaglandins Leukot. Essent. Fatty Acids
PD JUL
PY 2009
VL 81
IS 1
BP 41
EP 51
DI 10.1016/j.plefa.2009.04.011
PG 11
WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology &
Metabolism
SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology &
Metabolism
GA 475TM
UT WOS:000268384000007
PM 19541468
ER
PT J
AU Wang, R
Kern, JT
Goodfriend, TL
Ball, DL
Luesch, H
AF Wang, Rui
Kern, Jonathan T.
Goodfriend, Theodore L.
Ball, Dennis L.
Luesch, Hendrik
TI Activation of the antioxidant response element by specific oxidized
metabolites of linoleic acid
SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS
LA English
DT Article
DE Polyunsaturated fatty acids; Fatty acid oxidation; Fatty acid epoxides;
EKODE; Antioxidants; Antioxidant response element
ID HUMAN NEUROBLASTOMA-CELLS; OXIDATIVE STRESS; NAD(P)H-QUINONE
OXIDOREDUCTASE; CYCLOPENTENONE PROSTAGLANDINS; INDUCED APOPTOSIS; HEME
OXYGENASE-1; PALMITIC ACID; INDUCTION; ENZYMES; PROTECTION
AB Linoleic acid is required for normal mammalian health and development, but is also prone to oxidation, yielding metabolites with biological effects. We screened linoleic acid, other fatty acids, and some of their derivatives and found that an epoxy-keto derivative of linoleic acid (but neither linoleic acid itself nor others of its oxidation products) strongly activates the antioxidant response element (ARE) in IMR-32 neuroblastoma cells and cerebro-cortical neurons. The active compound, 12,13-epoxy-9-keto-10(trans)-octadecenoic acid (EKODE), induces the expression of ARE-regulated cytoprotective genes such as NQO1 at the transcript and protein levels. EKODE requires transcription factor NRF2 and PI3-kinase for ARE activity. The results suggest that specific oxidation products of linoleic acid may initiate responses that lessen damage caused by oxidative stress. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Wang, Rui; Luesch, Hendrik] Univ Florida, Dept Med Chem, Gainesville, FL 32610 USA.
[Kern, Jonathan T.] Univ Wisconsin, Sch Pharm, Dept Pharmaceut Sci, Madison, WI 53706 USA.
[Goodfriend, Theodore L.; Ball, Dennis L.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI USA.
[Goodfriend, Theodore L.; Ball, Dennis L.] Univ Wisconsin, Dept Pharmacol, Sch Med & Publ Hlth, Madison, WI 53706 USA.
[Goodfriend, Theodore L.; Ball, Dennis L.] Univ Wisconsin, William S Middleton Mem Vet Hosp, Madison, WI USA.
RP Luesch, H (reprint author), Univ Florida, Dept Med Chem, 1600 SW Archer Rd, Gainesville, FL 32610 USA.
EM luesch@cop.ufl.edu
FU NCI NIH HHS [R21 CA133681, R21 CA133681-01A1, R21CA133681]; NHLBI NIH
HHS [HL076238, R01 HL076238]; NIEHS NIH HHS [F32 ES013463, T32 ES007015,
T32ES07015]; PHS HHS [F32 ESO13463]
NR 36
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U1 0
U2 4
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0952-3278
J9 PROSTAG LEUKOTR ESS
JI Prostaglandins Leukot. Essent. Fatty Acids
PD JUL
PY 2009
VL 81
IS 1
BP 53
EP 59
DI 10.1016/j.plefa.2009.04.008
PG 7
WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology &
Metabolism
SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology &
Metabolism
GA 475TM
UT WOS:000268384000008
PM 19481916
ER
PT J
AU Ferreira, GB
van Etten, E
Lage, K
Hansen, DA
Moreau, Y
Workman, CT
Waer, M
Verstuyf, A
Waelkens, E
Overbergh, L
Mathieu, C
AF Ferreira, Gabriela Bomfim
van Etten, Evelyne
Lage, Kasper
Hansen, Daniel Aaen
Moreau, Yves
Workman, Christopher T.
Waer, Mark
Verstuyf, Annemieke
Waelkens, Etienne
Overbergh, Lut
Mathieu, Chantal
TI Proteome analysis demonstrates profound alterations in human dendritic
cell nature by TX527, an analogue of vitamin D
SO PROTEOMICS
LA English
DT Article
DE 2-D DIGE; Dendritic cell; Immunotolerance; Network; Vitamin D analogue
ID MOLECULAR INTERACTION DATABASE; AUTOREACTIVE T-CELLS;
1,25-DIHYDROXYVITAMIN D-3; BIOLOGICAL-ACTIVITY; GENE-EXPRESSION;
PPAR-GAMMA; IN-VITRO; ACTIN; DIFFERENTIATION; MATURATION
AB Structural analogues of vitamin D have been put forward as therapeutic agents able to exploit the immunomodulatory effects of vitamin D, without its undesired calcemic side effects. We have demonstrated that TX527 affects dendritic cell (DC) maturation in vitro, resulting in the generation of a tolerogenic cell. In the present study, we aimed to explore the global protein changes induced by the analogue in immature DC (iDC) and mature human DC and to correlate them with alterations in DC morphology and function. Human CD14(+) monocytes were differentiated toward iDC or mature DCs, in the presence or absence of TX527 (10(-8) M) (n = 4). Protein samples were separated into two different pH ranges (pH4-7 and 6-9), analyzed by 2-D DIGE and differentially expressed spots (p<0.01) were identified by MALDI-TOF/TOF (76.3 and 70.7% in iDC and mature DCs, respectively). Differential protein expression revealed three protein groups predominantly affected by TX527 treatment, namely proteins involved in cytoskeleton structure, in protein biosynthesis/proteolysis and in metabolism. Moreover, protein interactome-network analysis demonstrated dose interaction between these different groups (p<0.001) and morphological and functional analyses confirmed the integrated effect of TX527 on human DCs, resulting in a cell with altered morphology, cell surface marker expression, endocytic and migratory capacity.
C1 [Ferreira, Gabriela Bomfim; van Etten, Evelyne; Verstuyf, Annemieke; Overbergh, Lut; Mathieu, Chantal] Catholic Univ Louvain, Lab Expt Med & Endocrinol LEGENDO, Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium.
[Lage, Kasper; Hansen, Daniel Aaen; Workman, Christopher T.] Tech Univ Denmark, Ctr Biol Sequence Anal, Lyngby, Denmark.
[Lage, Kasper] Massachusetts Gen Hosp, Pediat Surg Res Labs, MassGen Hosp Children, Boston, MA 02114 USA.
[Lage, Kasper] Harvard Univ, Sch Med, Boston, MA USA.
[Moreau, Yves] Catholic Univ Louvain, ESAT SDC, Dept Elect Engn, Heverlee, Belgium.
[Waer, Mark] Catholic Univ Louvain, Expt Transplantat Sect, Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium.
[Waelkens, Etienne] Catholic Univ Louvain, Lab Prot Phosphorylat & Prote, Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium.
RP Overbergh, L (reprint author), Catholic Univ Louvain, Lab Expt Med & Endocrinol LEGENDO, Univ Hosp Gasthuisberg, Herestr 49,Bus 902, B-3000 Louvain, Belgium.
EM lut.overbergh@med.kuleuven.be
RI Bomfim Ferreira, Gabriela/L-8343-2014; Workman, Christopher/K-1066-2015
OI Workman, Christopher/0000-0002-2210-3743
FU Catholic University of Leuven [GOA 2004/10, 2009/10]; Flemish Research
Foundation (FWO) [G.0552.06, G.0649.08]; Belgium Program on
Interuniversity Poles of Attraction initiated by the Belgian State
(IUAP) [P5/17, P6/40]; Centre of Excellence SymBioSys [EF/05/007];
Juvenile Diabetes Research Foundation [JDRF3-2006-33]; Forsknigsradet
for Sundhed og Sygdom; Villum Kann Rasmussen Foundation; Simon Spies
Foundation; National Institute of Child Health and Development (NICHD);
National Institute of Health (NIH); [E06D100904BR]
FX The technical experience of Karin Schildermans, Jos Depovere and Dirk
Valckx is greatly appreciated. This work was supported by the Catholic
University of Leuven (GOA 2004/10 and 2009/10), the Flemish Research
Foundation (FWO G.0552.06 G.0649.08), the Belgium Program on
Interuniversity Poles of Attraction initiated by the Belgian State (IUAP
P5/17 and P6/40) and the Centre of Excellence SymBioSys (Research
Council K.U.Leuven EF/05/007). G. B. F. is supported by a doctoral
fellowship (Alban, no. E06D100904BR), E. V. E. by a post-doctoral
fellowship (juvenile Diabetes Research Foundation, JDRF3-2006-33), K.L.
by a grant from Forsknigsradet for Sundhed og Sygdom and C. M. by a
clinical research fellowship (FWO). We further wish to thank the Villum
Kann Rasmussen Foundation, the Simon Spies Foundation, the National
Institute of Child Health and Development (NICHD) and the National
Institute of Health (NIH) for financial support.
NR 55
TC 26
Z9 27
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1615-9853
EI 1615-9861
J9 PROTEOMICS
JI Proteomics
PD JUL
PY 2009
VL 9
IS 14
BP 3752
EP 3764
DI 10.1002/pmic.200800848
PG 13
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 483MN
UT WOS:000268971000011
PM 19639594
ER
PT J
AU Mohamed, S
Neale, M
Rosenheck, RA
AF Mohamed, Somaia
Neale, Michael
Rosenheck, Robert A.
TI VA Intensive Mental Health Case Management in Urban and Rural Areas:
Veteran Characteristics and Service Delivery
SO PSYCHIATRIC SERVICES
LA English
DT Article
ID ASSERTIVE COMMUNITY TREATMENT; SUBSTANCE-ABUSE; SEVERITY; PROGRAM;
FIDELITY; SCALE; MODEL
AB Objective: The availability of mental health services in rural areas-particularly intensive services such as assertive community treatment (ACT)-has been of increasing concern and was the focus of this study. In recent decades the U. S. Department of Veterans Affairs (VA) has developed a national network of ACT-like programs called mental health intensive case management (MHICM), which have served veterans from diverse locations across the country, including urban and rural areas. Methods: This study used rural-urban commuting area codes and national VA administrative data to compare characteristics of veterans and patterns of MHICM service delivery among veterans with mental illness living in large urban, large rural, small rural, and isolated rural communities. Results: Among veterans enrolled in MHICM from FY 2000 to FY 2005 (N=5,221), 84% (N=4,373) resided in urban areas, 8% (N=421) in large cities, 6% (N=291) in small rural towns, and 3% (N=136) in isolated rural areas. MHICM participants who lived in rural areas had clinical problems broadly similar to those in urban areas, although more rural veterans were unemployed, disabled, received VA disability compensation, and had a payee or fiduciary. MHICM clients in smaller or isolated rural areas received slightly less frequent and less intensive contacts and less recovery-oriented services than those in large urban locations. Conclusions: These data highlight the need for intensive case management services in rural areas and note some challenges in providing them at the intensity and frequency observed in urban areas where travel distances and times are shorter. (Psychiatric Services 60:914-921, 2009)
C1 [Mohamed, Somaia; Neale, Michael; Rosenheck, Robert A.] US Dept Vet Affairs, Vet Integrated Serv Network 1, Mental Illness Res Educ & Clin Ctr, West Haven, CT 06516 USA.
[Mohamed, Somaia; Neale, Michael; Rosenheck, Robert A.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA.
RP Mohamed, S (reprint author), US Dept Vet Affairs, Vet Integrated Serv Network 1, Mental Illness Res Educ & Clin Ctr, 950 Campbell Ave, West Haven, CT 06516 USA.
EM somaia.mohamed@yale.edu
NR 19
TC 17
Z9 17
U1 0
U2 4
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 1075-2730
J9 PSYCHIAT SERV
JI Psychiatr. Serv.
PD JUL
PY 2009
VL 60
IS 7
BP 914
EP 921
PG 8
WC Health Policy & Services; Public, Environmental & Occupational Health;
Psychiatry
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Psychiatry
GA 463TU
UT WOS:000267455800008
PM 19564221
ER
PT J
AU Murphy, JM
Leighton, AH
AF Murphy, J. M.
Leighton, A. H.
TI Anxiety: its role in the history of psychiatric epidemiology
SO PSYCHOLOGICAL MEDICINE
LA English
DT Review
DE Autonomic hyperactivity; depression; DSM-V
ID COMMON MENTAL-DISORDERS; NATIONAL-COMORBIDITY-SURVEY; DSM-III-R;
GENERALIZED ANXIETY; DIAGNOSTIC INTERVIEW; 40-YEAR PERSPECTIVE; MAJOR
DEPRESSION; STIRLING-COUNTY; PANIC DISORDER; UNITED-STATES
AB Background. The role played by anxiety in the history of psychiatric epidemiology has not been well recognized. Such lack of understanding retarded the incremental growth of psychiatric research in general populations. It seems useful to look back oil this history while deliberations are being carried out about how anxiety will be presented in DSM-V.
Method. Drawing on the literature and our own research, we examined work that was carried out during and after the Second World War by a Research Branch of the United States War Department, by the Stirling County Study, and by the Midtown Manhattan Study. The differential influences of Meyerian psychobiology and Freudian psychoanalysis are noted.
Results. The instruments developed in the early epidemiologic endeavors used questions about nervousness, palpitations, sweating, trembling, shortness of breath, upset stomach, etc. These symptoms are important features of what the clinical literature called 'manifest', 'free-floating' or 'chronic anxiety'. A useful descriptive name is I autonomic anxiety'.
Conclusions. Although not focusing oil specific circumstances as in Panic and Phobic disorders, a non-specific form of autonomic anxiety is a common, disabling and usually chronic disorder that received empirical verification in studies of several community populations. It is suggested that two types of general anxiety may need to be recognized, one dominated by excessive worry and feelings of stress, as in the current DSM-IV definition of Generalized Anxiety Disorder (GAD), and another emphasizing frequent unexplainable autonomic fearfulness, as in the early epidemiologic studies.
C1 [Murphy, J. M.; Leighton, A. H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
RP Murphy, JM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, 5 Longfellow Pl,Room 215, Boston, MA 02114 USA.
EM murphy.jane@mgh.harvard.edu
FU NIMH [R01 MH39576-23, 80M0142800101D]
FX This report draws on experience in the Stirling County Study, which is
currently supported by NIMH Grant R01 MH39576-23 (J.M.M.) and on NIMH
Contract 80M0142800101D 'Psychiatric Screening Development for Primary
Care' (J.M.M.).
NR 76
TC 3
Z9 3
U1 0
U2 9
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0033-2917
J9 PSYCHOL MED
JI Psychol. Med.
PD JUL
PY 2009
VL 39
IS 7
BP 1055
EP 1064
DI 10.1017/S0033291708004625
PG 10
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 461TZ
UT WOS:000267296100002
PM 18940025
ER
PT J
AU Nicolaidis, C
McFarland, B
Curry, M
Gerrity, M
AF Nicolaidis, Christina
McFarland, Bentson
Curry, MaryAnn
Gerrity, Martha
TI Differences in Physical and Mental Health Symptoms and Mental Health
Utilization Associated With Intimate-Partner Violence Versus Childhood
Abuse
SO PSYCHOSOMATICS
LA English
DT Article
ID SELF-REPORTED ABUSE; PRIMARY-CARE; CLINICAL CHARACTERISTICS; DOMESTIC
VIOLENCE; SOMATIC SYMPTOMS; BATTERED WOMEN; CHECKLIST HSCL;
SEXUAL-ABUSE; CONSEQUENCES; EXPERIENCES
AB Background: There is ample evidence that both intimate-partner violence (IPV) and childhood abuse adversely affect the physical and mental health of adult women over the long term. Objective: The authors assessed the associations between abuse, symptoms, and mental health utilization. Method: The authors performed a cross-sectional survey of 380 adult female, internal-medicine patients. Results: Although both IPV and childhood abuse were associated with depressive and physical symptoms, IPV was independently associated with physical symptoms, and childhood abuse was independently associated with depression. Women with a history of childhood abuse had higher odds, whereas women with IPV had lower odds, of receiving care from mental health providers. Conclusion: IPV and childhood abuse may have different effects on women's symptoms and mental health utilization. (Psychosomatics 2009; 50: 340-346)
C1 [Nicolaidis, Christina] Oregon Hlth & Sci Univ, Div Gen Internal Med, Dept Med, Portland, OR 97239 USA.
Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA.
Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97239 USA.
Oregon Hlth & Sci Univ, Sch Nursing, Portland, OR 97239 USA.
Portland VA Med Ctr, Portland, OR USA.
RP Nicolaidis, C (reprint author), Oregon Hlth & Sci Univ, Div Gen Internal Med, Dept Med, 3181 SW Sam Jackson Pk Rd,L475, Portland, OR 97239 USA.
EM nicolaid@ohsu.edu
FU Robert Wood Johnson Foundation Depression; National Institute of Mental
Health [K23 MH073008-03]
FX This study was funded by a grant from the Robert Wood Johnson Foundation
Depression in Primary Care Program. Dr. Nicolaidis' time is supported by
a grant from the National Institute of Mental Health (K23 MH073008-03).
NR 31
TC 9
Z9 9
U1 2
U2 5
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0033-3182
J9 PSYCHOSOMATICS
JI Psychosomatics
PD JUL-AUG
PY 2009
VL 50
IS 4
BP 340
EP 346
PG 7
WC Psychiatry; Psychology
SC Psychiatry; Psychology
GA 484NJ
UT WOS:000269052200006
PM 19687174
ER
PT J
AU Bankier, B
Barajas, J
Martinez-Rumayor, A
Januzzi, JL
AF Bankier, Bettina
Barajas, Justine
Martinez-Rumayor, Abelardo
Januzzi, James L.
TI Association Between Anxiety and C-Reactive Protein Levels in Stable
Coronary Heart Disease Patients
SO PSYCHOSOMATICS
LA English
DT Article
ID POSTTRAUMATIC-STRESS-DISORDER; CARDIOVASCULAR EVENTS; STATIN THERAPY;
CARDIAC EVENTS; PHOBIC ANXIETY; RISK-FACTORS; DEPRESSION; MEN; SYMPTOMS;
PERSISTENCE
AB Background: Anxiety is highly prevalent among patients with stable coronary heart disease (CHD). However, the biologic effects that may connect these two seemingly unrelated disorders is not well understood. Objective: This study aimed for a comprehensive evaluation of anxiety in stable CHD patients, in addition to cardiac biomarkers such as C-reactive protein (CRP), troponin T, and amino-terminal pro-B-type brain natriuretic peptide. Method: The study included 43 CHD patients with anxiety disorder and 42 CHD patients without psychiatric disorder given the Structured Clinical Interview for DSM-IV. Results: Regression analyses showed an association between anxiety (anxiety disorder, not otherwise specified) and CRP levels, despite model adjustment for various related demographic and clinical variables. Anxiety was associated with CRP levels. Conclusion: There are significant associations between anxiety and CHD risk, with a potential biologic link between anxiety and elevations in a biomarker with powerful prognostic risk, namely CRP. It is not clear whether this association is directly causal or relates to other medical processes among patients with heightened anxiety. The findings suggest that the current focus on depressive disorders with respect to biomarkers and CHD outcomes should be broadened to include anxiety disorders, as well. (Psychosomatics 2009; 50: 347-353)
C1 [Bankier, Bettina] Med Univ Vienna, Dept Psychiat & Psychotherapy, A-1090 Vienna, Austria.
Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
RP Bankier, B (reprint author), Med Univ Vienna, Dept Psychiat & Psychotherapy, Wahringer Gurtel 18-20, A-1090 Vienna, Austria.
EM bettina.bankier@meduniwien.ac.at
FU NARSAD Young Investigator Award; Mental Health Research Association,
Great Neck, NY [760-2339-5, 218960]
FX This work was fully supported by a NARSAD Young Investigator Award 2005,
Mental Health Research Association, Great Neck, NY (NARSAD Fund No.
760-2339-5, Grant 218960 to B. B).
NR 26
TC 16
Z9 18
U1 0
U2 5
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0033-3182
J9 PSYCHOSOMATICS
JI Psychosomatics
PD JUL-AUG
PY 2009
VL 50
IS 4
BP 347
EP 353
PG 7
WC Psychiatry; Psychology
SC Psychiatry; Psychology
GA 484NJ
UT WOS:000269052200007
PM 19687175
ER
PT J
AU Welch, CA
Czerwinski, D
Ghimire, B
Bertsimas, D
AF Welch, Charles A.
Czerwinski, David
Ghimire, Bijay
Bertsimas, Dimitris
TI Depression and Costs of Health Care
SO PSYCHOSOMATICS
LA English
DT Article
ID MAINTENANCE ORGANIZATION; ADMINISTRATIVE DATABASES; DIABETES
COMPLICATIONS; COMORBID DEPRESSION; OUTCOMES RESEARCH; MAJOR DEPRESSION;
MEDICAL ILLNESS; MOOD DISORDERS; RISK-FACTORS; CLAIMS DATA
AB Background: In spite of its global importance, the interaction between depression and chronic comorbid diseases remains incompletely understood with regard to prevalence, severity of disease, and potential causative factors mediating this interaction. Objective: The authors sought to compare overall medical costs in nondepressed and depressed individuals. Method: Insurance claims for 618,780 patients were examined for total annual non-mental health cost of care in 11 chronic diseases. In each disease cohort, median annual non-mental health cost was calculated for individuals with and without depression. Results: Patients with depression had higher median per-patient annual non-mental health costs than patients without depression in all 11 diseases studied. There was a higher-than-random comorbidity between depression and all 11 chronic comorbid diseases. Conclusion: Even when controlling for number of chronic comorbid diseases, depressed patients had significantly higher costs than non-depressed patients, in a magnitude consistent across 11 chronic comorbid diseases. (Psychosomatics 2009; 50: 392-401)
C1 [Welch, Charles A.] Massachusetts Gen Hosp, Somat Therapies Consultat Serv, Boston, MA 02114 USA.
MIT, Ctr Operat Res, Cambridge, MA 02139 USA.
D2 Hawkeye Inc, Waltham, MA USA.
RP Welch, CA (reprint author), Massachusetts Gen Hosp, Somat Therapies Consultat Serv, Warren 601, Boston, MA 02114 USA.
EM cwelch1@partners.org
NR 37
TC 26
Z9 26
U1 0
U2 3
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0033-3182
J9 PSYCHOSOMATICS
JI Psychosomatics
PD JUL-AUG
PY 2009
VL 50
IS 4
BP 392
EP 401
PG 10
WC Psychiatry; Psychology
SC Psychiatry; Psychology
GA 484NJ
UT WOS:000269052200012
PM 19687180
ER
PT J
AU Chakraborty, A
Held, KD
Prise, KM
Liber, HL
Redmond, RW
AF Chakraborty, Asima
Held, Kathryn D.
Prise, Kevin M.
Liber, Howard L.
Redmond, Robert W.
TI Bystander Effects Induced by Diffusing Mediators after Photodynamic
Stress
SO RADIATION RESEARCH
LA English
DT Article
ID SISTER-CHROMATID EXCHANGES; LYMPHOBLASTOID CELL-LINES; ALPHA-PARTICLES;
HUMAN FIBROBLASTS; DNA-DAMAGE; INTERCELLULAR COMMUNICATION; CHROMOSOMAL
INSTABILITY; OXIDATIVE-METABOLISM; IONIZING-RADIATION; MAMMALIAN-CELLS
AB The bystander effect, whereby cells that are not traversed by ionizing radiation exhibit various responses when in proximity to irradiated cells, is well documented in the field of radiation biology, Here we demonstrate that considerable bystander responses are also observed after photodynamic stress using the membrane-localizing dye deuteroporphyrin (DP). Using cells of a WTK1 human lymphoblastoid cell line in suspension and a transwell insert system that precludes contact between targeted and bystander cells, we have shown that the bystander signaling is mediated by diffusing species. The extranuclear localization of the photosensitizer used suggests that primary DNA damage is not the trigger for initiating these bystander responses, which include elevated oxidative stress, DNA damage (micronucleus formation), mutagenesis and decreased clonogenic survival. In addition, oxidative stress in the bystander population was reduced by the presence of the membrane antioxidant vitamin E in the targeted cells, suggesting that lipid peroxidation may play a key role in mediating these bystander effects. The fluence responses for these bystander effects are non-linear, with larger effects seen at lower fluences and toxicity to the target cell population. Hence, when considering outcomes of photodynamic action in cells and tissue, bystander effects may be significant, especially at sublethal fluences. (C) 2009 by Radiation Research Society
C1 [Chakraborty, Asima; Redmond, Robert W.] Harvard Univ, Wellman Ctr Photomed, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Chakraborty, Asima; Held, Kathryn D.] Harvard Univ, Dept Radiat Oncol, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Prise, Kevin M.] Queens Univ Belfast, Ctr Canc Res & Cell Biol, Belfast BT9 7BL, Antrim, North Ireland.
[Liber, Howard L.] Colorado State Univ, Dept Environm & Radiol Hlth Sci, Ft Collins, CO 80523 USA.
RP Redmond, RW (reprint author), Harvard Univ, Wellman Ctr Photomed, Sch Med, Massachusetts Gen Hosp, Thier 224, Boston, MA 02114 USA.
EM Redmond@helix.mgh.harvard.edu
RI Prise, Kevin/N-7872-2015
OI Prise, Kevin/0000-0001-6134-7946
FU NCI NIH HHS [T32 CA009078-30, P01 CA095227, P01 CA095227-01A2, P01
CA095227-01A20002, P01 CA095227-01A29002, P01 CA095227-02, P01
CA095227-020002, P01 CA095227-03, P01 CA095227-030002, P01 CA095227-04,
P01 CA095227-040002, T32 CA009078, T32 CA009078-26, T32 CA009078-27, T32
CA009078-28, T32 CA009078-29, T32 CA009078-31, T32 CA009078-32, T32
CA009078-33, T32 CA009078-34]
NR 58
TC 25
Z9 27
U1 0
U2 5
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 JUL
PY 2009
VL 172
IS 1
BP 74
EP 81
DI 10.1667/RR1669.1
PG 8
WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology,
Nuclear Medicine & Medical Imaging
GA 465WF
UT WOS:000267619200008
PM 19580509
ER
PT J
AU Pomerantz, SR
Choy, G
AF Pomerantz, Stuart R.
Choy, Garry
TI Net Assets: The Social Web for Radiology. Part I. Social Bookmarking to
Social Citation
SO RADIOLOGY
LA English
DT Editorial Material
C1 [Pomerantz, Stuart R.] Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA.
[Choy, Garry] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
RP Pomerantz, SR (reprint author), Massachusetts Gen Hosp, Dept Neuroradiol, 55 Fruit St,Gray 2-B285, Boston, MA 02114 USA.
EM netassets@rsna.org
NR 3
TC 0
Z9 0
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 JUL
PY 2009
VL 252
IS 1
BP 23
EP 28
DI 10.1148/radiol.2521090515
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 475ME
UT WOS:000268362900004
PM 19561248
ER
PT J
AU Wu, O
Sorensen, AG
Benner, T
Singhal, AB
Furie, KL
Greer, DM
AF Wu, Ona
Sorensen, A. Gregory
Benner, Thomas
Singhal, Aneesh B.
Furie, Karen L.
Greer, David M.
TI Comatose Patients with Cardiac Arrest: Predicting Clinical Outcome with
Diffusion-weighted MR Imaging
SO RADIOLOGY
LA English
DT Article
ID CEREBRAL-ISCHEMIA; CARDIOPULMONARY-RESUSCITATION; HUMAN BRAIN; INJURY;
COEFFICIENT; SURVIVORS; PERFUSION; ENCEPHALOPATHY; HYPOTHERMIA; HYPOXIA
AB Purpose: To examine whether the severity and spatial distribution of reductions in apparent diffusion coefficient ( ADC) are associated with clinical outcomes in patients who become comatose after cardiac arrest.
Materials and Methods: This was an institutional review board-approved, HIPAA-compliant retrospective study of 80 comatose patients with cardiac arrest who underwent diffusion-weighted magnetic resonance imaging. The need to obtain informed consent was waived except when follow-up phone calls were required; in those cases, informed consent was obtained from the families. Mean patient age was 57 years +/- 16 (standard deviation); 31 (39%) patients were women. ADC maps were semiautomatically segmented into the following regions: subcortical white matter; cerebellum; insula; frontal, occipital, parietal, and temporal lobes; caudate nucleus; putamen; and thalamus. Median ADCs were measured in these regions and in the whole brain and were compared ( with a two-tailed Wilcoxon test) as a function of clinical outcome. Outcome was defined by both early eye opening in the 1st week after arrest ( either spontaneously or in response to external stimuli) and 6-month modified Rankin scale score.
Results: Whole-brain median ADC was a significant predictor of poor outcome as measured by no eye opening (specificity, 100% [95% confidence interval {CI}: 86%, 100%]; sensitivity, 30% [ 95% CI: 18%, 45%]) or 6-month modified Rankin scale score greater than 3 ( specificity, 100% [ 95% CI: 73%, 100%]; sensitivity, 41% [95% CI: 29%, 54%]), with patients with poor outcomes having significantly lower ADCs for both outcome measures (P <= .001). Differences in ADC between patients with good and those with poor outcomes varied according to brain region, involving predominantly the occipital and parietal lobes and the putamen, and were dependent on the timing of imaging.
Conclusion: Spatial and temporal differences in ADCs may provide insight into mechanisms of hypoxic-ischemic brain injury and, hence, recovery.
C1 [Wu, Ona; Sorensen, A. Gregory; Benner, Thomas] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Singhal, Aneesh B.; Furie, Karen L.; Greer, David M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
RP Wu, O (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St,CNY 2301, Charlestown, MA 02129 USA.
EM ona@nmr.mgh.harvard.edu
NR 36
TC 83
Z9 84
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 JUL
PY 2009
VL 252
IS 1
BP 173
EP 181
DI 10.1148/radiol.2521081232
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 475ME
UT WOS:000268362900021
PM 19420318
ER
PT J
AU Singh, S
Kalra, MK
Moore, MA
Shailam, R
Liu, B
Toth, TL
Grant, E
Westra, SJ
AF Singh, Sarabjeet
Kalra, Mannudeep K.
Moore, Michael A.
Shailam, Randheer
Liu, Bob
Toth, Thomas L.
Grant, Ellen
Westra, Sjirk J.
TI Dose Reduction and Compliance with Pediatric CT Protocols Adapted to
Patient Size, Clinical Indication, and Number of Prior Studies
SO RADIOLOGY
LA English
DT Article
ID TUBE CURRENT MODULATION; IMAGE QUALITY; FOLLOW-UP; ROW CT; RADIATION;
CHILDREN; ABDOMEN; PELVIS; OPTIMIZATION; UK
AB Purpose: To assess compliance and resultant radiation dose reduction with new pediatric chest and abdominal computed tomographic (CT) protocols based on patient weight, clinical indication, number of prior CT studies, and automatic exposure control.
Materials and Methods: The study was institutional review board approved and HIPAA compliant. Informed consent was waived. The new pediatric CT protocols, which were organized into six color zones based on clinical indications and number of prior CT examinations in a given patient, were retrospectively assessed. Scanning parameters were adjusted on the basis of patient weight. For gradual dose reduction, pediatric CT (n = 692) examinations were performed in three phases of incremental stepwise dose reduction during a 17-month period. There were 245 male patients and 193 female patients (mean age, 12.6 years). Two radiologists independently reviewed CT images for image quality. Data were analyzed by using multivariate analysis of variance.
Results: Compliance with the new protocols in the early stage of implementation ( chest CT, 58.9%; abdominal CT, 65.2%) was lower than in the later stage ( chest CT, 88%; abdominal CT, 82%) ( P < .001). For chest CT, there was 52.6% (9.1 vs 19.2 mGy) to 85.4% (2.8 vs 19.2 mGy) dose reduction in the early stage of implementation and 73.5% (4.9 vs 18.5 mGy) to 83.2% (3.1 vs 18.5 mGy) dose reduction in the later stages compared with dose at noncompliant examinations (P < .001); there was no loss of clinically relevant image quality. For abdominal CT, there was 34.3% (9.0 vs 13.7 mGy) to 80.2% (2.7 vs 13.7 mGy) dose reduction in the early stage of implementation and 62.4% (6.5 vs 17.3) to 83.8% ( 2.8 vs 17.3 mGy) dose reduction in the later stage ( P < .001).
Conclusion: Substantial dose reduction and high compliance can be obtained with pediatric CT protocols tailored to clinical indications, patient weight, and number of prior studies.
C1 [Singh, Sarabjeet; Kalra, Mannudeep K.; Moore, Michael A.; Shailam, Randheer; Liu, Bob; Grant, Ellen; Westra, Sjirk J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Toth, Thomas L.] GE Healthcare, Waukesha, WI USA.
RP Singh, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, 25 New Chardon St,4th Floor, Boston, MA 02114 USA.
EM ssingh6@partners.org
NR 21
TC 104
Z9 115
U1 0
U2 9
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 JUL
PY 2009
VL 252
IS 1
BP 200
EP 208
DI 10.1148/radiol.2521081554
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 475ME
UT WOS:000268362900024
PM 19435938
ER
PT J
AU Lewis, SL
Miner-Williams, D
Novian, A
Escamilla, MI
Blackwell, PH
Kretzschmar, JH
Arevalo-Flechas, LC
Bonner, PN
AF Lewis, Sharon L.
Miner-Williams, Denise
Novian, Allen
Escamilla, Monica I.
Blackwell, Paula H.
Kretzschmar, Jennifer Hale
Arevalo-Flechas, Lyda C.
Bonner, Peter N.
TI A Stress-Busting Program for Family Caregivers
SO REHABILITATION NURSING
LA English
DT Article
DE Alzheimer's disease; Alzheimer's disease and related dementias;
caregiving.; intervention; stress
ID RELAXATION THERAPY; SYMPTOM QUESTIONNAIRE; HEALTH; DEPRESSION; SPOUSAL;
IMPACT
AB Aging baby boomers, longer life spans, and rising levels of Alzheimer's disease and related dementias (ADRD) will result in a caregiver crisis in the near future. The ways in which caregivers deal with stresses related to caregiving will be critical to both their own well-being and their ability to care for others. The purpose of this article is to describe the Stress-Busting Program (SBP) for family caregivers and its effectiveness. The essential components of the SBP are education, stress management, problem solving, and support delivered in a group setting for 9 weeks. Results of the SBP indicate that throughout the program, caregivers experienced significant improvements in general health, vitality, social function, and mental health scores and decreases in anxiety anger/hostility, depression, perceived stress, and caregiver burden. The SBP is a cost-effective health-promotion strategy for caregivers who have substantial ongoing stress.
C1 [Lewis, Sharon L.] Univ Texas Hlth Sci Ctr San Antonio, Sch Nursing & Med, San Antonio, TX 78229 USA.
[Lewis, Sharon L.] S Texas Vet Hlth Care Syst, San Antonio, TX USA.
[Miner-Williams, Denise; Novian, Allen; Escamilla, Monica I.; Blackwell, Paula H.; Kretzschmar, Jennifer Hale; Arevalo-Flechas, Lyda C.] Univ Texas Hlth Sci Ctr San Antonio, Sch Nursing, San Antonio, TX 78229 USA.
[Bonner, Peter N.] Data & Stat Inc, Boerne, TX USA.
RP Lewis, SL (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Sch Nursing & Med, San Antonio, TX 78229 USA.
EM lewissl@uthscsa.edu
NR 32
TC 6
Z9 6
U1 1
U2 17
PU ASSOC REHABILITATION NURSES
PI GLENVIEW
PA 4700 W LAKE AVE, GLENVIEW, IL 60025-1485 USA
SN 0278-4807
J9 REHABIL NURS
JI Rehabil. Nurs.
PD JUL-AUG
PY 2009
VL 34
IS 4
BP 151
EP 159
PG 9
WC Nursing; Rehabilitation
SC Nursing; Rehabilitation
GA 461AK
UT WOS:000267235300004
PM 19583056
ER
PT J
AU Maciejewski, ML
Chen, SY
Au, DH
AF Maciejewski, Matthew L.
Chen, Shih-Yin
Au, David H.
TI Adult Asthma Disease Management: An Analysis of Studies, Approaches,
Outcomes, and Methods
SO RESPIRATORY CARE
LA English
DT Review
DE asthma; disease management; outcomes; study design; study quality
ID GENERAL-PRACTICE; CARE POPULATION; NURSE PRACTICE; MEDICATION USE;
HEALTH-CARE; PROGRAM; MORBIDITY; INTERVENTIONS; REGRESSION; EMERGENCY
AB BACKGROUND: Disease management has been implemented for patients with asthma in various ways. We describe the approaches to and components of adult asthma disease-management interventions, examine the outcomes evaluated, and assess the quality of published studies. METHODS: We searched the MEDLINE, EMBASE, CINAHL, PsychInfo, and Cochrane databases for studies published in 1986 through 2008, on adult asthma management. With the studies that met our inclusion criteria, we examined the clinical, process, medication, economic, and patient-reported outcomes reported, and the study designs, provider collaboration during the studies, and statistical methods. RESULTS: Twenty-nine articles describing 27 studies satisfied our inclusion criteria. There was great variation in the content, extent of collaboration between physician and non-physician providers responsible for intervention delivery, and outcomes examined across the 27 studies. Because of limitations in the design of 22 of the 27 studies, the differences in outcomes assessed, and the lack of rigorous statistical adjustment, we could not draw definitive conclusions about the effectiveness or cost-effectiveness of the asthma disease-management programs or which approach was most effective. CONCLUSIONS: Few well-designed studies with rigorous evaluations have been conducted to evaluate disease-management interventions for adults with asthma. Current evidence is insufficient to recommend any particular intervention.
C1 [Maciejewski, Matthew L.] Durham Vet Affairs Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC 27701 USA.
[Maciejewski, Matthew L.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
[Maciejewski, Matthew L.] Univ N Carolina, Sch Pharm, Div Pharmaceut Outcomes & Policy, Chapel Hill, NC USA.
[Chen, Shih-Yin] Abt Biopharma Solut, Lexington, MA USA.
[Au, David H.] Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA.
[Au, David H.] Univ Washington, Med Ctr, Dept Med, Seattle, WA 98195 USA.
RP Maciejewski, ML (reprint author), Durham Vet Affairs Med Ctr, Ctr Hlth Serv Res Primary Care, Legacy Tower,411 W Chapel Hill St, Durham, NC 27701 USA.
EM mlm34@duke.edu
NR 40
TC 9
Z9 9
U1 0
U2 0
PU DAEDALUS ENTERPRISES INC
PI IRVING
PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA
SN 0020-1324
J9 RESP CARE
JI Respir. Care
PD JUL
PY 2009
VL 54
IS 7
BP 878
EP 886
DI 10.4187/002013209793800385
PG 9
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 471DX
UT WOS:000268036400008
PM 19558739
ER
PT J
AU Luk, AJ
Levin, GP
Moore, EE
Zhou, XH
Kestenbaum, BR
Choi, HK
AF Luk, Andrew J.
Levin, Gregory P.
Moore, Elya E.
Zhou, Xiao-Hua
Kestenbaum, Bryan R.
Choi, Hyon K.
TI Allopurinol and mortality in hyperuricaemic patients
SO RHEUMATOLOGY
LA English
DT Article
DE Allopurinol; Mortality; Hyperuricaemia; Gout
ID XANTHINE-OXIDASE INHIBITION; CHRONIC HEART-FAILURE; ENDOTHELIAL
DYSFUNCTION; URIC-ACID; CARDIOVASCULAR RISK; HYPERTENSION; GOUT; DISEASE
AB Methods. From a population of hyperuricaemic veterans of [serum urate level 416 mol/l (7.0 mg/dl)] at least 40 years of age, we compared the risk of death between incident allopurinol users (n 2483) and non-users (n 7441). We estimated the multivariate mortality hazard ratio (HR) of allopurinol use with Cox proportional hazards models.
Results. Of the 9924 veterans (males, 98 and mean age 62.7 years), 1021 died during the follow-up. Patients who began treatment with allopurinol had worse prognostic factors for mortality, including higher BMI and comorbidities. After adjusting for baseline urate levels, allopurinol treatment was associated with a lower risk of all-cause mortality (HR 0.78; 95 CI 0.67, 0.91). Further adjustment with other prognostic factors did not appreciably alter this estimate (HR 0.77; 95 CI 0.65, 0.91). The mean change from baseline in serum urate within the allopurinol group was 111 mol/l (1.86 mg/dl). Adjusting for baseline urate level, allopurinol users had a 40 mol/l (0.68 mg/dl) lower follow-up serum urate value than controls (95 CI 0.55, 0.81).
Conclusion. Our findings indicate that allopurinol treatment may provide a survival benefit among patients with hyperuricaemia.
C1 [Choi, Hyon K.] Univ British Columbia, Dept Med, Div Rheumatol, Arthrit Res Ctr Canada, Vancouver, BC V5Z 1L7, Canada.
[Luk, Andrew J.; Zhou, Xiao-Hua] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA.
[Levin, Gregory P.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Moore, Elya E.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Kestenbaum, Bryan R.] Univ Washington, Dept Med, Seattle, WA USA.
RP Choi, HK (reprint author), Univ British Columbia, Dept Med, Div Rheumatol, Arthrit Res Ctr Canada, 895 W 10th Ave, Vancouver, BC V5Z 1L7, Canada.
EM hchoi@arthritisresearch.ca
FU Takeda Pharmaceuticals North America, Inc
FX Supported by a grant from Takeda Pharmaceuticals North America, Inc.
NR 18
TC 43
Z9 43
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1462-0324
J9 RHEUMATOLOGY
JI RHEUMATOLOGY
PD JUL
PY 2009
VL 48
IS 7
BP 804
EP 806
DI 10.1093/rheumatology/kep069
PG 3
WC Rheumatology
SC Rheumatology
GA 460XY
UT WOS:000267227400018
PM 19447769
ER
PT J
AU Petrocca, F
Lieberman, J
AF Petrocca, Fabio
Lieberman, Judy
TI Micromanipulating cancer microRNA-based therapeutics?
SO RNA BIOLOGY
LA English
DT Review
DE cancer; microRNA; RNAi; delivery; therapeutics; oncomir
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; CELL-CYCLE ARREST; LET-7 MICRORNA; MIR-200
FAMILY; BREAST-CANCER; IN-VIVO; MESENCHYMAL TRANSITION; REPRESSORS ZEB1;
DOWN-REGULATION; MESSENGER-RNAS
AB Because microRNAs regulate cancer cell differentiation, proliferation, survival and metastasis, manipulating microRNA function, either by mimicking or inhibiting miRNAs implicated in cancer, could provide a powerful therapeutic strategy to interfere with key pathways for cancer progression. This review will explore some of the opportunities and obstacles to harnessing microRNA biology for cancer therapy.
C1 [Lieberman, Judy] Harvard Univ, Sch Med, Childrens Hosp Boston, Immune Dis Inst,Program Cellular & Mol Med, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Dept Pediat, Boston, MA USA.
RP Lieberman, J (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Immune Dis Inst,Program Cellular & Mol Med, Boston, MA 02115 USA.
EM lieberman@idi.harvard.edu
RI Lieberman, Judy/A-2717-2015
NR 59
TC 20
Z9 20
U1 1
U2 3
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA
SN 1547-6286
J9 RNA BIOL
JI RNA Biol.
PD JUL-AUG
PY 2009
VL 6
IS 3
BP 335
EP 340
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 545FA
UT WOS:000273716700020
PM 19535911
ER
PT J
AU Goldstein, KE
Hazlett, EA
New, AS
Haznedar, MM
Newmark, RE
Zelmanova, Y
Passarelli, V
Weinstein, SR
Canfield, EL
Meyerson, DA
Tang, CY
Buchsbaum, MS
Siever, LJ
AF Goldstein, Kim E.
Hazlett, Erin A.
New, Antonia S.
Haznedar, M. Mehmet
Newmark, Randall E.
Zelmanova, Yuliya
Passarelli, Vincent
Weinstein, Shauna R.
Canfield, Emily L.
Meyerson, David A.
Tang, Cheuk Y.
Buchsbaum, Monte S.
Siever, Larry J.
TI Smaller superior temporal gyrus volume specificity in schizotypal
personality disorder
SO SCHIZOPHRENIA RESEARCH
LA English
DT Article
DE Schizotypal personality disorder; Borderline personality disorder;
Schizophrenia; MRI; Brodmann area 22; Auditory cortex
ID VOXEL-BASED MORPHOMETRY; BORDERLINE PERSONALITY; SCHIZOPHRENIA SPECTRUM;
BRAIN ABNORMALITIES; MRI ABNORMALITIES; CINGULATE GYRUS;
AUDITORY-CORTEX; GRAY-MATTER; AMYGDALA; WOMEN
AB Background: Superior temporal gyrus (STG/BA22) volume is reduced in schizophrenia and to a milder degree in schizotypal personality disorder (SPD), representing a less severe disorder in the schizophrenia spectrum. SPD and Borderline personality disorder (BPD) are severe personality disorders characterized by social and cognitive dysfunction. However, while SPD is characterized by social withdrawal/anhedonia, BPD is marked by hyper-reactivity to interpersonal stimuli and hyper-emotionality. This is the first morphometric study to directly compare SPD and BPD patients in temporal lobe volume.
Methods: We compared three age-, sex-, and education-matched groups: 27 unmedicated SPD individuals with no BPD traits, 52 unmedicated BPD individuals with no SPD traits, and 45 healthy controls. We examined gray matter volume of frontal and temporal lobe Brodmann areas (BAs), and dorsal/ventral amygdala from 3-T magnetic resonance imaging.
Results: In the STG, an auditory association area reported to be dysfunctional in SPD and BPD, the SPD patients had significantly smaller volume than healthy controls and BPD patients. No group differences were found between BPD patients and controls. Smaller BA22 volume was associated with greater symptom severity in SPD patients. Reduced STG volume may be an important endophenotype for schizophrenia-spectrum disorders. SPD is distinct from BPD in terms of STG volume abnormalities which may reflect different underlying pathophysiological mechanisms and could help discriminate between them. (C) 2009 Elsevier B.V. All rights reserved.
C1 [Goldstein, Kim E.; Hazlett, Erin A.; New, Antonia S.; Haznedar, M. Mehmet; Newmark, Randall E.; Zelmanova, Yuliya; Passarelli, Vincent; Weinstein, Shauna R.; Canfield, Emily L.; Meyerson, David A.; Siever, Larry J.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA.
[New, Antonia S.; Weinstein, Shauna R.; Siever, Larry J.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA.
[New, Antonia S.; Weinstein, Shauna R.; Siever, Larry J.] MIRECC, Bronx, NY USA.
[Tang, Cheuk Y.] Mt Sinai Sch Med, Dept Radiol, New York, NY USA.
[Buchsbaum, Monte S.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA.
[Buchsbaum, Monte S.] Univ Calif San Diego, Dept Neurol, San Diego, CA 92103 USA.
RP Hazlett, EA (reprint author), Mt Sinai Sch Med, Dept Psychiat, Box 1505, New York, NY 10029 USA.
EM erin.hazlett@mssm.edu
FU NIMH [MH073911, MH067918]; VA MERIT [7609-28]; National Center for
Research Resources (NCRR) [RR-00071]; NIH; Mental Illness Research
Education and Clinical Center; VISN 3 Veterans Health Administration
FX This work was supported by NIMH grants MH073911 to Dr. Hazlett, MH067918
to Dr. New, and VA MERIT grant 7609-28 to Dr. Siever. Other support came
from Grant Number M01 - Patient Care RR-00071 from the National Center
for Research Resources (NCRR), a component of the NIH and the Mental
Illness Research Education and Clinical Center, VISN 3 Veterans Health
Administration.
NR 60
TC 29
Z9 29
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 JUL
PY 2009
VL 112
IS 1-3
BP 14
EP 23
DI 10.1016/j.schres.2009.04.027
PG 10
WC Psychiatry
SC Psychiatry
GA 472TA
UT WOS:000268153900003
PM 19473820
ER
PT J
AU Noda, SE
El-Jawahri, A
Patel, D
Lautenschlaeger, T
Siedow, M
Chakravarti, A
AF Noda, Shin-ei
El-Jawahri, Areej
Patel, Disha
Lautenschlaeger, Tim
Siedow, Michael
Chakravarti, Arnab
TI Molecular Advances of Brain Tumors in Radiation Oncology
SO SEMINARS IN RADIATION ONCOLOGY
LA English
DT Article
ID GROWTH-FACTOR RECEPTOR; FARNESYL TRANSFERASE INHIBITORS; PRIMARY
GLIOBLASTOMA-MULTIFORME; RADIOTHERAPY PLUS CONCOMITANT; HISTONE
DEACETYLASE INHIBITOR; HUMAN-MALIGNANT GLIOMAS; ADJUVANT TEMOZOLOMIDE;
IN-VITRO; GENETIC ALTERATIONS; IONIZING-RADIATION
AB Glioblastoma, grade IV malignant glioma based on the World Health Organization classification, is the most common primary brain tumor in adults. The average survival time of less than 1 year has not improved notably over the last 3 decades. Surgery and radiotherapy, the traditional cornerstones of therapy, provide palliative benefit, whereas the value of chemotherapy has been marginal and controversial. The dismal prognosis of glioblastoma patients is largely caused by the striking radioresistance of these tumors. A better understanding of the molecular mechanisms that underlie the malignant phenotype of glioblastomas and plausible mechanisms of radiation resistance can provide new possibilities in terms of targeted therapeutic strategies. Despite the genetic heterogeneity of malignant gliomas, common aberrations in the signaling elements of the growth and survival pathways are found. New treatments have emerged to target molecules in these signaling pathways with the goal to increase specific efficacy and minimize toxicity. Monoclonal antibodies and low molecular-weight kinase inhibitors are the most common classes of agents in targeted cancer treatment. This review introduces these new targeted therapies in the context of current treatment options for patients with glioblastoma. It is hoped that this combined approach will overcome the current limitations in the treatment of patients with glioblastoma and result in a better prognosis for these patients. Semin Radiat Oncol 19:171-178 (C) 2009 Elsevier Inc. All rights reserved.
C1 [Chakravarti, Arnab] Ohio State Univ, Dept Radiat Oncol, Sch Med, Columbus, OH 43210 USA.
[Noda, Shin-ei; El-Jawahri, Areej; Patel, Disha; Lautenschlaeger, Tim; Siedow, Michael] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA.
RP Chakravarti, A (reprint author), Ohio State Univ, Dept Radiat Oncol, Sch Med, 300 W 10th Ave,Room 080B, Columbus, OH 43210 USA.
EM arnab.chakravarti@osumc.edu
FU Ohio State Urnversity-James Cancer Center
FX This article is supported by funds from the Ohio State Urnversity-James
Cancer Center.
NR 86
TC 42
Z9 42
U1 0
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 1053-4296
EI 1532-9461
J9 SEMIN RADIAT ONCOL
JI Semin. Radiat. Oncol.
PD JUL
PY 2009
VL 19
IS 3
BP 171
EP 178
DI 10.1016/j.semradonc.2009.02.005
PG 8
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 454JF
UT WOS:000266677500006
PM 19464632
ER
PT J
AU Noda, SE
Lautenschlaeger, T
Siedow, MR
Patel, DR
El-Jawahri, A
Suzuki, Y
Loeffler, JS
Bussiere, MR
Chakravarti, A
AF Noda, Shin-ei
Lautenschlaeger, Tim
Siedow, Michael R.
Patel, Disha R.
El-Jawahri, Areej
Suzuki, Yoshiyuki
Loeffler, Jay S.
Bussiere, Marc R.
Chakravarti, Arnab
TI Technological Advances in Radiation Oncology for Central Nervous System
Tumors
SO SEMINARS IN RADIATION ONCOLOGY
LA English
DT Article
ID NEUTRON-CAPTURE THERAPY; INTENSITY-MODULATED RADIOTHERAPY; RECURRENT
MALIGNANT GLIOMAS; WHOLE-BRAIN RADIOTHERAPY; HIGH-GRADE GLIOMAS;
GLIOBLASTOMA-MULTIFORME; STEREOTACTIC RADIOSURGERY; RANDOMIZED-TRIAL;
DOSE-ESCALATION; HYPOFRACTIONATED RADIOTHERAPY
AB Advances in computer software technology have led to enormous progress that has enabled increasing levels of complexity to be incorporated into radiotherapy treatment planning systems. Because of these changes, the delivery of radiotherapy evolved from therapy designed primarily on plain 2-dimensional X-ray images and hand calculations to therapy based on 3-dimensional images incorporating increasingly complex computer algorithms in the planning process. In addition, challenges in treatment planning and radiation delivery, such as problems with setup error and organ movement, have begun to be systematically addressed, ushering in an era of so-called 4-dimensional radiotherapy. This review article discusses how these advances have changed the way in which many common neoplasms of the central nervous system are being treated at present. Semin Radiat Oncol 19:179-186 (C) 2009 Elsevier Inc. All rights reserved.
C1 [Chakravarti, Arnab] Ohio State Univ, Sch Med, Dept Radiat Oncol, Columbus, OH 43210 USA.
[Noda, Shin-ei; Lautenschlaeger, Tim; Siedow, Michael R.; Patel, Disha R.; El-Jawahri, Areej; Loeffler, Jay S.; Bussiere, Marc R.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Suzuki, Yoshiyuki] Gunma Univ, Dept Radiat Oncol, Grad Sch Med, Gunma, Japan.
RP Chakravarti, A (reprint author), Ohio State Univ, Sch Med, Dept Radiat Oncol, 300W 10th Ave,Room 0808, Columbus, OH 43210 USA.
EM arnab.chakravarti@osumc.edu
FU Ohio State University-James Cancer Center
FX This article is supported by funds from the Ohio State University-James
Cancer Center.
NR 75
TC 6
Z9 7
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 1053-4296
J9 SEMIN RADIAT ONCOL
JI Semin. Radiat. Oncol.
PD JUL
PY 2009
VL 19
IS 3
BP 179
EP 186
DI 10.1016/j.semradonc.2009.02.006
PG 8
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 454JF
UT WOS:000266677500007
PM 19464633
ER
PT J
AU Burns, SM
Hough, S
Boyd, BL
Hill, J
AF Burns, Shaun Michael
Hough, Sigmund
Boyd, Briana L.
Hill, Justin
TI Sexual Desire and Depression Following Spinal Cord Injury: Masculine
Sexual Prowess as a Moderator
SO SEX ROLES
LA English
DT Article
DE Gender roles; Masculinity; Mental health; Sexual functioning; Spinal
cord injury
ID QUALITY-OF-LIFE; ADJUSTMENT FOLLOWING TREATMENT; ERECTILE DYSFUNCTION;
PROSTATE-CANCER; MENS ADJUSTMENT; RELATIONSHIP QUESTIONNAIRE;
UNMITIGATED AGENCY; SOCIAL SUPPORT; SELF-ESTEEM; SATISFACTION
AB Men's adherence to masculine norms stressing sexual prowess may contribute to their adjustment to changes in sexual functioning following spinal cord injury. The authors test this hypothesis by examining the moderating role of men's conformity to gender norms for sexual prowess on the relationship between sexual desire and depression. One hundred and sixteen male citizens of the United States with spinal cord injuries were recruited for participation in the internet-based survey. Results indicated that participants with strong sexual desire evinced higher rates of depression when they conformed to masculine norms emphasizing sexual prowess. Men with little reported sexual desire, by contrast, demonstrated lower rates of depression when they endorsed norms for prowess. Directions for future research and treatment interventions are offered.
C1 [Burns, Shaun Michael; Hough, Sigmund; Hill, Justin] Boston Univ, Sch Med, Harvard Univ, VA Boston Healthcare Syst, Boston, MA 02118 USA.
[Boyd, Briana L.] Hartford Hosp, Inst Living, Hartford, CT 06115 USA.
RP Burns, SM (reprint author), Boston Univ, Sch Med, Harvard Univ, VA Boston Healthcare Syst, Boston, MA 02118 USA.
EM shaun.burns@va.gov
NR 55
TC 4
Z9 4
U1 3
U2 3
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0360-0025
J9 SEX ROLES
JI Sex Roles
PD JUL
PY 2009
VL 61
IS 1-2
BP 120
EP 129
DI 10.1007/s11199-009-9615-7
PG 10
WC Psychology, Developmental; Psychology, Social; Women's Studies
SC Psychology; Women's Studies
GA 460XC
UT WOS:000267224000010
ER
PT J
AU Vartanians, VM
Karchmer, AW
Giurini, JM
Rosenthal, DI
AF Vartanians, Vartan M.
Karchmer, Adolf W.
Giurini, John M.
Rosenthal, Daniel I.
TI Is there a role for imaging in the management of patients with diabetic
foot?
SO SKELETAL RADIOLOGY
LA English
DT Article
ID CHRONIC OSTEOMYELITIS; DIAGNOSIS; SCINTIGRAPHY; METAANALYSIS;
INFECTIONS; ULCERS; BONE; MRI; ABNORMALITIES; ACCURACY
C1 [Vartanians, Vartan M.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Karchmer, Adolf W.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA.
[Giurini, John M.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Podiatr Surg, Boston, MA 02215 USA.
[Rosenthal, Daniel I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
RP Vartanians, VM (reprint author), Massachusetts Gen Hosp, Dept Radiol, 25 New Chardon St,Suite 427-B, Boston, MA 02114 USA.
EM vvartanians@partners.org
NR 27
TC 9
Z9 9
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0364-2348
J9 SKELETAL RADIOL
JI Skeletal Radiol.
PD JUL
PY 2009
VL 38
IS 7
BP 633
EP 636
DI 10.1007/s00256-009-0663-4
PG 4
WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging
SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging
GA 450IT
UT WOS:000266394900001
PM 19241076
ER
PT J
AU Thomas, RJ
Weiss, MD
Mietus, JE
Peng, CK
Goldberger, AL
Gottlieb, DJ
AF Thomas, Robert Joseph
Weiss, Matthew D.
Mietus, Joseph E.
Peng, Chung-Kang
Goldberger, Ary L.
Gottlieb, Daniel J.
TI Prevalent Hypertension and Stroke in the Sleep Heart Health Study:
Association with an ECG-derived Spectrographic Marker of Cardiopulmonary
Coupling
SO SLEEP
LA English
DT Article
DE ECG; cardiopulmonary coupling; Sleep Heart Health Study; sleep
spectrogram; hypertension stroke
ID CHEMICAL CONTROL STABILITY; UPPER AIRWAY MECHANICS; APNEA; INSTABILITY;
RESPIRATION; BYPASS
AB Study Objectives: The electrocardiogram (ECG)-based sleep spectrogram generates a map of cardiopulmonary coupling based on heart rate variability and respiration derived from QRS amplitude variations. A distinct spectrographic phenotype, designated as narrow-band elevated low frequency coupling (e-LFC(NB)), has been associated with central apneas and periodic breathing and predicts sleep laboratory failure of continuous positive airway pressure therapy. This study assesses, at a population level, the associations of this spectrographic biomarker with prevalent cardiovascular disease using the Sleep Heart Health Study (SHHS)-I dataset.
Design: Retrospective analysis of the Sleep Heart Health Study-I dataset.
Setting: Laboratory for complex physiologic signals analysis.
Measurements and Results: The fully-automated ECG-derived sleep spectrogram technique was applied to 5247 (of the original 6441) polysomnograms from the SHHS-I. Associations were estimated with use of various drugs and pathologies including prevalent hypertension and cardiovascular and cerebrovascular disease. Increasing with age and more common in males, e-LFC(NB) is also associated with greater severity of sleep apnea and fragmented sleep. After adjustment for potential confounders, an independent association with prevalent hypertension and stroke was found.
Conclusions: An ECG-derived spectrographic marker related to low frequency cardiopulmonary coupling is associated with greater sleep apnea severity. Whether this biomarker is solely a sign of more severe disease or whether it reflects primary alterations in sleep apnea pathophysiology (which may either cause or result from sleep apnea) is unknown. This ECG-based spectral marker is associated with a higher prevalence of hypertension and stroke.
C1 [Thomas, Robert Joseph] Beth Israel Deaconess Med Ctr, Pulm Off, Div Pulm Crit Care & Sleep Med, Boston, MA 02215 USA.
[Mietus, Joseph E.; Peng, Chung-Kang; Goldberger, Ary L.] Beth Israel Deaconess Med Ctr, Div Interdisciplinary Med & Biotechnol, Boston, MA 02215 USA.
[Gottlieb, Daniel J.] Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA.
[Gottlieb, Daniel J.] VA Boston Healthcare Syst, W Roxbury, MA USA.
RP Thomas, RJ (reprint author), Beth Israel Deaconess Med Ctr, Pulm Off, Div Pulm Crit Care & Sleep Med, KB 023, Boston, MA 02215 USA.
EM rthomas1@bidmc.harvard.edu
RI Peng, Chung-Kang/E-1489-2011
OI Peng, Chung-Kang/0000-0003-3666-9833
FU National Heart, Lung and Blood Institute [R-21 HL079248]; Periodic
Breathing Foundation; G. Harold and Leila Y. Mathers Foundation; James
S. McDonnell Foundation; NIH [UOIEB008577]; Wyss Institute
FX This work was supported in part by the grants from the National Heart,
Lung and Blood Institute R-21 HL079248 (RJT), the Periodic Breathing
Foundation, and following to ALG: G. Harold and Leila Y. Mathers
Foundation, the James S. McDonnell Foundation, the NIH-sponsored
Research Resource for Complex Physiologic Signals (UOIEB008577), and the
Wyss Institute for Biologically Inspired Engineering.
NR 24
TC 23
Z9 25
U1 0
U2 3
PU AMER ACAD SLEEP MEDICINE
PI WESTCHESTER
PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA
SN 0161-8105
J9 SLEEP
JI Sleep
PD JUL 1
PY 2009
VL 32
IS 7
BP 897
EP 904
PG 8
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 472JG
UT WOS:000268126000009
PM 19639752
ER
PT J
AU Prasad, A
Cevallos, ME
Riosa, S
Darouiche, RO
Trautner, BW
AF Prasad, A.
Cevallos, M. E.
Riosa, S.
Darouiche, R. O.
Trautner, B. W.
TI A bacterial interference strategy for prevention of UTI in persons
practicing intermittent catheterization
SO SPINAL CORD
LA English
DT Article
DE urinary tract infection; spinal cord injury; Escherichia coli
ID BLADDER MANAGEMENT; URETHRAL CATHETERS; URINARY CATHETERS;
ESCHERICHIA-COLI; PILOT TRIAL; COLONIZATION; INFECTION; ADHERENCE
AB Study design: Non-randomized pilot trial.
Objectives: To determine whether Escherichia coli 83972-coated urinary catheters in persons with spinal cord injury (SCI) practicing an intermittent catheterization program (ICP) could (1) achieve bladder colonization with this benign organism and (2) decrease the rate of symptomatic urinary tract infection (UTI).
Setting: Outpatient SCI clinic in a Veterans Affairs hospital (USA).
Methods: Participants had neurogenic bladders secondary to SCI, were practicing ICP, had experienced at least one UTI and had documented bacteruria within the past year. All participants received a urinary catheter that had been pre-inoculated with E. coli 83972. The catheter was left in place for 3 days and then removed. Participants were followed with urine cultures and telephone calls weekly for 28 days and then monthly until E. coli 83972 was lost from the urine. Outcome measures were (1) the rate of successful bladder colonization, defined as the detection (>= 10(2) cfu ml(-1)) of E. coli 83972 in urine cultures for >3 days after catheter removal and (2) the rate of symptomatic UTI during colonization with E. coli 83972.
Results: Thirteen participants underwent 19 insertions of study catheters. Eight participants (62%) became successfully colonized for 43 days after catheter removal. In these 8 participants, the rate of UTI during colonization was 0.77 per patient-year, in comparison with the rate of 2.27 UTI per patient-year before enrollment.
Conclusions: E. coli 83972-coated urinary catheters are a viable means of achieving bladder colonization with this potentially protective strain in persons practicing ICP. Spinal Cord (2009) 47, 565-569; doi: 10.1038/sc.2008.166; published online 13 January 2009
C1 [Cevallos, M. E.; Riosa, S.; Darouiche, R. O.; Trautner, B. W.] Baylor Coll Med, Dept Med, Div Infect Dis, Houston, TX 77030 USA.
[Prasad, A.] New York Med Coll, Westchester Med Ctr, Dept Internal Med, Westchester, NY USA.
[Cevallos, M. E.; Riosa, S.; Darouiche, R. O.; Trautner, B. W.] Baylor Coll Med, Ctr Prosthesis Infect, Dept Phys Med & Rehabil, Houston, TX 77030 USA.
[Darouiche, R. O.; Trautner, B. W.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA.
RP Trautner, BW (reprint author), Baylor Coll Med, Dept Med, Div Infect Dis, 1 Baylor Plaza,BCM 286,N1319, Houston, TX 77030 USA.
EM trautner@bcm.edu
FU Department of Veterans Affairs Rehabilitation Research and Development
Service [B4623R, B4087R, B4387P]; NIH [HD42014, DK77313]
FX This study was supported by Department of Veterans Affairs
Rehabilitation Research and Development Service grants B4623R, B4087R
and B4387P as well as by NIH grants HD42014 and DK77313.
NR 20
TC 17
Z9 18
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1362-4393
J9 SPINAL CORD
JI Spinal Cord
PD JUL
PY 2009
VL 47
IS 7
BP 565
EP 569
DI 10.1038/sc.2008.166
PG 5
WC Clinical Neurology; Rehabilitation
SC Neurosciences & Neurology; Rehabilitation
GA 465QV
UT WOS:000267602800011
PM 19139758
ER
PT J
AU Li, Y
Tang, HC
Lin, XH
AF Li, Yi
Tang, Haicheng
Lin, Xihong
TI SPATIAL LINEAR MIXED MODELS WITH COVARIATE MEASUREMENT ERRORS
SO STATISTICA SINICA
LA English
DT Article
DE Asymptotic bias; consistency and asymptotic normality; EM
algorithmMeasurement error; increasing domain asymptotics; spatial data;
structural modeling; variance components
ID DISEASE RATES; REGRESSION
AB Spatial data with covariate measurement errors have been commonly observed in public health studies. Existing work mainly concentrates on parameter estimation using Gibbs sampling, and no work has been conducted to understand and quantify the theoretical impact of ignoring measurement error on spatial data analysis in the form of the asymptotic biases in regression coefficients and variance components when measurement error is ignored. Plausible implementations, from frequentist perspectives, of maximum likelihood estimation in spatial covariate measurement error models are also elusive. In this paper, we propose a new class of linear mixed models for spatial data in the presence of covariate measurement errors. We show that the naive estimators of the regression coefficients are attenuated while the naive estimators of the variance components are inflated, if measurement error is ignored. We further develop a structural modeling approach to obtaining the maximum likelihood estimator by accounting for the measurement error. We study the large sample properties of the proposed maximum likelihood estimator, and propose an EM algorithm to draw inference. All the asymptotic properties are shown tinder the increasing-domain asymptotic framework. We illustrate the method by analyzing the Scottish lip cancer data, and evaluate its performance through a simulation study, all of which elucidate the importance of adjusting for covariate measurement errors.
C1 [Li, Yi] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Li, Yi; Lin, Xihong] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Tang, Haicheng] Amer Express, New York, NY 10285 USA.
RP Li, Y (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, 44 Binney St, Boston, MA 02115 USA.
EM yili@hsph.harvard.edu; haicheng.k.tang@aexp.com; xlin@hsph.harvard.edu
FU NCI NIH HHS [R37 CA076404, P01 CA134294-01, P01 CA134294, R37
CA076404-12]
NR 22
TC 8
Z9 8
U1 0
U2 2
PU STATISTICA SINICA
PI TAIPEI
PA C/O DR H C HO, INST STATISTICAL SCIENCE, ACADEMIA SINICA, TAIPEI 115,
TAIWAN
SN 1017-0405
J9 STAT SINICA
JI Stat. Sin.
PD JUL
PY 2009
VL 19
IS 3
BP 1077
EP 1093
PG 17
WC Statistics & Probability
SC Mathematics
GA 465SY
UT WOS:000267608900011
PM 20046975
ER
PT J
AU Lee, HJ
Teixeira, J
AF Lee, Ho-Joon
Teixeira, Jose
TI Parthenogenesis in Human Oocytes that Were Collected From Resected
Ovarian Tissue and Matured In Vitro
SO STEM CELLS AND DEVELOPMENT
LA English
DT Article
ID STEM-CELL LINES; MULLERIAN-INHIBITING SUBSTANCE; MOUSE OVARY;
MATURATION; BLASTOCYSTS; DERIVATION; HORMONE; CULTURE; CRYOPRESERVATION;
ESTABLISHMENT
AB Currently, a major hurdle in the progress of human embryonic stem (hES) cell research is the lack of human oocytes with which to perform experiments. The collection process is a logistical and ethical challenge and usually involves the use of excess oocytes donated after assisted reproduction procedures. We collected resected human ovarian tissue after routine surgical procedures. Oocytes were isolated from the tissue and matured in vitro to the meiosis II (MII) stage, when the first polar body is extruded. With the large antral and smaller preantral follicles, the efficiencies of the maturation were nearly 50% and 25%, respectively. The quality of the matured oocytes was assessed by inducing parthenogenesis and > 50% of the in vitro matured oocytes were competent enough to develop pronuclei and 33% developed at least to the two-cell stage 48 h after activation. Parthenotes continued to develop by 72 h but with significant blastomere fragmentation. These results provide evidence that resected ovarian tissue, which is normally discarded, may be a suitable alternative source for oocytes in hES cell research.
C1 Massachusetts Gen Hosp, Vincent Mem Hosp, Dept Obstet Gynecol & Reprod, Vincent Ctr Reprod Biol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Teixeira, J (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol Thier 913, 55 Fruit St, Boston, MA 02114 USA.
EM teixeira@helix.mgh.harvard.edu
OI Teixeira, Jose/0000-0002-6438-5064
NR 34
TC 2
Z9 2
U1 0
U2 15
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1547-3287
J9 STEM CELLS DEV
JI Stem Cells Dev.
PD JUL
PY 2009
VL 18
IS 6
BP 941
EP 946
DI 10.1089/scd.2009.0004
PG 6
WC Cell & Tissue Engineering; Hematology; Medicine, Research &
Experimental; Transplantation
SC Cell Biology; Hematology; Research & Experimental Medicine;
Transplantation
GA 464ET
UT WOS:000267488800014
PM 19249941
ER
PT J
AU Romero, JR
Frey, JL
Schwamm, LH
Demaerschalk, BM
Chaliki, HP
Parikh, G
Burke, RF
Babikian, VL
AF Romero, Jose R.
Frey, James L.
Schwamm, Lee H.
Demaerschalk, Bart M.
Chaliki, Hari P.
Parikh, Gunjan
Burke, Robert F.
Babikian, Viken L.
TI Cerebral Ischemic Events Associated With 'Bubble Study' for
Identification of Right to Left Shunts
SO STROKE
LA English
DT Article
DE atrial heart septal defects; arteriovenous fistula; echocardiography;
patent foramen ovale; stroke; transcranial Doppler ultrasonography;
transesophageal echocardiography; transient ischemic attack
ID CONTRAST ECHOCARDIOGRAPHY; AIR-EMBOLISM; STROKE; COMMITTEE
AB Background and Purpose-Detection of an intracardiac shunt is frequently sought during the evaluation of patients with cryptogenic ischemic stroke and agitated saline intravenous injection, or "bubble study" (BS), is performed in most cases. We present the first attempt to identify the clinical features in patients who had cerebral ischemic events with BS.
Methods-Using a list serve established by the American Academy of Neurology, a member posted a question regarding the safety of BS in patients with patent foramen ovale. A standardized questionnaire was used to gather data about patients with cerebral ischemic events, details of each case were reviewed, and the findings pooled.
Results-Five patients with ischemic complications of BS (all female, aged 42 to 90 years) were identified from 4 institutions, 3 ischemic strokes and 2 transient ischemic attacks. Events occurred either during or within 5 minutes of BS. Early brain MRIs confirmed acute infarction in 3, including one who had transient symptoms. MRI infarct volumes were small, and deficits were mild in those who developed stroke. Diagnostic evaluation revealed a patent foramen ovale alone in one case, a pulmonary arteriovenous malformation in one case, and a patent foramen ovale and/or pulmonary shunt in 3 cases.
Conclusions-Ischemic cerebrovascular complications can occur in patients who undergo BS and are associated with the presence of cardiac or pulmonary shunts. The true incidence and degree of disability remains unknown, and further study is indicated to assess the impact of technical differences in BS methodology. Novel methods to promote physician communication such as the use of electronic list serves may reduce barriers to reporting of drug, technique, or device complications and should be explored to identify rare complications that otherwise will likely go unappreciated. (Stroke. 2009; 40: 2343-2348.)
C1 [Romero, Jose R.; Babikian, Viken L.] Boston Univ, Dept Neurol, Sch Med, Med Ctr, Boston, MA 02118 USA.
[Romero, Jose R.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
[Frey, James L.; Parikh, Gunjan] Barrow Neurol Inst, Div Neurol, Phoenix, AZ 85013 USA.
[Schwamm, Lee H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA.
[Demaerschalk, Bart M.] Mayo Clin Hosp, Dept Neurol, Phoenix, AZ USA.
[Chaliki, Hari P.; Burke, Robert F.] Mayo Clin, Dept Cardiol, Scottsdale, AZ USA.
RP Romero, JR (reprint author), Boston Univ, Dept Neurol, Sch Med, Med Ctr, 72 E Concord St,C-329, Boston, MA 02118 USA.
EM joromero@bmc.org
OI Schwamm, Lee/0000-0003-0592-9145
FU St Jude Medical; RESPECT Trial; AGA
FX J.L.F. is on the speakers bureaus for Bristol Myers Squibb, EKT Pharma,
Genentech, and Sanofi-Aventis. B. M. D. is the ESCAPE Trial site
principal investigator sponsored by St Jude Medical and the RESPECT
Trial site principal investigator sponsored by AGA. V. L. B. is a
consultant for Boston Scientific and is on the speakers Bureau for
Boehringer Ingelheim.
NR 16
TC 34
Z9 36
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD JUL
PY 2009
VL 40
IS 7
BP 2343
EP 2348
DI 10.1161/STROKEAHA.109.549683
PG 6
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 463XR
UT WOS:000267467900010
PM 19498192
ER
PT J
AU Greenberg, SM
Nandigam, RNK
Delgado, P
Betensky, RA
Rosand, J
Viswanathan, A
Frosch, MP
Smith, EE
AF Greenberg, Steven M.
Nandigam, R. N. Kaveer
Delgado, Pilar
Betensky, Rebecca A.
Rosand, Jonathan
Viswanathan, Anand
Frosch, Matthew P.
Smith, Eric E.
TI Microbleeds Versus Macrobleeds Evidence for Distinct Entities
SO STROKE
LA English
DT Article
DE cerebral amyloid angiopathy; intracerebral hemorrhage; microbleeds
ID CEREBRAL AMYLOID ANGIOPATHY; INTRACEREBRAL HEMORRHAGE; ISCHEMIC-STROKE;
RISK-FACTORS; ECHO MRI; PREVALENCE; CADASIL; ASSOCIATIONS; VALIDATION;
DEMENTIA
AB Background and Purpose-Small, asymptomatic microbleeds commonly accompany larger symptomatic macrobleeds. It is unclear whether microbleeds and macrobleeds represent arbitrary categories within a single continuum versus truly distinct events with separate pathophysiologies.
Methods-We performed 2 complementary retrospective analyses. In a radiographic analysis, we measured and plotted the volumes of all hemorrhagic lesions detected by gradient-echo MRI among 46 consecutive patients with symptomatic primary lobar intracerebral hemorrhage diagnosed as probable or possible cerebral amyloid angiopathy. In a second neuropathologic analysis, we performed blinded qualitative and quantitative examinations of amyloid-positive vessel segments in 6 autopsied subjects whose MRI scans demonstrated particularly high microbleed counts (>50 microbleeds on MRI, n=3) or low microbleed counts (<3 microbleeds, n=3).
Results-Plotted on a logarithmic scale, the volumes of 163 hemorrhagic lesions identified on scans from the 46 subjects fell in a distinctly bimodal distribution with mean volumes for the 2 modes of 0.009 cm(3) and 27.5 cm3. The optimal cut point for separating the 2 peaks (determined by receiver operating characteristics) corresponded to a lesion diameter of 0.57 cm. On neuropathologic analysis, the high microbleed-count autopsied subjects showed significantly thicker amyloid-positive vessel walls than the low microbleed-count subjects (proportional wall thickness 0.53 +/- 0.01 versus 0.37 +/- 0.01; P<0.0001; n=333 vessel segments analyzed).
Conclusions-These findings suggest that cerebral amyloid angiopathy-associated microbleeds and macrobleeds comprise distinct entities. Increased vessel wall thickness may predispose to formation of microbleeds relative to macrobleeds. (Stroke. 2009; 40: 2382-2386.)
C1 [Greenberg, Steven M.; Nandigam, R. N. Kaveer; Delgado, Pilar; Rosand, Jonathan; Viswanathan, Anand; Smith, Eric E.] Massachusetts Gen Hosp, Dept Neurol, Hemorrhag Stroke Res Program, Boston, MA 02114 USA.
[Frosch, Matthew P.] Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA 02114 USA.
[Betensky, Rebecca A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA 02115 USA.
RP Greenberg, SM (reprint author), MGH Stroke Res Ctr, 55 Fruit St,CPZ 175,Suite 300, Boston, MA 02114 USA.
EM sgreenberg@partners.org
RI Smith, Eric/C-5443-2012
OI Smith, Eric/0000-0003-3956-1668
FU NCI NIH HHS [R29 CA075971]; NIA NIH HHS [P50 AG005134, R01 AG026484, R01
AG026484-04]; NINDS NIH HHS [K24 NS056207, K24 NS056207-03, T32
NS048005]
NR 24
TC 72
Z9 79
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD JUL
PY 2009
VL 40
IS 7
BP 2382
EP 2386
DI 10.1161/STROKEAHA.109.548974
PG 5
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 463XR
UT WOS:000267467900016
PM 19443797
ER
PT J
AU Oleinik, A
Romero, JM
Schwab, K
Lev, MH
Jhawar, N
Almandoz, JED
Smith, EE
Greenberg, SM
Rosand, J
Goldstein, JN
AF Oleinik, Alexandra
Romero, Javier M.
Schwab, Kristin
Lev, Michael H.
Jhawar, Nupur
Almandoz, Josser E. Delgado
Smith, Eric E.
Greenberg, Steven M.
Rosand, Jonathan
Goldstein, Joshua N.
TI CT Angiography for Intracerebral Hemorrhage Does Not Increase Risk of
Acute Nephropathy
SO STROKE
LA English
DT Article
DE cerebral hemorrhage; tomography; X-ray computed; contrast media
ID CONTRAST-INDUCED NEPHROPATHY; PREDICTS HEMATOMA EXPANSION; ACUTE STROKE;
TOMOGRAPHY ANGIOGRAPHY; COMPUTED-TOMOGRAPHY; SAFETY; TRIAL;
EXTRAVASATION; PERFUSION; WARFARIN
AB Background and Purpose-CT angiography (CTA) is receiving increased attention in intracerebral hemorrhage (ICH) for its role in ruling out vascular abnormalities and potentially predicting ongoing bleeding. Its use is limited by the concern for contrast induced nephropathy (CIN); however, the magnitude of this risk is not known.
Methods-We performed a retrospective analysis of a prospectively collected cohort of consecutive patients with ICH presenting to a single tertiary care hospital from 2002 to 2007. Demographic, clinical, and radiographic data were prospectively collected for all patients. Laboratory data and clinical course over the first 48 hours were retrospectively reviewed. Acute nephropathy was defined as any rise in creatinine of >25% or >0.5 mg/dL, such that the highest creatinine value was above 1.5 mg/dL.
Results-539 patients presented during the study period and had at least 2 creatinine measurements. 348 (65%) received a CTA. Acute nephropathy developed in 6% of patients who received a CTA and in 10% of those who did not (P=0.1). Risk of nephropathy was 14% in those receiving no contrast (130 patients), 5% in those receiving 1 contrast study (124 patients), and 6% in those receiving >1 contrast study (244 patients). Neither CTA nor any use of contrast predicted nephropathy in univariate or multivariate analysis.
Conclusion-The risk of acute nephropathy after ICH was not increased by use of CTA. Studies of CIN that do not include a control group may overestimate the influence of contrast. Patients with ICH appear to have an 8% risk of developing "Hospital-Acquired Nephropathy." (Stroke. 2009; 40: 2393-2397.)
C1 [Jhawar, Nupur; Goldstein, Joshua N.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
[Oleinik, Alexandra; Schwab, Kristin; Greenberg, Steven M.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Romero, Javier M.; Lev, Michael H.; Almandoz, Josser E. Delgado] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Smith, Eric E.] Univ Calgary, Dept Clin Neurosci, Calgary Stroke Program, Calgary, AB T2N 1N4, Canada.
RP Goldstein, JN (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Zero Emerson Pl,Suite 3B, Boston, MA 02114 USA.
EM jgoldstein@partners.org
RI Smith, Eric/C-5443-2012; Goldstein, Joshua/H-8953-2016
OI Smith, Eric/0000-0003-3956-1668;
FU National Institute of Neurological Disorders and Stroke [NIH
R01NS059727]; Deane Institute for Integrative Study of Atrial
Fibrillation and Stroke
FX This work was supported by a grant from the National Institute of
Neurological Disorders and Stroke (NIH R01NS059727), an American Heart
Association Grant-in-Aid Award, and the Deane Institute for Integrative
Study of Atrial Fibrillation and Stroke.
NR 31
TC 41
Z9 42
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD JUL
PY 2009
VL 40
IS 7
BP 2393
EP 2397
DI 10.1161/STROKEAHA.108.546127
PG 5
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 463XR
UT WOS:000267467900018
PM 19461032
ER
PT J
AU Saver, JL
Gornbein, J
Grotta, J
Liebeskind, D
Lutsep, H
Schwamm, L
Scott, P
Starkman, S
AF Saver, Jeffrey L.
Gornbein, Jeffrey
Grotta, James
Liebeskind, David
Lutsep, Helmi
Schwamm, Lee
Scott, Phillip
Starkman, Sidney
TI Number Needed to Treat to Benefit and to Harm for Intravenous Tissue
Plasminogen Activator Therapy in the 3-to 4.5-Hour Window
SO STROKE
LA English
DT Article
DE cerebral infarction; clinical trial; fibrinolysis; ischemic stroke;
thrombolysis
ID ACUTE ISCHEMIC-STROKE; QUALITY-OF-LIFE; RT-PA STROKE; ENTIRE RANGE;
THROMBOLYTIC THERAPY; TRIALS; DISABILITY; DERIVATION; SHIFTS; TIME
AB Background and Purpose-Measures of a therapy's effect size are important guides to clinicians, patients, and policy-makers on treatment decisions in clinical practice. The ECASS 3 trial demonstrated a statistically significant benefit of intravenous tissue plasminogen activator for acute cerebral ischemia in the 3- to 4.5-hour window, but an effect size estimate incorporating benefit and harm across all levels of poststroke disability has not previously been derived.
Methods-Joint outcome table specification was used to derive number needed to treat to benefit (NNTB) and number needed to treat to harm (NNTH) values summarizing treatment impact over the entire outcome range on the modified Rankin scale of global disability, including both expert-dependent and expert-independent (algorithmic and repeated random sampling) array generation.
Results-For the full 7-category modified Rankin scale, algorithmic analysis demonstrated that the NNTB for 1 additional patient to have a better outcome by >= 1 grades than with placebo must lie between 4.0 and 13.0. In bootstrap simulations, the mean NNTB was 7.1. Expert joint outcome table analyses indicated that the NNTB for improved final outcome was 6.1 (95% CI, 5.6-6.7) and the NNTH 37.5 (95% CI, 34.6-40.5). Benefit per 100 patients treated was 16.3 and harm per 100 was 2.7. The likelihood of help to harm ratio was 6.0.
Conclusions-Treatment with tissue plasminogen activator in the 3- to 4.5-hour window confers benefit on approximately half as many patients as treatment <3 hours, with no increase in the conferral of harm. Approximately 1 in 6 patients has a better and 1 in 35 has a worse outcome as a result of therapy. (Stroke. 2009; 40: 2433-2437.)
C1 [Saver, Jeffrey L.; Liebeskind, David; Starkman, Sidney] Univ Calif Los Angeles, David Geffen Sch Med, Stroke Ctr, Los Angeles, CA 90095 USA.
[Saver, Jeffrey L.; Liebeskind, David; Starkman, Sidney] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA.
[Gornbein, Jeffrey] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biomath, Los Angeles, CA 90095 USA.
[Starkman, Sidney] Univ Calif Los Angeles, David Geffen Sch Med, Dept Emergency Med, Los Angeles, CA 90095 USA.
[Grotta, James] Univ Texas Houston, Dept Neurol, Sch Med, Houston, TX USA.
[Lutsep, Helmi] Oregon Hlth & Sci Univ, Oregon Stroke Ctr, Portland, OR 97201 USA.
[Schwamm, Lee] Massachusetts Gen Hosp, Div Neurol, Boston, MA 02114 USA.
[Scott, Phillip] Univ Michigan, Dept Emergency Med, Ann Arbor, MI 48109 USA.
RP Saver, JL (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Stroke Ctr, 710 Westwood Plaza, Los Angeles, CA 90095 USA.
EM jsaver@ucla.edu
FU NIH-NINDS Awards [U01 NS 44364, P50 NS044378]
FX This work was supported in part by NIH-NINDS Awards NIH-NINDS U01 NS
44364 and NIH-NINDS P50 NS044378.
NR 22
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Z9 56
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD JUL
PY 2009
VL 40
IS 7
BP 2433
EP 2437
DI 10.1161/STROKEAHA.108.543561
PG 5
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 463XR
UT WOS:000267467900025
PM 19498197
ER
PT J
AU Subramanian, S
Zhang, B
Kosaka, Y
Burrows, GG
Grafe, MR
Vandenbark, AA
Hurn, PD
Offner, H
AF Subramanian, Sandhya
Zhang, Bing
Kosaka, Yasuharu
Burrows, Gregory G.
Grafe, Marjorie R.
Vandenbark, Arthur A.
Hurn, Patricia D.
Offner, Halina
TI Recombinant T Cell Receptor Ligand Treats Experimental Stroke
SO STROKE
LA English
DT Article
DE autoreactive T cells; immunotherapy; recombinant TCR ligands; stroke
ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; ISCHEMIC-STROKE;
MULTIPLE-SCLEROSIS; TRANSGENIC MICE; ACTIVATION; INJURY; LYMPHOCYTES;
SYSTEM; ASSOCIATION; INDUCTION
AB Background and Purpose-Experimental stroke induces a biphasic effect on the immune response that involves early activation of peripheral leukocytes followed by severe immunodepression and atrophy of the spleen and thymus. In tandem, the developing infarct is exacerbated by influx of numerous inflammatory cell types, including T and B lymphocytes. These features of stroke prompted our use of recombinant T cell receptor ligands (RTL), partial major histocompatibility complex Class II molecules covalently bound to myelin peptides. We tested the hypothesis that RTL would improve ischemic outcome in the brain without exacerbating defects in the peripheral immune system function.
Methods-Four daily doses of RTL were administered subcutaneously to C57BL/6 mice after middle cerebral artery occlusion, and lesion size and cellular composition were assessed in the brain and cell numbers were assessed in the spleen and thymus.
Results-Treatment with RTL551 (I-A(b) molecule linked to MOG-35-55 peptide) reduced cortical and total stroke lesion size by approximately 50%, inhibited the accumulation of inflammatory cells, particularly macrophages/activated microglial cells and dendritic cells, and mitigated splenic atrophy. Treatment with RTL1000 (HLA-DR2 moiety linked to human MOG-35-55 peptide) similarly reduced the stroke lesion size in HLA-DR2 transgenic mice. In contrast, control RTL with a nonneuroantigen peptide or a mismatched major histocompatibility complex Class II moiety had no effect on stroke lesion size.
Conclusions-These data are the first to demonstrate successful treatment of experimental stroke using a neuroantigen-specific immunomodulatory agent administered after ischemia, suggesting therapeutic potential in human stroke. (Stroke. 2009; 40: 2539-2545.)
C1 [Subramanian, Sandhya; Vandenbark, Arthur A.; Offner, Halina] Oregon Hlth & Sci Univ, Vet Affairs Med Ctr, Portland, OR 97201 USA.
[Zhang, Bing; Kosaka, Yasuharu; Grafe, Marjorie R.; Hurn, Patricia D.; Offner, Halina] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97201 USA.
[Burrows, Gregory G.; Vandenbark, Arthur A.; Offner, Halina] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA.
[Vandenbark, Arthur A.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA.
[Grafe, Marjorie R.] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97201 USA.
RP Offner, H (reprint author), Portland VA Med Ctr, R&D 31,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA.
EM offnerva@ohsu.edu
FU US Public Health Service National Institutes of Health [NS33668,
NRO3521, NS49210, AI43960, NS47661]; National Multiple Sclerosis Society
[RG379-A-4]; The Nancy Davis Center Without Walls; Biomedical Laboratory
R&D Service, Department of Veterans' Affairs
FX This work was supported by US Public Health Service National Institutes
of Health grants NS33668, NRO3521, NS49210, AI43960, and NS47661;
National Multiple Sclerosis Society grant RG379-A-4; The Nancy Davis
Center Without Walls; and the Biomedical Laboratory R&D Service,
Department of Veterans' Affairs.
NR 34
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U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD JUL
PY 2009
VL 40
IS 7
BP 2539
EP 2545
DI 10.1161/STROKEAHA.108.543991
PG 7
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 463XR
UT WOS:000267467900041
PM 19443805
ER
PT J
AU Smith, EE
Greenberg, SM
AF Smith, Eric E.
Greenberg, Steven M.
TI beta-Amyloid, Blood Vessels, and Brain Function
SO STROKE
LA English
DT Review
DE Alzheimer disease; cerebral amyloid angiopathy; vascular cognitive
impairment
ID LOBAR INTRACEREBRAL HEMORRHAGE; ALZHEIMERS-DISEASE PATHOLOGY; TRANSGENIC
MOUSE MODEL; PITTSBURGH COMPOUND-B; WHITE-MATTER LESIONS;
SMOOTH-MUSCLE-CELLS; PRECURSOR PROTEIN; COGNITIVE IMPAIRMENT; A-BETA;
CEREBROVASCULAR DYSFUNCTION
AB Cerebrovascular disease and Alzheimer disease are common diseases of aging and frequently coexist in the same brain. Accumulating evidence suggests that the presence of brain infarction, including silent infarction, influences the course of Alzheimer disease. Conversely, there is evidence that beta-amyloid can impair blood vessel function. Vascular beta-amyloid deposition, also known as cerebral amyloid angiopathy, is associated with vascular dysfunction in animal and human studies. Alzheimer disease is associated with morphological changes in capillary networks, and soluble beta-amyloid produces abnormal vascular responses to physiological and pharmacological stimuli. In this review, we discuss current evidence linking beta-amyloid metabolism with vascular function and morphological changes in animals and humans. (Stroke. 2009; 40: 2601-2606.)
C1 [Smith, Eric E.] Univ Calgary, Dept Clin Neurosci, Div Neurol, Calgary, AB, Canada.
[Greenberg, Steven M.] Massachusetts Gen Hosp, Dept Neurol, Hemorrhag Stroke Res Program, Boston, MA 02114 USA.
RP Greenberg, SM (reprint author), Kistler Stroke Res Ctr, 175 Cambridge St,Suite 300, Boston, MA 02114 USA.
EM sgreenberg@partners.org
OI Smith, Eric/0000-0003-3956-1668
FU National Institute of Neurological Disorders and Stroke [R01 NS062028,
K24 NS056207, R01 NS042147]; Canadian Stroke Network; National Institute
of Aging [R01 AG026484, R01 AG021084]; Alzheimer's Association
FX E. E. S. has received funding from the National Institute of
Neurological Disorders and Stroke ( R01 NS062028) and the Canadian
Stroke Network. S. M. G. has received funding from the National
Institute of Neurological Disorders and Stroke ( K24 NS056207, R01
NS042147), National Institute of Aging ( R01 AG026484, R01 AG021084),
and the Alzheimer's Association.
NR 72
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U1 0
U2 14
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD JUL
PY 2009
VL 40
IS 7
BP 2601
EP 2606
DI 10.1161/STROKEAHA.108.536839
PG 6
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 463XR
UT WOS:000267467900057
PM 19443808
ER
PT J
AU Kvale, EA
Murthy, R
Taylor, R
Lee, JY
Nabors, LB
AF Kvale, Elizabeth A.
Murthy, Rashmi
Taylor, Richard
Lee, Jeannette Y.
Nabors, L. B.
TI Distress and quality of life in primary high-grade brain tumor patients
SO SUPPORTIVE CARE IN CANCER
LA English
DT Article
DE Glioblastoma multiforme; Brain tumor; Quality of life; Distress
ID FUNCTIONAL OUTCOMES; CANCER-PATIENTS; GLIOMAS; ADULTS; SCALE;
DETERMINANTS; RECOGNITION; DEPRESSION; SURVIVAL; THERAPY
AB We report on the routine use of the NCCN Distress Thermometer and the Functional Assessment of Cancer Therapy-Brain (FACT-Br) to assess patient distress and quality of life in GBM patients. The purpose of this study was to examine the relationship between patient quality of life and distress.
Data from 50 GBM patients presenting to a neuro-oncology clinic were evaluated. Descriptive statistics and correlations between the distress score and the FACT-Br subscale scores were generated.
The mean distress score was 2.15 (std 2.66), and 28.9% of brain tumor patients identified a distress score of 4 or above. The mean FACT-Br total was 127.34 (std 21.29), with patients scoring lowest in the EWB (18.95 std 4.4) and FWB (15.06 std 6.80) subscales. No differences between demographic groups were identified with regard to distress or quality of life. Statistically significant correlations were identified between the distress score and the SWB (R = -0.46, P = 0.001) and EWB (R = -0.56, P = 0.001) subscales of the FACT-Br. Fifty percent of participants who did not complete the FACT-Br reported clinically significant distress, but this did not differ significantly from participants who completed it.
Assessment of distress in brain tumor patients provides clinically relevant information and suggests interventions that may support quality of life. Further research is needed to explore the relationship between distress and quality of life. Current approaches to measuring quality of life in brain tumor patients may systematically undersample patients with advanced illness or significant psychosocial distress.
C1 [Kvale, Elizabeth A.] Univ Alabama, Birmingham VA Med Ctr, Birmingham, AL USA.
[Murthy, Rashmi] Baylor Coll Med, Houston, TX 77030 USA.
[Lee, Jeannette Y.] Univ Arkansas Med Sci, Fayetteville, AR USA.
RP Kvale, EA (reprint author), Univ Alabama, Birmingham VA Med Ctr, Birmingham, AL USA.
EM ekvale@aging.uab.edu
NR 25
TC 24
Z9 24
U1 3
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0941-4355
J9 SUPPORT CARE CANCER
JI Support. Care Cancer
PD JUL
PY 2009
VL 17
IS 7
BP 793
EP 799
DI 10.1007/s00520-008-0551-9
PG 7
WC Oncology; Health Care Sciences & Services; Rehabilitation
SC Oncology; Health Care Sciences & Services; Rehabilitation
GA 456FK
UT WOS:000266827000006
PM 19421789
ER
PT J
AU Serebruany, VL
Kogushi, M
Dastros-Pitei, D
Flather, M
Bhatt, DL
AF Serebruany, Victor L.
Kogushi, Motoji
Dastros-Pitei, Daniela
Flather, Marcus
Bhatt, Deepak L.
TI The in-vitro effects of E5555, a protease-activated receptor (PAR)-1
antagonist, on platelet biomarkers in healthy volunteers and patients
with coronary artery disease
SO THROMBOSIS AND HAEMOSTASIS
LA English
DT Article
DE E5555; PAR-1; thrombin receptor antagonists; platelets; aspirin;
clopidogrel; in vitro; coronary artery disease
ID ACUTE MYOCARDIAL-INFARCTION; THROMBIN RECEPTOR; CLOPIDOGREL; RESISTANCE;
ASPIRIN
AB E5555 is a potent protease-activated receptor (PAR-1) antagonist targeting the G-coupled receptor and modulating thrombinplatelet-endothelial interactions. The drug is currently being tested in phase 11 trials in patients with coronary artery disease (CAD) and has potential antithrombotic and anti-inflammatory benefits. We investigated the in-vitro effects of E5555 on platelet function beyond PAR-1 blockade in healthy volunteers and CAD patients treated with aspirin (ASA) with or without clopidogrel. Conventional aggregation induced by 5 mu M ADP, 1 mu g/ml collagen, 10 mu M TRAP, whole blood aggregation with 1 mu g/ml collagen, and expression of 14 intact, and TRAP-stimulated receptors by flow cytometry were utilised to assess platelet activity after preincubation with escalating concentrations of E5555 (20 ng/ml, 50 ng/ml, and 100 ng/ml) in healthy volunteers, CAD patients treated with ASA, and CAD patients treated with ASA and clopidogrel combination (n= 10,for each group). E5555 inhibited a number of platelet biomarkers. Platelet inhibition was usually moderate, present already at 20 ng/ml, and was not seemingly dose-dependent without TRAP stimulation. E5555 caused 10-15% inhibition of ADP- and collagen-induced platelet aggregation in plasma, but not in whole blood. TRAP-induced aggregation was inhibited almost completely. PECAM-1, GP IIb/IIIa antigen, and activity with PAC-1, GPIb, thrombospondin, vitronectin receptor expression, and formation of platelet-monocyte aggregates were also significantly reduced by E5555. TRAP stimulation caused dose-dependent effects between 20 and 50 ng/ml E5555 doses. P-selectin, LAMP-1, LAMP, and CD40-ligand were not affected by E5555. In conclusion, E5555 in vitro moderately but significantly inhibits platelet activity beyond PAR-1 blockade. Antiplatelet potency of ASA alone, and the combination of ASA and clopidogrel may be enhanced by E5555 providing rationale for their synergistic use. Selective blockade of platelet receptors suggests unique antiplatelet properties of E5555 as a potential addition to current antithrombotic regimens.
C1 [Serebruany, Victor L.] Johns Hopkins Univ, HeartDrug Res Labs, Baltimore, MD USA.
[Kogushi, Motoji] Eisai & Co Ltd, Innovat Biol Labs, Tsukuba, Ibaraki, Japan.
[Dastros-Pitei, Daniela] Eisai Ltd, Eisai Global Clin Dev, London, England.
[Flather, Marcus] Royal Brompton Hosp, London SW3 6LY, England.
[Flather, Marcus] Univ London Imperial Coll Sci Technol & Med, London, England.
[Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA.
[Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA.
RP Serebruany, VL (reprint author), Osler Med Ctr, 7600 Osler Dr,St 307, Towson, MD 21204 USA.
EM Heartdrug@aol.com
NR 18
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U1 0
U2 4
PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN
PI STUTTGART
PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY
SN 0340-6245
J9 THROMB HAEMOSTASIS
JI Thromb. Haemost.
PD JUL
PY 2009
VL 102
IS 1
BP 111
EP 119
DI 10.1160/TH08-12-0805
PG 9
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 474XJ
UT WOS:000268317900018
PM 19572075
ER
PT J
AU Lewis, CM
Chang, KP
Pitman, M
Faquin, WC
Randolph, GW
AF Lewis, Carol M.
Chang, Kuo-Ping
Pitman, Martha
Faquin, William C.
Randolph, Gregory W.
TI Thyroid Fine-Needle Aspiration Biopsy: Variability in Reporting
SO THYROID
LA English
DT Article; Proceedings Paper
CT 111th Annual Meeting of the
American-Academy-of-Otolaryngology-Head-and-Neck-Surgery-Foundation
CY SEP 16-19, 2007
CL Washington, DC
SP Amer Acad Otolaryngol Head & Neck Surg Fdn
ID FROZEN-SECTION ANALYSIS; SURGICAL-MANAGEMENT; CYTOLOGY; NODULES;
EXPERIENCE; DIAGNOSIS; ACCURACY; CANCER; ULTRASONOGRAPHY; GUIDELINES
AB Background: The low incidence of thyroid cancer despite the high prevalence of thyroid nodules necessitates a screening tool to determine which patients require surgical management. The utility of fine-needle aspiration biopsy (FNAB) for this purpose requires a low false-negative (FN) rate and an acceptable sensitivity and specificity for the detection of malignancy. While reviewing our institution's experience with thyroid FNAB, we found significant discrepancies in how statistics of thyroid FNAB were tabulated and reported in the literature. Here we examine the sources of these discrepancies by evaluating large series of thyroid FNAB with regard to cytopathologic reporting and statistical calculation.
Methods: Published series of thyroid FNAB with >200 FNAB and available histological data with sufficient raw data to recalculate statistics were analyzed. Considering indeterminate and malignant results to be positive FNAB results, since, in a four-tier system, both lead to surgical management, specificity, sensitivity, accuracy, positive predictive value, negative predictive value, FN, and false-positive (FP) rates were recalculated. Differences between reported and recalculated statistics were then evaluated for significance.
Results: Nineteen studies and 20 series were identified. The following are reported and recalculated means, respectively: for sensitivity, 81% and 86%; for specificity, 81% and 62%; for accuracy, 77% and 71%; for positive predictive value, 65% and 50%; for negative predictive value, 84% and 93%; for FN rates, 13% and 14%; for FP rates, 10% and 38%. FP rates had a mean of 1.4% when recalculated considering only malignant FNAB as positive tests. Specificity and FP rates had statistically significant differences between the means of reported and recalculated values.
Conclusions: Thyroid FNAB remains the screening tool of choice in the evaluation of thyroid nodules. However, the variability in the calculation of reported thyroid FNAB statistics highlights the need for uniformity in statistical reporting for accurate understanding of thyroid FNAB's clinical utility.
C1 [Lewis, Carol M.; Chang, Kuo-Ping; Randolph, Gregory W.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA.
[Lewis, Carol M.; Chang, Kuo-Ping; Randolph, Gregory W.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
[Pitman, Martha; Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Pitman, Martha; Faquin, William C.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Randolph, GW (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA.
EM gregory_randolph@meei.harvard.edu
NR 31
TC 76
Z9 78
U1 0
U2 3
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1050-7256
EI 1557-9077
J9 THYROID
JI Thyroid
PD JUL
PY 2009
VL 19
IS 7
BP 717
EP 723
DI 10.1089/thy.2008.0425
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467SO
UT WOS:000267762900006
PM 19485775
ER
PT J
AU Mintz, PD
Dzik, WH
AF Mintz, Paul D.
Dzik, Walter H.
TI Double standard for double ABO grouping?
SO TRANSFUSION
LA English
DT Editorial Material
ID SAMPLE COLLECTION; TRANSFUSION SAFETY; BLOOD; PATIENT; PERFORMANCE
C1 [Mintz, Paul D.] Univ Virginia Hlth Syst, Div Clin Pathol Clin Labs & Transfus Serv, Charlottesville, VA USA.
[Dzik, Walter H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Blood Transfus Serv, Boston, MA USA.
RP Mintz, PD (reprint author), Univ Virginia Hlth Syst, Div Clin Pathol Clin Labs & Transfus Serv, Charlottesville, VA USA.
EM mintz@virginia.edu
NR 18
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
EI 1537-2995
J9 TRANSFUSION
JI Transfusion
PD JUL
PY 2009
VL 49
IS 7
BP 1282
EP 1285
PN 1
PG 4
WC Hematology
SC Hematology
GA 467CX
UT WOS:000267715300003
PM 19602208
ER
PT J
AU Steiner, ME
Stowell, C
AF Steiner, Marie E.
Stowell, Christopher
TI Does red blood cell storage affect clinical outcome? When in doubt, do
the experiment
SO TRANSFUSION
LA English
DT Editorial Material
ID CRITICALLY-ILL; TRANSFUSION PRACTICES; TRIAL; GUIDELINES; CARE
C1 [Steiner, Marie E.] Univ Minnesota, Minneapolis, MN 55455 USA.
[Stowell, Christopher] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
RP Steiner, ME (reprint author), Univ Minnesota, Minneapolis, MN 55455 USA.
EM stein083@umn.edu
NR 26
TC 30
Z9 31
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD JUL
PY 2009
VL 49
IS 7
BP 1286
EP 1290
PG 5
WC Hematology
SC Hematology
GA 467CX
UT WOS:000267715300004
PM 19602209
ER
PT J
AU Driver, J
Blankenburg, F
Bestmann, S
Vanduffel, W
Ruff, CC
AF Driver, Jon
Blankenburg, Felix
Bestmann, Sven
Vanduffel, Wim
Ruff, Christian C.
TI Concurrent brain-stimulation and neuroimaging for studies of cognition
SO TRENDS IN COGNITIVE SCIENCES
LA English
DT Review
ID TRANSCRANIAL MAGNETIC STIMULATION; THETA-BURST-STIMULATION; FRONTAL EYE
FIELD; VISUAL-CORTEX; TMS-FMRI; EVOKED-POTENTIALS; MOTOR CORTEX;
POSTERIOR PARIETAL; PREFRONTAL CORTEX; SPATIAL ATTENTION
AB Neuroimaging can address activity across the entire brain in relation to cognition, but is typically correlative rather than causal. Brain stimulation can target a local brain area causally, but without revealing the entire network affected. Combining brain stimulation with concurrent neuroimaging allows a new causal approach to how interplay between extended networks of brain regions can support cognition. Brain stimulation does not affect only the targeted local region but also activity in remote interconnected regions. These remote effects depend on cognitive factors (e.g. task-condition), revealing dynamic changes in interplay between brain areas. We illustrate this with examples from top-down modulation of visual cortex, response-competition, interhemispheric rivalry and motor tasks; but the new approach should be applicable to many domains of cognition.
C1 [Driver, Jon; Blankenburg, Felix; Bestmann, Sven; Ruff, Christian C.] UCL, Inst Cognit Neurosci, London WC1N 3AR, England.
[Driver, Jon; Ruff, Christian C.] UCL, Wellcome Trust Ctr Neuroimaging, London WC1N 3BG, England.
[Blankenburg, Felix] Humboldt Univ, Bernstein Ctr Computat Neurosci, D-10115 Berlin, Germany.
[Bestmann, Sven] UCL, Sobell Dept Motor Neurosci, London WC1N 3BG, England.
[Vanduffel, Wim] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Vanduffel, Wim] Katholieke Univ Leuven, Sch Med, Lab Neurofysiol & Psychofysiol, B-3000 Louvain, Belgium.
[Vanduffel, Wim] Harvard Univ, Sch Med, Dept Radiol, Charlestown, MA 02129 USA.
[Ruff, Christian C.] Univ Zurich, Lab Social & Neural Syst Res, Inst Empir Res Econ, CH-8006 Zurich, Switzerland.
RP Ruff, CC (reprint author), UCL, Inst Cognit Neurosci, London WC1N 3AR, England.
EM ruff@iew.uzh.ch
OI Ruff, Christian/0000-0002-3964-2364
FU European Commission [HEALTH-F2-2008-200728]; Wellcome Trust; Medical
Research Council
FX Our research was funded in London and Leuven by the European Commission,
7th Framework Programme (BrainSync: HEALTH-F2-2008-200728) and in London
by the Wellcome Trust and the Medical Research Council.
NR 49
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U1 1
U2 8
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 1364-6613
J9 TRENDS COGN SCI
JI TRENDS COGN. SCI.
PD JUL
PY 2009
VL 13
IS 7
BP 319
EP 327
DI 10.1016/j.tics.2009.04.007
PG 9
WC Behavioral Sciences; Neurosciences; Psychology, Experimental
SC Behavioral Sciences; Neurosciences & Neurology; Psychology
GA 475RW
UT WOS:000268379400008
PM 19540793
ER
PT J
AU Ji, RR
Xu, ZZ
Wang, XY
Lo, EH
AF Ji, Ru-Rong
Xu, Zhen-Zhong
Wang, Xiaoying
Lo, Eng H.
TI Matrix metalloprotease regulation of neuropathic pain
SO TRENDS IN PHARMACOLOGICAL SCIENCES
LA English
DT Review
ID SPINAL NERVE LIGATION; PRIMARY SENSORY NEURONS; NECROSIS-FACTOR-ALPHA;
MECHANICAL ALLODYNIA; PERIPHERAL NEUROPATHY; CENTRAL SENSITIZATION;
PERSISTENT PAIN; RAT MODEL; GLIA; ACTIVATION
AB Neuropathic pain affects millions of people globally and could be a disease on its own right. Current treatments focus on blocking neurotransmission and have resulted in limited success. Recent progress points to an important role of neuroinflammation in the pathogenesis of neuropathic pain. Matrix metalloproteases (MMPs) comprise a large family of zinc endopeptidases that have been implicated in the generation of neuroinflammation via cleavage of extracellular matrix proteins and activation of proinflammatory cytokines and chemokines. However, little is known about the role of MMPs in chronic pain regulation. Our recent study has shown that neuropathic pain development in the early and late phase requires MMP-9 and MMP-2, respectively. Inhibition of MMP-9 or MMP-2 might provide a new strategy for the prevention and treatment of neuropathic pain.
C1 [Ji, Ru-Rong; Xu, Zhen-Zhong] Brigham & Womens Hosp, Dept Anesthesiol, Pain Res Ctr, Boston, MA 02115 USA.
[Ji, Ru-Rong; Xu, Zhen-Zhong] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Wang, Xiaoying; Lo, Eng H.] Massachusetts Gen Hosp, Dept Neurol, Neuroprotect Res Lab, Charlestown, MA 02129 USA.
[Wang, Xiaoying; Lo, Eng H.] Massachusetts Gen Hosp, Dept Radiol, Hillsborough, 02129, North Ireland.
[Wang, Xiaoying; Lo, Eng H.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
RP Ji, RR (reprint author), Brigham & Womens Hosp, Dept Anesthesiol, Pain Res Ctr, Boston, MA 02115 USA.
EM rrji@zeus.bwh.harvard.edu
OI Ji, Ru-Rong/0000-0002-9355-3688
FU National Institutes of Health [R01-NS54932, R01-DE17794, R01-NS48422,
R01-NS56458, R37-NS37074, P01-NS55104]
FX This work was supported by National Institutes of Health grants
R01-NS54932 and R01-DE17794 to R-R.J. and R01-NS48422, R01-NS56458,
R37-NS37074 and P01-NS55104 to E.H.L and X.W.
NR 49
TC 45
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U1 0
U2 7
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0165-6147
J9 TRENDS PHARMACOL SCI
JI Trends Pharmacol. Sci.
PD JUL
PY 2009
VL 30
IS 7
BP 336
EP 340
DI 10.1016/j.tips.2009.04.002
PG 5
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 475RQ
UT WOS:000268378700005
PM 19523695
ER
PT J
AU Morris, KR
Lutz, RD
Bai, XY
McGibney, MT
Cook, D
Ordway, D
Chan, ED
AF Morris, Kristin R.
Lutz, Ryan D.
Bai, Xiyuan
McGibney, Mischa T.
Cook, Danielle
Ordway, Diane
Chan, Edward D.
TI Suppression of IFN gamma plus mycobacterial lipoarabinomannan-induced NO
by IL-4 is due to decreased IRF-1 expression
SO TUBERCULOSIS
LA English
DT Article
DE Lipoarabinomannan; Nitric oxide; Interleukin-4; Inducible nitric oxide
synthase; Interferon-gamma; Transcriptional regulation
ID NITRIC-OXIDE SYNTHASE; TUMOR-NECROSIS-FACTOR; GROWTH-FACTOR-BETA;
NF-KAPPA-B; HUMAN PULMONARY TUBERCULOSIS; RAT-LIVER ARGINASE;
INTERFERON-GAMMA; FACTOR-ALPHA; ALTERNATIVE ACTIVATION; MURINE
MACROPHAGES
AB In mice, and possibly in humans, nitric oxide (NO) is an important host-defense molecule against Mycobacterium tuberculosis. Inducible nitric oxide synthase (iNOS) and NO are upregulated in murine macrophages stimulated with interferon-gamma (IFN gamma) and mannose-capped lipoarabinomannan (ManLAM), a major lipoglycan in the cell wall of M. tuberculosis. Interleukin-4 (IL-4) can inhibit NO expression and may impair host immune response to M. tuberculosis. Therefore, we sought to determine the mechanism by which IL-4 inhibits IFN gamma + ManLAM-induced NO production. Since L-arginine is the substrate for both iNOS and arginase, and IL-4 increases arginase activity by inducing its production, a plausible mechanism of IL-4 inhibition of NO expression is via depletion of L-arginine through increased arginase activity. Herein, we show that IL-4 inhibited iNOS gene expression at the transcriptional level, suggesting an inhibitory mechanism that is independent of the competition for L-arginine between iNOS and arginase. Furthermore, pharmacologic inhibition of IL-4-induced arginase activity did not abrogate IL-4 inhibition of IFN gamma + ManLAM-induced NO expression. Instead, inhibition by IL-4 was mediated principally by the ability of IL-4 to inhibit the production of IFN gamma-induced interferon-gamma response factor-1 (IRF-1) protein, a critically important transcriptional element that enhances expression of IFN gamma-inducible genes such as iNOS. Published by Elsevier Ltd.
C1 [Chan, Edward D.] Univ Colorado, Hlth Sci Ctr, Resp Dept, Denver Vet Affairs Med Ctr, Denver, CO USA.
[Morris, Kristin R.; Lutz, Ryan D.; Cook, Danielle; Chan, Edward D.] Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA.
[Chan, Edward D.] Univ Colorado, Hlth Sci Ctr, Cell Biol Program, Denver, CO USA.
[Bai, Xiyuan; McGibney, Mischa T.; Chan, Edward D.] Univ Colorado, Hlth Sci Ctr, Div Pulm Sci & Crit Care Med, Denver, CO USA.
[Ordway, Diane] Colorado State Univ, Dept Microbiol, Ft Collins, CO 80523 USA.
RP Chan, ED (reprint author), K720,Goodman Bldg,1400 Jackson St, Denver, CO 80206 USA.
EM chane@njhealth.org
FU Department of Veterans Affairs; Veterans Health Administration; Office
of Research and Development (EDC); [N01-Al-75320]
FX This material is based upon work supported in part by the Department of
Veterans Affairs, Veterans Health Administration, Office of Research and
Development (EDC). The authors wish to thank Drs. Patrick Brennan, John
Belisle, and Karen Dobos of Colorado State University in Ft. Collins,
Colorado for the ManLAM, the procurement of which is supported by
N01-Al-75320.
NR 47
TC 11
Z9 11
U1 0
U2 1
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 1472-9792
J9 TUBERCULOSIS
JI Tuberculosis
PD JUL
PY 2009
VL 89
IS 4
BP 294
EP 303
DI 10.1016/j.tube.2009.03.004
PG 10
WC Immunology; Microbiology; Respiratory System
SC Immunology; Microbiology; Respiratory System
GA 484NG
UT WOS:000269051800009
PM 19556165
ER
PT J
AU Benacerraf, BR
Shipp, TD
Bromley, B
AF Benacerraf, B. R.
Shipp, T. D.
Bromley, B.
TI Three-dimensional ultrasound detection of abnormally located
intrauterine contraceptive devices which are a source of pelvic pain and
abnormal bleeding
SO ULTRASOUND IN OBSTETRICS & GYNECOLOGY
LA English
DT Article
DE 3D ultrasound; IUD; pelvic pain
ID SONOGRAPHY; UTERUS
AB Objective To determine whether intrauterine contraceptive devices (IUDs) that are located abnormally within the myometrium or cervix cause a higher incidence of pelvic pain and abnormal bleeding compared with normally positioned devices.
Methods Over a period of 9 months, all patients with an IUD presenting at our unit for two-dimensional pelvic ultrasound underwent a three-dimensional (3D) volume reconstruction of the coronal view, to visualize the entire IUD within the cavity. The IUD was deemed malpositioned if any part extended past the cavity, into the myometrium or cervix. The indications for ultrasound were recorded at presentation for the exam. The presenting symptoms of patients with an abnormally located IUD were compared with those with normally positioned ones.
Results Among 167 consecutive patients with an IUD evaluated using the 3D reconstructed coronal view, 28 (16.8%) bad an IUD with side arms abnormally located within the myometrium. The abnormal positioning of the IUD arms was only detected using the 3D coronal view. A higher proportion of patients with an abnormally located IUD presented with bleeding (35.7%) or pain (39.3%) compared with those with normally positioned IUDs (15.1% with bleeding and 19.4% with pain) (P = 0.02 and 0.03, respectively). Seventy-five Percent of Patients with an abnormally located IUD presented with bleeding or pain compared with 34.5% of those whose IUD was normally placed (P = 0.0001). Twenty of 21 patients with an abnormally located IUD presenting with pelvic pain or bleeding reported improvement in their symptoms after IUD removal.
Conclusion A 3D coronal view of the uterus is useful in the visualization of IUDs. The coronal view showing the entire device and its position within the uterus may help in identifying the cause of pelvic pain and bleeding in patients with an embedded IUD. Copyright (c) 2009 ISUOG. Published by John Wiley & Sons, Ltd.
C1 [Benacerraf, B. R.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA.
[Benacerraf, B. R.; Shipp, T. D.; Bromley, B.] Brigham & Womens Hosp, Dept OB GYN, Boston, MA 02115 USA.
[Benacerraf, B. R.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Benacerraf, B. R.; Shipp, T. D.; Bromley, B.] Massachusetts Gen Hosp, Dept OB GYN, Boston, MA 02114 USA.
[Benacerraf, B. R.; Shipp, T. D.; Bromley, B.] Harvard Univ, Med Scbool, Boston, MA USA.
RP Benacerraf, BR (reprint author), Diagnost Ultrasound Associates, 333 Longwood Ave, Boston, MA 02115 USA.
EM bbsono@aol.com
NR 10
TC 34
Z9 34
U1 2
U2 4
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 0960-7692
J9 ULTRASOUND OBST GYN
JI Ultrasound Obstet. Gynecol.
PD JUL
PY 2009
VL 34
IS 1
BP 110
EP 115
DI 10.1002/uog.6421
PG 6
WC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine &
Medical Imaging
SC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine &
Medical Imaging
GA 473OT
UT WOS:000268217800020
PM 19565532
ER
PT J
AU Exadaktylos, AK
Alam, HB
AF Exadaktylos, A. K.
Alam, H. B.
TI The war on (too many) fluids
SO UNFALLCHIRURG
LA German
DT Article
DE Fluids; Review; Bleeding; Trauma
ID RESUSCITATION; CASUALTIES; UPDATE; BLOOD; MODEL
AB In the coming years, our approach to the bleeding patient will have to change radically. The inevitable knowledge from the wars in Iraq and Afghanistan permits the prediction that conventional crystalloids will sooner or later disappear from volume replacement therapy. The dogma that fluids must always be given will be abandoned, to be replaced by the practice of careful and goal-directed resuscitation. In the near future, we would rely on designer fluids and sophisticated pharmacological agents to deliver personalized resuscitation based upon the specific needs of the individual patient.
C1 [Exadaktylos, A. K.] Univ Bern, Dept Acad Emergency Med, Inselspital, CH-3010 Bern, Switzerland.
[Alam, H. B.] Harvard Univ, Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA USA.
RP Exadaktylos, AK (reprint author), Univ Bern, Dept Acad Emergency Med, Inselspital, CH-3010 Bern, Switzerland.
EM aristomenis@exadaktylos.ch
NR 12
TC 1
Z9 1
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0177-5537
J9 UNFALLCHIRURG
JI Unfallchirurg
PD JUL
PY 2009
VL 112
IS 7
BP 670
EP +
DI 10.1007/s00113-008-1562-1
PG 3
WC Emergency Medicine; Surgery
SC Emergency Medicine; Surgery
GA 471KN
UT WOS:000268056600007
PM 19603217
ER
PT J
AU Saenz, AJ
Koreishi, AF
Rosenberg, AE
Kradin, RL
AF Saenz, A. J.
Koreishi, A. F.
Rosenberg, A. E.
Kradin, R. L.
TI Immune cell subsets in necrotizing fasciitis: an immunohistochemical
analysis
SO VIRCHOWS ARCHIV
LA English
DT Article
DE Skin; Immunohistochemistry; Toxic shock; Streptococci
ID TUMOR-NECROSIS-FACTOR; TOXIC SHOCK SYNDROME; STREPTOCOCCUS-PYOGENES;
INFECTIONS; SUPERANTIGEN
AB Current concepts of the pathophysiology of necrotizing fasciitis (NF), a life-threatening infection of soft tissues associated with a toxic shock syndrome, emphasizes the role of bacterial superantigens as mediators of cytokine release by immune lymphocytes. In order to assess the cellular basis of immune activation, immunohistochemistry was applied to the analysis of inflammatory cell subsets in situ in 13 patients with NF. The percentage of inflammatory cells in skin and soft tissue was scored from 0 to 3+ (> 50%). Substantial numbers of CD15+ polymorphonuclear leukocytes were present in 12 of 13 patients. CD3+ T-lymphocytes accounted for > 10%, CD68+ macrophages for > 50%, and Factor XIIIa+ mononuclear cells for > 10% of the mononuclear cell infiltrates, respectively, in 10 of 13 patients, whereas CD1a+ cells were present in only 3 of 13 cases and accounted for < 10% of mononuclear inflammatory cells. We conclude that immune lymphocytes and accessory immune cells are represented in substantial numbers in the early lesions of NF, and their presence supports current concepts with respect to the pathophysiology of this disorder.
C1 [Saenz, A. J.; Koreishi, A. F.; Rosenberg, A. E.; Kradin, R. L.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Saenz, A. J.; Koreishi, A. F.; Rosenberg, A. E.; Kradin, R. L.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Saenz, A. J.; Koreishi, A. F.; Rosenberg, A. E.; Kradin, R. L.] Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA.
[Kradin, R. L.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
RP Kradin, RL (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
EM rlkradin@partners.org
NR 19
TC 3
Z9 3
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0945-6317
J9 VIRCHOWS ARCH
JI Virchows Arch.
PD JUL
PY 2009
VL 455
IS 1
BP 87
EP 92
DI 10.1007/s00428-009-0781-3
PG 6
WC Pathology
SC Pathology
GA 466UJ
UT WOS:000267688100010
PM 19529958
ER
PT J
AU Cozzi, E
Tallacchini, M
Flanagan, EB
Pierson, RN
Sykes, M
Vanderpool, HY
AF Cozzi, Emanuele
Tallacchini, Mariachiara
Flanagan, Enda B.
Pierson, Richard N., III
Sykes, Megan
Vanderpool, Harold Y.
TI The International Xenotransplantation Association consensus statement on
conditions for undertaking clinical trials of porcine islet products in
type 1 diabetes - Chapter 1: Key ethical requirements and progress
toward the definition of an international regulatory framework
SO XENOTRANSPLANTATION
LA English
DT Article
DE ethics; islets of Langerhans; regulation; xenotransplantation
ID NONHUMAN-PRIMATES; SELECTION
AB The outstanding results recently obtained in islet xenotransplantation suggest that porcine islet clinical trials may soon be scientifically appropriate. Before the initiation of such clinical studies, however, it is essential that a series of key ethical and regulatory conditions are satisfied. As far as ethics is concerned, the fundamental requirements have been previously reported in a position paper of the Ethics Committee of the International Xenotransplantation Association. These include aspects related to the selection of adequately informed, appropriate recipients; animal breeding and welfare; safety issues and the need for a favorable risk/benefit assessment based on strong efficacy data in relevant xenotransplantation studies in the primate. As most diabetic patients are not at risk of short-term mortality without islet transplantation, only a small subset of patients could currently be considered for any type of islet transplant. However, there are potential advantages to xenotransplantation that could result in a favorable benefit-over-harm determination for islet xenotransplantation in this subpopulation and ultimately in a broader population of diabetic patients. With regard to regulatory aspects, the key concepts underlying the development of the regulatory models in existence in the United States, Europe and New Zealand are discussed. Each of these models provides an example of a well-defined regulatory approach to ensure the initiation of well-regulated and ethically acceptable clinical islet xenotransplantation trials. At this stage, it becomes apparent that only a well-coordinated international effort such as that initiated by the World Health Organization, aimed at harmonizing xenotransplantation procedures according to the highest ethical and regulatory standards on a global scale, will enable the initiation of clinical xenotransplantation trials under the best auspices for its success and minimize any risk of failure.
C1 [Cozzi, Emanuele] Univ Padua, Dept Surg & Gastroenterol Sci Pier Giuseppe Ceves, Clin Chirurg 3, I-35128 Padua, Italy.
[Cozzi, Emanuele] Padua Hosp, Direz Sanit, Padua, Italy.
[Cozzi, Emanuele] Consortium Res Organ Transplantat CORIT, Padua, Italy.
[Tallacchini, Mariachiara] Univ Milan, Biotechnol Fac, Catholic Univ Piacenza, Fac Law, Milan, Italy.
[Flanagan, Enda B.] Univ Minnesota, Schulze Diabet Inst, Minneapolis, MN USA.
[Flanagan, Enda B.] Univ Minnesota, Dept Surg, Minneapolis, MN 55455 USA.
[Pierson, Richard N., III] Univ Maryland, Sch Med, Dept Surg, Baltimore, MD 21201 USA.
[Pierson, Richard N., III] Baltimore Vet Affairs Med Ctr, Baltimore, MD USA.
[Sykes, Megan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Surg Serv, Boston, MA USA.
[Vanderpool, Harold Y.] Univ Texas Med Branch, Inst Med Humanities, Galveston, TX USA.
RP Cozzi, E (reprint author), Univ Padua, Dept Surg & Gastroenterol Sci Pier Giuseppe Ceves, Clin Chirurg 3, Via Giustiniani 2, I-35128 Padua, Italy.
EM emanuele.cozzi@unipd.it
FU CORIT (Consorzio per la Ricerca sul Trapianto d'Organi, Padua, Italy);
Italian Ministry of Health; Veneto Region; EU [LSHB-CT-2006-037377]
FX This study was supported by CORIT (Consorzio per la Ricerca sul
Trapianto d'Organi, Padua, Italy), the Italian Ministry of Health, the
Veneto Region, and the EU FP6 Integrated Project "Xenome," contract #
LSHB-CT-2006-037377. The authors wish to thank Dr. Stewart Jessamine
(Medsafe, Ministry of Health, New Zealand) for providing information on
the regulatory framework related to xenotransplantation in New Zealand,
Niketa Walawalkar for assistance with references, and Suzanne Schoenfelt
for editing the manuscript.
NR 25
TC 23
Z9 23
U1 1
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0908-665X
J9 XENOTRANSPLANTATION
JI Xenotransplantation
PD JUL-AUG
PY 2009
VL 16
IS 4
BP 203
EP 214
DI 10.1111/j.1399-3089.2009.00540.x
PG 12
WC Medicine, Research & Experimental; Transplantation
SC Research & Experimental Medicine; Transplantation
GA 499QG
UT WOS:000270238900003
PM 19799760
ER
PT J
AU Mukerji, S
Brown, MC
Lee, DJ
AF Mukerji, Sudeep
Brown, M. Christian
Lee, Daniel J.
TI A morphologic study of Fluorogold labeled tensor tympani motoneurons in
mice
SO BRAIN RESEARCH
LA English
DT Article
DE Middle ear; Pons; Auditory reflex; Trigerminal nucleus; Dendrite;
Retrograde tracer; Synaptic input
ID VENTRAL COCHLEAR NUCLEUS; MIDDLE-EAR MUSCLES; HORSERADISH-PEROXIDASE;
GUINEA-PIG; OLIVOCOCHLEAR NEURONS; MOTOR NEURONS; BRAIN-STEM; CAT; RAT;
MOUSE
AB The tensor tympani is one of two middle ear muscles that regulates the transmission of sound through the middle ear. Contraction of the tensor tympani in response to both auditory and non-auditory stimulation is mediated by the tensor tympani motoneurons (TTMNs). There are interesting differences among species in the acoustic thresholds for contraction of the middle ear muscles, which may be a reflection of underlying anatomical differences such as the number of TTMNs. However anatomical data for mice are lacking, even though the mouse is becoming the most common animal model for auditory and neuroscience research. We investigated the number and morphology of TTMNs in mice using Fluorogold, a retrograde neuronal tracer. After injections of Fluorogold into the tensor tympani muscle, a column of labeled TTMNs was identified ventro-lateral to the ipsilateral trigeminal nucleus. The labeled TTMNs were classified according to their morphological characteristics into three subtypes: "octopus-like", "fusiform" and "stellate", suggesting underlying differences in function. All three subtypes formed sparsely branched and radiating dendrites, some longer than 600 mu m. Dendrites were longest and most numerous in the dorso-medial direction. In 18 cases, the mean number of mouse TTMNs was 51; the largest numbers were 70, 74 and 90 (n = 3 injections). The mean size of mouse TTMNs was 13.0 mu m (minor axis) and 23.5 mu m (major axis). Compared with studies of TTMNs in larger species (cats and rats), mouse TTMNs are both fewer in number and smaller in size. (C) 2009 Elsevier B.V. All rights reserved.
C1 [Lee, Daniel J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Eaton Peabody Lab, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Lee, DJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA.
EM daniel_lee@meei.harvard.edu
FU NIDCD [RO1 DC01089, K08 DC06285]; Norwegian State Lending Agency
FX This study was supported by NIDCD grants RO1 DC01089, K08 DC06285 and
The Norwegian State Lending Agency.
NR 49
TC 4
Z9 4
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
J9 BRAIN RES
JI Brain Res.
PD JUN 30
PY 2009
VL 1278
BP 59
EP 65
DI 10.1016/j.brainres.2009.04.035
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA 466PJ
UT WOS:000267674200006
PM 19397898
ER
PT J
AU Kutcher, MA
Klein, LW
Ou, FS
Wharton, TP
Dehmer, GJ
Singh, M
Anderson, HV
Rumsfeld, JS
Weintraub, WS
Shaw, RE
Sacrinty, MT
Woodward, A
Peterson, ED
Brindis, RG
AF Kutcher, Michael A.
Klein, Lloyd W.
Ou, Fang-Shu
Wharton, Thomas P., Jr.
Dehmer, Gregory J.
Singh, Mandeep
Anderson, H. Vernon
Rumsfeld, John S.
Weintraub, William S.
Shaw, Richard E.
Sacrinty, Matthew T.
Woodward, Albert
Peterson, Eric D.
Brindis, Ralph G.
CA NCDR
TI Percutaneous Coronary Interventions in Facilities Without Cardiac
Surgery On Site: A Report From the National Cardiovascular Data Registry
(NCDR)
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE percutaneous coronary intervention; cardiac surgery; outcomes analysis
ID ACUTE MYOCARDIAL-INFARCTION; ARTERY-BYPASS-SURGERY; ON-SITE; PRIMARY
ANGIOPLASTY; AMERICAN-COLLEGE; SURGICAL BACKUP; ACC-NCDR; THROMBOLYTIC
THERAPY; HOSPITALS; COMMUNITY
C1 [Kutcher, Michael A.; Sacrinty, Matthew T.] Wake Forest Univ, Sch Med, Winston Salem, NC 27157 USA.
[Klein, Lloyd W.] Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA.
[Ou, Fang-Shu; Peterson, Eric D.] Duke Clin Res Inst, Durham, NC USA.
[Wharton, Thomas P., Jr.] Royal Devon & Exeter Hosp, Exeter, NH USA.
[Dehmer, Gregory J.] Texas A&M Univ, Coll Med, Scott & White HealthCare, Temple, TX 76508 USA.
[Singh, Mandeep] Mayo Clin, Rochester, MN USA.
[Anderson, H. Vernon] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA.
[Rumsfeld, John S.] Denver VA Med Ctr, Denver, CO USA.
[Weintraub, William S.] Christiana Care Hlth Syst, Newark, DE USA.
[Shaw, Richard E.] Sutter Pacific Heart Ctr, San Francisco, CA USA.
[Woodward, Albert] Natl Cardiovasc Data Registry, Washington, DC USA.
[Brindis, Ralph G.] No Calif Kaiser Permanente, San Francisco, CA USA.
RP Kutcher, MA (reprint author), Wake Forest Univ, Sch Med, Med Ctr Blvd, Winston Salem, NC 27157 USA.
EM mkutcher@wfubmc.edu
NR 30
TC 49
Z9 50
U1 0
U2 1
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 JUN 30
PY 2009
VL 54
IS 1
BP 16
EP 24
DI 10.1016/j.jacc.2009.03.038
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 465AJ
UT WOS:000267552000002
PM 19555835
ER
PT J
AU Braunwald, E
AF Braunwald, Eugene
TI Noninvasive Detection of Vulnerable Coronary Plaques Locking the Barn
Door Before the Horse Is Stolen
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Editorial Material
DE coronary artery disease; atherosclerosis; acute coronary syndrome;
computed tomography; primary prevention
ID ROW COMPUTED-TOMOGRAPHY; ANGIOGRAPHY; PREDICTION; ULTRASOUND
C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA.
RP Braunwald, E (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 350 Longwood Ave,1st Off Floor, Boston, MA 02115 USA.
EM ebraunwald@partners.org
NR 13
TC 16
Z9 17
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 JUN 30
PY 2009
VL 54
IS 1
BP 58
EP 59
DI 10.1016/j.jacc.2009.03.040
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 465AJ
UT WOS:000267552000008
PM 19555841
ER
PT J
AU Prescot, A
Becerra, L
Pendse, G
Tully, S
Jensen, E
Hargreaves, R
Renshaw, P
Burstein, R
Borsook, D
AF Prescot, Andrew
Becerra, Lino
Pendse, Gautam
Tully, Shannon
Jensen, Eric
Hargreaves, Richard
Renshaw, Perry
Burstein, Rami
Borsook, David
TI Excitatory neurotransmitters in brain regions in interictal migraine
patients
SO MOLECULAR PAIN
LA English
DT Article
ID ANTERIOR CINGULATE CORTEX; EVOKED CORTICAL POTENTIALS;
CENTRAL-NERVOUS-SYSTEM; IN-VIVO; MAGNETIC-RESONANCE;
N-ACETYLASPARTYLGLUTAMATE; CENTRAL SENSITIZATION; MATTER ABNORMALITIES;
CUTANEOUS ALLODYNIA; VISUAL-STIMULATION
AB Objective: To examine biochemical differences in the anterior cingulate cortex (ACC) and insula during the interictal phase of migraine patients. We hypothesized that there may be differences in levels of excitatory amino acid neurotransmitters and/or their derivatives in migraine group based on their increased sensitivity to pain.
Methods: 2D J-resolved proton magnetic resonance spectroscopy ((1)H-MRS) data were acquired at 4.0 Tesla (T) from the ACC and insula in 10 migraine patients (7 women, 3 men, age 43 +/- 11 years) and 8 age gender matched controls (7 women, 3 men, age 41 +/- 9 years).
Results: Standard statistical analyses including analysis of variance (ANOVA) showed no significant metabolite differences between the two subject cohorts in the ACC nor the insula. However, linear discriminant analysis (LDA) introduced a clear separation between subject cohorts based on N-acetyl aspartylglutamate (NAAG) and glutamine (Gln) in the ACC and insula.
Conclusion: These results are consistent with glutamatergic abnormalities in the ACC and insula in migraine patients during their interictal period compared to healthy controls. An alteration in excitatory amino acid neurotransmitters and their derivatives may be a contributing factor for migraineurs for a decrease in sensitivity for migraine or a consequence of the chronic migraine state. Such findings, if extrapolated to other regions of the brain would offer new opportunities to modulate central system as interictal or preemptive medications in these patients.
C1 [Prescot, Andrew; Becerra, Lino; Jensen, Eric; Renshaw, Perry; Borsook, David] McLean Hosp, Brain Imaging Ctr, Belmont, MA 02478 USA.
[Becerra, Lino; Pendse, Gautam; Tully, Shannon; Borsook, David] McLean Hosp, PAIN Grp, Belmont, MA 02478 USA.
[Becerra, Lino; Borsook, David] Massachusetts Gen Hosp, Martinos Ctr, PAIN Grp, Charlestown, MA USA.
[Hargreaves, Richard] Merck & Co Inc, Imaging, West Point, PA USA.
[Burstein, Rami] Harvard Univ, Sch Med, Dept Anesthesia, Beth Israel Deaconess Hosp, Boston, MA 02115 USA.
RP Prescot, A (reprint author), McLean Hosp, Brain Imaging Ctr, Belmont, MA 02478 USA.
EM andrew.prescot@utah.edu; lbecerra@mclean.harvard.edu;
gpendse@mclean.harvard.edu; stully@mclean.harvard.edu;
ejensen@bicserve.mclean.harvard.edu; richard_hargreaves@merck.com;
perry_renshaw@yahoo.com; rburstei@bidmc.harvard.edu;
dborsook@partners.org
FU NIDA NIH HHS [K24 DA015116, DA015116]; NINDS NIH HHS [NS056195, R01
NS051484, NS051484, R01 NS056195]
NR 95
TC 47
Z9 48
U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1744-8069
J9 MOL PAIN
JI Mol. Pain
PD JUN 30
PY 2009
VL 5
AR 34
DI 10.1186/1744-8069-5-34
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 475DS
UT WOS:000268339200002
PM 19566960
ER
PT J
AU Adelson, D
Lao, L
Zhang, G
Kim, W
Marvizon, JCG
AF Adelson, D.
Lao, L.
Zhang, G.
Kim, W.
Marvizon, J. C. G.
TI SUBSTANCE P RELEASE AND NEUROKININ 1 RECEPTOR ACTIVATION IN THE RAT
SPINAL CORD INCREASE WITH THE FIRING FREQUENCY OF C-FIBERS
SO NEUROSCIENCE
LA English
DT Article
DE A delta-fiber; neurokinin A; neuropeptide; pain; presynaptic terminal;
tachykinins
ID LONG-TERM POTENTIATION; PRIMARY AFFERENT-FIBERS; DORSAL-HORN NEURONS;
METHYL-D-ASPARTATE; PRIMARY SENSORY NEURONS; UNITS IN-VITRO; LAMINA-I;
EVOKED POTENTIALS; CONDUCTION-VELOCITY; NEUROTROPHIC FACTOR
AB Both the firing frequency of primary afferents and neurokinin I receptor (NK1R) internalization in dorsal horn neurons increase with the intensity of noxious stimulus. Accordingly, we studied how the pattern of firing of primary afferent influences NK1R internalization. In rat spinal cord slices, electrical stimulation of the dorsal root evoked NK1R internalization in lamina I neurons by inducing substance P release from primary afferents. The stimulation frequency had pronounced effects on NK1R internalization, which increased up to 100 Hz and then diminished abruptly at 200 Hz. Peptidase inhibitors increased NK1R internalization at frequencies below 30 Hz, indicating that peptidases limit the access of substance P to the receptor at moderate firing rates. NK1R internalization increased with number of pulses at all frequencies, but maximal internalization was substantially lower at 1-10 Hz than at 30 Hz. Pulses organized into bursts produced the same NK1R internalization as sustained 30 Hz stimulation. To determine whether substance P release induced at high stimulation frequencies was from C-fibers, we recorded compound action potentials in the sciatic nerve of anesthetized rats. We observed substantial NK1R internalization when stimulating at intensities evoking a C-elevation, but not at intensities evoking only an A delta-elevation. Each pulse in trains at frequencies up to 100 Hz evoked a C-elevation, demonstrating that C-fibers can follow these high frequencies. C-elevation amplitudes declined progressively with increasing stimulation frequency, which was likely caused by a combination of factors including temporal dispersion. In conclusion, the instantaneous firing frequency in C-fibers determines the amount of substance P released by noxious stimuli. Published by Elsevier Ltd on behalf of IBRO.
C1 [Adelson, D.; Marvizon, J. C. G.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA.
[Adelson, D.; Lao, L.; Zhang, G.; Kim, W.; Marvizon, J. C. G.] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurobiol Stress, CURE Digest Dis Res Ctr,Div Digest Dis,Dept Med, Los Angeles, CA 90095 USA.
RP Marvizon, JCG (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Bldg 115,Room 119,11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
EM marvizon@ucla.edu
OI Adelson, David/0000-0002-4623-6030
FU Rehabilitation Research and Development Service [B47661]; Department of
Veteran Affairs; National Institutes of Health [1R01DA012609]
FX Supported by grants B47661 from the Rehabilitation Research and
Development Service, Department of Veteran Affairs and 1R01DA012609 from
the National Institutes of Health to J.C.G.M. Confocal images were
acquired at Carol Moss Spivak Cell Imaging Facility of the Brain
Research Institute at UCLA, with the assistance of Dr. Matthew J.
Schibler.
NR 59
TC 14
Z9 14
U1 0
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4522
J9 NEUROSCIENCE
JI Neuroscience
PD JUN 30
PY 2009
VL 161
IS 2
BP 538
EP 553
DI 10.1016/j.neuroscience.2009.03.058
PG 16
WC Neurosciences
SC Neurosciences & Neurology
GA 455VC
UT WOS:000266794100020
PM 19336248
ER
PT J
AU Brunet, E
Simsek, D
Tomishima, M
DeKelver, R
Choi, VM
Gregory, P
Urnov, F
Weinstock, DM
Jasin, M
AF Brunet, Erika
Simsek, Deniz
Tomishima, Mark
DeKelver, Russell
Choi, Vivian M.
Gregory, Philip
Urnov, Fyodor
Weinstock, David M.
Jasin, Maria
TI Chromosomal translocations induced at specified loci in human stem cells
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE double-strand break repair (DSB repair); zinc finger nucleases;
mesenchymal cells; gene targeting; nonhomologous end-joining (NHEJ)
ID ZINC-FINGER NUCLEASES; DOUBLE-STRAND BREAKS; MAMMALIAN-CELLS;
DNA-RECOGNITION; REPAIR; GENOME; GENE; CANCER; RECOMBINATION; FUSION
AB The precise genetic manipulation of stem and precursor cells offers extraordinary potential for the analysis, prevention, and treatment of human malignancies. Chromosomal translocations are hallmarks of several tumor types where they are thought to have arisen in stem or precursor cells. Although approaches exist to study factors involved in translocation formation in mouse cells, approaches in human cells have been lacking, especially in relevant cell types. The technology of zinc finger nucleases (ZFNs) allows DNA double-strand breaks (DSBs) to be introduced into specified chromosomal loci. We harnessed this technology to induce chromosomal translocations in human cells by generating concurrent DSBs at 2 endogenous loci, the PPP1R12C/p84 gene on chromosome 19 and the IL2R gamma gene on the X chromosome. Translocation breakpoint junctions for t(19;X) were detected with nested quantitative PCR in a high throughput 96-well format using denaturation curves and DNA sequencing in a variety of human cell types, including embryonic stem (hES) cells and hES cell-derived mesenchymal precursor cells. Although readily detected, translocations were less frequent than repair of a single DSB by gene targeting or nonhomologous end-joining, neither of which leads to gross chromosomal rearrangements. While previous studies have relied on laborious genetic modification of cells and extensive growth in culture, the approach described in this report is readily applicable to primary human cells, including mutipotent and pluripotent cells, to uncover both the underlying mechanisms and phenotypic consequences of targeted translocations and other genomic rearrangements.
C1 [Brunet, Erika; Simsek, Deniz; Tomishima, Mark; Jasin, Maria] Mem Sloan Kettering Canc Ctr, Dev Biol Program, New York, NY 10021 USA.
[Tomishima, Mark] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst Stem Cell Res Facil, New York, NY 10021 USA.
[Weinstock, David M.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA.
[DeKelver, Russell; Choi, Vivian M.; Gregory, Philip; Urnov, Fyodor] Sangamo BioSci Inc, Richmond, CA USA.
[Weinstock, David M.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Jasin, M (reprint author), Mem Sloan Kettering Canc Ctr, Dev Biol Program, 1275 York Ave, New York, NY 10021 USA.
EM m-jasin@ski.mskcc.org
FU Byrne Fund; Heckscher Foundation for Children; National Institutes of
Health [GM54668]
FX We thank Margaret Leversha and Lei Zhang at the Memorial Sloan-Kettering
Cancer Center Molecular Cytogenetics Core Facility for performing the
FISH analysis, Yufuko Akamatsu, Francesca Cole, and other members of
Jasin laboratory for helpful discussions, and Gene Bryant and Daniel
Spagna in Mark Ptashne's laboratory for technical assistance. This work
was supported by the Byrne Fund, the Heckscher Foundation for Children,
and Grant R01 National Institutes of Health GM54668 (to M. J.).
NR 39
TC 101
Z9 105
U1 2
U2 18
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 JUN 30
PY 2009
VL 106
IS 26
BP 10620
EP 10625
DI 10.1073/pnas.0902076106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 465EI
UT WOS:000267564300043
PM 19549848
ER
PT J
AU Zhou, EH
Trepat, X
Park, CY
Lenormand, G
Oliver, MN
Mijailovich, SM
Hardin, C
Weitz, DA
Butler, JP
Fredberg, JJ
AF Zhou, E. H.
Trepat, X.
Park, C. Y.
Lenormand, G.
Oliver, M. N.
Mijailovich, S. M.
Hardin, C.
Weitz, D. A.
Butler, J. P.
Fredberg, J. J.
TI Universal behavior of the osmotically compressed cell and its analogy to
the colloidal glass transition
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE compression; cytoplasm; cytoskeleton; mechanotransduction; stiffness
ID AIRWAY SMOOTH-MUSCLE; LIVING CELL; VOLUME; STIFFNESS; LIQUIDS; STRESS;
VISCOELASTICITY; CYTOSKELETON; MECHANICS; DYNAMICS
AB Mechanical robustness of the cell under different modes of stress and deformation is essential to its survival and function. Under tension, mechanical rigidity is provided by the cytoskeletal network; with increasing stress, this network stiffens, providing increased resistance to deformation. However, a cell must also resist compression, which will inevitably occur whenever cell volume is decreased during such biologically important processes as anhydrobiosis and apoptosis. Under compression, individual filaments can buckle, thereby reducing the stiffness and weakening the cytoskeletal network. However, the intracellular space is crowded with macromolecules and organelles that can resist compression. A simple picture describing their behavior is that of colloidal particles; colloids exhibit a sharp increase in viscosity with increasing volume fraction, ultimately undergoing a glass transition and becoming a solid. We investigate the consequences of these 2 competing effects and show that as a cell is compressed by hyperosmotic stress it becomes progressively more rigid. Although this stiffening behavior depends somewhat on cell type, starting conditions, molecular motors, and cytoskeletal contributions, its dependence on solid volume fraction is exponential in every instance. This universal behavior suggests that compression-induced weakening of the network is overwhelmed by crowding-induced stiffening of the cytoplasm. We also show that compression dramatically slows intracellular relaxation processes. The increase in stiffness, combined with the slowing of relaxation processes, is reminiscent of a glass transition of colloidal suspensions, but only when comprised of deformable particles. Our work provides a means to probe the physical nature of the cytoplasm under compression, and leads to results that are universal across cell type.
C1 [Zhou, E. H.; Trepat, X.; Park, C. Y.; Lenormand, G.; Oliver, M. N.; Mijailovich, S. M.; Butler, J. P.; Fredberg, J. J.] Harvard Univ, Sch Publ Hlth, Program Mol & Integrat Physiol Sci, Boston, MA 02115 USA.
[Hardin, C.] Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA.
[Weitz, D. A.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
[Butler, J. P.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Trepat, X.] Univ Barcelona, Inst Bioengn Catalonia & Ciber Enfermedades Resp, E-08036 Barcelona, Spain.
RP Fredberg, JJ (reprint author), Harvard Univ, Sch Publ Hlth, Program Mol & Integrat Physiol Sci, 665 Huntington Ave, Boston, MA 02115 USA.
EM jeffrey_fredberg@harvard.edu
FU National Institutes of Health
FX We thank Michael Wasserman and Emil Millet for technical assistance;
Karen Kasza and Dhananjay Tambe for discussions; Reynold Panettieri
(University of Pennsylvania Medical Center, Philadelphia), Tao Lu
(Harvard Medical School, Boston), Daniel Tschumperlin (Harvard School of
Public Health, Boston), and Fei Liu (Harvard School of Public Health,
Boston) for providing cells; and Nenad Filipovic, Milos Kojic, and
Velibor Isailovic for performing the finite element calculations. This
work was supported by grants from National Institutes of Health. The AFM
experiments were performed at the Center for Nanoscale Systems (CNS) at
Harvard University.
NR 42
TC 79
Z9 80
U1 0
U2 28
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 JUN 30
PY 2009
VL 106
IS 26
BP 10632
EP 10637
DI 10.1073/pnas.0901462106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 465EI
UT WOS:000267564300045
PM 19520830
ER
PT J
AU Yuan, XL
Ansari, MJ
D'Addio, F
Paez-Cortez, J
Schmitt, I
Donnarumma, M
Boenisch, O
Zhao, XZ
Popoola, J
Clarkson, MR
Yagita, H
Akiba, H
Freeman, GJ
Iacomini, J
Turka, LA
Glimcher, LH
Sayegh, MH
AF Yuan, Xueli
Ansari, M. Javeed
D'Addio, Francesca
Paez-Cortez, Jesus
Schmitt, Isabella
Donnarumma, Michela
Boenisch, Olaf
Zhao, Xiaozhi
Popoola, Joyce
Clarkson, Michael R.
Yagita, Hideo
Akiba, Hisaya
Freeman, Gordon J.
Iacomini, John
Turka, Laurence A.
Glimcher, Laurie H.
Sayegh, Mohamed H.
TI Targeting Tim-1 to overcome resistance to transplantation tolerance
mediated by CD8 T17 cells
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE costimulation; IL-17; rejection; immunosuppression
ID CARDIAC ALLOGRAFT-REJECTION; T-CELLS; IFN-GAMMA; TH17 CELLS;
BLOCKADE-RESISTANT; TUMOR-GROWTH; IN-VIVO; IL-17; INTERLEUKIN-17; MICE
AB The ability to induce durable transplantation tolerance predictably and consistently in the clinic is a highly desired but elusive goal. Progress is hampered by lack of appropriate experimental models in which to study resistance to transplantation tolerance. Here, we demonstrate that T helper 1-associated T box 21 transcription factor (Tbet) KO recipients exhibit allograft tolerance resistance specifically mediated by IL-17-producing CD8 T (T17) cells. Neutralization of IL-17 facilitates long-term cardiac allograft survival with combined T cell co-stimulation (CD28-CD80/86 and CD154-CD40) blockade in Tbet KO recipients. We have used this T17-biased Tbet KO model of allograft tolerance resistance to study the impact of targeting a T cell-costimulatory pathway, and demonstrate that targeting T cell Ig and mucin domain-1 (Tim-1) with anti-Tim-1 overcomes this resistance by specifically inhibiting the pathogenic IL-17-producing CD8 T17 cells. These data indicate that in the absence of Th1 immunity, CD8 T17 alloreactivity constitutes a barrier to transplantation tolerance. Targeting TIM-1 provides an approach to overcome resistance to tolerance in clinical transplantation.
C1 [Yuan, Xueli; Ansari, M. Javeed; D'Addio, Francesca; Paez-Cortez, Jesus; Schmitt, Isabella; Donnarumma, Michela; Boenisch, Olaf; Zhao, Xiaozhi; Popoola, Joyce; Clarkson, Michael R.; Iacomini, John; Sayegh, Mohamed H.] Brigham & Womens Hosp, Transplantat Res Ctr, Div Renal, Boston, MA 02115 USA.
[Yuan, Xueli; Ansari, M. Javeed; D'Addio, Francesca; Paez-Cortez, Jesus; Schmitt, Isabella; Donnarumma, Michela; Boenisch, Olaf; Zhao, Xiaozhi; Popoola, Joyce; Clarkson, Michael R.; Iacomini, John; Sayegh, Mohamed H.] Childrens Hosp Boston, Boston, MA USA.
[Freeman, Gordon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Ansari, M. Javeed] Northwestern Univ, Div Nephrol & Organ Transplantat, Feinberg Sch Med, Chicago, IL 60611 USA.
[Yagita, Hideo; Akiba, Hisaya] Juntendo Univ, Sch Med, Dept Immunol, Tokyo 1138421, Japan.
[Turka, Laurence A.] Hosp Univ Penn, Renal Elect & Hypertens Div, Philadelphia, PA 19104 USA.
[Glimcher, Laurie H.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
RP Sayegh, MH (reprint author), Brigham & Womens Hosp, Transplantat Res Ctr, Div Renal, Boston, MA 02115 USA.
EM msayegh@rics.bwh.harvard.edu
RI D'Addio, Francesca/F-3417-2017
OI D'Addio, Francesca/0000-0002-0345-0694
FU National Institutes of Health (NIH) [RO1 AI-51559, R01AI-37691, R01
AI-70820, P01 AI-41521, CA112663, NS038037, K08 AI080836-01]; American
Society of Transplantation (AST) Basic Science Faculty Development;
AST-Wyeth Basic Science Faculty Development
FX This work was supported by National Institutes of Health (NIH) Grants:
RO1 AI-51559, R01AI-37691, R01 AI-70820, and P01 AI-41521 (to M. H. S.)
and CA112663 and NS038037 (to L. H. G.). X. Y. was supported in part by
American Society of Transplantation (AST) Basic Science Faculty
Development Grant Award. M. J. A. is supported in part by the AST-Wyeth
Basic Science Faculty Development Grant Award and NIH Grant K08
AI080836-01.
NR 39
TC 46
Z9 47
U1 1
U2 2
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 JUN 30
PY 2009
VL 106
IS 26
BP 10734
EP 10739
DI 10.1073/pnas.0812538106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 465EI
UT WOS:000267564300063
PM 19528638
ER
PT J
AU Koenigsberg, HW
Siever, LJ
Lee, H
Pizzarello, S
New, AS
Goodman, M
Cheng, H
Flory, J
Prohovnik, I
AF Koenigsberg, Harold W.
Siever, Larry J.
Lee, Hedok
Pizzarello, Scott
New, Antonia S.
Goodman, Marianne
Cheng, Hu
Flory, Janine
Prohovnik, Isak
TI Neural correlates of emotion processing in borderline personality
disorder
SO PSYCHIATRY RESEARCH-NEUROIMAGING
LA English
DT Article
DE Affective instability; Emotion; fMRI; Social-emotional cues; Borderline
personality disorder
ID POSITRON-EMISSION-TOMOGRAPHY; AFFECTIVE INSTABILITY; AMYGDALA;
ACTIVATION; STIMULI; PERCEPTION; WOMEN; FMRI; FACE; CUES
AB Emotional instability is a hallmark feature of borderline personality disorder (BPD), yet its biological underpinnings are poorly understood. We employed functional magnetic resonance imaging (fMRI) to compare patterns of regional brain activation in BPD patients and healthy volunteers as they process positive and negative social emotional stimuli. fMRI images were acquired while 19 BPD patients and 17 healthy controls (HC) viewed emotion-inducing pictures from the International Affective Pictures System set. Activation data were analyzed with SPM5 ANCOVA models to derive the effects of diagnosis and stimulus type. BPD patients demonstrated greater differences in activation than controls, when viewing negative pictures compared with rest, in the amygdala, fusiform gyrus, primary visual areas, superior temporal gyrus (STG), and premotor areas, while healthy controls showed greater differences than BPD patients in the insula, middle temporal gyrus and dorsolateral prefrontal cortex (BA46). When viewing positive pictures compared with rest, BPD patients showed greater differences in the STG, premotor cortex, and ventrolateral prefrontal cortex. These findings suggest that BPD patients show greater amygdala activity and heightened activity of visual processing regions relative to findings for HC subjects in the processing of negative social emotional pictures compared with rest. The patients activate neural networks in emotion processing that are phylogeneticall older and more reflexive than those activated by HC subjects. Published by Elsevier Ireland Ltd.
C1 [Koenigsberg, Harold W.; Siever, Larry J.; Lee, Hedok; New, Antonia S.; Goodman, Marianne; Prohovnik, Isak] Mt Sinai Sch Med, James J Peters VA Med Ctr, Bronx, NY 10468 USA.
[Koenigsberg, Harold W.; Siever, Larry J.; New, Antonia S.; Goodman, Marianne; Prohovnik, Isak] Mt Sinai Sch Med, New York, NY USA.
[Cheng, Hu] Indiana Univ, Bloomington, IN 47405 USA.
[Flory, Janine] CUNY Queens Coll, Dept Psychol, Flushing, NY 11367 USA.
[Pizzarello, Scott] Florida State Univ, Dept Psychol, Tallahassee, FL 32306 USA.
RP Koenigsberg, HW (reprint author), Mt Sinai Sch Med, James J Peters VA Med Ctr, 116A,130 W Kingsbridge Rd, Bronx, NY 10468 USA.
EM HWarrenK@nyc.rr.com
FU National Center for Research Resources (NCRR) [MO1-RR-00071]; National
Institutes of Health (NIH); Mental Illness Research Education and
Clinical Center; Siemens Medical Systems, Inc
FX This work was supported by Grant Number MO1-RR-00071 from the National
Center for Research Resources (NCRR), a component of the National
Institutes of Health (NIH) and the Mental Illness Research Education and
Clinical Center, VISN 3 Veterans Health Administration, and an
educational grant from the Siemens Medical Systems, Inc. Its contents
are solely the responsibility of the authors and do not necessarily
represent the official views of NCRR, NIH, or the VA. We thank Dr.
Sergei Pakhomov (Institute of the Human Brain, St. Petersburg, Russia)
for the MSU software.
NR 54
TC 96
Z9 96
U1 3
U2 18
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0925-4927
J9 PSYCHIAT RES-NEUROIM
JI Psychiatry Res. Neuroimaging
PD JUN 30
PY 2009
VL 172
IS 3
BP 192
EP 199
DI 10.1016/j.pscychresns.2008.07.010
PG 8
WC Clinical Neurology; Neuroimaging; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 452ZX
UT WOS:000266580800004
PM 19394205
ER
PT J
AU El-Din, MAA
Hughes, KS
Raad, RA
Goldberg, SI
Aisenberg, AC
Niemierko, A
Taghian, AG
AF El-Din, Mohamed A. Alm
Hughes, Kevin S.
Raad, Rita A.
Goldberg, Saveli I.
Aisenberg, Alan C.
Niemierko, Andrzej
Taghian, Alphonse G.
TI Clinical outcome of breast cancer occurring after treatment for
Hodgkin's lymphoma: case-control analysis
SO RADIATION ONCOLOGY
LA English
DT Article
ID ATOMIC-BOMB SURVIVORS; CONTRALATERAL BREAST; RISK-FACTORS; PATHOLOGICAL
ANALYSIS; MANTLE IRRADIATION; RADIATION-THERAPY; 2ND MALIGNANCY;
DISEASE; RADIOTHERAPY; CARCINOMA
AB Background: To evaluate diagnosis, management and outcome of breast cancer (BC) occurring after irradiation for Hodgkin's lymphoma (HL).
Methods: 39 cases of BC in 28 HL survivors were retrospectively reviewed. 21 patients were included in a case-control analysis.
Results: The median age at diagnosis of HL and BC was 25.3 and 45.3 years, respectively. The median interval to develop BC was 16.1 years. Eleven women (39.2%) had bilateral disease. Mode of detection of the index breast cancers was by mammographic screening in 17 patients (60.7%), palpable lump in 8 patients (28.6%), clinical examination in two patients (7.1%), and unknown in one patient (3.6%). Case-control analysis showed that histological features and prognosis of BC after HL were similar to those of primary BC, however, for BC after HL, mastectomy was the predominant surgery (P = .001) and adjuvant radiotherapy and anthracycline-based chemotherapy were less frequently used as compared to primary BC (P < .001 and .003, respectively).
Conclusion: The previous history of HL does not appear to be a poor prognostic factor for BC occurring thereafter.
C1 [El-Din, Mohamed A. Alm; Raad, Rita A.; Goldberg, Saveli I.; Niemierko, Andrzej; Taghian, Alphonse G.] Harvard Univ, Massachusetts Gen Hosp, Dept Radiat Oncol, Sch Med, Boston, MA 02114 USA.
[Hughes, Kevin S.] Harvard Univ, Massachusetts Gen Hosp, Dept Surg Oncol, Sch Med, Boston, MA 02114 USA.
[Aisenberg, Alan C.] Harvard Univ, Massachusetts Gen Hosp, Dept Med Oncol, Sch Med, Boston, MA 02114 USA.
[El-Din, Mohamed A. Alm] Tanta Univ Hosp, Tanta Fac Med, Dept Radiat Oncol, Tanta, Egypt.
RP Taghian, AG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Radiat Oncol, Sch Med, Boston, MA 02114 USA.
EM almeldin@gmail.com; kshughes@partners.org; rabiraad@partners.org;
sigoldberg@partners.org; aaisenberg@partners.org;
aniemierko@partners.org; ataghian@partners.org
OI Hughes, Kevin/0000-0003-4084-6484
FU Jane Mailloux fund; Blanche Montesi fund; Tim Levy fund for breast
cancer research; National Institutes of Health [CA50628]
FX Results of this study were published in part at the 43rd
annual meeting of the American Society of Clinical Oncology (ASCO), June
2007, Chicago, IL. Supported in part by the Jane Mailloux fund, the
Blanche Montesi fund, the Tim Levy fund for breast cancer research (AGT)
and grant CA50628 from the National Institutes of Health (AN).
NR 43
TC 8
Z9 8
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
J9 RADIAT ONCOL
JI Radiat. Oncol.
PD JUN 30
PY 2009
VL 4
AR 19
DI 10.1186/1748-717X-4-19
PG 8
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 475SI
UT WOS:000268380600001
ER
PT J
AU Pinne, M
Haake, DA
AF Pinne, Marija
Haake, David A.
TI A Comprehensive Approach to Identification of Surface-Exposed, Outer
Membrane-Spanning Proteins of Leptospira interrogans
SO PLOS ONE
LA English
DT Article
AB Leptospirosis is a zoonosis with worldwide distribution caused by pathogenic spirochetes belonging to the genus Leptospira. The leptospiral life cycle involves transmission via fresh water and colonization of the renal tubules of their reservoir hosts or infection of accidental hosts, including humans. Bacterial outer membrane proteins (OMPs), particularly those with surface-exposed regions, play crucial roles in virulence mechanisms of pathogens and the adaptation to various environmental conditions, including those of the mammalian host. Little is known about the surface-exposed OMPs in Leptospira, particularly those with outer membrane-spanning domains. Herein, we describe a comprehensive strategy for identification and characterization of leptospiral transmembrane OMPs. The genomic sequence of L. interrogans serovar Copenhageni strain Fiocruz L1-130 allowed us to employ the beta-barrel prediction programs, PRED-TMBB and TMBETA-NET, to identify potential transmembrane OMPs. Several complementary methods were used to characterize four novel OMPs, designated OmpL36, OmpL37, OmpL47 and OmpL54. In addition to surface immunofluorescence and surface biotinylation, we describe surface proteolysis of intact leptospires as an improved method for determining the surface exposure of leptospiral proteins. Membrane integration was confirmed using techniques for removal of peripheral membrane proteins. We also demonstrate deficiencies in the Triton X-114 fractionation method for assessing the outer membrane localization of transmembrane OMPs. Our results establish a broadly applicable strategy for the elucidation of novel surface-exposed outer membrane-spanning proteins of Leptospira, an essential step in the discovery of potential virulence factors, diagnostic antigens and vaccine candidates.
RP Pinne, M (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA.
EM mpinne@ucla.edu
FU NIAID NIH HHS [AI-34431, R01 AI034431, R01 AI034431-12, R21 AI034431,
R29 AI034431]
NR 84
TC 38
Z9 38
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 29
PY 2009
VL 4
IS 6
AR e6071
DI 10.1371/journal.pone.0006071
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 463XB
UT WOS:000267465900007
PM 19562037
ER
PT J
AU Okpara, N
Aswad, B
Baffy, G
AF Okpara, Nnenna
Aswad, Bassam
Baffy, Gyorgy
TI Eosinophilic colitis
SO WORLD JOURNAL OF GASTROENTEROLOGY
LA English
DT Review
DE Eosinophilia; Colitis; Gastrointestinal disease; Ascites
ID GASTROINTESTINAL DISORDERS; ENTEROBIUS-VERMICULARIS; FOOD ALLERGIES;
ACUTE ABDOMEN; GASTROENTERITIS; ESOPHAGITIS; DIAGNOSIS; PATIENT;
INTUSSUSCEPTION; ENTEROCOLITIS
AB Eosinophilic colitis (EC) is a rare form of primary eosinophilic gastrointestinal disease with a bimodal peak of prevalence in neonates and young adults. EC remains a little understood condition in contrast to the increasingly recognized eosinophilic esophagitis. Clinical presentation of EC is highly variable according to mucosal, transmural, or serosal predominance of inflammation. EC has a broad differential diagnosis because colon tissue eosinophilia often occurs in parasitic infection, drug-induced allergic reactions, inflammatory bowel disease, and various connective tissue disorders, which require thorough searching for secondary causes that may be specifically treated with antibiotics or dietary and drug elimination. Like eosinophilic gastrointestinal disease involving other segments of the gastrointestinal tract, EC responds very well to steroids that may be spared by using antihistamines, leukotriene inhibitors and biologics. (c) 2009 The WJG Press and Baishideng. All rights reserved.
C1 [Okpara, Nnenna; Baffy, Gyorgy] Rhode Isl Hosp, Div Gastroenterol, Dept Med, Providence, RI 02130 USA.
[Okpara, Nnenna; Aswad, Bassam; Baffy, Gyorgy] Brown Univ, Alpert Med Sch, Providence, RI 02130 USA.
[Aswad, Bassam] Rhode Isl Hosp, Dept Pathol, Providence, RI 02130 USA.
RP Baffy, G (reprint author), VA Boston Healthcare Syst, Gastroenterol Sect, 150 S Huntington Ave,Rm A6-46, Boston, MA 02130 USA.
EM gbaffy@partners.org
NR 51
TC 31
Z9 36
U1 0
U2 2
PU W J G PRESS
PI BEIJING
PA APT 1066, YISHOU GARDEN, NO 58, NORTH LANGXINZHUANG RD, PO BOX 2345,
BEIJING 100023, PEOPLES R CHINA
SN 1007-9327
J9 WORLD J GASTROENTERO
JI World J. Gastroenterol.
PD JUN 28
PY 2009
VL 15
IS 24
BP 2975
EP 2979
DI 10.3748/wig.15.2975
PG 5
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 464HN
UT WOS:000267496100003
PM 19554649
ER
PT J
AU Surman, OS
Cosimi, AB
DiMartini, A
AF Surman, Owen S.
Cosimi, A. Benedict
DiMartini, Andrea
TI Psychiatric Care of Patients Undergoing Organ Transplantation
SO TRANSPLANTATION
LA English
DT Review
DE Transplantation; Psychiatry; Selection; Consent; Compliance
ID ALCOHOLIC LIVER-DISEASE; DRUG-DRUG INTERACTIONS; RENAL-TRANSPLANTATION;
HEPATITIS-C; NONADHERENCE; DEPRESSION; RISK; COMPLICATIONS; PREDICTORS;
MEDICATION
AB Transplantation provides life-saving therapy to critically ill patients with end-stage organ failure. We found that the specialized knowledge of mental health clinicians and physicians, committed to the evaluation and management of transplant recipients, is essential for the optimal care of these patients who require a life-long regimen of immunosuppressive medication and dependency on the transplant team. Critical issues requiring psychiatric input are frequently encountered in the following areas (1) patient selection and informed consent; (2) recognition and pretransplant treatment of psychiatric disorders; (3) substance or alcohol abuse; (4) compliance with medical regimens; (5) posttransplant psychosis; and (6) immunosuppressive/psychiatric drug-drug interactions. This review focuses on the priorities in psychological and psychiatric care of these unique patients.
C1 [Surman, Owen S.; Cosimi, A. Benedict] Massachusetts Gen Hosp, Dept Psychiat & Surg, Boston, MA 02114 USA.
[Surman, Owen S.; DiMartini, Andrea] Univ Pittsburgh, Med Ctr, Dept Psychiat & Surg, Pittsburgh, PA USA.
RP Surman, OS (reprint author), WANG Ambulatory Care Ctr, Suite 812,15 Parkman St, Boston, MA 02114 USA.
EM osurman@partners.org
NR 49
TC 19
Z9 20
U1 2
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0041-1337
EI 1534-6080
J9 TRANSPLANTATION
JI Transplantation
PD JUN 27
PY 2009
VL 87
IS 12
BP 1753
EP 1761
DI 10.1097/TP.0b013e3181a754d4
PG 9
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA 462NO
UT WOS:000267361000001
PM 19543050
ER
PT J
AU Xia, Y
Ongusaha, P
Lee, SW
Liou, YC
AF Xia, Yun
Ongusaha, Pat
Lee, Sam W.
Liou, Yih-Cherng
TI Loss of Wip1 Sensitizes Cells to Stress- and DNA Damage-induced
Apoptosis
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID C-JUN; SIGNAL-TRANSDUCTION; TRANSCRIPTION FACTOR; PROTEIN PHOSPHATASE;
KINASE; P53; ACTIVATION; PATHWAYS; PPM1D; PHOSPHORYLATION
AB In response to various environmental stresses, the stress-responsive MAPKs p38 and JNK are activated and phosphorylate ATF2 and c-Jun transcription factors, thereby affecting cell-fate decision. Targeted gene disruption studies have established that JNK-c-Jun signaling plays a vital role in stress-induced apoptosis. The oncogenic phosphatase Wip1 acts as an important regulator in DNA damage pathway by dephosphorylating a spectrum of proteins including p53, p38, Chk1, Chk2, and ATM. In this study we show that Wip1 negatively regulates the activation of MKK4-JNK-c-Jun signaling during stress-induced apoptosis. The loss of Wip1 function sensitizes mouse embryonic fibroblasts to stress-induced apoptosis via the activation of both p38-ATF2 and JNK-c-Jun signaling. Here we reveal that Wip1 has dual roles in alternatively regulating stress- and DNA damage-induced apoptosis through p38/JNK MAPKs and p38/p53-dependent pathways, respectively. Our results point to Wip1 as a general regulator of apoptosis, which further supports its role in tumorigenesis.
C1 [Xia, Yun; Liou, Yih-Cherng] Natl Univ Singapore, Fac Sci, Dept Biol Sci, Singapore 117543, Singapore.
[Ongusaha, Pat; Lee, Sam W.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02129 USA.
[Ongusaha, Pat; Lee, Sam W.] Harvard Univ, Sch Med, Boston, MA 02129 USA.
RP Liou, YC (reprint author), 14 Sci Dr 4, Singapore 117543, Singapore.
EM dbslyc@nus.edu.sg
RI Xia, Yun/K-4128-2015
OI Xia, Yun/0000-0003-2184-4870
FU Biomedical Research Council [06/1/21/19/473]; Agency for Science,
Research and Technology, Singapore
FX This work was supported, in whole or in part, by Grant 06/1/21/19/473
from the Biomedical Research Council, the Agency for Science, Research
and Technology, Singapore (to Y.C.L.).
NR 49
TC 22
Z9 23
U1 0
U2 3
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 JUN 26
PY 2009
VL 284
IS 26
BP 17428
EP 17437
DI 10.1074/jbc.M109.007823
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 460QP
UT WOS:000267202500009
PM 19395378
ER
PT J
AU Zarei, S
Schwenter, F
Luy, P
Aurrand-Lions, M
Morel, P
Kopf, M
Dranoff, G
Mach, N
AF Zarei, Shohreh
Schwenter, Frank
Luy, Patricia
Aurrand-Lions, Michel
Morel, Philippe
Kopf, Manfred
Dranoff, Glenn
Mach, Nicolas
TI Role of GM-CSF signaling in cell-based tumor immunization
SO BLOOD
LA English
DT Article
ID COLONY-STIMULATING FACTOR; REFRACTORY PROSTATE-CANCER; POTENT ANTITUMOR
IMMUNITY; MYELOID SUPPRESSOR-CELLS; DENDRITIC CELLS; IN-VIVO; DEFICIENT
MICE; T-CELLS; HEMATOPOIETIC-CELLS; MELANOMA-CELLS
AB Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a potent adjuvant in cancer vaccination; however, the specific role of endogenous GM-CSF remains unknown. We performed cell-based vaccination in 2 tumor models. First, we vaccinated C57BL/6 mice lacking either GM-CSF, IL-5, or beta-common chain (beta c), a receptor subunit essential for GM-CSF and IL-5 signaling, with melanoma cells engineered to produce GM-CSF. Tumor vaccination was effective in both GM-CSF(-/-) and IL-5(-/-) mice, showing that protective immunization is independent of both endogenous cytokines. However, all beta c(-/-) animals developed tumor. Loss of tumor immunity in beta c(-/-) mice does not reflect global impairment in cell-mediated immunity, as contact hypersensitivity reaction to haptens is unaltered. The importance of tumor cell-derived GM-CSF was highlighted by recruitment of dendritic cells at the vaccination site in wildtype, GM-CSF(-/-), and IL-5(-/-) but not in beta c(-/-) mice. In the second model, vaccination with unmodified RENCA cells showed similar results with efficient immunization in BALB/c wild-type and GM-CSF(-/-), whereas all beta c(-/-) animals died. Altogether, our results strongly suggest that although endogenous GM-CSF and IL-5 are not required to induce tumor immunity, signaling through beta c receptor is critically needed for efficient cancer vaccination in both genetically modified GM-CSF-secreting tumor cells and a spontaneously immunogenic models. (Blood. 2009;113:6658-6668)
C1 [Zarei, Shohreh; Schwenter, Frank; Luy, Patricia; Mach, Nicolas] Univ Hosp Geneva, Dept Internal Med, Div Oncol, CH-1205 Geneva, Switzerland.
[Schwenter, Frank; Morel, Philippe] Univ Hosp Geneva, Dept Surg, Visceral & Transplantat Unit, CH-1205 Geneva, Switzerland.
[Zarei, Shohreh; Schwenter, Frank; Luy, Patricia; Mach, Nicolas] Geneva Sch Med, Dept Internal Med, Div Oncol, Geneva, Switzerland.
[Schwenter, Frank; Morel, Philippe] Geneva Sch Med, Dept Surg, Visceral & Transplantat Unit, Geneva, Switzerland.
[Aurrand-Lions, Michel] Canc Res Ctr, INSERM, Inst J Paoli I Calmettes, Marseille, France.
[Kopf, Manfred] Swiss Fed Inst Technol, Dept Environm Sci, Zurich, Switzerland.
[Dranoff, Glenn] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA.
[Dranoff, Glenn] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
RP Mach, N (reprint author), Univ Hosp Geneva, Dept Internal Med, Div Oncol, 24 Rue Micheli du Crest, CH-1205 Geneva, Switzerland.
EM nicolas.mach@medecine.unige.ch
RI Aurrand-Lions, Michel/O-9953-2016
OI Aurrand-Lions, Michel/0000-0002-8361-3034
FU Swiss National Science Foundation, Berne, Switzerland [PNR 37]; La Ligue
genevoise contre le cancer (Geneva, Switzerland); la Fondation pour la
lutte contre le cancer (Zurich, Switzerland; Cancer Research
Institute/Partridge Foundation (New York, NY); Clinical Scholar of the
Leukemia & Lymphoma Society (White Plains, NY); [CA 74886]
FX This work was supported by the Swiss National Science Foundation (PNR
37) (Berne, Switzerland), La Ligue genevoise contre le cancer (Geneva,
Switzerland), la Fondation pour la lutte contre le cancer (Zurich,
Switzerland; N. M.), the Cancer Research Institute/Partridge Foundation
(New York, NY), and CA 74886 (G. D). G. D. is a Clinical Scholar of the
Leukemia & Lymphoma Society (White Plains, NY).
NR 50
TC 20
Z9 24
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 JUN 25
PY 2009
VL 113
IS 26
BP 6658
EP 6668
DI 10.1182/blood-2008-06-161075
PG 11
WC Hematology
SC Hematology
GA 468BY
UT WOS:000267789600026
PM 19282460
ER
PT J
AU Roccaro, AM
Sacco, A
Thompson, B
Leleu, X
Azab, AK
Azab, F
Runnels, J
Jia, XY
Ngo, HT
Melhem, MR
Lin, CP
Ribatti, D
Rollins, BJ
Witzig, TE
Anderson, KC
Ghobrial, IM
AF Roccaro, Aldo M.
Sacco, Antonio
Thompson, Brian
Leleu, Xavier
Azab, Abdel Kareem
Azab, Feda
Runnels, Judith
Jia, Xiaoying
Ngo, Hai T.
Melhem, Molly R.
Lin, Charles P.
Ribatti, Domenico
Rollins, Barrett J.
Witzig, Thomas E.
Anderson, Kenneth C.
Ghobrial, Irene M.
TI MicroRNAs 15a and 16 regulate tumor proliferation in multiple myeloma
SO BLOOD
LA English
DT Article
ID NF-KAPPA-B; ENDOTHELIAL-CELLS; WALDENSTROM MACROGLOBULINEMIA;
MALIGNANT-MELANOMA; PATHWAY; PROTEIN; GROWTH; EXPRESSION; INHIBITOR;
FREQUENT
AB Detailed genomic studies have shown that cytogenetic abnormalities contribute to multiple myeloma (MM) pathogenesis and disease progression. Nevertheless, little is known about the characteristics of MM at the epigenetic level and specifically how microRNAs regulate MM progression in the context of the bone marrow milieu. Therefore, we performed microRNA expression profiling of bone marrow derived CD138(+) MM cells versus their normal cellular counterparts and validated data by qRT-PCR. We identified a MM-specific microRNA signature characterized by down-expression of microRNA-15a/-16 and overexpression of microRNA-222/-221/-382/-181a/-181b (P < .01). We investigated the functional role of microRNA-15a and -16 and showed that they regulate proliferation and growth of MM cells in vitro and in vivo by inhibiting AKT serine/threonineprotein-kinase (AKT3), ribosomal-protein-S6, MAP-kinases, and NF-kappa B-activator MAP3KIP3. Moreover, miRNA-15a and -16 exerted their anti-MM activity even in the context of the bone marrow milieu in vitro and in vivo. These data indicate that microRNAs play a pivotal role in the biology of MM and represent important targets for novel therapies in MM. (Blood. 2009;113:6669-6680)
C1 [Roccaro, Aldo M.; Sacco, Antonio; Leleu, Xavier; Azab, Abdel Kareem; Azab, Feda; Runnels, Judith; Jia, Xiaoying; Ngo, Hai T.; Melhem, Molly R.; Rollins, Barrett J.; Anderson, Kenneth C.; Ghobrial, Irene M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Roccaro, Aldo M.; Sacco, Antonio; Leleu, Xavier; Azab, Abdel Kareem; Azab, Feda; Runnels, Judith; Jia, Xiaoying; Ngo, Hai T.; Melhem, Molly R.; Rollins, Barrett J.; Anderson, Kenneth C.; Ghobrial, Irene M.] Harvard Univ, Sch Med, Boston, MA USA.
[Roccaro, Aldo M.] Univ Brescia, Sch Med, Unit Blood Dis & Cell Therapies, Brescia, Italy.
[Roccaro, Aldo M.] Univ Bari, Dept Internal Med & Clin Oncol, Sch Med, Bari, Italy.
[Thompson, Brian; Lin, Charles P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA.
[Witzig, Thomas E.] Mayo Clin, Dept Hematol, Rochester, MN USA.
[Ribatti, Domenico] Univ Bari, Dept Human Anat & Histol, Sch Med, Bari, Italy.
RP Ghobrial, IM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA.
EM irene_ghobrial@dfci.harvard.edu
RI Sacco, Antonio/K-4681-2016;
OI Sacco, Antonio/0000-0003-2945-9416; Roccaro, Aldo/0000-0002-1872-5128
FU Claudia Adams Barr Foundation (Boston, MA) [RO1 CA125690-01]; Italian
Association for Cancer Research (Milan, Italy); Doctors Cancer
Foundation (New Rochelle, NY)
FX This work was supported by in part by RO1 CA125690-01, Claudia Adams
Barr Foundation (Boston, MA); Italian Association for Cancer Research
(Milan, Italy); and The Doctors Cancer Foundation (New Rochelle, NY).
NR 53
TC 141
Z9 155
U1 2
U2 15
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 JUN 25
PY 2009
VL 113
IS 26
BP 6669
EP 6680
DI 10.1182/blood-2009-01-198408
PG 12
WC Hematology
SC Hematology
GA 468BY
UT WOS:000267789600027
PM 19401561
ER
PT J
AU Bongiovanni, M
Bloom, L
Krane, JF
Baloch, ZW
Powers, CN
Hintermann, S
Pache, JC
Faquin, WC
AF Bongiovanni, Massimo
Bloom, Leonard
Krane, Jeffrey F.
Baloch, Zubair W.
Powers, Celeste N.
Hintermann, Suzanne
Pache, Jean-Claude
Faquin, William C.
TI Cytomorphologic Features of Poorly Differentiated Thyroid Carcinoma A
Multi-Institutional Analysis of 40 Cases
SO CANCER CYTOPATHOLOGY
LA English
DT Article
DE fine-needle aspiration; thyroid; insular; poorly differentiated;
carcinoma
ID FINE-NEEDLE-ASPIRATION; INSULAR CARCINOMA; CYTOLOGIC FEATURES; INTACT
INSULAE; BIOPSY; GLAND; CYTOPATHOLOGY; STRUMA
AB BACKGROUND: Poorly differentiated thyroid carcinoma (PDTC) is an uncommon and aggressive malignancy. Despite the significant clinical implications of a diagnosis of PDTC, its cytomorphologic features have not been well defined. Statistical analysis was applied to a series of 40 PDTCs to identify a specific set of cytomorphologic features that characterized these tumors on fine-needle aspiration biopsy (FNAB). METHODS: In total, 40 thyroid FNABs that were highly diagnosed histologically as PDTC (19 insular carcinomas and 21 noninsular carcinomas) comprised the study group. A control group of 40 well differentiated thyroid neoplasms were selected for comparison. All FNABs were reviewed and scored for a series of 32 cytomorphologic features. The results were evaluated using univariate and stepwise logistic regression (SLR) analyses. RESULTS: In univariate analysis, 17 cytomorphologic features were identified that characterized the 40 PDTCs: insular, solid, or trabecular cytoarchitecture (P < .001); high cellularity (P = .007); necrosis (P = .025) or background debris (P = .025); plasmacytoid appearance (P = .0007); single cells (P < .0001); high nuclear/cytoplasmic ratio (P < .0001); scant cytoplasm (P = .03); nuclear atypia (P < .0001), including nuclear pleomorphism (P = .0052) and anisokaryosis (P < .0001); granular/coarse chromatin (P = .026); naked nuclei (P = .01); mitotic activity (P = .0001) and apoptosis (P < .0001); endothelial wrapping (P = .0053); and severe crowding (P < .0001). In logistic regression analysis, severe crowding (P = .0008) and cytoarchitecture (P < .0001) were identified as the most significant cytomorphologic features of PDTCs, and the combination of cytoarchitecture, severe crowding, single cells, and high nuclear/cytoplasmic ratio was the most predictive of PDTC. CONCLUSIONS: PDTCs have characteristic cytomorphologic features. By using logistic regression analysis, the features that were identified as the most predictive of PDTC were severe crowding, insular/solid/trabecular morphology, single cells, and high nuclear/cytoplasmic ratio. Cancer (Cancer Cytopathol) 2009;117:185-94. (C) 2009 American Cancer Society.
C1 [Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Bongiovanni, Massimo; Pache, Jean-Claude] Univ Hosp Geneva, Dept Pathol, Geneva, Switzerland.
[Bloom, Leonard] Univ Tennessee, Ctr Hlth Sci, Clin Sci Lab, Memphis, TN 38163 USA.
[Krane, Jeffrey F.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Baloch, Zubair W.] Univ Penn, Dept Pathol, Med Ctr, Philadelphia, PA 19104 USA.
[Powers, Celeste N.] Virginia Commonwealth Univ, Dept Pathol, Richmond, VA USA.
[Hintermann, Suzanne] Unilabs Cypa, Lausanne, Switzerland.
RP Faquin, WC (reprint author), Massachusetts Gen Hosp, Dept Pathol, WRN 219,55 Fruit St, Boston, MA 02114 USA.
EM wfaquin@partners.org
RI Bongiovanni, Massimo/C-3144-2017
OI Bongiovanni, Massimo/0000-0001-9846-6682
NR 30
TC 23
Z9 28
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1934-662X
EI 1934-6638
J9 CANCER CYTOPATHOL
JI Cancer Cytopathol.
PD JUN 25
PY 2009
VL 117
IS 3
BP 185
EP 194
DI 10.1002/cncy.20023
PG 10
WC Oncology; Pathology
SC Oncology; Pathology
GA 459IT
UT WOS:000267095900007
PM 19365842
ER
PT J
AU Shen, J
Brugge, WR
DiMaio, CJ
Pitman, MB
AF Shen, Jian
Brugge, William R.
DiMaio, Christopher J.
Pitman, Martha B.
TI Molecular Analysis of Pancreatic Cyst Fluid A Comparative Analysis With
Current Practice of Diagnosis
SO CANCER CYTOPATHOLOGY
LA English
DT Article
DE pancreatic neoplastic mucinous cysts; mucinous cystic neoplasm;
intraductal papillary mucinous neoplasm; k-ras gene; loss of
heterozygosity; molecular diagnosis; clinical consensus diagnosis
ID FINE-NEEDLE-ASPIRATION; PAPILLARY MUCINOUS NEOPLASMS; ETHANOL LAVAGE;
LESIONS; MANAGEMENT; CYTOLOGY; TUMORS; INJECTION; SAMPLES
AB BACKGROUND: The management of patients with pancreatic cysts is based on the preoperative distinction of nonmucinous and mucinous cysts in general and of benign and malignant cysts in particular. An accurate diagnosis is challenging, because endoscopic ultrasound (EUS) and cyst fluid analysis for carcinoembryonic antigen (CEA) and cytology have low sensitivity and specificity. Currently, molecular analysis is a commercially available test that promises an accurate diagnosis. The objective of the current study was to correlate a commercially provided molecular diagnosis (MDx) with a clinical consensus diagnosis (CCD) in the general categories of malignant, benign mucinous, and benign nonmucinous pancreatic cysts. METHODS: Pancreatic cysts that had aspirated fluid submitted for a commercially available molecular test (PathFinderTG) were reviewed. The CCD, defined by histology, malignant cytology, or 2 concordant tests (such as EUS, cytology, or CEA >= 192 ng/mL for mucinous cysts), was categorized as malignant, benign mucinous, or benign nonmucinous cyst in 35 patients. Their MDx, based on the PathFinderTG report, including analysis of k-ras mutation, loss of heterozygosity, and quantity/quality of DNA, also was classified as malignant, benign mucinous, or benign nonmucinous cyst. These 2 diagnoses were compared and correlated. RESULTS: The concordance between CCD and MDx was 5 of 6 (83%),13 of 15 (87%), and 13 of 14 (93%), respectively, for malignant, benign mucinous, and benign nonmucinous cysts, with an overall Cohen kappa statistic of 0.816. The sensitivity, specificity, and positive predictive value of the MDx were 83%, 100%, and 100%, respectively, for a malignant cyst and 86%, 93%, and 95%, respectively for a benign mucinous cyst. CONCLUSIONS: Molecular analysis of pancreatic cyst fluid adds diagnostic value to the preoperative diagnosis with high sensitivity, specificity, and positive predictive value for the diagnosis of malignant and benign mucinous pancreatic cysts. Cancer (Cancer Cytopathol) 2009;117:217-27. (C) 2009 American Cancer Society.
C1 [Pitman, Martha B.] Harvard Univ, Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Sch Med,Dept Pathol, Boston, MA 02114 USA.
[Brugge, William R.; DiMaio, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Dept Med, Sch Med, Boston, MA 02114 USA.
RP Pitman, MB (reprint author), Harvard Univ, Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Sch Med,Dept Pathol, 55 Fruit St, Boston, MA 02114 USA.
EM mpitman@partners.org
FU RedPath IP
FX This article was not supported financially by RedPath IP or any other
entity.
NR 29
TC 67
Z9 67
U1 0
U2 2
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1934-662X
J9 CANCER CYTOPATHOL
JI Cancer Cytopathol.
PD JUN 25
PY 2009
VL 117
IS 3
BP 217
EP 227
DI 10.1002/cncy.20027
PG 11
WC Oncology; Pathology
SC Oncology; Pathology
GA 459IT
UT WOS:000267095900011
PM 19415731
ER
PT J
AU Curran, SP
Wu, XY
Riedel, CG
Ruvkun, G
AF Curran, Sean P.
Wu, Xiaoyun
Riedel, Christian G.
Ruvkun, Gary
TI A soma-to-germline transformation in long-lived Caenorhabditis elegans
mutants
SO NATURE
LA English
DT Article
ID OXIDATIVE-STRESS-RESPONSE; GENOME-WIDE RNAI; C-ELEGANS; LIFE-SPAN;
POSTMITOTIC CELLS; GENE-EXPRESSION; FACTOR SKN-1; DNA-DAMAGE; DAF-16;
IDENTIFICATION
AB Unlike the soma, which ages during the lifespan of multicellular organisms, the germ line traces an essentially immortal lineage. Genomic instability in somatic cells increases with age, and this decline in somatic maintenance might be regulated to facilitate resource reallocation towards reproduction at the expense of cellular senescence. Here we show that Caenorhabditis elegans mutants with increased longevity exhibit a soma-to-germline transformation of gene expression programs normally limited to the germ line. Decreased insulin-like signalling causes the somatic misexpression of the germline-limited pie-1 and pgl family of genes in intestinal and ectodermal tissues. The forkhead boxO1A (FOXO) transcription factor DAF-16, the major transcriptional effector of insulin-like signalling, regulates pie-1 expression by directly binding to the pie-1 promoter. The somatic tissues of insulin-like mutants are more germline-like and protected from genotoxic stress. Gene inactivation of components of the cytosolic chaperonin complex that induce increased longevity also causes somatic misexpression of PGL-1. These results indicate that the acquisition of germline characteristics by the somatic cells of C. elegans mutants with increased longevity contributes to their increased health and survival.
C1 [Curran, Sean P.; Wu, Xiaoyun; Riedel, Christian G.; Ruvkun, Gary] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Curran, Sean P.; Wu, Xiaoyun; Riedel, Christian G.; Ruvkun, Gary] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA.
RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
EM ruvkun@molbio.mgh.harvard.edu
OI Riedel, Christian/0000-0002-3689-8022
FU National Institutes of Health; National Institute on Aging
[F32-AG026207, R01-AG016636]; European Molecular Biology Organization;
Human Frontier Science Program
FX Some strains were provided by the Caenorhabditis Genetics Center, which
is funded by the National Institutes of Health National Center for
Research Resources. We thank A. Conery, H. Gabel, J. Melo, E. O'Rourke,
D. Simon, A. Soukas and M. Wang for reagents, discussion and reading of
the manuscript; G. Seydoux and members of the Ruvkun, Ausubel and Kaplan
laboratories for discussion; S. Strome for the pie-1p::gfp::pgl-1 strain
and C. Mello for monoclonal antisera against PGL-1, S. S. Lee, S. Ercan
and the Kingston laboratory for technical advice on ChIP. This work was
supported by grants from the National Institutes of Health and the
National Institute on Aging F32-AG026207 to S. P. C. and R01-AG016636 to
G. R. and the European Molecular Biology Organization and the Human
Frontier Science Program to C. G. R.
NR 49
TC 68
Z9 92
U1 1
U2 17
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 25
PY 2009
VL 459
IS 7250
BP 1079
EP U60
DI 10.1038/nature08106
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 466BX
UT WOS:000267636700033
PM 19506556
ER
PT J
AU Scott, KL
Kabbarah, O
Liang, MC
Ivanova, E
Anagnostou, V
Wu, J
Dhakal, S
Wu, M
Chen, SJ
Feinberg, T
Huang, J
Saci, A
Widlund, HR
Fisher, DE
Xiao, YH
Rimm, DL
Protopopov, A
Wong, KK
Chin, L
AF Scott, Kenneth L.
Kabbarah, Omar
Liang, Mei-Chih
Ivanova, Elena
Anagnostou, Valsamo
Wu, Joyce
Dhakal, Sabin
Wu, Min
Chen, Shujuan
Feinberg, Tamar
Huang, Joseph
Saci, Abdel
Widlund, Hans R.
Fisher, David E.
Xiao, Yonghong
Rimm, David L.
Protopopov, Alexei
Wong, Kwok-Kin
Chin, Lynda
TI GOLPH3 modulates mTOR signalling and rapamycin sensitivity in cancer
SO NATURE
LA English
DT Article
ID P70 S6 KINASE; CELL-SIZE; GOLGI; TARGET; GROWTH; TOR;
GLYCOSYLTRANSFERASES; PHOSPHORYLATION; LOCALIZATION; PROGRESSION
AB Genome-wide copy number analyses of human cancers identified a frequent 5p13 amplification in several solid tumour types, including lung (56%), ovarian (38%), breast (32%), prostate (37%) and melanoma ( 32%). Here, using integrative analysis of a genomic profile of the region, we identify a Golgi protein, GOLPH3, as a candidate targeted for amplification. Gain- and loss-of-function studies in vitro and in vivo validated GOLPH3 as a potent oncogene. Physically, GOLPH3 localizes to the trans- Golgi network and interacts with components of the retromer complex, which in yeast has been linked to target of rapamycin ( TOR) signalling. Mechanistically, GOLPH3 regulates cell size, enhances growth-factor-induced mTOR (also known as FRAP1) signalling in human cancer cells, and alters the response to an mTOR inhibitor in vivo. Thus, genomic and genetic, biological, functional and biochemical data in yeast and humans establishes GOLPH3 as a new oncogene that is commonly targeted for amplification in human cancer, and is capable of modulating the response to rapamycin, a cancer drug in clinical use.
C1 [Scott, Kenneth L.; Kabbarah, Omar; Liang, Mei-Chih; Wu, Joyce; Dhakal, Sabin; Wu, Min; Chen, Shujuan; Feinberg, Tamar; Huang, Joseph; Wong, Kwok-Kin; Chin, Lynda] Harvard Univ, Ctr Canc, Dept Med Oncol, Boston, MA 02115 USA.
[Ivanova, Elena; Xiao, Yonghong; Protopopov, Alexei; Chin, Lynda] Harvard Univ, Ctr Canc, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA.
[Widlund, Hans R.; Fisher, David E.] Harvard Univ, Ctr Canc, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Wong, Kwok-Kin] Harvard Univ, Ctr Canc, Ludwig Ctr Dana Farber, Boston, MA 02115 USA.
[Anagnostou, Valsamo; Rimm, David L.] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA.
[Saci, Abdel] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
[Widlund, Hans R.; Chin, Lynda] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA.
[Fisher, David E.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA.
RP Chin, L (reprint author), Harvard Univ, Ctr Canc, Dept Med Oncol, Boston, MA 02115 USA.
EM lynda_chin@dfci.harvard.edu
OI wong, kwok kin/0000-0001-6323-235X
FU American Cancer Society [PF-07-039-01-CSM]; National Institutes of
Health (NIH) [5-T32-AR07098-31, R01 AG2400401, R01 CA122794, RO-1 CA
114277, RO1 CA93947, P50 CA93683]; Program of Research Excellence
(SPORE) grant [P50 CA090578]
FX We thank R. DePinho for critical reading of the manuscript, and L.
Cantley, as well as members of the Chin laboratory, for helpful
discussion. We thank H. Ying for assistance with confocal microscopy.
The rabbit polyclonal antibody against human GOLPH3 was kindly provided
by J. J. Bergeron of McGill University. Mouse monoclonal antibody
against human GOLPH3, C19, was generated at the Dana-Farber/Harvard
Cancer Center Monoclonal Antibody Core Facility. K. L. S. is at present
supported by a Postdoctoral Fellowship from the American Cancer Society
(PF-07-039-01-CSM), and K. L. S. and O. K. were previously supported by
a National Institutes of Health (NIH) Training Grant appointment in the
Department of Dermatology at Brigham and Women's Hospital
(5-T32-AR07098-31). K.-K. W. was supported by a Program of Research
Excellence (SPORE) grant (P50 CA090578) and NIH grants (R01 AG2400401;
R01 CA122794). The AQUA immunofluorescence study was supported by a
grant from the NIH to D. L. R. (RO-1 CA 114277). This work is primarily
supported by grants from the NIH to L. C. (RO1 CA93947; P50 CA93683).
NR 33
TC 146
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U1 1
U2 19
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 25
PY 2009
VL 459
IS 7250
BP 1085
EP U68
DI 10.1038/nature08109
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 466BX
UT WOS:000267636700034
PM 19553991
ER
PT J
AU Baek, KH
Zaslavsky, A
Lynch, RC
Britt, C
Okada, Y
Siarey, RJ
Lensch, MW
Park, IH
Yoon, SS
Minami, T
Korenberg, JR
Folkman, J
Daley, GQ
Aird, WC
Galdzicki, Z
Ryeom, S
AF Baek, Kwan-Hyuck
Zaslavsky, Alexander
Lynch, Ryan C.
Britt, Carmella
Okada, Yoshiaki
Siarey, Richard J.
Lensch, M. William
Park, In-Hyun
Yoon, Sam S.
Minami, Takashi
Korenberg, Julie R.
Folkman, Judah
Daley, George Q.
Aird, William C.
Galdzicki, Zygmunt
Ryeom, Sandra
TI Down's syndrome suppression of tumour growth and the role of the
calcineurin inhibitor DSCR1
SO NATURE
LA English
DT Article
ID CRITICAL REGION; ENDOTHELIAL-CELLS; GENE-EXPRESSION; CYCLOSPORINE-A;
MOUSE MODEL; ANGIOGENESIS; VEGF; TARGET; CHROMOSOME-21; REGRESSION
AB The incidence of many cancer types is significantly reduced in individuals with Down's syndrome(1-4), and it is thought that this broad cancer protection is conferred by the increased expression of one or more of the 231 supernumerary genes on the extra copy of chromosome 21. One such gene is Down's syndrome candidate region-1 (DSCR1, also known as RCAN1), which encodes a protein that suppresses vascular endothelial growth factor ( VEGF)mediated angiogenic signalling by the calcineurin pathway(5-10). Here we show that DSCR1 is increased in Down's syndrome tissues and in a mouse model of Down's syndrome. Furthermore, we show that the modest increase in expression afforded by a single extra transgenic copy of Dscr1 is sufficient to confer significant suppression of tumour growth in mice, and that such resistance is a consequence of a deficit in tumour angiogenesis arising from suppression of the calcineurin pathway. We also provide evidence that attenuation of calcineurin activity by DSCR1, together with another chromosome 21 gene Dyrk1a, may be sufficient to markedly diminish angiogenesis. These data provide a mechanism for the reduced cancer incidence in Down's syndrome and identify the calcineurin signalling pathway, and its regulators DSCR1 and DYRK1A, as potential therapeutic targets in cancers arising in all individuals.
C1 [Baek, Kwan-Hyuck; Zaslavsky, Alexander; Lynch, Ryan C.; Britt, Carmella; Folkman, Judah; Ryeom, Sandra] Childrens Hosp Boston, Dept Surg, Vasc Biol Program, Boston, MA 02115 USA.
[Okada, Yoshiaki; Aird, William C.] Beth Israel Deaconess Med Ctr, Div Mol & Vasc Med, Vasc Biol Res Ctr, Boston, MA 02115 USA.
[Siarey, Richard J.; Galdzicki, Zygmunt] Uniformed Serv Univ Hlth Serv, Sch Med, Mol & Cellular Biol Program, Dept Anat Physiol & Genet Neurosci, Bethesda, MD 20814 USA.
[Lensch, M. William; Park, In-Hyun; Daley, George Q.] Childrens Hosp Boston, Div Pediat Hematol Oncol, Dept Med, Boston, MA 02115 USA.
[Lensch, M. William; Park, In-Hyun; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Yoon, Sam S.] Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, Boston, MA 02114 USA.
[Minami, Takashi] Univ Tokyo, Adv Sci & Technol Res Ctr, Tokyo 1538904, Japan.
[Korenberg, Julie R.] Univ Utah, Inst Brain, Salt Lake City, UT 84108 USA.
[Korenberg, Julie R.] Univ Utah, Dept Pediat, Salt Lake City, UT 84108 USA.
RP Ryeom, S (reprint author), Childrens Hosp Boston, Dept Surg, Vasc Biol Program, Boston, MA 02115 USA.
EM sandra.ryeom@childrens.harvard.edu
FU Howard Hughes Medical Institute; Harvard Stem Cell Institute; National
Institute of Health Director's Pioneer Award; NHLBI; Jerome Lejeune
Foundation; USUHS; Smith Family Medical Foundation; Garrett B. Smith
Foundation; Annie's Fun Foundation
FX We thank G. Evan, C. Kim, K. Cichowski and J. Italiano for critical
discussions and advice. This work was supported by the Howard Hughes
Medical Institute ( G. Q. D.), Harvard Stem Cell Institute ( G. Q. D.),
the National Institute of Health Director's Pioneer Award ( G. Q. D.),
NHLBI ( W. C. A.), Jerome Lejeune Foundation ( Z. G.), USUHS ( Z. G.),
the Smith Family Medical Foundation ( S. R.), the Garrett B. Smith
Foundation ( S. R.) and Annie's Fun Foundation ( S. R.).
NR 30
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U1 0
U2 38
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 25
PY 2009
VL 459
IS 7250
BP 1126
EP U113
DI 10.1038/nature08062
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 466BX
UT WOS:000267636700043
PM 19458618
ER
PT J
AU Adamo, L
Naveiras, O
Wenzel, PL
McKinney-Freeman, S
Mack, PJ
Gracia-Sancho, J
Suchy-Dicey, A
Yoshimoto, M
Lensch, MW
Yoder, MC
Garcia-Cardena, G
Daley, GQ
AF Adamo, Luigi
Naveiras, Olaia
Wenzel, Pamela L.
McKinney-Freeman, Shannon
Mack, Peter J.
Gracia-Sancho, Jorge
Suchy-Dicey, Astrid
Yoshimoto, Momoko
Lensch, M. William
Yoder, Mervin C.
Garcia-Cardena, Guillermo
Daley, George Q.
TI Biomechanical forces promote embryonic haematopoiesis
SO NATURE
LA English
DT Article
ID NITRIC-OXIDE SYNTHASE; STEM-CELLS; MOUSE EMBRYO; DEFINITIVE
HEMATOPOIESIS; IN-VITRO; YOLK-SAC; EXPRESSION DEFINES;
ENDOTHELIAL-CELLS; PROGENITOR CELLS; FLOW
AB Biomechanical forces are emerging as critical regulators of embryogenesis, particularly in the developing cardiovascular system(1,2). After initiation of the heartbeat in vertebrates, cells lining the ventral aspect of the dorsal aorta, the placental vessels, and the umbilical and vitelline arteries initiate expression of the transcription factor Runx1 (refs 3-5), a master regulator of haematopoiesis, and give rise to haematopoietic cells(4). It remains unknown whether the biomechanical forces imposed on the vascular wall at this developmental stage act as a determinant of haematopoietic potential(6). Here, using mouse embryonic stem cells differentiated in vitro, we show that fluid shear stress increases the expression of Runx1 in CD41(+)c-Kit(+) haematopoietic progenitor cells(7), concomitantly augmenting their haematopoietic colony-forming potential. Moreover, we find that shear stress increases haematopoietic colony-forming potential and expression of haematopoietic markers in the para-aortic splanchnopleura/aorta-gonads-mesonephros of mouse embryos and that abrogation of nitric oxide, a mediator of shear-stress-induced signalling(8), compromises haematopoietic potential in vitro and in vivo. Collectively, these data reveal a critical role for biomechanical forces in haematopoietic development.
C1 [Naveiras, Olaia; Wenzel, Pamela L.; McKinney-Freeman, Shannon; Lensch, M. William; Daley, George Q.] Childrens Hosp Boston, Div Pediat Hematol Oncol, Stem Cell Transplantat Program, Boston, MA 02115 USA.
[Adamo, Luigi; Mack, Peter J.; Gracia-Sancho, Jorge; Suchy-Dicey, Astrid; Garcia-Cardena, Guillermo] Brigham & Womens Hosp, Dept Pathol, Ctr Excellence Vasc Biol, Boston, MA 02115 USA.
[Naveiras, Olaia; Wenzel, Pamela L.; McKinney-Freeman, Shannon; Lensch, M. William; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Naveiras, Olaia; Wenzel, Pamela L.; McKinney-Freeman, Shannon; Lensch, M. William; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Naveiras, Olaia; Wenzel, Pamela L.; McKinney-Freeman, Shannon; Lensch, M. William; Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA.
[Naveiras, Olaia; Wenzel, Pamela L.; McKinney-Freeman, Shannon; Lensch, M. William; Daley, George Q.] Harvard Univ, Stem Cell Inst, Boston, MA 02115 USA.
[Naveiras, Olaia; Wenzel, Pamela L.; McKinney-Freeman, Shannon; Lensch, M. William; Daley, George Q.] Manton Ctr Orphan Dis Res, Boston, MA 02115 USA.
[Naveiras, Olaia; Wenzel, Pamela L.; McKinney-Freeman, Shannon; Lensch, M. William; Daley, George Q.] Howard Hughes Med Inst, Boston, MA 02115 USA.
[Yoshimoto, Momoko; Yoder, Mervin C.] Indiana Univ, Sch Med, Dept Pediat, Indianapolis, IN 46202 USA.
RP Daley, GQ (reprint author), Childrens Hosp Boston, Div Pediat Hematol Oncol, Stem Cell Transplantat Program, Boston, MA 02115 USA.
EM guillermo_garcia-cardena@hms.harvard.edu;
george.daley@childrens.harvard.edu
RI Wenzel, Pamela/A-2992-2010; Gracia-Sancho, Jordi/C-8920-2014; Yoshimoto,
Momoko/N-4238-2014;
OI Gracia-Sancho, Jordi/0000-0001-7736-4089; Yoshimoto,
Momoko/0000-0002-7272-6682; Suchy-Dicey, Astrid/0000-0002-5608-7817
FU Giovanni Armenise- Harvard Foundation; Barrie de la Maza Foundation;
National Institutes of Health; NIH Director's Pioneer Award of the NIH
Roadmap for Medical Research; Burroughs Wellcome Fund Clinical Scientist
Award; Howard Hughes Medical Institute
FX We thank G. Losyev for assistance with flow cytometry, S. Schmitt for
critical help in optimizing AGM culture conditions, C. Lengerke and Y.
Mukouyama for critical discussions. L. A. was partially funded by the
Giovanni Armenise- Harvard Foundation. O. N. was partially funded by the
Barrie de la Maza Foundation. G. G.-C. was supported by grants from the
National Institutes of Health and G. Q. D was supported by grants from
the National Institutes of Health ( NIH), and the NIH Director's Pioneer
Award of the NIH Roadmap for Medical Research. G. Q. D. is a recipient
of the Burroughs Wellcome Fund Clinical Scientist Award in Translational
Research and is an Investigator of the Howard Hughes Medical Institute.
NR 33
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U1 3
U2 39
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 25
PY 2009
VL 459
IS 7250
BP 1131
EP U120
DI 10.1038/nature08073
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 466BX
UT WOS:000267636700044
PM 19440194
ER
PT J
AU Avram, MM
Hoang, M
AF Avram, Mathew M.
Hoang, Mai
TI A Woman with a Blistering Cutaneous Eruption Acute generalized
exanthematous pustulosis due to hydroxychloroquine
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID EUROSCAR; AGEP
C1 [Avram, Mathew M.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA.
[Hoang, Mai] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Avram, Mathew M.] Harvard Univ, Sch Med, Dept Dermatol, Cambridge, MA 02138 USA.
[Hoang, Mai] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA.
RP Avram, MM (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA.
NR 13
TC 2
Z9 2
U1 0
U2 2
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUN 25
PY 2009
VL 360
IS 26
BP 2771
EP 2777
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 461RC
UT WOS:000267286600013
PM 19553651
ER
PT J
AU Cheng, S
Keyes, MJ
Larson, MG
McCabe, EL
Newton-Cheh, C
Levy, D
Benjamin, EJ
Vasan, RS
Wang, TJ
AF Cheng, Susan
Keyes, Michelle J.
Larson, Martin G.
McCabe, Elizabeth L.
Newton-Cheh, Christopher
Levy, Daniel
Benjamin, Emelia J.
Vasan, Ramachandran S.
Wang, Thomas J.
TI Long-term Outcomes in Individuals With Prolonged PR Interval or
First-Degree Atrioventricular Block
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID CORONARY HEART-DISEASE; ATRIAL-FIBRILLATION; RISK-FACTORS;
NATURAL-HISTORY; WAVE DURATION; CONDUCTION; REGURGITATION; POPULATION;
PROGNOSIS; FEATURES
AB Context Prolongation of the electrocardiographic PR interval, known as first-degree atrioventricular block when the PR interval exceeds 200 milliseconds, is frequently encountered in clinical practice.
Objective To determine the clinical significance of PR prolongation in ambulatory individuals.
Design, Setting, and Participants Prospective, community-based cohort including 7575 individuals from the Framingham Heart Study (mean age, 47 years; 54% women) who underwent routine 12-lead electrocardiography. The study cohort underwent prospective follow-up through 2007 from baseline examinations in 1968-1974. Multivariable-adjusted Cox proportional hazards models were used to examine the associations of PR interval with the incidence of arrhythmic events and death.
Main Outcome Measures Incident atrial fibrillation (AF), pacemaker implantation, and all-cause mortality.
Results During follow-up, 481 participants developed AF, 124 required pacemaker implantation, and 1739 died. At the baseline examination, 124 individuals had PR intervals longer than 200 milliseconds. For those with PR intervals longer than 200 milliseconds compared with those with PR intervals of 200 milliseconds or shorter, incidence rates per 10 000 person-years were 140 (95% confidence interval [CI], 95-208) vs 36 (95% CI, 32-39) for AF, 59 (95% CI, 40-87) vs 6 (95% CI, 5-7) for pacemaker implantation, and 334 (95% CI, 260-428) vs 129 (95% CI, 123-135) for all-cause mortality. Corresponding absolute risk increases were 1.04% (AF), 0.53% (pacemaker implantation), and 2.05% (all-cause mortality) per year. In multivariable analyses, each 20-millisecond increment in PR was associated with an adjusted hazard ratio (HR) of 1.11 (95% CI, 1.02-1.22; P = .02) for AF, 1.22 (95% CI, 1.14-1.30; P < .001) for pacemaker implantation, and 1.08 (95% CI, 1.02-1.13; P = .005) for all-cause mortality. Individuals with first-degree atrioventricular block had a 2-fold adjusted risk of AF (HR, 2.06; 95% CI, 1.36-3.12; P < .001), 3-fold adjusted risk of pacemaker implantation (HR, 2.89; 95% CI, 1.83-4.57; P < .001), and 1.4-fold adjusted risk of all-cause mortality (HR, 1.44, 95% CI, 1.09-1.91; P = .01).
Conclusion Prolongation of the PR interval is associated with increased risks of AF, pacemaker implantation, and all-cause mortality. JAMA. 2009; 301(24):2571-2577
C1 [Cheng, Susan; McCabe, Elizabeth L.; Newton-Cheh, Christopher; Wang, Thomas J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Cheng, Susan; Keyes, Michelle J.; Larson, Martin G.; McCabe, Elizabeth L.; Newton-Cheh, Christopher; Levy, Daniel; Benjamin, Emelia J.; Vasan, Ramachandran S.; Wang, Thomas J.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
[Newton-Cheh, Christopher] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Cheng, Susan] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc Med,Dept Med, Boston, MA 02114 USA.
[Cheng, Susan] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Clin Investigator Training Program, Boston, MA 02114 USA.
[Keyes, Michelle J.; Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Newton-Cheh, Christopher] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.
[Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA.
[Levy, Daniel; Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Sect Prevent Med, Boston, MA 02118 USA.
[Levy, Daniel; Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
RP Wang, TJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, GRB 800,55 Fruit St, Boston, MA 02114 USA.
EM tjwang@partners.org
OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin,
Emelia/0000-0003-4076-2336
FU National Institutes of Health [N01-HC-25195]; [K24-HL-04334]
FX Funding/Support: The Framingham Heart Study is funded by National
Institutes of Health contract N01-HC-25195. Dr Vasan was supported in
part by grant K24-HL-04334.
NR 37
TC 197
Z9 202
U1 1
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 JUN 24
PY 2009
VL 301
IS 24
BP 2571
EP 2577
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 461KU
UT WOS:000267266500022
PM 19549974
ER
PT J
AU Strenzke, N
Chanda, S
Kopp-Scheinpflug, C
Khimich, D
Reim, K
Bulankina, AV
Neef, A
Wolf, F
Brose, N
Xu-Friedman, MA
Moser, T
AF Strenzke, Nicola
Chanda, Soham
Kopp-Scheinpflug, Cornelia
Khimich, Darina
Reim, Kerstin
Bulankina, Anna V.
Neef, Andreas
Wolf, Fred
Brose, Nils
Xu-Friedman, Matthew A.
Moser, Tobias
TI Complexin-I Is Required for High-Fidelity Transmission at the Endbulb of
Held Auditory Synapse
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID ANTEROVENTRAL COCHLEAR NUCLEUS; RETINAL RIBBON SYNAPSES;
NEUROTRANSMITTER RELEASE; HAIR-CELLS; HEARING-LOSS; TRANSMITTER RELEASE;
RECIPROCAL SYNAPSES; MEMBRANE-FUSION; NERVE FIBERS; SNARE
AB Complexins (CPXs I-IV) presumably act as regulators of the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complex, but their function in the intact mammalian nervous system is not well established. Here, we explored the role of CPXs in the mouse auditory system. Hearing was impaired in CPXI knock-out mice but normal in knock-out mice for CPXs II, III, IV, and III/IV as measured by auditory brainstem responses. Complexins were not detectable in cochlear hair cells but CPX I was expressed in spiral ganglion neurons (SGNs) that give rise to the auditory nerve. Ca(2+)-dependent exocytosis of inner hair cells and sound encoding by SGNs were unaffected in CPX I knock-out mice. In the absence of CPX I, the resting release probability in the endbulb of Held synapses of the auditory nerve fibers with bushy cells in the cochlear nucleus was reduced. As predicted by computational modeling, bushy cells had decreased spike rates at sound onset as well as longer and more variable first spike latencies explaining the abnormal auditory brainstem responses. In addition, we found synaptic transmission to outlast the stimulus at many endbulb of Held synapses in vitro and in vivo, suggesting impaired synchronization of release to stimulus offset. Although sound encoding in the cochlea proceeds in the absence of complexins, CPX I is required for faithful processing of sound onset and offset in the cochlear nucleus.
C1 [Strenzke, Nicola; Khimich, Darina; Bulankina, Anna V.; Moser, Tobias] Univ Gottingen, Sch Med, InnerEarLab, Dept Otolaryngol, D-37099 Gottingen, Germany.
[Strenzke, Nicola] Harvard Univ, Eaton Peabody Lab, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
[Chanda, Soham; Xu-Friedman, Matthew A.] SUNY Buffalo, Dept Biol Sci, Buffalo, NY 14260 USA.
[Kopp-Scheinpflug, Cornelia] Univ Leipzig, Inst Zool, D-04103 Leipzig, Germany.
[Reim, Kerstin; Brose, Nils] Max Planck Inst Expt Med, Dept Mol Neurobiol, D-37075 Gottingen, Germany.
[Reim, Kerstin; Brose, Nils] Max Planck Inst Expt Med, Ctr Mol Physiol Brain, D-37075 Gottingen, Germany.
[Neef, Andreas; Wolf, Fred; Moser, Tobias] Univ Gottingen, Bernstein Ctr Computat Neurosci, D-37073 Gottingen, Germany.
[Wolf, Fred] Max Planck Inst Dynam & Self Org, D-37073 Gottingen, Germany.
RP Moser, T (reprint author), Univ Gottingen, Sch Med, InnerEarLab, Dept Otolaryngol, D-37099 Gottingen, Germany.
EM brose@em.mpg.de; tmoser@gwdg.de
RI Wolf, Fred/D-5771-2011; Moser, Tobias/L-5068-2014
OI Wolf, Fred/0000-0002-7068-3762; Moser, Tobias/0000-0001-7145-0533
FU Max Planck Society; German Federal Ministry of Education and Research
[01GQ0433]; German Research Foundation [FZT-103]; European Council;
National Institutes of Health [DC008125]; Bernstein Center for
Computational Neuroscience Gottingen
FX This work was supported by a Max Planck Society Tandem-Project grant
(N.B., T. M.); the German Federal Ministry of Education and Research
[Bernstein Center Grant 01GQ0433 (T. M.)]; the German Research
Foundation [ fellowship (N.S.); Center for Molecular Physiology of the
Brain Grant FZT-103 (N.B., T. M.); a grant to Dr. R. Rubsamen,
University of Leipzig, Leipzig, Germany (supporting C. K.-S.)]; a
European Council Eurohear grant (T. M.); and National Institutes of
Health Grant DC008125 (M. A. X.-F.). A.N. is a Fellow of the Bernstein
Center for Computational Neuroscience Gottingen. We thank M. C. Liberman
for ample mentoring concering auditory nerve fiber recordings and A.
Gehrt, M. Koppler, M. Degenhardt, and C. Rudiger for expert technical
assistance. This study was designed by T. M. and N.B. with contributions
of N. S., M. A. X.-F., D. K., C. K.-S., and K. R. The experimental work
was performed by N. S., D. K., K. R., C. K.-S., A. V. B., and S. C. A.
N. performed the computational modeling, collaborating with M. A. X.-F.
T. M., N. S., D. K., M. A. X.-F., C. K.-S., A. N., and N. B. prepared
this manuscript.
NR 52
TC 54
Z9 54
U1 0
U2 5
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 JUN 24
PY 2009
VL 29
IS 25
BP 7991
EP 8004
DI 10.1523/JNEUROSCI.0632-09.2009
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA 462GL
UT WOS:000267339000006
PM 19553439
ER
PT J
AU Scalapino, KJ
Daikh, DI
AF Scalapino, Kenneth J.
Daikh, David I.
TI Suppression of Glomerulonephritis in NZB/NZW Lupus Prone Mice by
Adoptive Transfer of Ex Vivo Expanded Regulatory T Cells
SO PLOS ONE
LA English
DT Article
AB Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown cause characterized by expansion of autoreactive lymphocytes. Regulatory T cells (T(regs)) are a component of the normal immune system and contribute to the maintenance of peripheral tolerance. T(reg) abnormalities have been associated with several autoimmune diseases and there is interest in the role of T(regs) in SLE. We previously demonstrated that transfer of expanded CD4(+)CD25(+)CD62L(HI) T(regs) slows the development of lupus in (NZBxNZW)F(1) (B/W) mice. However in the absence of T(reg) specific surface antigens, cell purification remains a compromise between the breadth and purity of the population isolated. Importantly, purified populations always contain Foxp3(-) effector T cells (T(effs)) that theoretically could exacerbate autoimmunity in the recipient. Here we explore the impact of transferring the more comprehensive, but less pure T(reg) subset defined by CD4(+)CD25(+) expression on development of murine lupus. All cells were FACS sorted and expanded prior to adoptive transfer. Development of proteinuria and survival were measured. We found that exogenous expansion of CD4(+)CD25(+) cells produced a population containing 70-85% CD4(+)Foxp3(+) T(regs). Expanded T(regs) had higher CTLA-4 and Foxp3 expression, increased in vitro suppression capacity, and prolonged in vivo survival as compared to freshly isolated cells. Adoptive transfer of expanded CD4(+)CD25(+) T(regs) inhibited the onset of glomerulonephritis and prolonged survival in mice. Importantly the population of T(eff) contained within the adoptively transferred cells had reduced survival and proliferation capacity as compared to either co-transferred T(regs) or transferred T(effs) expanded in the absence of T(regs). These studies demonstrate that adoptive transfer of expanded CD4(+)CD25(+)Foxp3(+) T(regs) has the capacity to inhibit the onset of murine lupus and that this capacity is significant despite transfer of co-cultured T(eff) cells. These data indicate that when co-expanded with regulatory T cells, exogenously activated T(effs) from autoimmune patients may not pose a significant risk of promoting disease.
RP Scalapino, KJ (reprint author), San Francisco VA Med Ctr, Arthrit Sect, San Francisco, CA USA.
EM daikh@itsa.ucsf.edu
NR 36
TC 21
Z9 23
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 24
PY 2009
VL 4
IS 6
AR e6031
DI 10.1371/journal.pone.0006031
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 462MF
UT WOS:000267356500015
PM 19551149
ER
PT J
AU Rigotti, NA
AF Rigotti, Nancy A.
TI Helping smokers with cardiac disease to abstain from tobacco after a
stay in hospital
SO CANADIAN MEDICAL ASSOCIATION JOURNAL
LA English
DT Editorial Material
ID SMOKING-CESSATION; MYOCARDIAL-INFARCTION; INTERVENTION; MORTALITY
C1 [Rigotti, Nancy A.] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA.
[Rigotti, Nancy A.] Harvard Univ, Sch Med, Boston, MA USA.
RP Rigotti, NA (reprint author), Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, 50 Staniford St,9th Fl, Boston, MA 02114 USA.
EM nrigotti@partners.org
NR 11
TC 10
Z9 10
U1 0
U2 2
PU CMA-CANADIAN MEDICAL ASSOC
PI OTTAWA
PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 3Y6, CANADA
SN 0820-3946
J9 CAN MED ASSOC J
JI Can. Med. Assoc. J.
PD JUN 23
PY 2009
VL 180
IS 13
BP 1283
EP 1284
DI 10.1503/cmaj.090729
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 458IH
UT WOS:000267010200002
PM 19546446
ER
PT J
AU Lee, DS
Gona, P
Vasan, RS
Larson, MG
Benjamin, EJ
Wang, TJ
Tu, JV
Levy, D
AF Lee, Douglas S.
Gona, Philimon
Vasan, Ramachandran S.
Larson, Martin G.
Benjamin, Emelia J.
Wang, Thomas J.
Tu, Jack V.
Levy, Daniel
TI Relation of Disease Pathogenesis and Risk Factors to Heart Failure With
Preserved or Reduced Ejection Fraction Insights From the Framingham
Heart Study of the National Heart, Lung, and Blood Institute
SO CIRCULATION
LA English
DT Article
DE coronary disease; epidemiology; heart diseases; heart failure;
hypertension; mortality; ventricles
ID VENTRICULAR SYSTOLIC FUNCTION; CLINICAL DETERMINANTS; QRS DURATION;
MORTALITY; POPULATION; CARDIOMYOPATHY; DYSFUNCTION; PREVALENCE;
SURVIVAL; SPECTRUM
AB Background-The contributions of risk factors and disease pathogenesis to heart failure with preserved ejection fraction (HFPEF) versus heart failure with reduced ejection fraction (HFREF) have not been fully explored.
Methods and Results-We examined clinical characteristics and risk factors at time of heart failure onset and long-term survival in Framingham Heart Study participants according to left ventricular ejection fraction <= 45% (n = 314; 59%) versus >45% (n = 220; 41%) and hierarchical causal classification. Heart failure was attributed to coronary heart disease in 278 participants (52%), valvular heart disease in 42 (8%), hypertension in 140 (26%), or other/unknown causes in 74 (14%). Multivariable predictors of HFPEF (versus HFREF) included elevated systolic blood pressure (odds ratio [OR] = 1.13 per 10 mm Hg; 95% confidence interval [CI], 1.04 to 1.22), atrial fibrillation (OR = 4.23; 95% CI, 2.38 to 7.52), and female sex (OR = 2.29; 95% CI, 1.35 to 3.90). Conversely, prior myocardial infarction (OR = 0.32; 95% CI, 0.19 to 0.53) and left bundle-branch block QRS morphology (OR = 0.21; 95% CI, 0.10 to 0.46) reduced the odds of HFPEF. Long-term prognosis was grim, with a median survival of 2.1 years (5-year mortality rate, 74%), and was equally poor in men and women with HFREF or HFPEF.
Conclusions-Among community patients with new-onset heart failure, there are differences in causes and time-of-onset clinical characteristics between those with HFPEF versus HFREF. In people with HFREF, mortality is increased when coronary heart disease is the underlying cause. These findings suggest that heart failure with reduced left ventricular systolic function and heart failure with preserved left ventricular systolic function are partially distinct entities, with potentially different approaches to early detection and prevention. (Circulation. 2009; 119: 3070-3077.)
C1 [Gona, Philimon; Vasan, Ramachandran S.; Larson, Martin G.; Benjamin, Emelia J.; Wang, Thomas J.; Levy, Daniel] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[Lee, Douglas S.; Tu, Jack V.] Inst Clin Evaluat Sci, Toronto, ON, Canada.
[Lee, Douglas S.] Univ Toronto, Univ Hlth Network, Toronto, ON, Canada.
[Gona, Philimon; Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Prevent Med & Epidemiol, Boston, MA 02118 USA.
[Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA.
[Tu, Jack V.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Toronto, ON, Canada.
[Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA.
RP Levy, D (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.
EM levyd@nih.gov
RI Lee, Douglas/J-4315-2014;
OI Larson, Martin/0000-0002-9631-1254; Tu, Jack/0000-0003-0111-722X;
Ramachandran, Vasan/0000-0001-7357-5970; Benjamin,
Emelia/0000-0003-4076-2336
FU National Institutes of Health [N01-HL-25195]; Canadian Institutes of
Health Research Operating Grant [MOP 86718]; Team Grant; Canadian
Institutes of Health Research clinician-scientist award; Canada Research
Chair in Health Services Research; National Heart, Lung, and Blood
Institute [2K24 H-04334]
FX This study was supported by National Institutes of Health contract
N01-HL-25195 to the Framingham Heart Study, a Canadian Institutes of
Health Research Operating Grant (MOP 86718) and Team Grant in
Cardiovascular Outcomes Research, a Canadian Institutes of Health
Research clinician-scientist award (D. S. L.), and a Canada Research
Chair in Health Services Research (J. V. T.). Dr Vasan was supported in
part by 2K24 H-04334 (National Heart, Lung, and Blood Institute).
NR 25
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U1 4
U2 12
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD JUN 23
PY 2009
VL 119
IS 24
BP 3070
EP 3077
DI 10.1161/CIRCULATIONAHA.108.815944
PG 8
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 461PI
UT WOS:000267279900006
PM 19506115
ER
PT J
AU Goldman, S
McCarren, M
Morkin, E
Ladenson, PW
Edson, R
Warren, S
Ohm, J
Thai, H
Churby, L
Barnhill, J
O'Brien, T
Anand, I
Warner, A
Hattler, B
Dunlap, M
Erikson, J
Shih, MC
Lavori, P
AF Goldman, Steven
McCarren, Madeline
Morkin, Eugene
Ladenson, Paul W.
Edson, Robert
Warren, Stuart
Ohm, Janet
Thai, Hoang
Churby, Lori
Barnhill, Jamie
O'Brien, Terrence
Anand, Inder
Warner, Alberta
Hattler, Brack
Dunlap, Mark
Erikson, John
Shih, Mei-Chiung
Lavori, Phil
TI DITPA (3,5-Diiodothyropropionic Acid), a Thyroid Hormone Analog to Treat
Heart Failure Phase II Trial Veterans Affairs Cooperative Study
SO CIRCULATION
LA English
DT Article
DE cardiac output; hemodynamics; thyroid; heart failure; pharmacology
ID LEFT-VENTRICULAR PERFORMANCE; CHOLESTEROL; ACTIVATION; WEIGHT
AB Background-In animal studies and a pilot trial in patients with congestive heart failure, the thyroid hormone analog 3,5 diiodothyropropionic acid (DITPA) had beneficial hemodynamic effects.
Methods and Results-This was a phase II multicenter, randomized, placebo-controlled, double-blind trial of New York Heart Association class II to IV congestive heart failure patients randomized (2: 1) to DITPA or placebo and treated for 6 months. The study enrolled 86 patients (n = 57 to DITPA, n = 29 to placebo). The primary objective was to assess the effect of DITPA on a composite congestive heart failure end point that classifies patients as improved, worsened, or unchanged based on symptom changes and morbidity/mortality. DITPA was poorly tolerated, which obscured the interpretation of congestive heart failure-specific effects. Fatigue and gastrointestinal complaints, in particular, were more frequent in the DITPA group. DITPA increased cardiac index (by 18%) and decreased systemic vascular resistance (by 11%), serum cholesterol (-20%), low-density lipoprotein cholesterol (-30%), and body weight (-11 lb). Thyroid-stimulating hormone was suppressed in patients given DITPA, which reflects its thyromimetic effect; however, no symptoms or signs of potential hypothyroidism or thyrotoxicosis were seen.
Conclusions-DITPA improved some hemodynamic and metabolic parameters, but there was no evidence for symptomatic benefit in congestive heart failure. (Circulation. 2009; 119: 3093-3100.)
C1 [Goldman, Steven] So Arizona VA Hlth Care Syst, Cardiol Sect 1 111C, Tucson, AZ 85723 USA.
[McCarren, Madeline] VA Pharm Benefits Management, Hines, IL USA.
[Morkin, Eugene] Univ Arizona, Tucson, AZ USA.
[Ladenson, Paul W.] Johns Hopkins Univ, Baltimore, MD USA.
[Edson, Robert; Churby, Lori; Shih, Mei-Chiung; Lavori, Phil] Vet Affairs Med Ctr, R&D Serv, Palo Alto, CA 94304 USA.
[Warren, Stuart; Barnhill, Jamie] Vet Affairs Med Ctr, R&D Serv, Albuquerque, NM USA.
[O'Brien, Terrence] Vet Affairs Med Ctr, Charleston, SC 29403 USA.
[Anand, Inder] Vet Affairs Med Ctr, Minneapolis, MN USA.
[Warner, Alberta] Vet Affairs Med Ctr, Los Angeles, CA USA.
[Hattler, Brack] Vet Affairs Med Ctr, Denver, CO USA.
[Dunlap, Mark] Vet Affairs Med Ctr, Cleveland, OH USA.
[Erikson, John] Vet Affairs Med Ctr, San Antonio, TX USA.
RP Goldman, S (reprint author), So Arizona VA Hlth Care Syst, Cardiol Sect 1 111C, 3601 S 6th Ave, Tucson, AZ 85723 USA.
EM steven.goldman@va.gov
FU Department of Veterans Affairs, Veterans Health Administration, Office
of Research and Development, Clinical Science Research and Development
Service, Cooperative Studies Program
FX This study was supported by the Department of Veterans Affairs, Veterans
Health Administration, Office of Research and Development, Clinical
Science Research and Development Service, Cooperative Studies Program.
NR 28
TC 50
Z9 52
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD JUN 23
PY 2009
VL 119
IS 24
BP 3093
EP U84
DI 10.1161/CIRCULATIONAHA.108.834424
PG 10
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 461PI
UT WOS:000267279900009
PM 19506112
ER
PT J
AU Vincent, JL
AF Vincent, Justin L.
TI Learning and Memory: While You Rest, Your Brain Keeps Working
SO CURRENT BIOLOGY
LA English
DT Editorial Material
ID SLEEP; FLUCTUATIONS; ADAPTATION; SEQUENCES; CORTEX; REPLAY
C1 [Vincent, Justin L.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA.
[Vincent, Justin L.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA.
[Vincent, Justin L.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
RP Vincent, JL (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St,WJH 274, Cambridge, MA 02138 USA.
EM vincent@nmr.mgh.harvard.edu
RI Vincent, Justin/B-5033-2012
NR 20
TC 6
Z9 6
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0960-9822
J9 CURR BIOL
JI Curr. Biol.
PD JUN 23
PY 2009
VL 19
IS 12
BP R484
EP R486
DI 10.1016/j.cub.2009.05.024
PG 3
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 462GH
UT WOS:000267338500013
PM 19549494
ER
PT J
AU Losina, E
Walensky, RP
Kessler, CL
Emrani, PS
Reichmann, WM
Wright, EA
Holt, HL
Solomon, DH
Yelin, E
Paltiel, AD
Katz, JN
AF Losina, Elena
Walensky, Rochelle P.
Kessler, Courtenay L.
Emrani, Parastu S.
Reichmann, William M.
Wright, Elizabeth A.
Holt, Holly L.
Solomon, Daniel H.
Yelin, Edward
Paltiel, A. David
Katz, Jeffrey N.
TI Cost-effectiveness of Total Knee Arthroplasty in the United States
Patient Risk and Hospital Volume
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Article
ID TOTAL HIP; REPLACEMENT; OSTEOARTHRITIS; OUTCOMES; ARTHRITIS; HEALTH;
SURGERY; UNCERTAINTY; ADULTS; MODEL
AB Background: Total knee arthroplasty (TKA) relieves pain and improves quality of life for persons with advanced knee osteoarthritis. However, to our knowledge, the cost-effectiveness of TKA and the influences of hospital volume and patient risk on TKA cost-effectiveness have not been investigated in the United States.
Methods: We developed a Markov, state-transition, computer simulation model and populated it with Medicare claims data and cost and outcomes data from national and multinational sources. We projected lifetime costs and quality-adjusted life expectancy (QALE) for different risk populations and varied TKA intervention and hospital volume. Cost-effectiveness of TKA was estimated across all patient risk and hospital volume permutations. Finally, we conducted sensitivity analyses to determine various parameters' influences on cost-effectiveness.
Results: Overall, TKA increased QALE from 6.822 to 7.957 quality-adjusted life years (QALYs). Lifetime costs rose from $37 100 (no TKA) to $57 900 after TKA, resulting in an incremental cost-effectiveness ratio of $18 300 per QALY. For high-risk patients, TKA increased QALE from 5.713 to 6.594 QALY, yielding a cost-effectiveness ratio of $28 100 per QALY. At all risk levels, TKA was more costly and less effective in low-volume centers than in high-volume centers. Results were insensitive to variations of key input parameters within policy-relevant, clinically plausible ranges. The greatest variations were seen for the quality of life gain after TKA and the cost of TKA.
Conclusions: Total knee arthroplasty appears to be cost-effective in the US Medicare-aged population, as currently practiced across all risk groups. Policy decisions should be made on the basis of available local options for TKA. However, when a high-volume hospital is available, TKAs performed in a high-volume hospital confer even greater value per dollar spent than TKAs performed in low-volume centers.
C1 [Losina, Elena; Kessler, Courtenay L.; Emrani, Parastu S.; Reichmann, William M.; Wright, Elizabeth A.; Holt, Holly L.; Katz, Jeffrey N.] Brigham & Womens Hosp, Dept Orthoped Surg, Orthoped & Arthrit Ctr Outcomes Res, Boston, MA 02115 USA.
[Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA.
[Losina, Elena; Wright, Elizabeth A.; Solomon, Daniel H.; Katz, Jeffrey N.] Brigham & Womens Hosp, Clin Sci Sect, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA.
[Losina, Elena; Reichmann, William M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Walensky, Rochelle P.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Walensky, Rochelle P.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
[Yelin, Edward] Univ Calif San Francisco, Rosalind Russell Med Res Ctr Arthrit, San Francisco, CA 94143 USA.
[Paltiel, A. David] Yale Univ, Sch Med, New Haven, CT USA.
[Katz, Jeffrey N.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Katz, Jeffrey N.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA.
RP Losina, E (reprint author), Brigham & Womens Hosp, Dept Orthoped Surg, Orthoped & Arthrit Ctr Outcomes Res, 75 Francis St,BC-4, Boston, MA 02115 USA.
EM elosina@partners.org
OI Walensky, Rochelle P./0000-0002-8795-379X
FU National Institutes of Health; National Institute of Arthritis and
Musculoskeletal and Skin Diseases [R01 AR053112, P60 AR 47782, K24 AR
02123]; Arthritis Foundation Innovative
FX This research was supported in part by National Institutes of Health,
National Institute of Arthritis and Musculoskeletal and Skin Diseases
grants R01 AR053112, P60 AR 47782, and K24 AR 02123, and an Arthritis
Foundation Innovative Research Grant.
NR 41
TC 190
Z9 192
U1 4
U2 12
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD JUN 22
PY 2009
VL 169
IS 12
BP 1113
EP 1121
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 461BN
UT WOS:000267239300005
PM 19546411
ER
PT J
AU Ratai, EM
Pilkenton, SJ
Greco, JB
Lentz, MR
Bombardier, JP
Turk, KW
He, JL
Joo, CG
Lee, V
Westmoreland, S
Halpern, E
Lackner, AA
Gonzalez, RG
AF Ratai, Eva-Maria
Pilkenton, Sarah J.
Greco, Jane B.
Lentz, Margaret R.
Bombardier, Jeffrey P.
Turk, Katherine W.
He, Julian
Joo, Chan-Gyu
Lee, Vallent
Westmoreland, Susan
Halpern, Elkan
Lackner, Andrew A.
Gonzalez, R. Gilberto
TI In vivo proton magnetic resonance spectroscopy reveals region specific
metabolic responses to SIV infection in the macaque brain
SO BMC NEUROSCIENCE
LA English
DT Article
ID SIMIAN IMMUNODEFICIENCY VIRUS; AIDS DEMENTIA COMPLEX; H-1 MR
SPECTROSCOPY; HIV-INFECTION; N-ACETYLASPARTATE; NEURONAL INJURY;
SEROPOSITIVE INDIVIDUALS; RHESUS MACAQUES; NMR-SPECTRA; MODEL
AB Background: In vivo proton magnetic resonance spectroscopy ((1)H-MRS) studies of HIV-infected humans have demonstrated significant metabolic abnormalities that vary by brain region, but the causes are poorly understood. Metabolic changes in the frontal cortex, basal ganglia and white matter in 18 SIV-infected macaques were investigated using MRS during the first month of infection.
Results: Changes in the N-acetylaspartate (NAA), choline (Cho), myo-inositol (MI), creatine (Cr) and glutamine/glutamate (Glx) resonances were quantified both in absolute terms and relative to the creatine resonance. Most abnormalities were observed at the time of peak viremia, 2 weeks post infection (wpi). At that time point, significant decreases in NAA and NAA/Cr, reflecting neuronal injury, were observed only in the frontal cortex. Cr was significantly elevated only in the white matter. Changes in Cho and Cho/Cr were similar across the brain regions, increasing at 2 wpi, and falling below baseline levels at 4 wpi. MI and MI/Cr levels were increased across all brain regions.
Conclusion: These data best support the hypothesis that different brain regions have variable intrinsic vulnerabilities to neuronal injury caused by the AIDS virus.
C1 [Ratai, Eva-Maria; Pilkenton, Sarah J.; Greco, Jane B.; Lentz, Margaret R.; Bombardier, Jeffrey P.; Turk, Katherine W.; He, Julian; Joo, Chan-Gyu; Lee, Vallent; Gonzalez, R. Gilberto] Massachusetts Gen Hosp, Neuroradiol Div, Dept Radiol, Charlestown, MA 02129 USA.
[Ratai, Eva-Maria; Pilkenton, Sarah J.; Greco, Jane B.; Lentz, Margaret R.; Bombardier, Jeffrey P.; Turk, Katherine W.; He, Julian; Joo, Chan-Gyu; Lee, Vallent; Gonzalez, R. Gilberto] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Ratai, Eva-Maria; Pilkenton, Sarah J.; Greco, Jane B.; Lentz, Margaret R.; He, Julian; Joo, Chan-Gyu; Westmoreland, Susan; Halpern, Elkan; Gonzalez, R. Gilberto] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Westmoreland, Susan] New England Reg Primate Res Ctr, Southborough, MA 01772 USA.
[Halpern, Elkan] Massachusetts Gen Hosp, Dept Radiol, Inst Technol Assessment, Charlestown, MA 02129 USA.
[Lackner, Andrew A.] Tulane Univ, Hlth Sci Ctr, Tulane Natl Primate Res Ctr, Covington, LA 70433 USA.
RP Gonzalez, RG (reprint author), Massachusetts Gen Hosp, Neuroradiol Div, Dept Radiol, Charlestown, MA 02129 USA.
EM ratai@nmr.mgh.harvard.edu; spilkenton@framingham.edu;
jrb@alumni.caltech.edu; mlentz@nmr.mgh.harvard.edu;
bombardi@nmr.mgh.harvard.edu; kwtster@gmail.com;
hej@helix.mgh.harvard.edu; cjoo@nmr.mgh.harvard.edu;
vallent@nmr.mgh.harvard.edu; susan_westmorelant@hms.harvard.edu;
elk@mgh-ita.org; alackner@tpc.tulane.edu; rggonzalez@partners.org
FU NIH, including National Center for Research Resources (NCRR) [RR13214,
RR13213, NS34626, RR000150, RR00168, NS051129, NS30769, MH61192,
R21NS059331]; National Institute of Allergy and Infectious Diseases
[A1028691]; National Center for Research Resources grant [P41RR14075];
Mental Illness and Neuroscience Discovery (MIND) Institute
FX We thank Drs. Angela Carville and Elisabeth Ludlage-Moeller for animal
care at the NERPRC, Eric Broadbent and Ernest Neale for veterinary
technical assistance, Elizabeth Curran and Mike O'Connell for pathology
support, and Robert Fuller and John Kim for participating in MR
experiments and analysis. This work was supported by grants from the
NIH, including National Center for Research Resources (NCRR) RR13214,
RR13213, NS34626 (to RGG), and RR000150 and RR00168 (to NERPRC),
NS051129 (MRL), NS30769 and MH61192 (to AAL), R21NS059331 (to EMR), and
National Institute of Allergy and Infectious Diseases A1028691 (to EMR).
The MGH A. A. Martinos Center for Biomedical Imaging is also supported
by P41RR14075 (National Center for Research Resources grant) and the
Mental Illness and Neuroscience Discovery (MIND) Institute.
NR 58
TC 23
Z9 23
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1471-2202
J9 BMC NEUROSCI
JI BMC Neurosci.
PD JUN 22
PY 2009
VL 10
AR 63
DI 10.1186/1471-2202-10-63
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 470PI
UT WOS:000267987700001
PM 19545432
ER
PT J
AU Yaqoob, Z
Choi, W
Oh, S
Lue, N
Park, Y
Fang-Yen, C
Dasari, RR
Badizadegan, K
Feld, MS
AF Yaqoob, Zahid
Choi, Wonshik
Oh, Seungeun
Lue, Niyom
Park, Yongkeun
Fang-Yen, Christopher
Dasari, Ramachandra R.
Badizadegan, Kamran
Feld, Michael S.
TI Improved phase sensitivity in spectral domain phase microscopy using
line-field illumination and self phase-referencing
SO OPTICS EXPRESS
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; DYNAMICS; INTERFEROMETRY
AB We report a quantitative phase microscope based on spectral domain optical coherence tomography and line-field illumination. The line illumination allows self phase-referencing method to reject common-mode phase noise. The quantitative phase microscope also features a separate reference arm, permitting the use of high numerical aperture (NA > 1) microscope objectives for high resolution phase measurement at multiple points along the line of illumination. We demonstrate that the path-length sensitivity of the instrument can be as good as 41 pm / root Hz, which makes it suitable for nanometer scale study of cell motility. We present the detection of natural motions of cell surface and two-dimensional surface profiling of a HeLa cell. (C) 2009 Optical Society of America
C1 [Yaqoob, Zahid; Choi, Wonshik; Oh, Seungeun; Lue, Niyom; Park, Yongkeun; Fang-Yen, Christopher; Dasari, Ramachandra R.; Badizadegan, Kamran; Feld, Michael S.] MIT, George R Harrison Spect Lab, Cambridge, MA 02139 USA.
[Choi, Wonshik] Korea Univ, Dept Phys, Seoul 136701, South Korea.
[Badizadegan, Kamran] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA.
[Badizadegan, Kamran] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Choi, W (reprint author), MIT, George R Harrison Spect Lab, Cambridge, MA 02139 USA.
EM wonshik@mit.edu
RI Park, YongKeun/B-9017-2009;
OI Fang-Yen, Christopher/0000-0002-4568-3218
FU National Center for Research Resources of the National Institutes of
Health [P41-RR02594-18]; National Science Foundation [DBI-0754339];
Hamamatsu Corporation
FX This work was funded by the National Center for Research Resources of
the National Institutes of Health ( P41-RR02594-18), the National
Science Foundation ( DBI-0754339), and Hamamatsu Corporation.
NR 21
TC 23
Z9 23
U1 1
U2 10
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 JUN 22
PY 2009
VL 17
IS 13
BP 10681
EP 10687
DI 10.1364/OE.17.010681
PG 7
WC Optics
SC Optics
GA 467RW
UT WOS:000267761100025
PM 19550464
ER
PT J
AU Spalke, T
Craft, D
Bortfeld, T
AF Spalke, Tobias
Craft, David
Bortfeld, Thomas
TI Analyzing the main trade-offs in multiobjective radiation therapy
treatment planning databases
SO PHYSICS IN MEDICINE AND BIOLOGY
LA English
DT Article
ID RADIOTHERAPY; OPTIMIZATION
AB Multiobjective radiotherapy planning aims to capture all clinically relevant trade-offs between the various planning goals. This is accomplished by calculating a representative set of Pareto optimal solutions and storing them in a database. The structure of these representative Pareto sets is still not fully investigated. We propose two methods for a systematic analysis of multiobjective databases: principal component analysis and the isomap method. Both methods are able to extract the key trade-offs from a database and provide information which can lead to a better understanding of the clinical case and intensity-modulated radiation therapy planning in general.
C1 [Spalke, Tobias] DKFZ Heidelberg, Dept Med Phys Radiat Oncol, Heidelberg, Germany.
[Craft, David; Bortfeld, Thomas] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Craft, David; Bortfeld, Thomas] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Spalke, T (reprint author), DKFZ Heidelberg, Dept Med Phys Radiat Oncol, Heidelberg, Germany.
EM t.spalke@dkfz-heidelberg.de
FU DAAD(GermanAcademic Exchange Service) [CA103904]; National Institute of
Health of the United States of America.
FX This work was supported by a scholarship of the DAAD(GermanAcademic
Exchange Service) and by grant CA103904 from the National Institute of
Health of the United States of America.
NR 10
TC 13
Z9 13
U1 2
U2 2
PU IOP PUBLISHING LTD
PI BRISTOL
PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND
SN 0031-9155
J9 PHYS MED BIOL
JI Phys. Med. Biol.
PD JUN 21
PY 2009
VL 54
IS 12
BP 3741
EP 3754
DI 10.1088/0031-9155/54/12/009
PG 14
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA 453AM
UT WOS:000266582300009
PM 19478382
ER
PT J
AU van den Bent, MJ
Vogelbaum, MA
Wen, PY
Macdonald, DR
Chang, SM
AF van den Bent, Martin J.
Vogelbaum, Michael A.
Wen, Patrick Y.
Macdonald, David R.
Chang, Susan M.
TI End Point Assessment in Gliomas: Novel Treatments Limit Usefulness of
Classical Macdonald's Criteria
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID RECURRENT MALIGNANT GLIOMA; PROGRESSION-FREE SURVIVAL; PHASE-III TRIAL;
BRAIN-TUMOR; RADIATION-THERAPY; GLIOBLASTOMA-MULTIFORME; EUROPEAN
ORGANIZATION; RESPONSE CRITERIA; CLINICAL-TRIALS; MR
C1 [van den Bent, Martin J.] Erasmus Univ Hosp, Daniel den Hoed Canc Ctr, Neurooncol Unit, Rotterdam, Netherlands.
[Vogelbaum, Michael A.] Cleveland Clin, Dept Neurosurg, Brain Tumor & Neurooncol Ctr, Cleveland, OH 44106 USA.
[Wen, Patrick Y.] Brigham & Womens Hosp, Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA 02115 USA.
[Wen, Patrick Y.] Brigham & Womens Hosp, Div Neurol, Boston, MA 02115 USA.
[Macdonald, David R.] Univ Western Ontario, Dept Oncol, London Reg Canc Program, London, ON, Canada.
[Macdonald, David R.] Univ Western Ontario, Div Med Oncol, London, ON, Canada.
[Chang, Susan M.] Univ Calif San Francisco, Dept Neurol Surg, Div Neurooncol, San Francisco, CA 94143 USA.
RP van den Bent, MJ (reprint author), Erasmus Univ Hosp, Daniel den Hoed Canc Ctr, Neurooncol Unit, Rotterdam, Netherlands.
FU NCI NIH HHS [P01 CA118816]
NR 38
TC 153
Z9 154
U1 0
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 JUN 20
PY 2009
VL 27
IS 18
BP 2905
EP 2908
DI 10.1200/JCO.2009.22.4998
PG 4
WC Oncology
SC Oncology
GA 459TP
UT WOS:000267133300007
PM 19451418
ER
PT J
AU Bilimoria, KY
Bentrem, DJ
Hansen, NM
Bethke, KP
Rademaker, AW
Ko, CY
Winchester, DP
Winchester, DJ
AF Bilimoria, Karl Y.
Bentrem, David J.
Hansen, Nora M.
Bethke, Kevin P.
Rademaker, Alfred W.
Ko, Clifford Y.
Winchester, David P.
Winchester, David J.
TI Comparison of Sentinel Lymph Node Biopsy Alone and Completion Axillary
Lymph Node Dissection for Node-Positive Breast Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article; Proceedings Paper
CT 94th Annual Clinical Congress of the American-College-of-Surgeons/63rd
Annual Sessions of the Owen H Wangensteen Forum on Fundamental Surgical
Problems
CY OCT 12-16, 2008
CL San Francisco, CA
SP Amer Coll Surg
ID FOLLOW-UP; CONTROLLED-TRIALS; TOTAL MASTECTOMY; ACOSOG Z0011; CARCINOMA;
NOMOGRAM; IRRADIATION; WOMEN
AB Purpose
For women with breast cancer, the role of completion axillary lymph node dissection (ALND) after identification of nodal metastases by sentinel lymph node biopsy (SLNB) has been questioned. Our objectives were to assess national nodal evaluation practice patterns and to examine differences in recurrence and survival for SLNB alone versus SLNB with completion ALND.
Patients and Methods
From the National Cancer Data Base (1998 to 2005), women with clinically node-negative breast cancer who underwent SLNB and who had nodal metastases were identified. Practice patterns and outcomes were examined for patients who underwent SLNB alone versus SLNB with completion ALND (median follow-up, 63 months).
Results
Of 97,314 patients, 20.8% underwent SLNB alone, and 79.2% underwent SLNB with completion ALND. In 2004 to 2005, patients were significantly more likely to undergo SLNB alone if they were older, had smaller tumors, or were treated at non-National Cancer Institute-designated cancer centers. In patients with macroscopic nodal metastases (n = 20,075 during 1998 to 2000), there was a nonsignificant trend toward better outcomes for completion ALND (v SLNB alone) after analysis was adjusted for differences between the two groups: axillary recurrence (hazard ratio [HR], 0.58; 95% CI, 0.32 to 1.06) and overall survival (HR, 0.89; 95% CI, 0.76 to 1.04). In patients with microscopic nodal metastases (n = 2,203 during 1998 to 2000), there were no significant differences in axillary recurrence or survival for patients who underwent SLNB alone versus completion ALND.
Conclusion
Compared with SLNB alone, completion ALND does not appear to improve outcomes for breast cancer patients with microscopic nodal metastases; however, there was a nonsignificant trend toward better outcomes with completion ALND for those with macroscopic disease. J Clin Oncol 27: 2946-2953. (C) 2009 by American Society of Clinical Oncology
C1 [Winchester, David P.] Northwestern Univ, Amer Coll Surg, Canc Programs, Chicago, IL 60611 USA.
Northwestern Univ, Feinberg Sch Med, Dept Surg, Chicago, IL 60611 USA.
Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA.
NorthShore Univ HealthSyst, Dept Surg, Evanston, IL USA.
Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA.
Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
RP Winchester, DP (reprint author), Northwestern Univ, Amer Coll Surg, Canc Programs, 633 N St Claire, Chicago, IL 60611 USA.
EM dwinchester@facs.org
NR 43
TC 177
Z9 183
U1 0
U2 5
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 JUN 20
PY 2009
VL 27
IS 18
BP 2946
EP 2953
DI 10.1200/JCO.2008.19.5750
PG 8
WC Oncology
SC Oncology
GA 459TP
UT WOS:000267133300013
PM 19364968
ER
PT J
AU Dowsett, M
Procter, M
McCaskill-Stevens, W
de Azambuja, E
Dafni, U
Rueschoff, J
Jordan, B
Dolci, S
Abramovitz, M
Stoss, O
Viale, G
Gelber, RD
Piccart-Gebhart, M
Leyland-Jones, B
AF Dowsett, Mitch
Procter, Marion
McCaskill-Stevens, Worta
de Azambuja, Evandro
Dafni, Urania
Rueschoff, Josef
Jordan, Bruce
Dolci, Stella
Abramovitz, Mark
Stoss, Oliver
Viale, Giuseppe
Gelber, Richard D.
Piccart-Gebhart, Martine
Leyland-Jones, Brian
TI Disease-Free Survival According to Degree of HER2 Amplification for
Patients Treated With Adjuvant Chemotherapy With or Without 1 Year of
Trastuzumab: The HERA Trial
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article; Proceedings Paper
CT 30th Annual San Antonio Breast Cancer Symposium
CY DEC 13-16, 2007
CL San Antonio, TX
SP San Antonio Canc Inst, Baylor Coll Med
ID HER2-POSITIVE BREAST-CANCER; GENE; HER-2/NEU; ONCOGENE
AB Purpose
To determine whether (1) immunohistochemical (IHC) HER2 status (ie, 2+ or 3+), (2) degree of fluorescence in situ hybridization (FISH) amplification according to (2a) HER2/CEP17 ratio or (2b) HER2 gene copy number, or (3) polysomy significantly influenced clinical outcome for patients with human epidermal growth factor receptor 2 (HER2) -positive breast cancer enrolled in the Herceptin Adjuvant trial of trastuzumab versus no trastuzumab administered after completion of chemotherapy.
Patients and Methods
IHC and/or FISH analyses were performed locally and required central confirmation as indicating HER2 positivity for trial entry. FISH data from the central HER2 analysis on patients in the 1-year trastuzumab and no trastuzumab arms were assessed in relation to disease-free survival (DFS) after a median 2 years of follow-up.
Results
Central FISH results were available for 2,071 (61%) of the 3,401 patients randomized to the 2 arms. Among patients with FISH-positive disease, (1) the hazard ratios for trastuzumab versus no trastuzumab were 0.56 (95% CI, 0.32 to 0.99) for locally IHC2+ cases (n = 340) and 0.80 (95% CI, 0.40 to 1.61) for centrally IHC2+ cases (n = 299). There was no significant prognostic relationship between (2a) HER2 FISH ratio, (2b) HER2 copy number, or (3) polysomy and DFS in the control arm or predictive relationship defining differential benefit from trastuzumab.
Conclusion
There was no evidence for reduced benefit of trastuzumab in HER2 IHC2+ FISH+ cases. The degree of HER2 amplification does not influence prognosis or benefit from adjuvant trastuzumab in patients treated with prior adjuvant chemotherapy. J Clin Oncol 27: 2962-2969. (C) 2009 by American Society of Clinical Oncology
C1 [Dowsett, Mitch] Royal Marsden Hosp, Dept Acad Biochem, London SW3 6JJ, England.
Frontier Sci Scotland Ltd, Kincraig, Kingussie, Scotland.
NCI, NIH, Bethesda, MD 20892 USA.
Univ Libre Bruxelles, Inst Jules Bordet, Dept Med Oncol, Brussels, Belgium.
Univ Libre Bruxelles, Inst Jules Bordet, Dept Med, Brussels, Belgium.
Breast European Adjuvant Studies Team, Brussels, Belgium.
Univ Athens, Sch Nursing, Dept Publ Hlth, Athens, Greece.
TARGOS Mol Pathol GmbH, Kassel, Germany.
F Hoffmann La Roche Ltd, Roche Profess Diagnost, Basel, Switzerland.
VM Inst Res, Montreal, PQ, Canada.
European Inst Oncol, Div Pathol & Lab Med, Milan, Italy.
Univ Milan, Milan, Italy.
Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
Emory Winship Canc Inst, Atlanta, GA USA.
RP Dowsett, M (reprint author), Royal Marsden Hosp, Dept Acad Biochem, Fulham Rd, London SW3 6JJ, England.
EM mitch.dowsett@icr.ac.uk
NR 25
TC 106
Z9 111
U1 1
U2 5
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 JUN 20
PY 2009
VL 27
IS 18
BP 2962
EP 2969
DI 10.1200/JCO.2008.19.7939
PG 8
WC Oncology
SC Oncology
GA 459TP
UT WOS:000267133300015
PM 19364966
ER
PT J
AU Willett, CG
Duda, DG
di Tomaso, E
Boucher, Y
Ancukiewicz, M
Sahani, DV
Lahdenranta, J
Chung, DC
Fischman, AJ
Lauwers, GY
Shellito, P
Czito, BG
Wong, TZ
Paulson, E
Poleski, M
Vujaskovic, Z
Bentley, R
Chen, HX
Clark, JW
Jain, RK
AF Willett, Christopher G.
Duda, Dan G.
di Tomaso, Emmanuelle
Boucher, Yves
Ancukiewicz, Marek
Sahani, Dushyant V.
Lahdenranta, Johanna
Chung, Daniel C.
Fischman, Alan J.
Lauwers, Gregory Y.
Shellito, Paul
Czito, Brian G.
Wong, Terence Z.
Paulson, Erik
Poleski, Martin
Vujaskovic, Zeljko
Bentley, Rex
Chen, Helen X.
Clark, Jeffrey W.
Jain, Rakesh K.
TI Efficacy, Safety, and Biomarkers of Neoadjuvant Bevacizumab, Radiation
Therapy, and Fluorouracil in Rectal Cancer: A Multidisciplinary Phase II
Study
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID VASCULAR ENDOTHELIAL GROWTH; TYROSINE KINASE INHIBITOR; METASTATIC
COLORECTAL-CANCER; ANTIANGIOGENIC THERAPY; TUMOR VASCULATURE; FACTOR
RECEPTOR; CHEMORADIOTHERAPY; CHEMOTHERAPY; CARCINOMA; MARKERS
AB Purpose
To assess the safety and efficacy of neoadjuvant bevacizumab with standard chemoradiotherapy in locally advanced rectal cancer and explore biomarkers for response.
Patients and Methods
In a phase I/II study, 32 patients received four cycles of therapy consisting of: bevacizumab infusion (5 or 10 mg/kg) on day 1 of each cycle; fluorouracil infusion (225 mg/m(2)/24 hours) during cycles 2 to 4; external-beam irradiation (50.4 Gy in 28 fractions over 5.5 weeks); and surgery 7 to 10 weeks after completion of all therapies. We measured molecular, cellular, and physiologic biomarkers before treatment, during bevacizumab monotherapy, and during and after combination therapy.
Results
Tumors regressed from a mass with mean size of 5 cm (range, 3 to 12 cm) to an ulcer/scar with mean size of 2.4 cm (range, 0.7 to 6.0 cm) in all 32 patients. Histologic examination revealed either no cancer or varying numbers of scattered cancer cells in a bed of fibrosis at the primary site. This treatment resulted in an actuarial 5-year local control and overall survival of 100%. Actuarial 5-year disease-free survival was 75% and five patients developed metastases postsurgery. Bevacizumab with chemoradiotherapy showed acceptable toxicity. Bevacizumab decreased tumor interstitial fluid pressure and blood flow. Baseline plasma soluble vascular endothelial growth factor receptor 1 (sVEGFR1), plasma vascular endothelial growth factor (VEGF), placental-derived growth factor (PlGF), and interleukin 6 (IL-6) during treatment, and circulating endothelial cells (CECs) after treatment showed significant correlations with outcome.
Conclusion
Bevacizumab with chemoradiotherapy appears safe and active and yields promising survival results in locally advanced rectal cancer. Plasma VEGF, PlGF, sVEGFR1, and IL-6 and CECs should be further evaluated as candidate biomarkers of response for this regimen. J Clin Oncol 27: 3020-3026. (C) 2009 by American Society of Clinical Oncology
C1 [Willett, Christopher G.] Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC 27710 USA.
Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA.
Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA.
Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA.
Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Dept Nucl Med, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Willett, CG (reprint author), Duke Univ, Med Ctr, Dept Radiat Oncol, Box 3085, Durham, NC 27710 USA.
EM christopher.willett@duke.edu
FU National Institutes of Health [R21CA099237, P01CA80124, R01CA115767];
National Foundation for Cancer Research
FX Supported by the Grants No. R21CA099237 (C. G. W.), P01CA80124, and
R01CA115767 from the National Institutes of Health, and a grant from the
National Foundation for Cancer Research (R. K. J.).
NR 18
TC 274
Z9 284
U1 4
U2 18
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 JUN 20
PY 2009
VL 27
IS 18
BP 3020
EP 3026
DI 10.1200/JCO.2008.21.1771
PG 7
WC Oncology
SC Oncology
GA 459TP
UT WOS:000267133300023
PM 19470921
ER
PT J
AU Zhu, AX
Sahani, DV
Duda, DG
di Tomaso, E
Ancukiewicz, M
Catalano, OA
Sindhwani, V
Blaszkowsky, LS
Yoon, SS
Lahdenranta, J
Bhargava, P
Meyerhardt, J
Clark, JW
Kwak, EL
Hezel, AF
Miksad, R
Abrams, TA
Enzinger, PC
Fuchs, CS
Ryan, DP
Jain, RK
AF Zhu, Andrew X.
Sahani, Dushyant V.
Duda, Dan G.
di Tomaso, Emmanuelle
Ancukiewicz, Marek
Catalano, Onofrio A.
Sindhwani, Vivek
Blaszkowsky, Lawrence S.
Yoon, Sam S.
Lahdenranta, Johanna
Bhargava, Pankaj
Meyerhardt, Jeffrey
Clark, Jeffrey W.
Kwak, Eunice L.
Hezel, Aram F.
Miksad, Rebecca
Abrams, Thomas A.
Enzinger, Peter C.
Fuchs, Charles S.
Ryan, David P.
Jain, Rakesh K.
TI Efficacy, Safety, and Potential Biomarkers of Sunitinib Monotherapy in
Advanced Hepatocellular Carcinoma: A Phase II Study
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; RECEPTOR TYROSINE KINASES; ADVANCED
BREAST-CANCER; TUMOR ANGIOGENESIS; CLINICAL-TRIALS; MYELOID CELLS;
THERAPY; EPIDEMIOLOGY; VASCULATURE; BEVACIZUMAB
AB Purpose
To assess the safety and efficacy of sunitinib in patients with advanced hepatocellular carcinoma (HCC) and explore biomarkers for sunitinib response.
Patients and Methods
We conducted a multidisciplinary phase II study of sunitinib, an antivascular endothelial growth factor receptor tyrosine kinase inhibitor, in advanced HCC. Patients received sunitinib 37.5 mg/d for 4 weeks followed by 2 weeks of rest per cycle. The primary end point was progression-free survival (PFS). We used functional magnetic resonance imaging to evaluate vascular changes in HCC after sunitinib treatment. Circulating molecular and cellular biomarkers were evaluated before and at six time points after sunitinib treatment.
Results
Thirty-four patients were enrolled. The objective response rate was 2.9%, and 50% of patients had stable disease. Median PFS was 3.9 months (95% CI, 2.6 to 6.9 months), and overall survival was 9.8 months (95% CI, 7.4 months to not available). Grade 3 or 4 toxicities included leukopenia/neutropenia, thrombocytopenia, elevation of aminotransferases, and fatigue. Sunitinib rapidly decreased vessel leakiness, and this effect was more pronounced in patients with delayed progression. When evaluated early (at baseline and day 14) as well as over three cycles of treatment, higher levels of inflammatory molecules (eg, interleukin-6, stromal-derived factor 1 alpha, soluble c-KIT) and circulating progenitor cells were associated with a poor outcome.
Conclusion
Sunitinib shows evidence of modest antitumor activity in advanced HCC with manageable adverse effects. Rapid changes in tumor vascular permeability and circulating inflammatory biomarkers are potential determinants of response and resistance to sunitinib in HCC. Our study suggests that control of inflammation might be critical for improving treatment outcome in advanced HCC. J Clin Oncol 27: 3027-3035. (C) 2009 by American Society of Clinical Oncology
C1 [Zhu, Andrew X.] Massachusetts Gen Hosp, Dept Radiol, Dept Radiat Oncol, Div Hematol Oncol,Div Surg Oncol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA.
Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA.
RP Zhu, AX (reprint author), Massachusetts Gen Hosp, Dept Radiol, Dept Radiat Oncol, Div Hematol Oncol,Div Surg Oncol, 55 Fruit St,LH-POB,Room 232, Boston, MA 02114 USA.
EM azhu@partners.org
OI Miksad, Rebecca/0000-0003-3194-5122
FU Pfizer; National Institutes of Health [P01CA80124, R01CA115767,
M01-RR-01066]; Harvard Clinical and Translational Science Center
FX Supported in part by Pfizer (A. X. Z.) and by National Institutes of
Health Grants No. P01CA80124 and R01CA115767 (R. K. J.) and
M01-RR-01066, Harvard Clinical and Translational Science Center. A. X.
Z.,
NR 38
TC 292
Z9 301
U1 1
U2 11
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 JUN 20
PY 2009
VL 27
IS 18
BP 3027
EP 3035
DI 10.1200/JCO.2008.20.9908
PG 9
WC Oncology
SC Oncology
GA 459TP
UT WOS:000267133300024
PM 19470923
ER
PT J
AU Freedman, A
Neelapu, SS
Nichols, C
Robertson, MJ
Djulbegovic, B
Winter, JN
Bender, JF
Gold, DP
Ghalie, RG
Stewart, ME
Esquibel, V
Hamlin, P
AF Freedman, Arnold
Neelapu, Sattva S.
Nichols, Craig
Robertson, Michael J.
Djulbegovic, Benjamin
Winter, Jane N.
Bender, John F.
Gold, Daniel P.
Ghalie, Richard G.
Stewart, Morgan E.
Esquibel, Vanessa
Hamlin, Paul
TI Placebo-Controlled Phase III Trial of Patient-Specific Immunotherapy
With Mitumprotimut-T and Granulocyte-Macrophage Colony-Stimulating
Factor After Rituximab in Patients With Follicular Lymphoma
SO JOURNAL OF CLINICAL ONCOLOGY
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 NON-HODGKINS-LYMPHOMA; MONOCLONAL-ANTIBODY THERAPY; B-CELL LYMPHOMA;
LOW-GRADE; VACCINATION; RESPONSES
AB Purpose
To evaluate patient-specific immunotherapy with mitumprotimut-T (idiotype keyhole limpet hemocyanin [Id-KLH]) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in CD20(+) follicular lymphoma.
Patients and Methods
Patients with treatment-naive or relapsed/refractory disease achieving a complete response (CR), partial response (PR), or stable disease (SD) with four weekly rituximab infusions were randomly assigned to mitumprotimut-T/GM-CSF or placebo/GM-CSF, with doses given monthly for six doses, every 2 months for six doses, and then every 3 months until disease progression (PD). Randomization was stratified by prior therapy (treatment-naive or relapsed/refractory) and response to rituximab (CR/PR or SD). The primary end point was time to progression (TTP) from randomization.
Results
A total of 349 patients were randomly assigned; median age was 54 years, 79% were treatment naive, and 86% had stage III/IV disease. Median TTP was 9.0 months for mitumprotimut-T/GMCSF and 12.6 months for placebo/GM-CSF (hazard ratio [HR] = 1.384; P = .019). TTP was comparable between the two arms in treatment-naive patients (HR = 1.196; P = .258) and shorter with mitumprotimut-T/GM-CSF in relapsed/refractory disease (HR = 2.265; P = .004). After adjusting for Follicular Lymphoma International Prognostic Index (FLIPI) scores, the difference in TTP between the two arms was no longer significant. Overall objective response rate, rate of response improvement, and duration of response were comparable between the two arms. Toxicity was similar in the two arms; 76% of adverse events were mild or moderate, and 94% of patients had injection site reactions.
Conclusion
TTP was shorter with mitumprotimut-T/GM-CSF compared with placebo/GM-CSF. This difference was possibly due to the imbalance in FLIPI scores. J Clin Oncol 27: 3036-3043. (C) 2009 by American Society of Clinical Oncology
C1 [Freedman, Arnold] Dana Farber Canc Inst, Boston, MA 02115 USA.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Earle A Chiles Res Inst, Providence Canc Ctr, Portland, OR USA.
Indiana Univ, Med Ctr, Indianapolis, IN USA.
Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA.
Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
Favrille Inc, San Diego, CA USA.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
RP Freedman, A (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA.
EM arnold_freedman@dfci.harvard.edu
RI Djulbegovic, Benjamin/I-3661-2012;
OI Djulbegovic, Benjamin/0000-0003-0671-1447; Ghalie,
Richard/0000-0001-6882-8179
NR 20
TC 78
Z9 79
U1 1
U2 8
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 JUN 20
PY 2009
VL 27
IS 18
BP 3036
EP 3043
DI 10.1200/JCO.2008.19.8903
PG 8
WC Oncology
SC Oncology
GA 459TP
UT WOS:000267133300025
PM 19414675
ER
PT J
AU Herbst, RS
Sun, Y
Korfee, S
Germonpre, P
Saijo, N
Zhou, C
Wang, J
Langmuir, P
Kennedy, SJ
Johnson, BE
AF Herbst, R. S.
Sun, Y.
Korfee, S.
Germonpre, P.
Saijo, N.
Zhou, C.
Wang, J.
Langmuir, P.
Kennedy, S. J.
Johnson, B. E.
TI Vandetanib plus docetaxel versus docetaxel as second-line treatment for
patients with advanced non-small cell lung cancer (NSCLC): A randomized,
double-blind phase III trial (ZODIAC)
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 29-JUN 02, 2009
CL Orlando, FL
SP Amer Soc Clin Oncol
C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Canc Hosp, Beijing, Peoples R China.
Univ Duisburg Essen, W German Tumor Ctr, Essen, Germany.
Univ Antwerp Hosp, Edegem, Belgium.
Natl Canc Ctr Hosp E, Chiba, Japan.
Tongji Univ, Shanghai 200092, Peoples R China.
Beijing Inst Canc Res, Beijing, Peoples R China.
AstraZeneca, Wilmington, DE USA.
AstraZeneca, Macclesfield, Cheshire, England.
Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
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 JUN 20
PY 2009
VL 27
IS 18
SU S
PG 2
WC Oncology
SC Oncology
GA 582OJ
UT WOS:000276607000034
ER
PT J
AU Rini, BI
Halabi, S
Rosenberg, J
Stadler, WM
Vaena, DA
Atkins, JN
Picus, J
Czaykowski, P
Dutcher, J
Small, EJ
AF Rini, B. I.
Halabi, S.
Rosenberg, J.
Stadler, W. M.
Vaena, D. A.
Atkins, J. N.
Picus, J.
Czaykowski, P.
Dutcher, J.
Small, E. J.
TI First results of a phase III multicenter randomized controlled trial of
intensity modulated (IMRT) versus conventional radiotherapy (RT) in head
and neck cancer (PARSPORT: ISRCTN48243537; CRUK/03/005)
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 29-JUN 02, 2009
CL Orlando, FL
SP Amer Soc Clin Oncol
C1 Cleveland Clin Taussig Canc Inst, Cleveland, OH USA.
CALGB Stat Off, Durham, NC USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Univ Chicago, Chicago, IL 60637 USA.
Univ Iowa, Iowa City, IA USA.
SE Canc Control Consortium Inc, Winston Salem, NC USA.
Washington Univ, St Louis, MO USA.
Natl Canc Inst Canada, Kingston, ON, Canada.
New York Med Coll, New York, NY USA.
Univ Calif San Francisco, San Francisco, CA 94143 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 JUN 20
PY 2009
VL 27
IS 18
SU S
PG 2
WC Oncology
SC Oncology
GA 582OJ
UT WOS:000276607000028
ER
PT J
AU Rini, BI
Halabi, S
Rosenberg, J
Stadler, WM
Vaena, DA
Atkins, JN
Picus, J
Czaykowski, P
Dutcher, J
Small, EJ
AF Rini, B. I.
Halabi, S.
Rosenberg, J.
Stadler, W. M.
Vaena, D. A.
Atkins, J. N.
Picus, J.
Czaykowski, P.
Dutcher, J.
Small, E. J.
TI Bevacizumab plus interferon-alpha versus interferon-alpha monotherapy in
patients with metastatic renal cell carcinoma: Results of overall
survival for CALGB 90206
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 29-JUN 02, 2009
CL Orlando, FL
SP Amer Soc Clin Oncol
C1 Cleveland Clin Taussig Canc Inst, Cleveland, OH USA.
CALGB Stat Off, Durham, NC USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Univ Chicago, Chicago, IL 60637 USA.
Univ Iowa, Iowa City, IA USA.
SE Canc Control Consortium Inc, Winston Salem, NC USA.
Washington Univ, St Louis, MO USA.
Natl Canc Inst Canada, Kingston, ON, Canada.
New York Med Coll, New York, NY USA.
Univ Calif San Francisco, San Francisco, CA 94143 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 JUN 20
PY 2009
VL 27
IS 18
SU S
PG 1
WC Oncology
SC Oncology
GA 582OJ
UT WOS:000276607000027
ER
PT J
AU Tutt, A
Robson, M
Garber, JE
Domchek, S
Audeh, MW
Weitzel, JN
Friedlander, M
Carmichael, J
AF Tutt, A.
Robson, M.
Garber, J. E.
Domchek, S.
Audeh, M. W.
Weitzel, J. N.
Friedlander, M.
Carmichael, J.
TI Phase II trial of the oral PARP inhibitor olaparib in BRCA-deficient
advanced breast cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 29-JUN 02, 2009
CL Orlando, FL
SP Amer Soc Clin Oncol
C1 Kings Coll London, Sch Med, Guys Hosp, Breakthrough Breast Canc Res Unit, London, England.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Univ Penn, Philadelphia, PA 19104 USA.
Cedars Sinai Outpatient Canc Ctr, Los Angeles, CA USA.
City Hope Comprehens Canc Ctr, Duarte, CA USA.
Prince Wales Canc Ctr, Sydney, NSW, Australia.
AstraZeneca, Macclesfield, Cheshire, England.
RI friedlander, michael/G-3490-2013
OI friedlander, michael/0000-0002-6488-0604
NR 0
TC 14
Z9 14
U1 0
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 JUN 20
PY 2009
VL 27
IS 18
SU S
PG 2
WC Oncology
SC Oncology
GA 582OJ
UT WOS:000276607000010
ER
PT J
AU Butt, AA
McGinnis, K
Rodriguez-Barradas, MC
Crystal, S
Simberkoff, M
Goetz, MB
Leaf, D
Justice, AC
AF Butt, Adeel A.
McGinnis, Kathleen
Rodriguez-Barradas, Maria C.
Crystal, Stephen
Simberkoff, Michael
Goetz, Matthew Bidwell
Leaf, David
Justice, Amy C.
CA Veterans Aging Cohort Study
TI HIV infection and the risk of diabetes mellitus
SO AIDS
LA English
DT Article
DE antiretroviral therapy; diabetes; HCV; HIV; risk
ID CHRONIC HEPATITIS-C; MULTICENTER AIDS COHORT; INSULIN-RESISTANCE;
VIRUS-INFECTION; ANTIRETROVIRAL THERAPY; POST-HAART; VETERANS;
PREVALENCE; HEALTH; HCV
AB Background: The influence of HIV infection on the risk of diabetes is unclear. We determined the association and predictors of prevalent diabetes mellitus in HIV infected and uninfected veterans.
Methods: We determined baseline prevalence and risk factors for diabetes between HIV infected and uninfected veterans in the Veterans Aging Cohort Study. Logistic regression was used to determine the odds of diabetes in HIV infected and uninfected persons.
Results: We studied 3227 HIV-infected and 3240 HIV-uninfected individuals. HIV-infected individuals were younger, more likely to be black males, have HCV coinfection and a lower BMI. HIV-infected individuals had a lower prevalence of diabetes at baseline (14.9 vs. 21.4%, P < 0.0001). After adjustment for known risk factors, HIV-infected individuals had a lower risk of diabetes (odds ratio = 0.84, 95% confidence interval = 0.72-0.97). Increasing age, male sex, minority race, and BMI were associated with an increased risk. The odds ratio for diabetes associated with increasing age, minority race and BMI were greater among HIV-infected veterans. HCV coinfection and nucleoside and nonnucleoside reverse transcriptase inhibitor therapy were associated with a higher risk of diabetes in HIV-infected veterans.
Conclusion: Although HIV infection itself is not associated with increased risk of diabetes, increasing age; HCV coinfection and BMI have a more profound effect upon the risk of diabetes among HIV-infected persons. Further, long-term ARV treatment also increases risk. Future studies will need to determine whether incidence of diabetes mellitus differs by HIV status. (c) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
C1 [Butt, Adeel A.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Butt, Adeel A.; McGinnis, Kathleen] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA.
[Rodriguez-Barradas, Maria C.] Baylor Coll Med, Houston, TX 77030 USA.
[Rodriguez-Barradas, Maria C.] Michael E DeBakey VA Med Ctr, Houston, TX USA.
[Crystal, Stephen] Rutgers State Univ, Ctr Pharmacotherapy Dr Crystal Chron Dis Manageme, New Brunswick, NJ 08903 USA.
[Simberkoff, Michael] New York VA Med Ctr, New York, NY USA.
[Goetz, Matthew Bidwell; Leaf, David] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Goetz, Matthew Bidwell; Leaf, David] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Justice, Amy C.] W Haven & Yale Univ, Sch Med & Publ Hlth, VA Connecticut Healthcare Syst, West Haven, CT USA.
RP Butt, AA (reprint author), 3601 5th Ave,Suite 3A, Pittsburgh, PA 15213 USA.
EM butta@dom.pitt.edu
OI Goetz, Matthew/0000-0003-4542-992X
FU National Institute on Alcohol Abuse and Alcoholism [U10 AA 13566]; VHA
Public Health Strategic Health Core Group; National Institutes of Health
/National Institute on Drug Abuse [DA01617501A1]
FX Veterans Aging Cohort Study funded by: National Institute on Alcohol
Abuse and Alcoholism (U10 AA 13566) and VHA Public Health Strategic
Health Core Group. Dr Butt is supported by a Career Developmnt Award
from the National Institutes of Health /National Institute on Drug Abuse
(DA01617501A1).
NR 29
TC 102
Z9 105
U1 2
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD JUN 19
PY 2009
VL 23
IS 10
BP 1227
EP 1234
DI 10.1097/QAD.0b013e32832bd7af
PG 8
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 461PH
UT WOS:000267279800005
PM 19444074
ER
PT J
AU Cha-Molstad, H
Saxena, G
Chen, JQ
Shalev, A
AF Cha-Molstad, Hyunjoo
Saxena, Geetu
Chen, Junqin
Shalev, Anath
TI Glucose-stimulated Expression of Txnip Is Mediated by Carbohydrate
Response Element-binding Protein, p300, and Histone H4 Acetylation in
Pancreatic Beta Cells
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID THIOREDOXIN-INTERACTING PROTEIN; TRANSCRIPTION FACTOR; ORDERED
RECRUITMENT; MICROARRAY ANALYSIS; GENE-TRANSCRIPTION; APOPTOSIS; MLX;
CHREBP; MONDOA; COACTIVATOR
AB Recently, we identified Txnip (thioredoxin-interacting protein) as a mediator of glucotoxic beta cell death and discovered that lack of Txnip protects against streptozotocin- and obesity-induced diabetes by preventing beta cell apoptosis and preserving endogenous beta cell mass. Txnip has therefore become an attractive target for diabetes therapy, but although we have found that txnip transcription is highly induced by glucose through a unique carbohydrate response element, the factors controlling this effect have remained unknown. Using transient transfection experiments, we now show that overexpression of the carbohydrate response element-binding protein (ChREBP) transactivates the txnip promoter, whereas ChREBP knockdown by small interfering RNA completely blunts glucose-induced txnip transcription. Moreover, chromatin immunoprecipitation demonstrated that glucose leads to a dose- and time-dependent recruitment of ChREBP to the txnip promoter in vivo in INS-1 beta cells as well as human islets. Furthermore, we found that the co-activator and histone acetyltransferase p300 co-immunoprecipitates with ChREBP and also binds to the txnip promoter in response to glucose. Interestingly, this is associated with specific acetylation of histone H4 and recruitment of RNA polymerase II as measured by chromatin immunoprecipitation. Thus, with this study we have identified ChREBP as the transcription factor that mediates glucose-induced txnip expression in human islets and INS-1 beta cells and have characterized the chromatin modification associated with glucose-induced txnip transcription. In addition, the results reveal for the first time that ChREBP interacts with p300. This may explain how ChREBP induces H4 acetylation and sheds new light on glucose-mediated regulation of chromatin structure and transcription.
C1 [Cha-Molstad, Hyunjoo; Saxena, Geetu; Chen, Junqin; Shalev, Anath] Univ Wisconsin, Dept Med, Madison, WI 53792 USA.
[Cha-Molstad, Hyunjoo; Saxena, Geetu; Chen, Junqin; Shalev, Anath] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA.
RP Shalev, A (reprint author), Univ Wisconsin, Dept Med, H4-526 Clin Sci Ctr,600 Highland Ave, Madison, WI 53792 USA.
EM as7@medicine.wisc.edu
FU National Institutes of Health [R01DK-078752, R21HL-089205]; American
Diabetes Association [7-07-CD-22]; Juvenile Diabetes Research Foundation
[1-2007-790]
FX This work was supported, in whole or in part, by National Institutes of
Health, NIDDK, Grant R01DK-078752 and National Institutes of Health,
NHLBI, Grant R21HL-089205. This work was also supported by American
Diabetes Association Grant 7-07-CD-22 and Juvenile Diabetes Research
Foundation Grant 1-2007-790.
NR 45
TC 82
Z9 86
U1 1
U2 6
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 JUN 19
PY 2009
VL 284
IS 25
BP 16898
EP 16905
DI 10.1074/jbc.M109.010504
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 457VM
UT WOS:000266962400026
PM 19411249
ER
PT J
AU Stone, RM
AF Stone, Richard M.
TI How I treat patients with myelodysplastic syndromes
SO BLOOD
LA English
DT Review
ID COLONY-STIMULATING FACTOR; BONE-MARROW-TRANSPLANTATION; LEUKEMIA
GROUP-B; QUALITY-OF-LIFE; HEMATOPOIETIC-CELL TRANSPLANTATION; RANDOMIZED
PHASE-III; SYNDROME MDS; REFRACTORY-ANEMIA; MYELOID-LEUKEMIA; LOW-RISK
C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Stone, RM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA.
EM rstone@partners.org
NR 72
TC 50
Z9 54
U1 0
U2 3
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD JUN 18
PY 2009
VL 113
IS 25
BP 6296
EP 6303
DI 10.1182/blood-2008-09-038935
PG 8
WC Hematology
SC Hematology
GA 459XV
UT WOS:000267147400010
PM 19383969
ER
PT J
AU Niethammer, P
Grabher, C
Look, AT
Mitchison, TJ
AF Niethammer, Philipp
Grabher, Clemens
Look, A. Thomas
Mitchison, Timothy J.
TI A tissue-scale gradient of hydrogen peroxide mediates rapid wound
detection in zebrafish
SO NATURE
LA English
DT Article
ID TUMOR-SUPPRESSOR PTEN; ENDOTHELIAL-CELLS; NOX INHIBITOR; DUAL OXIDASES;
INFLAMMATION; CHEMOTAXIS; MIGRATION; GROWTH; NEUTROPHILS; EXPRESSION
AB Barrier structures (for example, epithelia around tissues and plasma membranes around cells) are required for internal homeostasis and protection from pathogens. Wound detection and healing represent a dormant morphogenetic program that can be rapidly executed to restore barrier integrity and tissue homeostasis. In animals, initial steps include recruitment of leukocytes to the site of injury across distances of hundreds of micrometres within minutes of wounding. The spatial signals that direct this immediate tissue response are unknown. Owing to their fast diffusion and versatile biological activities, reactive oxygen species, including hydrogen peroxide (H2O2), are interesting candidates for wound-to-leukocyte signalling. Here we probe the role of H2O2 during the early events of wound responses in zebrafish larvae expressing a genetically encoded H2O2 sensor(1). This reporter revealed a sustained rise in H2O2 concentration at the wound margin, starting similar to 3 min after wounding and peaking at similar to 20 min, which extended similar to 100-200 mu m into the tail-fin epithelium as a decreasing concentration gradient. Using pharmacological and genetic inhibition, we show that this gradient is created by dual oxidase (Duox), and that it is required for rapid recruitment of leukocytes to the wound. This is the first observation, to our knowledge, of a tissue-scale H2O2 pattern, and the first evidence that H2O2 signals to leukocytes in tissues, in addition to its known antiseptic role.
C1 [Niethammer, Philipp; Mitchison, Timothy J.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
[Grabher, Clemens; Look, A. Thomas] Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Look, A. Thomas] Harvard Univ, Sch Med, Dept Pediat,Childrens Hosp, Div Hematol Oncol, Boston, MA 02114 USA.
RP Niethammer, P (reprint author), Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
EM Philipp_Niethammer@hms.harvard.edu
RI Grabher, Clemens/H-2064-2013
FU National Institutes of Health [GM023928]
FX P. N. was supported by a Human Frontiers Science Program long-term
fellowship. This work was supported by the National Institutes of Health
grant GM023928. We would like to thank A. Huttenlocher and P. Crosier
for providing us with the mpo::GFP and lysC::DsRED2 transgenic zebrafish
lines, respectively.
NR 33
TC 572
Z9 587
U1 28
U2 129
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 18
PY 2009
VL 459
IS 7249
BP 996
EP U123
DI 10.1038/nature08119
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 458XS
UT WOS:000267063500045
PM 19494811
ER
PT J
AU Kwak, EL
Hong, TS
Berger, DL
Forcione, DG
Uppot, RN
Lauwers, GY
AF Kwak, Eunice L.
Hong, Theodore S.
Berger, David L.
Forcione, David G.
Uppot, Raul N.
Lauwers, Gregory Y.
TI A Woman with Carcinoma of the Gastroesophageal Junction Adenocarcinoma
of the gastroesophageal junction, pathological stage ypT2N1MX after
preoperative chemotherapy, arising in Barrett's esophagus.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID PHASE-III TRIAL; ESOPHAGOGASTRIC JUNCTION; PREDICTS SURVIVAL;
LYMPH-NODES; CANCER; CHEMORADIATION; RESECTION; SURGERY;
CHEMORADIOTHERAPY; LAPAROSCOPY
C1 [Kwak, Eunice L.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA.
[Forcione, David G.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
[Hong, Theodore S.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Hong, Theodore S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Berger, David L.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Uppot, Raul N.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Kwak, Eunice L.; Forcione, David G.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA.
[Hong, Theodore S.] Harvard Univ, Sch Med, Dept Radiat Oncol, Cambridge, MA 02138 USA.
[Berger, David L.] Harvard Univ, Sch Med, Dept Surg, Cambridge, MA 02138 USA.
[Uppot, Raul N.] Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA.
[Lauwers, Gregory Y.] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA.
RP Kwak, EL (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA.
NR 20
TC 2
Z9 2
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUN 18
PY 2009
VL 360
IS 25
BP 2656
EP 2664
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 458WR
UT WOS:000267060000012
PM 19535805
ER
PT J
AU Jain, RK
AF Jain, Rakesh K.
TI A New Target for Tumor Therapy
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID ANTI-ANGIOGENIC THERAPY; NORMALIZATION; OXYGENATION
C1 [Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA.
[Jain, Rakesh K.] Harvard Univ, Sch Med, Boston, MA USA.
RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA.
FU NCI NIH HHS [P01 CA080124]
NR 5
TC 35
Z9 41
U1 0
U2 1
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUN 18
PY 2009
VL 360
IS 25
BP 2669
EP 2671
DI 10.1056/NEJMcibr0902054
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 458WR
UT WOS:000267060000015
PM 19535806
ER
PT J
AU Santini, S
Crowet, JM
Thomas, A
Paquot, M
Vandenbol, M
Thonart, P
Wathelet, JP
Blecker, C
Lognay, G
Brasseur, R
Lins, L
Charloteaux, B
AF Santini, S.
Crowet, J. M.
Thomas, A.
Paquot, M.
Vandenbol, M.
Thonart, P.
Wathelet, J. P.
Blecker, C.
Lognay, G.
Brasseur, R.
Lins, L.
Charloteaux, B.
TI Study of Thermomyces lanuginosa Lipase in the Presence of
Tributyrylglycerol and Water
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID RHIZOMUCOR-MIEHEI LIPASE; HUMICOLA-LANUGINOSA; PANCREATIC LIPASE;
INTERFACIAL ACTIVATION; MOLECULAR-DYNAMICS; PROCOLIPASE COMPLEX; LIGAND
COMPLEXES; MIXED MICELLES; CRYSTALLOGRAPHY; PATTERN
AB The Thermomyces lanuginosa lipase has been extensively studied in industrial and biotechnological research because of its potential for triacylglycerol transformation. This protein is known to catalyze both hydrolysis at high water contents and transesterification in quasi-anhydrous conditions. Here, we investigated the Thermomyces lanuginosa lipase structure in solution in the presence of a tributyrin aggregate using 30 ns molecular-dynamics simulations. The water content of the active-site groove was modified between the runs to focus on the protein-water molecule interactions and their implications for protein structure and protein-lipid interactions. The simulations confirmed the high plasticity of the lid fragment and showed that lipid molecules also bind to a secondary pocket beside the lid. Together, these results strongly suggest that the lid plays a role in the anchoring of the protein to the aggregate. The simulations also revealed the existence of a polar channel that connects the active-site groove to the outside solvent. At the inner extremity of this channel, a tyrosine makes hydrogen bonds with residues interacting with the catalytic triad. This system could function as a pipe (polar channel) controlled by a valve (the tyrosine) that could regulate the water content of the active site.
C1 [Santini, S.; Crowet, J. M.; Thomas, A.; Brasseur, R.; Lins, L.; Charloteaux, B.] Gembloux Agr Univ, Ctr Numer Mol Biophys, Gembloux, Belgium.
[Paquot, M.] Gembloux Agr Univ, Lab Ind Biol Chem, Gembloux, Belgium.
[Vandenbol, M.] Gembloux Agr Univ, Lab Anim & Microbial Biol, Gembloux, Belgium.
[Thonart, P.] Gembloux Agr Univ, Lab Bioind, Gembloux, Belgium.
[Wathelet, J. P.] Gembloux Agr Univ, Lab Gen & Organ Chem, Gembloux, Belgium.
[Blecker, C.] Gembloux Agr Univ, Lab Food Technol, Gembloux, Belgium.
[Lognay, G.] Gembloux Agr Univ, Analyt Chem Lab, Gembloux, Belgium.
RP Charloteaux, B (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Syst Biol, 44 Binney St, Boston, MA 02115 USA.
EM charloteaux.b@fsagx.ac.be
OI Lins, Laurence/0000-0001-7772-6748
FU Gembloux Agricultural University (Belgium); Belgian Program on
Interuniversity Attraction Poles [IAP. P6/19 PROFUSA]; Fonds National
pour la Recherche Scientifique (Belgium)
FX S.S. is supported by a grant front the Gembloux Agricultural University
(Belgium), and J.M.C. and B.C. are supported by the Belgian Program on
Interuniversity Attraction Poles initiated by the Federal Office for
Scientific, Technical and Cultural Affairs (IAP. P6/19 PROFUSA). L.L. is
a research associate and R.B. is a research director for the Fonds
National pour la Recherche Scientifique (Belgium). AT. is a research
director at the French Institute for Medical Research.
NR 41
TC 14
Z9 14
U1 1
U2 15
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
J9 BIOPHYS J
JI Biophys. J.
PD JUN 17
PY 2009
VL 96
IS 12
BP 4814
EP 4825
DI 10.1016/j.bpj.2009.03.040
PG 12
WC Biophysics
SC Biophysics
GA 460NO
UT WOS:000267194600006
PM 19527641
ER
PT J
AU Zeman, RJ
Bauman, WA
Wen, XL
Ouyang, N
Etlinger, JD
Cardozo, CR
AF Zeman, Richard J.
Bauman, William A.
Wen, Xialing
Ouyang, Nengtai
Etlinger, Joseph D.
Cardozo, Christopher R.
TI Improved functional recovery with oxandrolone after spinal cord injury
in rats
SO NEUROREPORT
LA English
DT Article
DE anabolic steroid; axonal sprouting; locomotor function; oxandrolone;
spinal cord injury
ID HISTOLOGICAL OUTCOMES; CONTUSION; LOCOMOTOR; AGONIST
AB At present only the corticosteroid, methylprednisolone, is used for acute spinal cord injury to improve function. However, improvements are modest, and are associated with myopathy and immunosuppression so that alternative treatments are needed. Oxandrolone is an androgenic steroid with potential neuroprotective properties that is used to prevent muscle loss and is not immunosuppressive. Oxandrolone increased locomotor recovery concomitant with reduced loss of cord tissue in a standard weight drop model of spinal cord contusion injury indicating oxandrolone as a possible alternative to methylprednisolone. Oxandrolone also increased axonal sprouting within the ventral horns distal to the injury consistent with formation of relay circuits mediating locomotor recovery. NeuroReport 20:864-868 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
C1 [Bauman, William A.; Cardozo, Christopher R.] James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Bronx, NY 10468 USA.
[Zeman, Richard J.; Wen, Xialing; Ouyang, Nengtai; Etlinger, Joseph D.] New York Med Coll, Dept Cell Biol & Anat, Valhalla, NY 10595 USA.
[Bauman, William A.; Cardozo, Christopher R.] Mt Sinai Sch Med, Dept Med, New York, NY USA.
[Bauman, William A.; Cardozo, Christopher R.] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY USA.
[Zeman, Richard J.; Etlinger, Joseph D.] MotoGen Inc, Mt Kisco, NY USA.
RP Cardozo, CR (reprint author), James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, 130 W Kingsbridge Rd, Bronx, NY 10468 USA.
EM chris.cardozo@mssm.edu
FU Veterans Health Administration, Rehabilitation Research and Development
Service [B4162C, B3347 K]
FX This study was supported by Veterans Health Administration,
Rehabilitation Research and Development Service (B4162C to WAB, B3347 K
to CC).
NR 19
TC 6
Z9 7
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0959-4965
J9 NEUROREPORT
JI Neuroreport
PD JUN 17
PY 2009
VL 20
IS 9
BP 864
EP 868
DI 10.1097/WNR.0b013e32832c5cc2
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 457DU
UT WOS:000266908300009
PM 19424096
ER
PT J
AU Lee, TH
Ferris, TG
AF Lee, Thomas H.
Ferris, Timothy G.
TI Pay for Performance A Work in Progress
SO CIRCULATION
LA English
DT Editorial Material
DE Editorials; hypertension; health policy and outcomes research
ID QUALITY; CARE
C1 [Lee, Thomas H.] Brigham & Womens Hosp, Partners Healthcare Syst, Boston, MA 02199 USA.
[Ferris, Timothy G.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
RP Lee, TH (reprint author), Brigham & Womens Hosp, Partners Healthcare Syst, Prudential Tower,11th Floor,800 Boylston St, Boston, MA 02199 USA.
EM thlee@partners.org
NR 7
TC 1
Z9 1
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD JUN 16
PY 2009
VL 119
IS 23
BP 2965
EP 2966
DI 10.1161/CIRCULATIONAHA.109.869958
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 458KH
UT WOS:000267016900001
PM 19487591
ER
PT J
AU Petersen, LA
Woodard, LD
Henderson, LM
Urech, TH
Pietz, K
AF Petersen, Laura A.
Woodard, LeChauncy D.
Henderson, Louise M.
Urech, Tracy H.
Pietz, Kenneth
TI Will Hypertension Performance Measures Used for Pay-for-Performance
Programs Penalize Those Who Care for Medically Complex Patients?
SO CIRCULATION
LA English
DT Article; Proceedings Paper
CT Annual Meeting of the
Veterans-Affairs-Health-Services-Research-and-Development-Service
CY FEB 21-23, 2007
CL Arlington, VA
SP Vet Affairs Hlth Serv Res & Dev Serv
DE comorbidity; hypertension; physician incentive plans; process assessment
(health care); quality indicators, health care
ID QUALITY-OF-CARE; DAILY DOSE FREQUENCY; HEALTH-CARE;
MYOCARDIAL-INFARCTION; COMPETING DEMANDS; DEPRESSION CARE;
BLOOD-PRESSURE; DIABETES CARE; MEDICATION; DISEASES
AB Background-There is concern that performance measures, patient ratings of their care, and pay-for-performance programs may penalize healthcare providers of patients with multiple chronic coexisting conditions. We examined the impact of coexisting conditions on the quality of care for hypertension and patient perception of overall quality of their health care.
Methods and Results-We classified 141 609 veterans with hypertension into 4 condition groups: those with hypertension-concordant ( diabetes mellitus, ischemic heart disease, dyslipidemia) and/or -discordant ( arthritis, depression, chronic obstructive pulmonary disease) conditions or neither. We measured blood pressure control at the index visit, overall good quality of care for hypertension, including a follow-up interval, and patient ratings of satisfaction with their care. Associations between condition type and number of coexisting conditions on receipt of overall good quality of care were assessed with logistic regression. The relationship between patient assessment and objective measures of quality was assessed. Of the cohort, 49.5% had concordant-only comorbidities, 8.7% had discordant-only comorbidities, 25.9% had both, and 16.0% had none. Odds of receiving overall good quality after adjustment for age were higher for those with concordant comorbidities ( odds ratio, 1.78; 95% confidence interval, 1.70 to 1.87), discordant comorbidities ( odds ratio, 1.32; 95% confidence interval, 1.23 to 1.41), or both ( odds ratio, 2.25; 95% confidence interval, 2.13 to 2.38) compared with neither. Findings did not change after adjustment for illness severity and/or number of primary care and specialty care visits. Patient assessment of quality did not vary by the presence of coexisting conditions and was not related to objective ratings of quality of care.
Conclusions-Contrary to expectations, patients with greater complexity had higher odds of receiving high-quality care for hypertension. Subjective ratings of care did not vary with the presence or absence of comorbid conditions. Our findings should be reassuring to those who care for the most medically complex patients and are concerned that they will be penalized by performance measures or patient ratings of their care. ( Circulation. 2009; 119: 2978-2985.)
C1 Houston VA Med Ctr, Hlth Serv Res & Dev, Houston Ctr Qual Care & Utilizat Studies, Ctr Excellence,Hlth Policy & Qual Program, Houston, TX 77030 USA.
Baylor Coll Med, Sect Hlth Serv Res, Houston, TX 77030 USA.
RP Petersen, LA (reprint author), Houston Vet Affairs Med Ctr, Hlth Serv Res & Dev 152, 2002 Holcombe Blvd, Houston, TX 77030 USA.
EM laurap@bcm.edu
FU NHLBI NIH HHS [R01 HL079173, R01 HL079173-01]
NR 41
TC 31
Z9 31
U1 1
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD JUN 16
PY 2009
VL 119
IS 23
BP 2978
EP 2985
PG 8
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 458KH
UT WOS:000267016900004
PM 19487595
ER
PT J
AU Ho, PM
Bryson, CL
Rumsfeld, JS
AF Ho, P. Michael
Bryson, Chris L.
Rumsfeld, John S.
TI Medication Adherence Its Importance in Cardiovascular Outcomes
SO CIRCULATION
LA English
DT Article
DE cardiovascular diseases; healthcare quality assessment; medication
adherence; outcomes research
ID ACUTE CORONARY SYNDROMES; ACUTE MYOCARDIAL-INFARCTION; EVIDENCE-BASED
PHARMACOTHERAPY; RANDOMIZED CONTROLLED-TRIALS; CHRONIC HEART-FAILURE;
LONG-TERM MORTALITY; DEPRESSIVE SYMPTOMS; BLOOD-PRESSURE; DRUG-THERAPY;
ANTIHYPERTENSIVE MEDICATION
AB Medication adherence usually refers to whether patients take their medications as prescribed (eg, twice daily), as well as whether they continue to take a prescribed medication. Medication nonadherence is a growing concern to clinicians, healthcare systems, and other stakeholders (eg, payers) because of mounting evidence that it is prevalent and associated with adverse outcomes and higher costs of care. To date, measurement of patient medication adherence and use of interventions to improve adherence are rare in routine clinical practice. The goals of the present report are to address (1) different methods of measuring adherence, (2) the prevalence of medication nonadherence, (3) the association between nonadherence and outcomes, (4) the reasons for nonadherence, and finally, (5) interventions to improve medication adherence. (Circulation. 2009; 119: 3028-3035.)
C1 [Ho, P. Michael; Rumsfeld, John S.] Denver VA Med Ctr, Denver, CO USA.
[Ho, P. Michael; Rumsfeld, John S.] Univ Colorado, Denver, CO 80202 USA.
[Ho, P. Michael; Rumsfeld, John S.] Kaiser Permanente, Inst Hlth Res, Aurora, CO USA.
[Bryson, Chris L.] Puget Sound VA Med Ctr, Seattle, WA USA.
[Bryson, Chris L.] Univ Washington, Seattle, WA 98195 USA.
RP Ho, PM (reprint author), 1055 Clermont St 111B, Denver, CO 80220 USA.
EM michael.ho@va.gov
FU Veterans Administration Health Service Research and Career Development
FX Drs Ho and Bryson are supported by Veterans Administration Health
Service Research and Career Development.
NR 79
TC 471
Z9 489
U1 3
U2 24
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD JUN 16
PY 2009
VL 119
IS 23
BP 3028
EP 3035
DI 10.1161/CIRCULATIONAHA.108.768986
PG 8
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 458KH
UT WOS:000267016900010
PM 19528344
ER
PT J
AU Bilimoria, KY
Bentrem, DJ
Lillemoe, KD
Talamonti, MS
Ko, CY
AF Bilimoria, Karl Y.
Bentrem, David J.
Lillemoe, Keith D.
Talamonti, Mark S.
Ko, Clifford Y.
CA Amer Coll Surg Pancreatic Canc
TI Assessment of Pancreatic Cancer Care in the United States Based on
Formally Developed Quality Indicators
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID NEW-YORK-STATE; HOSPITAL VOLUME; OF-CARE; SURGICAL MORTALITY;
CARDIAC-SURGERY; UNINTENDED CONSEQUENCES; CARDIOTHORACIC SURGEONS;
APPROPRIATENESS METHOD; COLORECTAL-CANCER; HEALTH-CARE
AB Pancreatic cancer outcomes vary considerably among hospitals. Assessing pancreatic cancer care by using quality indicators could help reduce this variability. However, valid quality indicators are not currently available for pancreatic cancer management, and a composite assessment of the quality of pancreatic cancer care in the United States has not been done.
Potential quality indicators were identified from the literature, consensus guidelines, and interviews with experts. A panel of 20 pancreatic cancer experts ranked potential quality indicators for validity based on the RAND/UCLA Appropriateness Methodology. The rankings were rated as valid (high or moderate validity) or not valid. Adherence with valid indicators at both the patient and the hospital levels and a composite measure of adherence at the hospital level were assessed using data from the National Cancer Data Base (2004-2005) for 49 065 patients treated at 1134 hospitals. Summary statistics were calculated for each individual candidate quality indicator to assess the median ranking and distribution.
Of the 50 potential quality indicators identified, 43 were rated as valid (29 as high and 14 as moderate validity). Of the 43 valid indicators, 11 (25.6%) assessed structural factors, 19 (44.2%) assessed clinical processes of care, four (9.3%) assessed treatment appropriateness, four (9.3%) assessed efficiency, and five (11.6%) assessed outcomes. Patient-level adherence with individual indicators ranged from 49.6% to 97.2%, whereas hospital-level adherence with individual indicators ranged from 6.8% to 99.9%. Of the 10 component indicators (contributing 1 point each) that were used to develop the composite score, most hospitals were adherent with fewer than half of the indicators (median score = 4; interquartile range = 3-5).
Based on the quality indicators developed in this study, there is considerable variability in the quality of pancreatic cancer care in the United States. Hospitals can use these indicators to evaluate the pancreatic cancer care they provide and to identify potential quality improvement opportunities.
C1 [Bilimoria, Karl Y.; Ko, Clifford Y.] Amer Coll Surg, Canc Programs, Chicago, IL 60611 USA.
[Bilimoria, Karl Y.; Bentrem, David J.; Talamonti, Mark S.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Chicago, IL 60611 USA.
[Lillemoe, Keith D.] Indiana Univ Sch Med, Dept Surg, Indianapolis, IN USA.
[Talamonti, Mark S.] NorthShore Univ Hlth Syst, Dept Surg, Evanston, IL USA.
[Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA.
[Ko, Clifford Y.] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA.
RP Bilimoria, KY (reprint author), Amer Coll Surg, Canc Programs, 633 N St Clair St,22nd Floor, Chicago, IL 60611 USA.
EM kbilimoria@facs.org
FU American College of Surgeons, Clinical Scholars in Residence program;
American Cancer Society, Illinois Division; National Cancer Institute
[NCI-60058-NE]
FX American College of Surgeons, Clinical Scholars in Residence program (to
K.Y.B); American Cancer Society, Illinois Division (to D. J. B);
National Cancer Institute (NCI-60058-NE to C.Y.K).
NR 62
TC 49
Z9 51
U1 1
U2 5
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 JUN 16
PY 2009
VL 101
IS 12
BP 848
EP 859
DI 10.1093/jnci/djp107
PG 12
WC Oncology
SC Oncology
GA 460XH
UT WOS:000267225000007
PM 19509366
ER
PT J
AU Gore, JL
Kwan, L
Lee, SP
Reiter, RE
Litwin, MS
AF Gore, John L.
Kwan, Lorna
Lee, Steve P.
Reiter, Robert E.
Litwin, Mark S.
TI Survivorship Beyond Convalescence: 48-Month Quality-of-Life Outcomes
After Treatment for Localized Prostate Cancer
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article; Proceedings Paper
CT 103rd Annual Meeting of the American-Urological-Association
CY MAY 17-22, 2008
CL Orlando, FL
SP Amer Urol Assoc
ID NEOADJUVANT HORMONAL-THERAPY; EXTERNAL-BEAM RADIOTHERAPY; RADICAL
PROSTATECTOMY; CONFORMAL RADIOTHERAPY; BRACHYTHERAPY; RADIATION; BOTHER;
CAPSURE; INDEX
AB Decision making for treatment of localized prostate cancer is often guided by therapeutic side-effect profiles. We sought to assess health-related quality-of-life outcomes for patients 48 months after treatment for localized prostate cancer. Men treated for localized prostate cancer (N = 475) were evaluated before treatment and at 11 intervals during the 48 months after intervention. Changes in mean health-related quality-of-life scores and the probability of regaining baseline levels of health-related quality of life were compared between treatment groups. All statistical tests were two-sided. Urinary incontinence was more common after prostatectomy (n = 307) than after brachytherapy (n = 90) or external beam radiation therapy (n = 78) (both P < .001), whereas voiding and storage urinary symptoms were more prevalent after brachytherapy than after prostatectomy (both P <.001). Sexual dysfunction profoundly affected all three treatment groups, with a lower likelihood of regaining baseline function after prostatectomy than after external beam radiation therapy or brachytherapy (P <.001). Bowel dysfunction was more common after either form of radiation therapy than after prostatectomy. These results may guide decision making for treatment selection and clinical management of patients with health-related quality-of-life impairments after treatment for localized prostate cancer.
C1 [Gore, John L.] Univ Calif Los Angeles, Robert Wood Johnson Clin Scholars Program, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res,Dept Med, Los Angeles, CA 90024 USA.
[Gore, John L.] VA Greater Los Angeles Healthcare Syst, Div Gen Internal Med, Los Angeles, CA USA.
[Kwan, Lorna; Reiter, Robert E.] Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA.
[Gore, John L.; Reiter, Robert E.; Litwin, Mark S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90024 USA.
[Lee, Steve P.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiat Oncol, Los Angeles, CA 90024 USA.
RP Gore, JL (reprint author), Univ Calif Los Angeles, Robert Wood Johnson Clin Scholars Program, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res,Dept Med, 911 Broxton Ave,3rd Floor, Los Angeles, CA 90024 USA.
EM jgore@mednet.ucla.edu
OI Gore, John/0000-0002-2847-5062
NR 21
TC 76
Z9 81
U1 1
U2 3
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 JUN 16
PY 2009
VL 101
IS 12
BP 888
EP 892
DI 10.1093/jnci/djp114
PG 5
WC Oncology
SC Oncology
GA 460XH
UT WOS:000267225000011
PM 19509365
ER
PT J
AU Makhani, N
Gorman, MP
Branson, HM
Stazzone, L
Banwell, BL
Chitnis, T
AF Makhani, N.
Gorman, M. P.
Branson, H. M.
Stazzone, L.
Banwell, B. L.
Chitnis, T.
TI Cyclophosphamide therapy in pediatric multiple sclerosis
SO NEUROLOGY
LA English
DT Article
ID INTENSIVE IMMUNOSUPPRESSION; PLASMA-EXCHANGE; INTERFERON-BETA;
FOLLOW-UP; CHILDHOOD; ONSET; CANCER; SAFETY; TOLERABILITY; MITOXANTRONE
AB Objective: To review our multicenter experience with cyclophosphamide in the treatment of children with multiple sclerosis (MS).
Methods: Retrospective chart review of children with MS treated with cyclophosphamide. Demographic, clinical, treatment, and MRI parameters were collected.
Results: We identified 17 children with MS treated with cyclophosphamide. All but one had worsening of Expanded Disability Status Scale scores or multiple relapses prior to treatment initiation. Children were treated with one of three regimens: 1) induction therapy alone; 2) induction therapy with pulse maintenance therapy; or 3) pulse maintenance therapy alone. Treatment resulted in a reduction in relapse rate and stabilization of disability scores assessed 1 year after treatment initiation in the majority of patients. Longer follow-up was available for most cases. Cyclophosphamide was well tolerated in most patients. However, side effects included vomiting, transient alopecia, osteoporosis, and amenorrhea. One patient developed bladder carcinoma that was successfully treated.
Conclusions: Cyclophosphamide is an option for the treatment of children with aggressive multiple sclerosis refractory to first-line therapies. Recommendations regarding patient selection, treatment administration, and monitoring are discussed. Neurology (R) 2009;72:2076-2082
C1 [Makhani, N.; Branson, H. M.; Banwell, B. L.] Univ Toronto, Hosp Sick Children, Toronto, ON M5S 1A1, Canada.
[Gorman, M. P.; Chitnis, T.] Massachusetts Gen Hosp Children, Partners Pediat Multiple Sclerosis Ctr, Boston, MA USA.
[Gorman, M. P.] Childrens Hosp, Boston, MA 02115 USA.
[Stazzone, L.; Chitnis, T.] Brigham & Womens Hosp, Partners Multiple Sclerosis Ctr, Boston, MA 02115 USA.
RP Chitnis, T (reprint author), Massachusetts Gen Hosp, Partners Pediat Multiple Sclerosis Ctr, ACC-708,55 Fruit St, Boston, MA 02114 USA.
EM tchitnis@partners.org
FU Pediatric Multiple Sclerosis Centers of Excellence Grant from the
National Multiple Sclerosis Society, USA ( T. C.); Multiple Sclerosis
Scientific Research Foundation of Canada ( B. L. B.).; National Multiple
Sclerosis Society (Central New England Chapter) Clinical Fellowship
FX Supported by the Pediatric Multiple Sclerosis Centers of Excellence
Grant from the National Multiple Sclerosis Society, USA ( T. C.), and by
the Multiple Sclerosis Scientific Research Foundation of Canada ( B. L.
B.). M. P. G. is supported by a National Multiple Sclerosis Society
(Central New England Chapter) Clinical Fellowship.
NR 38
TC 56
Z9 57
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD JUN 16
PY 2009
VL 72
IS 24
BP 2076
EP 2082
DI 10.1212/WNL.0b013e3181a8164c
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 458KC
UT WOS:000267016300005
PM 19439723
ER
PT J
AU Sims, JR
Gharai, LR
Schaefer, PW
Vangel, M
Rosenthal, ES
Lev, MH
Schwamm, LH
AF Sims, J. R.
Gharai, L. Rezai
Schaefer, P. W.
Vangel, M.
Rosenthal, E. S.
Lev, M. H.
Schwamm, L. H.
TI ABC/2 for rapid clinical estimate of infarct, perfusion, and mismatch
volumes
SO NEUROLOGY
LA English
DT Article
ID CEREBRAL-ARTERY INFARCTION; AGGRESSIVE DECOMPRESSIVE SURGERY;
TISSUE-PLASMINOGEN ACTIVATOR; HIGH-RESOLUTION MEASUREMENT; TRACER BOLUS
PASSAGES; ACUTE ISCHEMIC-STROKE; LESION VOLUME; MRI; TRIAL; THROMBOLYSIS
AB Background: Rapid and easy clinical assessments for volumes of infarction and perfusion mismatch are needed. We tested whether simple geometric models generated accurate estimates of these volumes.
Methods: Acute diffusion-weighted image (DWI) and perfusion (mean transit time [MTT]) in 63 strokes and established infarct volumes in 50 subacute strokes were measured by computerized planimetry. Mismatch was defined as MTT/DWI >= 1.2. Observers, blinded to planimetric values, measured lesions in three perpendicular axes A, B, and C. Geometric estimates of sphere, ellipsoid, bicone, and cylinder were compared to planimetric volume by least-squares linear regression.
Results: The ABC/2 formula (ellipsoid) was superior to other geometries for estimating volume of DWI (slope 1.16, 95% confidence interval [CI] 0.94 to 1.38; R(2) = 0.91, p = 0.001) and MTT (slope 1.11, 95% CI 0.99 to 1.23; R(2) = 0.89, p = 0.001). The intrarater and interrater reliability for ABC/2 was high for both DWI (0.992 and 0.965) and MTT (0.881 and 0.712). For subacute infarct, the ABC/2 formula also best estimated planimetric volume (slope 1.00, 95% CI 0.98 to 1.19; R(2) = 0.74, p = 0.001). In general, sphere and cylinder geometries overestimated all volumes and bicone underestimated all volumes. The positive predictive value for mismatch was 92% and negative predictive value was 33%.
Conclusions: Of the models tested, ABC/2 is reproducible, is accurate, and provides the best simple geometric estimate of infarction and mean transit time volumes. ABC/2 has a high positive predictive value for identifying mismatch greater than 20% and might be a useful tool for rapid determination of acute stroke treatment. Neurology (R) 2009;72:2104-2110
C1 [Sims, J. R.; Schwamm, L. H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Charlestown, MA 02129 USA.
[Sims, J. R.; Gharai, L. Rezai; Schaefer, P. W.; Vangel, M.; Rosenthal, E. S.; Lev, M. H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Charlestown, MA 02129 USA.
RP Sims, JR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, CNY149 Rm 6403,13th St, Charlestown, MA 02129 USA.
EM jsims@partners.org
OI Schwamm, Lee/0000-0003-0592-9145; Rosenthal, Eric/0000-0003-3900-356X
FU American Heart Association, Scientist Development [0535138N]; NIH [K08
NS049241]
FX Supported by the American Heart Association, Scientist Development Grant
0535138N and NIH K08 NS049241.
NR 34
TC 126
Z9 131
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD JUN 16
PY 2009
VL 72
IS 24
BP 2104
EP 2110
DI 10.1212/WNL.0b013e3181aa5329
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 458KC
UT WOS:000267016300009
PM 19528517
ER
PT J
AU Lu, PH
Edland, SD
Teng, E
Tingus, K
Petersen, RC
Cummings, JL
AF Lu, P. H.
Edland, S. D.
Teng, E.
Tingus, K.
Petersen, R. C.
Cummings, J. L.
CA Alzheimer's Dis Cooperative Study
TI Donepezil delays progression to AD in MCI subjects with depressive
symptoms
SO NEUROLOGY
LA English
DT Article
ID MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; NEUROPSYCHIATRIC
SYMPTOMS; FOLLOW-UP; DEVELOPING DEMENTIA; CONVERSION; APATHY;
GALANTAMINE; HYPOTHESIS; PREDICTION
AB Objective: To determine whether the presence of depression predicts higher rate of progression to Alzheimer disease (AD) in patients with amnestic mild cognitive impairment (aMCI) and whether donepezil treatment beneficially affect this relationship.
Methods: The study sample was composed of 756 participants with aMCI from the 3-year, double-blind, placebo-controlled Alzheimer's Disease Cooperative Study drug trial of donepezil and vitamin E. Beck Depression Inventory (BDI) was used to assess depressive symptoms at baseline and participants were followed either to the end of study or to the primary endpoint of progression to probable or possible AD.
Results: Cox proportional hazards regression, adjusted for age at baseline, gender, apolipoprotein genotype, and NYU paragraph delayed recall score, showed that higher BDI scores were associated with progression to AD (p = 0.03). The sample was stratified into depressed (BDI score >= 10; n = 208) and nondepressed (BDI < 10; n = 548) groups. Kaplan-Meier analysis showed that among the depressed subjects, the proportion progressing to AD was lower for the donepezil group than the combined vitamin E and placebo groups at 1.7 years (p = 0.023), at 2.2 years (p = 0.025), and remained marginally lower at 2.7 years (p = 0.070). The survival curves among the three treatment groups did not differ within the nondepressed participants.
Conclusions: Results suggest that depression is predictive of progression from amnestic mild cognitive impairment (aMCI) to Alzheimer disease (AD) and treatment with donepezil delayed progression to AD among depressed subjects with aMCI. Donepezil appears to modulate the increased risk of AD conferred by the presence of depressive symptoms. Neurology (R) 2009;72:2115-2121
C1 [Lu, P. H.; Teng, E.; Tingus, K.; Cummings, J. L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA.
[Cummings, J. L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA.
[Edland, S. D.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA.
[Teng, E.] Greater Los Angeles VA Healthcare Syst, Neurobehav Unit, Los Angeles, CA USA.
[Petersen, R. C.] Mayo Clin, Coll Med, Dept Neurol, Rochester, MN USA.
RP Lu, PH (reprint author), Mary S Easton Ctr Alzheimers Dis Res, 10911 Weyburn Ave,Suite 200, Los Angeles, CA 90095 USA.
EM plu@mednet.ucla.edu
OI Adler, Lawrence/0000-0002-6619-2493
FU National Institute on Aging [K23-AG028727, P50 AG-16570]; Alzheimer's
Association [NIRG-07-60424]; Alzheimer's Disease Cooperative Study [U01
AG010483]; Alzheimer's Disease Research Center of California, Jim
Easton, and the Sidell Kagan Foundation
FX Supported by grants from the National Institute on Aging (K23-AG028727),
Alzheimer's Association (NIRG-07-60424), the Alzheimer's Disease
Cooperative Study (U01 AG010483), the Alzheimer's Disease Research
Center (P50 AG-16570 from the National Institute on Aging), Alzheimer's
Disease Research Center of California, Jim Easton, and the Sidell Kagan
Foundation.
NR 40
TC 60
Z9 70
U1 3
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD JUN 16
PY 2009
VL 72
IS 24
BP 2115
EP 2121
DI 10.1212/WNL.0b013e3181aa52d3
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 458KC
UT WOS:000267016300011
PM 19528519
ER
PT J
AU Hayden, D
Lazar, P
Schoenfeld, D
AF Hayden, Douglas
Lazar, Peter
Schoenfeld, David
CA Inflammation Host Response Injury
TI Assessing Statistical Significance in Microarray Experiments Using the
Distance Between Microarrays
SO PLOS ONE
LA English
DT Article
AB We propose permutation tests based on the pairwise distances between microarrays to compare location, variability, or equivalence of gene expression between two populations. For these tests the entire microarray or some pre-specified subset of genes is the unit of analysis. The pairwise distances only have to be computed once so the procedure is not computationally intensive despite the high dimensionality of the data. An R software package, permtest, implementing the method is freely available from the Comprehensive R Archive Network at http://cran.r-project.org.
RP Hayden, D (reprint author), Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA.
EM dhayden@partners.org
FU NIGMS NIH HHS [U54 GM-62119-02, U54 GM062119]
NR 17
TC 6
Z9 6
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 16
PY 2009
VL 4
IS 6
AR e5838
DI 10.1371/journal.pone.0005838
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 458NA
UT WOS:000267029500001
PM 19529777
ER
PT J
AU Morris, ZS
McClatchey, AI
AF Morris, Zachary S.
McClatchey, Andrea I.
TI Aberrant epithelial morphology and persistent epidermal growth factor
receptor signaling in a mouse model of renal carcinoma
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE EGFR; kidney; Merlin; Nf2; renal cell carcinoma
ID CELL CARCINOMA; TUMOR-SUPPRESSOR; TYROSINE PHOSPHORYLATION; EMBRYONIC
LETHALITY; POLYCYSTIC KIDNEYS; TSC2 MUTATION; TUBULAR CELLS;
FACTOR-ALPHA; ABX-EGF; MICE
AB The epidermal growth factor receptor (EGFR) has frequently been implicated in hyperproliferative diseases of renal tubule epithelia. We have shown that the NF2 tumor suppressor Merlin inhibits EGFR internalization and signaling in a cell contact-dependent manner. Interestingly, despite the paucity of recurring mutations in human renal cell carcinoma (RCC), homozygous mutation of the NF2 gene is found in approximate to 2% of RCC patient samples in the Sanger COSMIC database. To examine the roles of Merlin and EGFR in kidney tumorigenesis, we generated mice with a targeted deletion of Nf2 in the proximal convoluted epithelium using a Villin-Cre transgene. All of these mice developed intratubular neoplasia by 3 months, which progressed to invasive carcinoma by 6-10 months. Kidneys from these mice demonstrated marked hyperproliferation and a concomitant increase in label-retaining putative progenitor cells. Early lumen-filling lesions in this model exhibited hyperactivation of EGFR signaling, altered solubility of adherens junctions components, and loss of epithelial polarity. Renal cortical epithelial cells derived from either early or late lesions were dependent on EGF for in vitro proliferation and were arrested by pharmacologic inhibition of EGFR or re-expression of Nf2. These cells formed malignant tumors upon s.c. injection into immunocompromised mice before in vitro passage. Treatment of Vil-Cre;Nf2(lox/lox) mice with the EGFR inhibitor erlotinib halted the proliferation of tumor cells. These studies give added credence to the role of EGFR signaling and perhaps Nf2 deficiency in RCC and describe a rare and valuable mouse model for exploring the molecular basis of this disease.
C1 [McClatchey, Andrea I.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA.
Harvard Univ, Sch Med, Dept Pathol, Charlestown, MA 02129 USA.
RP McClatchey, AI (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA.
EM mcclatch@helix.mgh.harvard.edu
OI Morris, Zachary/0000-0001-5558-3547
FU National Institutes of Health (NIH)/National Cancer Institute
[CA113733]; NIH/National Institute of General Medical Sciences [T32
GM07306]; Department of Defense [W81XWH-05-1-0189]
FX We thank Marco Giovannini and Sylvie Robine for Nf2lox/lox
and Villin-Cre mice, respectively; Othon Iliopoulos, Jordan Kreidberg,
and Marcello Curto for advice and discussion; Rod Bronson, Sabina
Signoretti, and Chin-Lee Wu for pathology consultation; and Andrew
Gladden and Brett Morris for assistance with FACS and
immunohistochemistry, respectively. This work was supported by National
Institutes of Health (NIH)/National Cancer Institute Grant CA113733 (to
A.I.M.); NIH/National Institute of General Medical Sciences Grant T32
GM07306 (to Z.S.M.); and Department of Defense Grant W81XWH-05-1-0189
(to A.I.M.).
NR 57
TC 30
Z9 30
U1 0
U2 0
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 JUN 16
PY 2009
VL 106
IS 24
BP 9767
EP 9772
DI 10.1073/pnas.0902031106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 458TD
UT WOS:000267045500041
PM 19487675
ER
PT J
AU Freston, JW
Hisada, M
Peura, DA
Haber, MM
Kovacs, TO
Atkinson, S
Hunt, B
AF Freston, J. W.
Hisada, M.
Peura, D. A.
Haber, M. M.
Kovacs, T. O.
Atkinson, S.
Hunt, B.
TI The clinical safety of long-term lansoprazole for the maintenance of
healed erosive oesophagitis
SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS
LA English
DT Article
ID GASTROESOPHAGEAL-REFLUX DISEASE; PROTON PUMP INHIBITORS;
CLOSTRIDIUM-DIFFICILE DIARRHEA; ESOMEPRAZOLE 20 MG; DOSE LANSOPRAZOLE;
COLORECTAL-CANCER; GASTRIC-MUCOSA; DOUBLE-BLIND; RISK; THERAPY
AB The clinical safety of long-term lansoprazole therapy for the maintenance of healed erosive oesophagitis has not been extensively studied in clinical trials.
To assess the long-term clinical safety of dose-titrated lansoprazole as maintenance therapy for up to 82 months in subjects with healed erosive oesophagitis.
Clinical safety was assessed by monitoring adverse events (AEs), laboratory data including serum gastrin levels, and endoscopy.
Mean duration (+/- s.d.) of lansoprazole treatment during the titrated open-label period was 56 +/- 24 months (range < 1-82 months). Overall, 189 of 195 (97%) subjects experienced a total of 2825 treatment-emergent AEs. Most AEs occurred during the first year of treatment, were mild-to-moderate in severity and resolved while on treatment. Of 155 serious AEs (in 74 subjects), only two (colitis and rectal haemorrhage in one subject) were considered treatment-related. Sixty-nine of 195 subjects (35%) experienced 187 treatment-related AEs, with diarrhoea (10%), headache (8%) and abdominal pain (6%) being the most common. Gastrin levels >= 400 pg/mL were seen in 9% of subjects; hypergastrinemia was not associated with gastro-intestinal AEs or nodules/polyps.
Lansoprazole maintenance therapy for up to 6 years is safe and well tolerated in subjects with healed erosive oesophagitis.
C1 [Hisada, M.; Atkinson, S.; Hunt, B.] Takeda Global Res & Dev Ctr Inc, Deerfield, IL 60015 USA.
[Freston, J. W.] Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA.
[Peura, D. A.] Univ Virginia Hlth Syst, Div Gastroenterol & Hepatol, Charlottesville, VA USA.
[Haber, M. M.] Drexel Univ, Dept Pathol, Coll Med, Philadelphia, PA 19104 USA.
[Kovacs, T. O.] VA Greater LA Healthcare Syst, CURE Clin, Los Angeles, CA USA.
RP Hisada, M (reprint author), Takeda Global Res & Dev Ctr Inc, 1 Takeda Pkwy, Deerfield, IL 60015 USA.
EM michie.hisada@tgrd.com
FU Takeda Global Research & Development Center, Inc [M94-140]; Gillian
Gummer of Rx Communications (UK); Takeda Pharmaceuticals North America,
Inc
FX This study (M94-140) was funded by Takeda Global Research & Development
Center, Inc. Writing support was provided by Gillian Gummer of Rx
Communications (UK) and funded by Takeda Pharmaceuticals North America,
Inc. The authors would like to thank the M94-140 investigators for
participating in the study.
NR 46
TC 15
Z9 15
U1 0
U2 2
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0269-2813
J9 ALIMENT PHARM THER
JI Aliment. Pharmacol. Ther.
PD JUN 15
PY 2009
VL 29
IS 12
BP 1249
EP 1260
DI 10.1111/j.1365-2036.2009.03998.x
PG 12
WC Gastroenterology & Hepatology; Pharmacology & Pharmacy
SC Gastroenterology & Hepatology; Pharmacology & Pharmacy
GA 448MT
UT WOS:000266267400004
PM 19416133
ER
PT J
AU Preis, SR
Hwang, SJ
Fox, CS
Massaro, JM
Levy, D
Hoffmann, U
O'Donnell, CJ
AF Preis, Sarah Rosner
Hwang, Shih-Jen
Fox, Caroline S.
Massaro, Joseph M.
Levy, Daniel
Hoffmann, Udo
O'Donnell, Christopher J.
TI Eligibility of Individuals With Subclinical Coronary Artery Calcium and
Intermediate Coronary Heart Disease Risk for Reclassification (from the
Framingham Heart Study)
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID ELECTRON-BEAM TOMOGRAPHY; C-REACTIVE PROTEIN; COMPUTED-TOMOGRAPHY;
EVENTS; PREDICTION; COHORT; ADULTS; AGE; REPRODUCIBILITY; QUANTIFICATION
AB Coronary artery calcium (CAC) predicts risk for coronary heart disease (CRD) events and perhaps CAC testing may further stratify risk in individuals at intermediate CHD risk. We sought to determine the percentage of participants at intermediate CHD risk who could potentially be reclassified as having a high CHD risk based on the presence of a high CAC score and the prevalence, treatment, and control of CHD risk factors in this group. Framingham Heart Study Offspring and Third Generation cohort participants underwent multidetector computed tomography (n = 3,529, mean age 51 years, 48% women). High CAC was defined as >= 90th age- and gender-specific percentiles based on a healthy reference group or by an absolute modified Agatston score of 100 HU. Prevalence of CHD risk factors (hypertension, hypercholesterolemia, high low-density lipoprotein cholesterol, low high-density lipoprotein cholesterol, smoking, and obesity), their treatment, and control was compared between nondiabetic participants with and without high CAC. Of the 595 participants at intermediate CHD risk, 22% had CAC 90th percentile and 39% had CAC 100 and could be eligible for reclassification as having a high CHD risk based on the presence of a high CAC score. There were no statistically significant differences in prevalence, treatment, and control of risk factors between those with and without high CAC. In conclusion, prevalence of CHD risk factors did not differ between intermediate-risk participants with and without high CAC. Approximately 25% of intermediate-risk individuals have high CAC scores and may be eligible for reclassification into a higher-risk category. (C) 2009 Published by Elsevier Inc. (Am J Cardiol 2009;103:1710-1715)
C1 [Preis, Sarah Rosner; Hwang, Shih-Jen; Fox, Caroline S.; Levy, Daniel; O'Donnell, Christopher J.] NHLBI, Ctr Populat Studies, Framingham Heart Study, Framingham, MA USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA 02115 USA.
[Massaro, Joseph M.] Boston Univ, Dept Math, Boston, MA 02215 USA.
[Hoffmann, Udo] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,MGH Cardiac MR PET CT Prog, Boston, MA 02115 USA.
[O'Donnell, Christopher J.] Harvard Univ, Sch Med, Div Cardiol, Massachusetts Gen Hosp,Dept Med, Boston, MA 02115 USA.
RP O'Donnell, CJ (reprint author), NHLBI, Ctr Populat Studies, Framingham Heart Study, Framingham, MA USA.
EM codonnell@nih.gov
OI Preis, Sarah/0000-0002-9360-4166; Massaro, Joseph/0000-0002-2682-4812
FU Intramural NIH HHS [ZIA HL006002-04, Z99 HL999999]; NHLBI NIH HHS
[N01-HC-25195, N01HC25195, N01 HC025195]
NR 28
TC 18
Z9 19
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 JUN 15
PY 2009
VL 103
IS 12
BP 1710
EP 1715
DI 10.1016/j.amjcard.2009.02.020
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 463CS
UT WOS:000267407000014
PM 19539080
ER
PT J
AU Thompson, LR
Boudreau, R
Hannon, MJ
Newman, AB
Chu, CR
Jansen, M
Nevitt, MC
Kwoh, CK
AF Thompson, Laura R.
Boudreau, Robert
Hannon, Michael J.
Newman, Anne B.
Chu, Constance R.
Jansen, Mary
Nevitt, Michael C.
Kwoh, C. Kent
CA Osteoarthritis Initiative Inves
TI The Knee Pain Map: Reliability of a Method to Identify Knee Pain
Location and Pattern
SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH
LA English
DT Article
ID BONE-MARROW; OSTEOARTHRITIS; ASSOCIATION
AB Objective. To describe the location and pattern of knee pain in patients with chronic, frequent knee pain using the Knee Pain Map, and to evaluate the inter- and intrarater reliability of the map.
Methods. A cohort of 799 participants from the University of Pittsburgh Osteoarthritis Initiative Clinical Center who had knee pain in the last 12 months were studied. Trained interviewers assessed and recorded participant-reported knee pain patterns into 8 local areas, 4 regional areas, or as diffuse. Inter- and intrarater reliability were assessed using Fleiss' kappa.
Results. Participants most often reported localized (69%) followed by regional (14%) or diffuse (10%) knee pain. In those with localized pain, the most commonly reported locations were the medial (56%) and lateral (43%) joint lines. In those with regional pain, the most commonly reported regions were the patella (44%) and medial region (38%). There was. excellent interrater reliability for the identification of localized and regional pain patterns (kappa = 0.7-0.9 and 0.7-0.8, respectively). The interrater reliability for specific locations was also excellent (kappa = 0.7-1.0) when the number of participants with pain in a location was >4. For regional pain, the kappa for specific regions varied from 0.7-1.0.
Conclusion. The majority of participants could identify the location of their knee pain, and trained interviewers could reliably record those locations. The variation in locations suggests that there are multiple sources of pain in knee OA. Additional studies are needed to determine whether specific knee pain patterns correlate with discrete pathologic findings on radiographs or magnetic resonance images.
C1 [Thompson, Laura R.; Boudreau, Robert; Hannon, Michael J.; Newman, Anne B.; Chu, Constance R.; Jansen, Mary; Kwoh, C. Kent] Univ Pittsburgh, Pittsburgh, PA USA.
[Nevitt, Michael C.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Kwoh, C. Kent] VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA.
RP Kwoh, CK (reprint author), S702 BSTWR,200 Lothrop St, Pittsburgh, PA 15261 USA.
EM kwoh@pitt.edu
RI Newman, Anne/C-6408-2013;
OI Newman, Anne/0000-0002-0106-1150; Boudreau, Robert/0000-0003-0162-5187
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases
[AR-12262]; National Institute of Aging Ruth L. Kirschstein National
Research Service Award Institutional Research [AG-021885]; University of
Pittsburgh School of Medicine Clinical Scientist
FX Supported in part by the National Institute of Arthritis and
Musculoskeletal and Skin Diseases (grant AR-12262), the National
Institute of Aging Ruth L. Kirschstein National Research Service Award
Institutional Research Training (grant AG-021885), and the University of
Pittsburgh School of Medicine Clinical Scientist Training Program.
NR 12
TC 25
Z9 26
U1 0
U2 2
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0004-3591
J9 ARTHRIT RHEUM-ARTHR
JI Arthritis Rheum-Arthritis Care Res.
PD JUN 15
PY 2009
VL 61
IS 6
BP 725
EP 731
DI 10.1002/art.24543
PG 7
WC Rheumatology
SC Rheumatology
GA 459PI
UT WOS:000267115300003
PM 19479703
ER
PT J
AU La Fountaine, MF
Heffernan, KS
Gossett, JD
Bauman, WA
De Meersman, RE
AF La Fountaine, Michael F.
Heffernan, Kevin S.
Gossett, James D.
Bauman, William A.
De Meersman, Ronald E.
TI Transient suppression of heart rate complexity in concussed athletes
SO AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL
LA English
DT Review
DE Mild traumatic brain injury; Concussion; Autonomic nervous system;
Approximate entropy; Heart rate complexity
ID TRAUMATIC BRAIN-INJURY; RATE-VARIABILITY; APPROXIMATE ENTROPY; DYNAMICS
AB Heart rate variability (HRV) and complexity (HRC) were calculated at rest and during an isometric hand grip test (IHGT) within 48-hours (48 h) and two weeks (Week Two) of a concussion in athletes (CG) and control subjects. No differences were present at rest or in HRV during IGHT. HRC was significantly lower in the CG compared to controls at 48 h during IHGT. In CG at Week Two during IHGT, HRC was significantly greater than 48 h observations and not significantly different than controls. The findings suggest that HRC may have utility in detecting efferent cardiac autonomic anomalies within two weeks of concussion. Published by Elsevier B.V.
C1 [La Fountaine, Michael F.; Bauman, William A.] James J Peter VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Bronx, NY 10468 USA.
[De Meersman, Ronald E.] Columbia Univ, Teachers Coll, Dept Biobehav Sci, New York, NY 10027 USA.
[Heffernan, Kevin S.] Tufts Med Ctr, Dept Med, Div Cardiol & Mol Cardiol, Res Inst, Boston, MA USA.
[Bauman, William A.] Mt Sinai Sch Med, Dept Med & Rehabil Med, New York, NY USA.
[Gossett, James D.] Columbia Univ, Dept Sports Med, New York, NY USA.
RP La Fountaine, MF (reprint author), James J Peter VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Room 1E-02,130 W Kingsbridge Rd, Bronx, NY 10468 USA.
EM Michael.LaFountaine@va.gov
FU Department of Veterans Affairs Rehabilitation Research and Development
Center of Excellence for the Medical Consequences of Spinal Cord Injury
[B4162C]; VIDDA Foundation
FX The authors would like to thank the athletes, coaches and administrators
of the Columbia University Athletics Department for their cooperation
during this study. Also, special recognition is warranted for the
Columbia University sports medicine staff for their professionalism and
enthusiasm. The study was conducted in cooperation with the Department
of Veterans Affairs Rehabilitation Research and Development Center of
Excellence for the Medical Consequences of Spinal Cord Injury (# B4162C)
and the VIDDA Foundation.
NR 19
TC 10
Z9 10
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1566-0702
J9 AUTON NEUROSCI-BASIC
JI Auton. Neurosci-Basic Clin.
PD JUN 15
PY 2009
VL 148
IS 1-2
BP 101
EP 103
DI 10.1016/j.autneu.2009.03.001
PG 3
WC Neurosciences
SC Neurosciences & Neurology
GA 455DW
UT WOS:000266738600015
PM 19303821
ER
PT J
AU Norton, D
McBain, R
Holt, DJ
Ongur, D
Chen, Y
AF Norton, Daniel
McBain, Ryan
Holt, Daphne J.
Ongur, Dost
Chen, Yue
TI Association of Impaired Facial Affect Recognition with Basic Facial and
Visual Processing Deficits in Schizophrenia
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Cognitive; emotion recognition; face recognition; neuroscience;
perception; schizophrenic
ID EMOTION RECOGNITION; PERCEPTION; FACE; AMYGDALA; DISCRIMINATION;
ACTIVATION
AB Background: Impaired emotion recognition has been reported in schizophrenia, yet the nature of this impairment is not completely understood. Recognition of facial emotion depends on processing affective and nonaffective facial signals, as well as basic visual attributes. We examined whether and how poor facial emotion recognition in schizophrenia is related to basic visual processing and nonaffective face recognition.
Methods: Schizophrenia patients (n = 32) and healthy control subjects (n = 29) performed emotion discrimination, identity discrimination, and visual contrast detection tasks, where the emotionality, distinctiveness of identity, or visual contrast was systematically manipulated. Subjects determined which of two presentations in a trial contained the target: the emotional face for emotion discrimination, a specific individual for identity discrimination, and a sinusoidal grating for contrast detection.
Results: Patients had significantly higher thresholds (worse performance) than control subjects for discriminating both fearful and happy faces. Furthermore, patients' poor performance in fear discrimination was predicted by performance in visual detection and face identity discrimination.
Conclusions: Schizophrenia patients require greater emotional signal strength to discriminate fearful or happy face images from neutral ones. Deficient emotion recognition in schizophrenia does not appear to be determined solely by affective processing but is also linked to the processing of basic visual and facial information.
C1 [Holt, Daphne J.; Ongur, Dost; Chen, Yue] Harvard Univ, Sch Med, Dept Psychiat, Belmont, MA 02478 USA.
[Holt, Daphne J.] Massachusetts Gen Hosp, Charlestown, MA USA.
[Norton, Daniel; McBain, Ryan; Ongur, Dost; Chen, Yue] McLean Hosp, Belmont, MA 02178 USA.
RP Chen, Y (reprint author), Harvard Univ, Sch Med, Dept Psychiat, 115 Mill St,Room G06,Ctr Bldg, Belmont, MA 02478 USA.
EM ychen@mclean.harvard.edu
FU National Institutes of Health (NIH); Harvard University
FX This work was supported in part by grants from the National Institutes
of Health (NIH) and Harvard University.
NR 20
TC 44
Z9 44
U1 2
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD JUN 15
PY 2009
VL 65
IS 12
BP 1094
EP 1098
DI 10.1016/j.biopsych.2009.01.026
PG 5
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 455IW
UT WOS:000266753300014
PM 19268917
ER
PT J
AU Jackson, NA
Barrueco, J
Soufi-Mahjoubi, R
Marshall, J
Mitchell, E
Zhang, XX
Meyerhardt, J
AF Jackson, Nadine A.
Barrueco, Jose
Soufi-Mahjoubi, Raoudha
Marshall, John
Mitchell, Edith
Zhang, Xiaoxi
Meyerhardt, Jeffrey
TI Comparing Safety and Efficacy of First-line Irinotecan/Fluoropyrimidine
Combinations in Elderly Versus Nonelderly Patients With Metastatic
Colorectal Cancer Findings From the Bolus, Infusional, or Capecitabine
With Camptostar-Celecoxib Study
SO CANCER
LA English
DT Article; Proceedings Paper
CT 43rd Annual Meeting of the American-Society-of-Clinical-Oncology
CY JUN 01-05, 2007
CL Chicago, IL
SP Amer Soc Clin Oncol
DE colorectal cancer; fluoropyrimidine; irinotecan; elderly
ID PHASE-II TRIAL; CLINICAL-TRIALS; UNDERREPRESENTED POPULATIONS; OLDER
PATIENTS; IRINOTECAN CPT-11; RANDOMIZED-TRIAL; FOLFIRI REGIMEN;
CHEMOTHERAPY; OXALIPLATIN; LEUCOVORIN
AB BACKGROUND: Irinotecan-based chemotherapy regimens are I option for treatment of metastatic colorectal cancer (mCRC). The authors report the safety and efficacy of such regimens in elderly patients using a large phase III trial (bolus, infusional, or capecitabine with camptostar-celecoxib [BICC-C]) cohort. METHODS: In period 1, 430 previously untreated patients with mCRC were randomized in a 3-by-2 design to receive irinotecan plus infusional 5-fluorouracil, and leucovorin (FOLFIRI), irinotecan plus bolus 5-fluorouracil/leucovorin (mIFL), and irinotecan plus oral capecitabine (CapeIRI). In period 2, an additional 117 patients were randomized to receive FOLFIRI or mIFL and bevacizumab. In both periods patients were also randomized to a double-blind treatment with celecoxib or placebo. A secondary analysis was conducted examining the safety and efficacy of these regimens in elderly (age >70 years) versus nonelderly (age <= 70 years) patients. RESULTS: In period 1, 19.5% of patients were elderly, compared with 24.8% in period 2. Rates of grade 3 and higher toxicity did not differ significantly between age groups in either period by treatment arm, with the exception of asthenia in the FOLFIRI and CapeIRI arms (P=.05 and P=.03, respectively) and dehydration in the CapeIRI arm in period I (P=.02). Overall progression-free survival for FOLFIRI in both periods was not statistically different by age. Objective responses and overall survival did not differ by patient age within treatment arms and periods. CONCLUSIONS: Irinotecan/fluoropyrimidine combinations are well tolerated in the elderly population, with similar efficacy to that found in nonelderly patients in first-line mCRC. Cancer 2009;115:2617-29. (C) 2009 American Cancer Society.
C1 [Jackson, Nadine A.; Meyerhardt, Jeffrey] Dana Farber Canc Inst, Dept Gastrointestinal Oncol, Boston, MA 02115 USA.
[Barrueco, Jose; Soufi-Mahjoubi, Raoudha; Zhang, Xiaoxi] Pfizer Global Pharmaceut, New York, NY USA.
[Marshall, John] Georgetown Univ, Dept Med Oncol, Lombardi Canc Ctr, Washington, DC USA.
[Mitchell, Edith] Thomas Jefferson Univ, Jefferson Med Coll, Dept Med Oncol, Philadelphia, PA 19107 USA.
RP Meyerhardt, J (reprint author), 44 Binney St, Boston, MA 02115 USA.
EM jmeyerhardt@partners.org
NR 50
TC 28
Z9 28
U1 0
U2 3
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0008-543X
J9 CANCER
JI Cancer
PD JUN 15
PY 2009
VL 115
IS 12
BP 2617
EP 2629
DI 10.1002/cncr.24305
PG 13
WC Oncology
SC Oncology
GA 455UD
UT WOS:000266790900008
PM 19382200
ER
PT J
AU Hassett, MJ
O'Malley, AJ
Keating, NL
AF Hassett, Michael J.
O'Malley, A. James
Keating, Nancy L.
TI Factors Influencing Changes in Employment Among Women With Newly
Diagnosed Breast Cancer
SO CANCER
LA English
DT Article
DE breast cancer; employment; disability; outcomes; risk factors
ID QUALITY-OF-LIFE; COMORBIDITY INDEX; CLAIMS DATA; LONG-TERM; SURVIVORS;
WORK; CHEMOTHERAPY; HEALTH; COHORT; RETURN
AB BACKGROUND: Although studies have demonstrated that women are less likely to work after they are diagnosed with breast cancer, the influence of cancer treatments on employment is less clear. The authors of this report assessed whether chemotherapy or radiation therapy was associated with a disruption in employment during the year after a breast cancer diagnosis. METHODS: Using a database of health insurance claims that covered 5.6 million US residents, 3233 women aged <= 63 years were identified who were working full time or part time when they were diagnosed with breast cancer between 1998 and 2002. All changes in employment during the year after a breast cancer diagnosis were identified. Using a Cox proportional hazards model that incorporated time-varying treatment variables, the authors evaluated the impact of chemotherapy and radiation therapy on the likelihood of experiencing an employment disruption. RESULTS: Although most women (93%) continued to work, chemotherapy recipients were more likely than nonrecipients to go on long-term disability, stop working, or retire (hazards ratio, 1.8; P<.01). Women aged :54 years were more likely to experience a change in employment than women aged <= 44 years (P<.01). Radiation therapy did not influence employment (P=.22). CONCLUSIONS: in this population of employed, insured women, chemotherapy had a negative impact on employment. This finding may aid treatment decision making and could foster the development of interventions that support a patient's ability to continue working after treatment. It also reinforces the need to assess the impact of treatments, especially new treatments, on patient-centered outcomes such as employment. Cancer 2009;115:2775-82. (C) 2009 American Cancer Society.
C1 [Hassett, Michael J.] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA.
[O'Malley, A. James; Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Keating, Nancy L.] Brigham & Womens Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02115 USA.
RP Hassett, MJ (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, 44 Binney St, Boston, MA 02115 USA.
EM mhassett@partners.org
FU Agency for Healthcare Research and Quality [PO1-HS10803]; National
Cancer Institute [R01 CA104118]; American Society of Clinical Oncology
Career Development Award [R25 CA092203]
FX Dr. Hassett received salary Support from Grant R25 CA092203 and an
American Society of Clinical Oncology Career Development Award.
NR 32
TC 30
Z9 30
U1 0
U2 8
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0008-543X
J9 CANCER
JI Cancer
PD JUN 15
PY 2009
VL 115
IS 12
BP 2775
EP 2782
DI 10.1002/cncr.24301
PG 8
WC Oncology
SC Oncology
GA 455UD
UT WOS:000266790900023
PM 19365847
ER
PT J
AU Zhang, J
Sattler, M
Tonon, G
Grabher, C
Lababidi, S
Zimmerhackl, A
Raab, MS
Vallet, S
Zhou, YM
Cartron, MA
Hideshima, T
Tai, YT
Chauhan, D
Anderson, KC
Podar, K
AF Zhang, Jing
Sattler, Martin
Tonon, Giovanni
Grabher, Clemens
Lababidi, Samir
Zimmerhackl, Alexander
Raab, Marc S.
Vallet, Sonia
Zhou, Yiming
Cartron, Marie-Astrid
Hideshima, Teru
Tai, Yu-Tzu
Chauhan, Dharminder
Anderson, Kenneth C.
Podar, Klaus
TI Targeting Angiogenesis via a c-Myc/Hypoxia-Inducible Factor-1
alpha-Dependent Pathway in Multiple Myeloma
SO CANCER RESEARCH
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; IN-VIVO; TUMOR PROGRESSION; KINASE INHIBITOR;
TRANSGENIC ZEBRAFISH; FACTOR 1-ALPHA; MYC; HYPOXIA; CANCER; CELLS
AB Bone marrow angiogenesis is associated with multiple myeloma (MM) progression. Here, we report high constitutive hypoxia-inducible factor-1 alpha (Hif-1 alpha) expression in MM cells, which is associated with oncogenic c-Myc. A drug screen for anti-MM agents that decrease Hif-1 alpha and c-Myc levels identified a variety of compounds, including bortezomib, lenalidomide, enzastaurin, and adaphostin. Functionally, based on transient knockdowns and overexpression, our data delineate a c-Myc/Hif-1 alpha-dependent pathway mediating vascular endothelial growth factor production and secretion. The antiangiogenic activity of our tool compound, adaphostin, was subsequently shown in a zebrafish model and translated into a preclinical in vitro and in vivo model of MM in the bone marrow milieu. Our data, therefore, identify Hif-1 alpha as a novel molecular target in MM and add another facet to anti-MM drug activity. [Cancer Res 2009;69(12):5082-90]
C1 [Podar, Klaus] Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA.
[Tonon, Giovanni] Dana Farber Canc Inst, Ctr Appl Canc Sci, Boston, MA 02115 USA.
[Grabher, Clemens] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Vallet, Sonia] Harvard Univ, Sch Med, Boston, MA USA.
[Vallet, Sonia] Massachusetts Gen Hosp, Ctr Multiple Myeloma, Boston, MA 02114 USA.
[Lababidi, Samir] US FDA, Div Biostat, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA.
[Zhou, Yiming; Cartron, Marie-Astrid] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA.
[Tonon, Giovanni] Ist Sci San Raffaele, I-20132 Milan, Italy.
[Podar, Klaus] Univ Heidelberg, Natl Ctr Tumor Dis NCT, Heidelberg, Germany.
RP Podar, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, LeBow Inst Myeloma Therapeut, 44 Binney St, Boston, MA 02115 USA.
EM klaus_podar@dfci.harvard.edu
RI Grabher, Clemens/H-2064-2013
FU Multiple Myeloma Research Foundation Senior Research Grant Award;
Dunkin' Donuts Rising Star Award; NIH [1P50 CA 1 00707, RO-1 CA 50947,
PO-1 78378, CA134660-01]; LeBow Family Fund to Cure Myeloma
FX Multiple Myeloma Research Foundation Senior Research Grant Award and
Dunkin' Donuts Rising Star Award (K. Podar); NIH grants 1P50 CA 1 00707,
RO-1 CA 50947, and PO-1 78378 and LeBow Family Fund to Cure Myeloma
(K.C. Anderson); and NIH grant CA134660-01 (M. Sattler)
NR 49
TC 43
Z9 46
U1 0
U2 4
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 JUN 15
PY 2009
VL 69
IS 12
BP 5082
EP 5090
DI 10.1158/0008-5472.CAN-08-4603
PG 9
WC Oncology
SC Oncology
GA 464LM
UT WOS:000267506400022
PM 19509231
ER
PT J
AU Raina, D
Ahmad, R
Joshi, MD
Yin, L
Wu, ZK
Kawano, T
Vasir, B
Avigan, D
Kharbanda, S
Kufe, D
AF Raina, Deepak
Ahmad, Rehan
Joshi, Maya Datt
Yin, Li
Wu, Zekui
Kawano, Takeshi
Vasir, Baldev
Avigan, David
Kharbanda, Surender
Kufe, Donald
TI Direct Targeting of the Mucin 1 Oncoprotein Blocks Survival and
Tumorigenicity of Human Breast Carcinoma Cells
SO CANCER RESEARCH
LA English
DT Article
ID BETA-CATENIN; C-SRC; APOPTOTIC RESPONSE; OXIDATIVE STRESS; DNA-DAMAGE; 2
PROTEINS; IN-VITRO; ANTIGEN; CANCER; GENE
AB The mucin 1 (MUC1) oncoprotein is aberrantly overexpressed by similar to 90% of human breast cancers. However, there are no effective agents that directly inhibit MUC1 and induce death of breast cancer cells. We have synthesized a MUC1 inhibitor (called GO-201) that binds to the MUC1 cytoplasmic domain and blocks the formation of MUC1 oligomers in cells. GO-201, and not an altered version, attenuates targeting of MUC1 to the nucleus of human breast cancer cells, disrupts redox balance, and activates the DNA damage response. GO-201 also arrests growth and induces necrotic death. By contrast, the MUC1 inhibitor has no effect on cells null for MUC1 expression or nonmalignant mammary epithelial cells. Administration of GO-201 to nude mice bearing human breast tumor xenografts was associated with loss of tumorigenicity and extensive necrosis, which results in prolonged regression of tumor growth. These findings show that targeting the MUC1 oncoprotein is effective in inducing death of human breast cancer cells in vitro and in tumor models. [Cancer Res 2009;69(12):5133-41]
C1 [Raina, Deepak; Ahmad, Rehan; Joshi, Maya Datt; Yin, Li; Wu, Zekui; Kawano, Takeshi; Vasir, Baldev; Kharbanda, Surender; Kufe, Donald] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Avigan, David] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA.
RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St,Dana 830, Boston, MA 02115 USA.
EM donald_kufe@dfci.harvard.edu
FU National Cancer Institute [CA97098, CA42802]
FX National Cancer Institute grants CA97098 and CA42802.
NR 39
TC 78
Z9 79
U1 1
U2 9
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 JUN 15
PY 2009
VL 69
IS 12
BP 5133
EP 5141
DI 10.1158/0008-5472.CAN-09-0854
PG 9
WC Oncology
SC Oncology
GA 464LM
UT WOS:000267506400028
PM 19491255
ER
PT J
AU Zhao, XS
Graves, C
Ames, SJ
Fisher, DE
Spanjaard, RA
AF Zhao, Xiansi
Graves, Carole
Ames, Sarah J.
Fisher, David E.
Spanjaard, Remco A.
TI Mechanism of Regulation and Suppression of Melanoma Invasiveness by
Novel Retinoic Acid Receptor-gamma Target Gene Carbohydrate
Sulfotransferase 10
SO CANCER RESEARCH
LA English
DT Article
ID DEPENDENT SIGNALING PATHWAY; CELL-ADHESION MOLECULE; RAR-ALPHA;
TRANSCRIPTIONAL ACTIVATION; NEUROBLASTOMA-CELLS; RNA ACTIVATOR; MUTANT
MICE; F9 CELLS; BETA 2; EXPRESSION
AB Retinoic acid (RA) induces growth arrest and differentiation of S91 murine melanoma cells and serves as a valuable model for this disease. RA acts through activation of RA receptors (RAR), which are members of the nuclear receptor superfamily of ligand-inducible transcription factors. Interestingly, differentiation is mediated by RAR gamma, but not by RAR alpha or RAR beta, suggesting that RAR gamma possesses unique and uncharacterized molecular properties. To address this question, DNA microarrays in combination with RAR isoform-specific agonists were employed to identify novel RAR gamma target genes that may play a role in this process. Here, we identified and validated carbohydrate sulfotransferase 10 (CHST10) as a novel RAR gamma target gene in S91 cells. The RAR gamma-inducible CHST10 promoter was obtained, and two atypical, independently functioning RA response elements were identified in a 425 bp region. Surprisingly, this fragment is bound by RAR gamma, but not by RAR alpha or RAR beta, thus providing a mechanism for the observed RAR gamma-specific regulation. CHST10 is a sulfotransferase that forms HNK-1 glycan on neural cell adhesion proteins and glycolipids, and HNK-1 is thought to modulate cell adhesion and possibly metastasis. We show that CHST10 is also regulated by RAR gamma in a significant subset of human melanoma cells, and three-dimensional cell culture migration assays suggest that CHST10 functions as a suppressor of invasiveness, but not proliferation, in these cells. Induction of CHST10 by RAR gamma-activating retinoids may present a novel therapeutic strategy to inhibit invasiveness in a subset of melanoma patients. [Cancer Res 2009;69(12):5218-25]
C1 [Graves, Carole; Ames, Sarah J.; Spanjaard, Remco A.] Boston Univ, Sch Med, Dept Otolaryngol, Canc Res Ctr, Boston, MA 02118 USA.
[Graves, Carole; Ames, Sarah J.; Spanjaard, Remco A.] Boston Univ, Sch Med, Dept Biochem, Canc Res Ctr, Boston, MA 02118 USA.
[Zhao, Xiansi; Fisher, David E.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02114 USA.
RP Spanjaard, RA (reprint author), Boston Univ, Sch Med, Dept Otolaryngol, Canc Res Ctr, 72 E Concord St,R-903, Boston, MA 02118 USA.
EM rspan@bu.edu
FU Marshall and Missy Carter Family Foundation; Elsa U. Pardee Foundation
FX Marshall and Missy Carter Family Foundation and Elsa U. Pardee
Foundation (R.A. Spanjaard).
NR 50
TC 15
Z9 15
U1 0
U2 2
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 JUN 15
PY 2009
VL 69
IS 12
BP 5218
EP 5225
DI 10.1158/0008-5472.CAN-09-0705
PG 8
WC Oncology
SC Oncology
GA 464LM
UT WOS:000267506400038
PM 19470764
ER
PT J
AU Dakhova, O
Ozen, M
Creighton, CJ
Li, RL
Ayala, G
Rowley, D
Ittmann, M
AF Dakhova, Olga
Ozen, Mustafa
Creighton, Chad J.
Li, Rile
Ayala, Gustavo
Rowley, David
Ittmann, Michael
TI Global Gene Expression Analysis of Reactive Stroma in Prostate Cancer
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID GROWTH-FACTOR-BETA; EXTRACELLULAR-MATRIX; STEM-CELLS; PERINEURAL
INVASION; BREAST-CANCER; IN-VITRO; PROGRESSION; CARCINOMA; TGF-BETA-1;
LUNG
AB Purpose: Marked reactive stroma formation, designated as grade 3 reactive stroma, is associated with poor outcome in clinically localized prostate cancer. To understand the biological processes and signaling mechanisms underlying the formation of such reactive stroma, we carried out microarray gene expression analysis of laser-captured reactive stroma and matched normal stroma.
Experimental Design: Seventeen cases of reactive stroma grade 3 cancer were used to laser-capture tumor and normal stroma. Expression analysis was carried out using Agilent 44K arrays. Up-regulation of selected genes was confirmed by quantitative reverse transcription-PCR. Expression data was analyzed to identify significantly up- and down-regulated genes, and gene ontology analysis was used to define pathways altered in reactive stroma.
Results: A total of 544 unique genes were significantly higher in the reactive stroma and 606 unique genes were lower. Gene ontology analysis revealed significant alterations in a number of novel processes in prostate cancer reactive stroma, including neurogenesis, axonogenesis, and the DNA damage/repair pathways, as well as evidence of increases in stem cells in prostate cancer reactive stroma.
Conclusions: Formation of reactive stroma in prostate cancer is a dynamic process characterized by significant alterations in growth factor and signal transduction pathways and formation of new structures, including nerves and axons.
C1 [Dakhova, Olga; Ozen, Mustafa; Li, Rile; Ayala, Gustavo; Ittmann, Michael] Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA.
[Creighton, Chad J.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
[Rowley, David] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
[Dakhova, Olga; Ozen, Mustafa; Ittmann, Michael] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA.
RP Ittmann, M (reprint author), Baylor Coll Med, Dept Pathol, 1 Baylor Plaza, Houston, TX 77030 USA.
EM mittmann@bcm.tmc.edu
FU National Cancer Institute [1U54CA126568]; P30 Cancer Center [P30
CA125123]; Baylor Prostate Cancer SPORE [P50CA058204]; Department of
Veterans Affairs Merit Review; Diana Helis Henry Medical Research
Foundation
FX Grant support: National Cancer Institute to the Tumor Microenvironment
Network (1U54CA126568; D. Rowley), the P30 Cancer Center support grant
(P30 CA125123), the Baylor Prostate Cancer SPORE (P50CA058204), the
Department of Veterans Affairs Merit Review program (M. Ittmann), the
Diana Helis Henry Medical Research Foundation (M. Ittmann, G. Ayala, D.
Rowley), and by the use of the facilities of the Michael E. DeBakey
Veterans Affairs Medical Center.
NR 54
TC 75
Z9 78
U1 0
U2 6
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 JUN 15
PY 2009
VL 15
IS 12
BP 3979
EP 3989
DI 10.1158/1078-0432.CCR-08-1899
PG 11
WC Oncology
SC Oncology
GA 459DP
UT WOS:000267080800012
PM 19509179
ER
PT J
AU Ikeda, H
Hideshima, T
Fulciniti, M
Lutz, RJ
Yasui, H
Okawa, Y
Kiziltepe, T
Vallet, S
Pozzi, S
Santo, L
Perrone, G
Tai, YT
Cirstea, D
Raje, NS
Uherek, C
Dalken, B
Aigner, S
Osterroth, F
Munshi, N
Richardson, P
Anderson, KC
AF Ikeda, Hiroshi
Hideshima, Teru
Fulciniti, Mariateresa
Lutz, Robert J.
Yasui, Hiroshi
Okawa, Yutaka
Kiziltepe, Tanyel
Vallet, Sonia
Pozzi, Samantha
Santo, Loredana
Perrone, Giulia
Tai, Yu-Tzu
Cirstea, Diana
Raje, Noopur S.
Uherek, Christoph
Daelken, Benjamin
Aigner, Silke
Osterroth, Frank
Munshi, Nikhil
Richardson, Paul
Anderson, Kenneth C.
TI The Monoclonal Antibody nBT062 Conjugated to Cytotoxic Maytansinoids Has
Selective Cytotoxicity Against CD138-Positive Multiple Myeloma Cells In
vitro and In vivo
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID DRUG-RESISTANCE; BONE-MARROW; GEMTUZUMAB OZOGAMICIN; ANTITUMOR-ACTIVITY;
CANCER-CELLS; GROWTH; SYNDECAN-1; APOPTOSIS; THERAPY; DIFFERENTIATION
AB Purpose: We investigated the antitumor effect of murine/human chimeric CD138-specific monoclonal antibody nBT062 conjugated with highly cytotoxic maytansinoid derivatives against multiple myeloma (MM) cells in vitro and in vivo.
Experimental Design: We examined the growth inhibitory effect of BT062-SPDB-DM4, BT062-SMCC-DM1, and BT062-SPP-DM1 against MM cell lines and primary tumor cells from MM patients. We also examined in vivo activity of these agents in murine MM cell xenograft model of human and severe combined immunodeficient (SCID) mice bearing implant bone chips injected with human MM cells (SCID-hu model).
Results: Anti-CD138 immunoconjugates significantly inhibited growth of MM cell lines and primary tumor cells from MM patients without cytotoxicity against peripheral blood mononuclear cells from healthy volunteers. In MM cells, they induced G(2)-M cell cycle arrest, followed by apoptosis associated with cleavage of caspase-3, caspase-8, caspase-9, and poly(ADP-ribose) polymerase. Nonconjugated nBT062 completely blocked cytotoxicity induced by nBT062-maytansinoid conjugate, confirming that specific binding is required for inducing cytotoxicity. Moreover, nBT062-maytansinoid conjugates blocked adhesion of MM cells to bone marrow stromal cells. The coculture of MM cells with bone marrow stromal cells protects against dexamethasone-induced death but had no effect on the cytotoxicity of immunoconjugates. Importantly, nBT062-SPDB-DM4 and nBT062-SPP-DM1 significantly inhibited MM tumor growth in vivo and prolonged host survival in both the xenograft mouse models of human MM and SCID-hu mouse model.
Conclusion: These results provide the preclinical framework supporting evaluation of nBT062-maytansinoid derivatives in clinical trials to improve patient outcome in MM.
C1 [Ikeda, Hiroshi; Hideshima, Teru; Fulciniti, Mariateresa; Yasui, Hiroshi; Okawa, Yutaka; Kiziltepe, Tanyel; Vallet, Sonia; Pozzi, Samantha; Santo, Loredana; Perrone, Giulia; Tai, Yu-Tzu; Cirstea, Diana; Raje, Noopur S.; Munshi, Nikhil; Richardson, Paul; Anderson, Kenneth C.] Harvard Univ, Dept Med Oncol, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut,Med Sch, Boston, MA 02115 USA.
[Ikeda, Hiroshi; Hideshima, Teru; Fulciniti, Mariateresa; Yasui, Hiroshi; Okawa, Yutaka; Kiziltepe, Tanyel; Vallet, Sonia; Pozzi, Samantha; Santo, Loredana; Perrone, Giulia; Tai, Yu-Tzu; Cirstea, Diana; Raje, Noopur S.; Munshi, Nikhil; Richardson, Paul; Anderson, Kenneth C.] Harvard Univ, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Dana Farber Canc Inst,Med Sch, Boston, MA 02115 USA.
[Ikeda, Hiroshi; Yasui, Hiroshi] Sapporo Med Univ, Dept Internal Med 1, Sapporo, Hokkaido, Japan.
[Lutz, Robert J.] ImmunoGen Inc, Waltham, MA USA.
[Uherek, Christoph; Daelken, Benjamin; Aigner, Silke; Osterroth, Frank] Biotest AG, Dreieich, Germany.
RP Anderson, KC (reprint author), Harvard Univ, Dept Med Oncol, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut,Med Sch, Mayer 557,44 Binney St, Boston, MA 02115 USA.
EM Kenneth_Anderson@dfci.harvard.edu
RI Pozzi, Samantha/A-7617-2012
OI Pozzi, Samantha/0000-0001-7917-1774
FU NIH [CA50947, CA78373, CA10070]; Biotest Fellowship; LeBow Family Fund
FX Grant support: NIH grants CA50947, CA78373, and CA10070; a Biotest
Fellowship; and The LeBow Family Fund to Cure Myeloma.
NR 36
TC 107
Z9 112
U1 1
U2 17
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 JUN 15
PY 2009
VL 15
IS 12
BP 4028
EP 4037
DI 10.1158/1078-0432.CCR-08-2867
PG 10
WC Oncology
SC Oncology
GA 459DP
UT WOS:000267080800017
PM 19509164
ER
PT J
AU Betts, RF
Nucci, M
Talwar, D
Gareca, M
Queiroz-Telles, F
Bedimo, RJ
Herbrecht, R
Ruiz-Palacios, G
Young, JAH
Baddley, JW
Strohmaier, KM
Tucker, KA
Taylor, AF
Kartsonis, NA
AF Betts, Robert F.
Nucci, Marcio
Talwar, Deepak
Gareca, Marcelo
Queiroz-Telles, Flavio
Bedimo, Roger J.
Herbrecht, Raoul
Ruiz-Palacios, Guillermo
Young, Jo-Anne H.
Baddley, John W.
Strohmaier, Kim M.
Tucker, Kimberly A.
Taylor, Arlene F.
Kartsonis, Nicholas A.
CA Caspofungin High-Dose Study Grp
TI A Multicenter, Double-Blind Trial of a High-Dose Caspofungin Treatment
Regimen versus a Standard Caspofungin Treatment Regimen for Adult
Patients with Invasive Candidiasis
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID HIGH DRUG CONCENTRATIONS; AMPHOTERICIN-B; FUNGAL-INFECTIONS;
RISK-FACTORS; CANDIDEMIA; FLUCONAZOLE; EPIDEMIOLOGY; CANDIDAEMIA;
MICAFUNGIN; MORTALITY
AB Background. The standard caspofungin treatment regimen (50 mg/day after a 70-mg dose on day 1) is effective and well tolerated for the treatment of invasive candidiasis, but experience with higher doses of caspofungin is limited. We evaluated the safety and efficacy of caspofungin at 3 times the standard dosing regimen.
Methods. Patients with proven invasive candidiasis were randomized to receive a standard or high-dose (150 mg/day) caspofungin treatment regimen. Safety was assessed in all patients as treated. Efficacy was assessed as a secondary objective in a full-analysis-set population. A favorable overall response was defined as symptom resolution and microbiological clearance at the end of caspofungin therapy.
Results. A total of 204 patients were included in the safety analysis (104 received the standard regimen, and 100 received the high-dose regimen), and 197 were included in the efficacy analysis (102 and 95 in the standard and high-dose treatment groups, respectively). Patient demographic characteristics, neutropenia status (6.7% and 8.0% had neutropenia, respectively), and Acute Physiology and Chronic Health Evaluation II scores (mean, 16.5 and 17, respectively) were similar between treatment groups. Significant drug-related adverse events occurred in 1.9% of patients receiving the standard regimen and 3.0% of patients receiving the high-dose regimen (difference, 1.1%; 95% confidence interval, -4.1% to 6.8%). The most-common drug-related adverse events in the standard and high-dose treatment groups were phlebitis (3.8% and 2.0%, respectively), increased alkaline phosphatase level (6.9% and 2.0%, respectively), and increased aspartate transaminase level (4.0% and 2.0%, respectively). Overall, 71.6% of patients who received the standard regimen and 77.9% of patients who received the high-dose regimen had favorable overall responses (difference, 6.3%; 95% confidence interval, -5.9% to 18.4%; not statistically significant). Mortality at 8 weeks after therapy was similar between groups.
Conclusions. Both caspofungin dosing regimens were effective and well tolerated in patients with invasive candidiasis. No safety concerns were found for caspofungin at a dosage of 150 mg/day.
C1 [Betts, Robert F.] Univ Rochester, Rochester, NY USA.
[Gareca, Marcelo] Lehigh Valley Hosp, Allentown, PA USA.
[Strohmaier, Kim M.; Tucker, Kimberly A.; Taylor, Arlene F.; Kartsonis, Nicholas A.] Merck Res Labs, West Point, PA USA.
[Young, Jo-Anne H.] Univ Minnesota, Minneapolis, MN USA.
[Bedimo, Roger J.] Vet Affairs N Texas Hlth Care Syst, Dallas, TX USA.
[Baddley, John W.] Univ Alabama, Birmingham, AL USA.
[Baddley, John W.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA.
[Nucci, Marcio] Univ Fed Rio de Janeiro, Univ Hosp, Rio De Janeiro, Brazil.
[Queiroz-Telles, Flavio] Univ Fed Parana, Hosp Clin, BR-80060000 Curitiba, Parana, Brazil.
[Talwar, Deepak] Metro Hosp, Noida, India.
[Herbrecht, Raoul] Univ Hosp, Strasbourg, France.
[Ruiz-Palacios, Guillermo] Natl Inst Med Sci & Nutr, Mexico City, DF, Mexico.
RP Kartsonis, NA (reprint author), Merck Res Labs, POB 1000,UG3D-56, N Wales, PA 19454 USA.
EM nicholas_kartsonis@merck.com
RI Nucci, Marcio/G-4515-2012; Herbrecht, Raoul/D-3471-2013; Young,
Jo-Anne/G-2617-2013;
OI Nucci, Marcio/0000-0003-4867-0014; Young, Jo-Anne/0000-0003-4182-341X;
Streinu-Cercel, Adrian/0000-0001-6382-5067; Herbrecht,
Raoul/0000-0002-9381-4876
FU Merck Co
FX Merck & Co.
NR 20
TC 100
Z9 106
U1 1
U2 3
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 JUN 15
PY 2009
VL 48
IS 12
BP 1676
EP 1684
DI 10.1086/598933
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 450YY
UT WOS:000266439100009
PM 19419331
ER
PT J
AU Horn, DL
Neofytos, D
Anaissie, EJ
Fishman, JA
Steinbach, WJ
Olyaei, AJ
Marr, KA
Pfaller, MA
Chang, CH
Webster, KM
AF Horn, David L.
Neofytos, Dionissios
Anaissie, Elias J.
Fishman, Jay A.
Steinbach, William J.
Olyaei, Ali J.
Marr, Kieren A.
Pfaller, Michael A.
Chang, Chi-Hsing
Webster, Karen M.
TI Epidemiology and Outcomes of Candidemia in 2019 Patients: Data from the
Prospective Antifungal Therapy Alliance Registry
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article; Proceedings Paper
CT 48th Annual Interscience Conference on Antimicrobial Agents and
Chemotherapy/46th Annual Meeting of the
Infectious-Diseases-Society-of-America
CY OCT 25, 2008
CL Washington, DC
SP Infect Dis Soc Amer
ID INTENSIVE-CARE-UNIT; HOSPITAL-ACQUIRED CANDIDEMIA; INVASIVE
FUNGAL-INFECTIONS; BLOOD-STREAM INFECTIONS; CRITICALLY-ILL PATIENTS;
ATTRIBUTABLE MORTALITY; RISK-FACTORS; HEMATOLOGIC MALIGNANCIES;
NOSOCOMIAL CANDIDEMIA; CANCER-PATIENTS
AB Background. Candidemia remains a major cause of morbidity and mortality in the health care setting, and the epidemiology of Candida infection is changing.
Methods. Clinical data from patients with candidemia were extracted from the Prospective Antifungal Therapy (PATH) Alliance database, a comprehensive registry that collects information regarding invasive fungal infections. A total of 2019 patients, enrolled from 1 July 2004 through 5 March 2008, were identified. Data regarding the candidemia episode were analyzed, including the specific fungal species and patient survival at 12 weeks after diagnosis.
Results. The incidence of candidemia caused by non-Candida albicans Candida species (54.4%) was higher than the incidence of candidemia caused by C. albicans (45.6%). The overall, crude 12-week mortality rate was 35.2%. Patients with Candida parapsilosis candidemia had the lowest mortality rate (23.7%; P < .001) and were less likely to be neutropenic (5.1%; P < .001) and to receive corticosteroids (33.5%; P < .001) or other immuno-suppressive drugs (7.9%; P = .002), compared with patients infected with other Candida species. Candida krusei candidemia was most commonly associated with prior use of antifungal agents (70.6%; P < .001), hematologic malignancy (52.9%; P < .001) or stem cell transplantation (17.7%; P < .001), neutropenia (45.1%; P < .001), and corticosteroid treatment (60.8%; P < .001). Patients with C. krusei candidemia had the highest crude 12-week mortality in this series (52.9%; P < .001). Fluconazole was the most commonly administered antimicrobial, followed by the echinocandins, and amphotericin B products were infrequently administered.
Conclusions. The epidemiology and choice of therapy for candidemia are rapidly changing. Additional study is warranted to differentiate host factors and differences in virulence among Candida species and to determine the best therapeutic regimen.
C1 [Horn, David L.; Neofytos, Dionissios] Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA.
[Neofytos, Dionissios; Marr, Kieren A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Anaissie, Elias J.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA.
[Fishman, Jay A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Steinbach, William J.] Duke Univ, Med Ctr, Durham, NC USA.
[Olyaei, Ali J.] Oregon Hlth & Sci Univ, Portland, OR USA.
[Pfaller, Michael A.] Univ Iowa Hlth Care, Iowa City, IA USA.
[Chang, Chi-Hsing] Info Spectrum, Markham, ON, Canada.
[Webster, Karen M.] EBM Consulting, Mississauga, ON, Canada.
RP Horn, DL (reprint author), Thomas Jefferson Univ, Div Infect Dis, Ste 210,211 S 9th St, Philadelphia, PA 19107 USA.
EM david.horn@jefferson.edu
NR 45
TC 390
Z9 418
U1 1
U2 25
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 JUN 15
PY 2009
VL 48
IS 12
BP 1695
EP 1703
DI 10.1086/599039
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 450YY
UT WOS:000266439100011
PM 19441981
ER
PT J
AU Nagy, N
Mwizerwa, O
Yaniv, K
Carmel, L
Pieretti-Vanmarcke, R
Weinstein, BM
Goldstein, AM
AF Nagy, Nandor
Mwizerwa, Olive
Yaniv, Karina
Carmel, Liran
Pieretti-Vanmarcke, Rafael
Weinstein, Brant M.
Goldstein, Allan M.
TI Endothelial cells promote migration and proliferation of enteric neural
crest cells via beta 1 integrin signaling
SO DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE Enteric nervous system; Endothelial cells; Blood vessels; Hirschsprung's
disease; Integrins; Avian; Zebrafish
ID EXTRACELLULAR-MATRIX; MONOCLONAL-ANTIBODY; NERVOUS-SYSTEM; TRANSGENIC
ZEBRAFISH; AGANGLIONIC BOWEL; AVIAN EMBRYO; LAMININ; FIBRONECTIN;
RECEPTOR; NEURONS
AB Enteric neural crest-derived cells (ENCCs) migrate along the intestine to form a highly organized network of ganglia that comprises the enteric nervous system (ENS). The signals driving the migration and patterning of these cells are largely unknown. Examining the spatiotemporal development of the intestinal neurovasculature in avian embryos, we find endothelial cells (ECs) present in the gut prior to the arrival of migrating ENCCs. These ECs are patterned in concentric rings that are predictive of the positioning of later arriving crest-derived cells, leading us to hypothesize that blood vessels may serve as a substrate to guide ENCC migration. Immunohistochemistry at multiple stages during ENS development reveals that ENCCs are positioned adjacent to vessels as they colonize the gut. A similar close anatomic relationship between vessels and enteric neurons was observed in zebrafish larvae. When EC development is inhibited in Cultured avian intestine, ENCC migration is arrested and distal aganglionosis results, suggesting that ENCCs require the presence of vessels to colonize the gut. Neural tube and avian midgut were explanted onto a variety of substrates, including components of the extracellular matrix and various cell types, such as fibroblasts, smooth muscle cells, and endothelial cells. We find that crest-derived cells from both the neural tube and the midgut migrate avidly onto Cultured endothelial cells. This EC-induced migration is inhibited by the presence of CSAT antibody, which blocks binding to beta 1 integrins expressed on the surface of crest-derived cells. These results demonstrate that ECs provide a Substrate for the migration of ENCCs via an interaction between beta 1 integrins on the ENCC surface and extracellular matrix proteins expressed by the intestinal vasculature. These interactions may play an important role in guiding migration and patterning in the developing ENS. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Nagy, Nandor; Mwizerwa, Olive; Pieretti-Vanmarcke, Rafael; Goldstein, Allan M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Surg, Boston, MA 02115 USA.
[Nagy, Nandor] Semmelweis Univ, Fac Med, Dept Human Morphol & Dev Biol, H-1094 Budapest, Hungary.
[Yaniv, Karina; Weinstein, Brant M.] NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA.
[Carmel, Liran] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
RP Goldstein, AM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Surg, Boston, MA 02115 USA.
EM agoldstein@partners.org
FU NIH [K08HD46655]; Hungarian Scientific Research Fund [K-69061];
Semmelweis University; NICHD; EMBO fellowship
FX We thank Drucilla Roberts and Joanne Chan for helpful discussions, Csaba
Bodor for Huvec cells, and Ajay Chitnis for the HuC:GFP transgenic
zebrafish line. Several antibodies in Table 1 were obtained from the
Developmental Studies Hybridoma Bank developed under the auspices of the
NICHD and maintained by University of Iowa, Dept. of Biological
Sciences, Iowa City, IA 52242. AMG is supported by NIH K08HD46655, NN by
a grant from the Hungarian Scientific Research Fund (K-69061) and a
Young Investigator Award from Semmelweis University, BMW by the
intramural program of the NICHD, and KY by an EMBO fellowship.
NR 54
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U1 1
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD JUN 15
PY 2009
VL 330
IS 2
BP 263
EP 272
DI 10.1016/j.ydbio.2009.03.025
PG 10
WC Developmental Biology
SC Developmental Biology
GA 452XN
UT WOS:000266574600005
PM 19345201
ER
PT J
AU Tan, MH
Smith, AJ
Pawlyk, B
Xu, XY
Liu, XQ
Bainbridge, JB
Basche, M
McIntosh, J
Tran, HV
Nathwani, A
Li, TS
Ali, RR
AF Tan, Mei Hong
Smith, Alexander J.
Pawlyk, Basil
Xu, Xiaoyun
Liu, Xiaoqing
Bainbridge, James B.
Basche, Mark
McIntosh, Jenny
Tran, Hoai Viet
Nathwani, Amit
Li, Tiansen
Ali, Robin R.
TI Gene therapy for retinitis pigmentosa and Leber congenital amaurosis
caused by defects in AIPL1: effective rescue of mouse models of partial
and complete Aipl1 deficiency using AAV2/2 and AAV2/8 vectors
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID RCS RAT MODEL; RETINAL DEGENERATION; PHOTORECEPTOR DEGENERATION; CGMP
PHOSPHODIESTERASE; CHILDHOOD BLINDNESS; REPLACEMENT THERAPY; RESTORES
VISION; CANINE MODEL; PROTEIN; MICE
AB Defects in the photoreceptor-specific gene encoding aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1) are clinically heterogeneous and present as Leber Congenital Amaurosis, the severest form of early-onset retinal dystrophy and milder forms of retinal dystrophies such as juvenile retinitis pigmentosa and dominant cone-rod dystrophy. [Perrault, I., Rozet, J.M., Gerber, S., Ghazi, I., Leowski, C., Ducroq, D., Souied, E., Dufier, J.L., Munnich, A. and Kaplan, J. (1999) Leber congenital amaurosis. Mol. Genet. Metab., 68, 200-208.] Although not yet fully elucidated, AIPL1 is likely to function as a specialized chaperone for rod phosphodiesterase (PDE). We evaluate whether AAV-mediated gene replacement therapy is able to improve photoreceptor function and survival in retinal degeneration associated with AIPL1 defects. We used two mouse models of AIPL1 deficiency simulating three different rates of photoreceptor degeneration. The Aipl1 hypomorphic (h/h) mouse has reduced Aipl1 levels and a relatively slow degeneration. Under light acceleration, the rate of degeneration in the Aipl1 h/h mouse is increased by 2-3-fold. The Aipl1-/- mouse has no functional Aipl1 and has a very rapid retinal degeneration. To treat the different rates of degeneration, two pseudotypes of recombinant adeno-associated virus (AAV) exhibiting different transduction kinetics are used for gene transfer. We demonstrate restoration of cellular function and preservation of photoreceptor cells and retinal function in Aipl1 h/h mice following gene replacement therapy using an AAV2/2 vector and in the light accelerated Aipl1 h/h model and Aipl1-/- mice using an AAV2/8 vector. We have thus established the potential of gene replacement therapy in varying rates of degeneration that reflect the clinical spectrum of disease. This is the first gene replacement study to report long-term rescue of a photoreceptor-specific defect and to demonstrate effective rescue of a rapid photoreceptor degeneration.
C1 [Pawlyk, Basil; Xu, Xiaoyun; Liu, Xiaoqing; Li, Tiansen] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA.
[Tan, Mei Hong; Smith, Alexander J.; Bainbridge, James B.; Basche, Mark; Tran, Hoai Viet; Ali, Robin R.] UCL, Inst Ophthalmol, NIHR Biomed Res Ctr, London, England.
[McIntosh, Jenny; Nathwani, Amit] UCL, Canc Res Inst, London, England.
RP Ali, RR (reprint author), 11-43 Bath St, London, England.
EM tli@meei.harvard.edu; r.ali@ucl.ac.uk
RI Smith, Alexander/A-5142-2009;
OI Bainbridge, James/0000-0003-1318-8201
FU Fonds National Suisse de la Recherche Scientifique; Roche Research
Foundation; Holcim Stiftung zur Forderung der wissenschaftlichen
Fortbildung; European Union (AAVEYE),; UK Department of Health; National
Institute of Health Research BMRC for Ophthalmology; NIH [EY10581];
Foundation Fighting Blindness
FX H. V. T. is supported by Fonds National Suisse de la Recherche
Scientifique, Roche Research Foundation and Holcim Stiftung zur
Forderung der wissenschaftlichen Fortbildung. This work was also
supported by grants from the European Union (AAVEYE), the UK Department
of Health, National Institute of Health Research BMRC for Ophthalmology,
NIH Grant EY10581 and Foundation Fighting Blindness.
NR 40
TC 81
Z9 85
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD JUN 15
PY 2009
VL 18
IS 12
BP 2099
EP 2114
DI 10.1093/hmg/ddp133
PG 16
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 449SD
UT WOS:000266349400001
PM 19299492
ER
PT J
AU Lee, DS
Burd, H
Liu, JX
Almaas, E
Wiest, O
Barabasi, AL
Oltvai, ZN
Kapatral, V
AF Lee, Deok-Sun
Burd, Henry
Liu, Jiangxia
Almaas, Eivind
Wiest, Olaf
Barabasi, Albert-Laszlo
Oltvai, Zoltan N.
Kapatral, Vinayak
TI Comparative Genome-Scale Metabolic Reconstruction and Flux Balance
Analysis of Multiple Staphylococcus aureus Genomes Identify Novel
Antimicrobial Drug Targets
SO JOURNAL OF BACTERIOLOGY
LA English
DT Article
ID ESCHERICHIA-COLI; SEQUENCE; NETWORK; GENES; IDENTIFICATION; INFECTIONS;
EVOLUTION; DISCOVERY; DRAFT
AB Mortality due to multidrug-resistant Staphylococcus aureus infection is predicted to surpass that of human immunodeficiency virus/AIDS in the United States. Despite the various treatment options for S. aureus infections, it remains a major hospital- and community-acquired opportunistic pathogen. With the emergence of multidrug-resistant S. aureus strains, there is an urgent need for the discovery of new antimicrobial drug targets in the organism. To this end, we reconstructed the metabolic networks of multidrug-resistant S. aureus strains using genome annotation, functional-pathway analysis, and comparative genomic approaches, followed by flux balance analysis-based in silico single and double gene deletion experiments. We identified 70 single enzymes and 54 pairs of enzymes whose corresponding metabolic reactions are predicted to be unconditionally essential for growth. Of these, 44 single enzymes and 10 enzyme pairs proved to be common to all 13 S. aureus strains, including many that had not been previously identified as being essential for growth by gene deletion experiments in S. aureus. We thus conclude that metabolic reconstruction and in silico analyses of multiple strains of the same bacterial species provide a novel approach for potential antibiotic target identification.
C1 [Burd, Henry; Kapatral, Vinayak] Integrated Genom Inc, Chicago, IL 60612 USA.
[Lee, Deok-Sun; Barabasi, Albert-Laszlo] Northeastern Univ, Ctr Complex Network Res, Boston, MA 02215 USA.
[Lee, Deok-Sun; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Phys, Boston, MA 02215 USA.
[Lee, Deok-Sun; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Biol, Boston, MA 02215 USA.
[Lee, Deok-Sun; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Comp Sci, Boston, MA 02215 USA.
[Lee, Deok-Sun; Barabasi, Albert-Laszlo] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02215 USA.
[Lee, Deok-Sun] Inha Univ, Dept Nat Med Sci, Inchon 402751, South Korea.
[Liu, Jiangxia; Oltvai, Zoltan N.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15261 USA.
[Almaas, Eivind] Lawrence Livermore Natl Lab, Biosci & Biotechnol Div, Livermore, CA 94551 USA.
[Wiest, Olaf] Univ Notre Dame, Dept Chem & Biochem, Notre Dame, IN 46556 USA.
RP Kapatral, V (reprint author), Integrated Genom Inc, 2201 W Campbell Pk Dr, Chicago, IL 60612 USA.
EM vinayak@integratedgenomics.com
RI Lee, Deok-Sun/D-1335-2011;
OI Almaas, Eivind/0000-0002-9125-326X
FU NIH [5U01AI070499-02]
FX Support for this work was provided by NIH grant 5U01AI070499-02.
NR 30
TC 82
Z9 86
U1 0
U2 22
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0021-9193
J9 J BACTERIOL
JI J. Bacteriol.
PD JUN 15
PY 2009
VL 191
IS 12
BP 4015
EP 4024
DI 10.1128/JB.01743-08
PG 10
WC Microbiology
SC Microbiology
GA 451ET
UT WOS:000266454200025
PM 19376871
ER
PT J
AU Mikhak, Z
Farsidjani, A
Luster, AD
AF Mikhak, Zamaneh
Farsidjani, Alireza
Luster, Andrew D.
TI Endotoxin Augmented Antigen-Induced Th1 Cell Trafficking Amplifies
Airway Neutrophilic Inflammation
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID INTERFERON-GAMMA-RECEPTOR; INHERITED INTERLEUKIN-12 DEFICIENCY; BACILLE
CALMETTE-GUERIN; MYCOBACTERIAL INFECTION; TARGETED DISRUPTION;
SALMONELLA-ENTERITIDIS; MICE; RESPONSES; GENE; CHEMOKINE
AB CD4(+) Th1 cells play a critical role in orchestrating host defense against pathogens and in the pathogenesis of many immune-mediated diseases. The control of Th1 cell trafficking into sites of infection and inflammation is an important determinant of Till cell function. We have previously shown that trafficking of adoptively transferred Ag-specific Th1 cells into the lung following airway Ag challenge depends on CXCR3 expression on Th1 cells and STAT1-inducible CXCR3 ligands in the lung. In this study, we show that LPS alters the mechanisms of Th1 cell recruitment. After a single intranasal dose of LPS, trafficking of adoptively transferred Ag-specific Th1 cell into the lung in response to airway Ag challenges was no longer dependent on CXCR3 and its ligands and instead was mediated through additional G alpha i-coupled chemoattractant receptor pathways, including CCR5. In addition, LPS markedly increased the magnitude of Ag-specific Th1 cell homing into the airways following airway Ag challenges. The increased trafficking of Ag-activated Th1 cells, in turn, dramatically amplified LPS-induced airway neutrophilic infiltration by maintaining high levels of the neutrophil active chemokines, KC and MIP-2, through an IFN-gamma dependent mechanism. Therefore, LPS increases Ag-specific Th1 cell trafficking into the airways and Ag-specific Th1 cells amplify the airway neutrophilic inflammatory response initiated by LPS. This reciprocal interaction between LPS and Ag-activated Th1 cells represents a collaborative connection between the innate and adaptive arms of the immune system. The Journal of Immunology, 2009, 182: 7946-7956.
C1 [Mikhak, Zamaneh; Farsidjani, Alireza; Luster, Andrew D.] Harvard Univ, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Massachusetts Gen Hosp,Med Sch, Boston, MA 02129 USA.
RP Luster, AD (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, 149 13th St,Suite 8301, Charlestown, MA 02129 USA.
EM aluster@mgh.harvard.edu
FU National Institute of Health [R37-AI40618, K08AI67519]
FX This work was supported by the National Institute of Health (R37-AI40618
to A.D.L. and K08AI67519 to Z.M.).
NR 44
TC 12
Z9 12
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 JUN 15
PY 2009
VL 182
IS 12
BP 7946
EP 7956
DI 10.4049/jimmunol.0803522
PG 11
WC Immunology
SC Immunology
GA 456HD
UT WOS:000266833900066
PM 19494319
ER
PT J
AU Wolters, PJ
Wray, C
Sutherland, RE
Kim, SS
Koff, J
Mao, Y
Frank, JA
AF Wolters, Paul J.
Wray, Charlie
Sutherland, Rachel E.
Kim, Sophia S.
Koff, Jon
Mao, Ying
Frank, James A.
TI Neutrophil-Derived IL-6 Limits Alveolar Barrier Disruption in
Experimental Ventilator-Induced Lung Injury
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID RESPIRATORY-DISTRESS-SYNDROME; INTERLEUKIN-6-DEFICIENT MICE;
INFLAMMATION; EXPRESSION; PROTECTION; MECHANISM; RESPONSES; BLOCKADE;
IMMUNE
AB IL-6 is a biological marker of ventilator-associated lung injury that may contribute to alveolar barrier dysfunction in acute respiratory distress syndrome. To determine whether IL-6 affects alveolar barrier disruption in a model of ventilator-induced lung injury, we examined alveolar barrier albumin flux in wild-type (WT) mice given an IL-6-blocking Ab (IL6AB) and mice deficient in IL-6 (LL6KO). Albumin flux was significantly higher in mice given IL6AB compared with mice given a control Ab. Unexpectedly, albumin flux was similar in WT and IL6KO mice. To examine the mechanisms for these findings, lung neutrophil accumulation (myeloperoxidase activity) was compared, revealing a correlation between lung neutrophil accumulation and albumin flux. IL6AB mice had significantly more lung neutrophils than WT and IL6KO mice, which were similar. Therefore, to determine whether the cellular source of IL-6 influences neutrophil accumulation and alveolar barrier function, chimeric mice were compared. WT/KO chimeras (WT mice with IL6KO hematopoietic cells) showed significantly greater albumin flux and neutrophil accumulation with mechanical ventilation than WT/WT mice. Neutrophil depletion decreased albumin flux in WT and WT/KO mice. IL6KO neutrophils were more adherent in an in vitro assay compared with WT neutrophils. IL-6 from a hematopoietic cell source limits alveolar barrier disruption potentially by reducing neutrophil contact with the endothelium. Modulation of IL-6 signaling in a cell type-specific fashion may be a therapeutic target for patients with acute lung injury. The Journal of Immunology, 2009, 182: 8056-8062.
C1 [Frank, James A.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA.
[Wolters, Paul J.; Sutherland, Rachel E.; Kim, Sophia S.; Koff, Jon; Frank, James A.] Univ Calif San Francisco, Dept Med, Div Pulm & Crit Care Med, San Francisco, CA 94121 USA.
[Wray, Charlie; Mao, Ying; Frank, James A.] Vet Hlth Res Inst, No Calif Inst Res & Educ, San Francisco, CA 94121 USA.
[Frank, James A.] San Francisco Vet Adm Med Ctr, San Francisco, CA 94121 USA.
RP Frank, JA (reprint author), Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco Vet Affairs Med Ctr, 4150 Clement St,Box 111D, San Francisco, CA 94121 USA.
EM james.frank@ucsf.edu
RI Wolters, Paul/A-7181-2009
FU National Institutes of Health and National Heart, Lung and Blood
Institute [HL088440, HL075026]
FX This work was supported by funding from the National Institutes of
Health and National Heart, Lung and Blood Institute Grants HL088440 (to
J.A.F.) and HL075026 (to P.J.W.).
NR 23
TC 34
Z9 36
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 JUN 15
PY 2009
VL 182
IS 12
BP 8056
EP 8062
PG 7
WC Immunology
SC Immunology
GA 456HD
UT WOS:000266833900078
PM 19494331
ER
PT J
AU Camargo, JF
Kulkarni, H
Agan, BK
Gaitan, AA
Beachy, LA
Srinivas, S
He, WJ
Anderson, S
Marconi, VC
Dolan, MJ
Ahuja, SK
AF Camargo, Jose F.
Kulkarni, Hemant
Agan, Brian K.
Gaitan, Alvaro A.
Beachy, Lisa A.
Srinivas, Sowmya
He, Weijing
Anderson, Stephanie
Marconi, Vincent C.
Dolan, Matthew J.
Ahuja, Sunil K.
TI Responsiveness of T Cells to Interleukin-7 Is Associated with Higher
CD4(+) T Cell Counts in HIV-1-Positive Individuals with Highly Active
Antiretroviral Therapy-Induced Viral Load Suppression
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; SURFACE CCR5 DENSITY; IL-7
RECEPTOR-ALPHA; DISEASE PROGRESSION; SINGLE-CELL; IN-VIVO; HOMEOSTATIC
PROLIFERATION; HIV-1-INFECTED PATIENTS; LYMPHOID HOMEOSTASIS; INFECTED
PATIENTS
AB Background. Despite suppression of the human immunodeficiency virus type 1 (HIV-1) load by highly active antiretroviral therapy (HAART), recovery of CD4(+) T cell counts can be impaired. We investigated whether this impairment may be associated with hyporesponsiveness of T cells to gamma-chain (gamma c) cytokines known to influence T cell homeostasis.
Methods. The responsiveness of T cells to interleukin (IL)-2, IL-7, and IL-15 was determined by assessing cytokine-induced phosphorylation of the signal transducer and activator of transcription 5 (STAT5) in peripheral T cells obtained from 118 HIV-positive subjects and 13 HIV-negative subjects.
Results. The responsiveness of T cells to interleukin (IL)-7 but not to IL-2 or IL-15 was lower among HIV-positive subjects than among HIV-negative subjects. Among subjects with viral load suppression, the degree of IL-7 responsiveness (1) correlated with naive CD4(+) T cell counts and was a better immune correlate of the prevailing CD4(+) T cell count than were levels of human leukocyte antigen-DR1 or programmed death-1, which are predictors of T cell homeostasis during HIV infection; and (2) was greater in subjects with complete (i.e., attainment of >= 500 CD4(+) T cells/mm(3) >= 5 years after initiation of HAART) versus incomplete immunologic responses. The correlation between plasma levels of IL-7 and CD4(+) T cell counts during HAART was maximal in subjects with increased IL-7 responsiveness.
Conclusions. Responsiveness of T cells to IL-7 is associated with higher CD4(+) T cell counts during HAART and thus may be a determinant of the extent of immune reconstitution.
C1 [Camargo, Jose F.; Kulkarni, Hemant; Gaitan, Alvaro A.; Beachy, Lisa A.; Srinivas, Sowmya; He, Weijing; Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA.
[Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol, San Antonio, TX 78229 USA.
[Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Immunol, San Antonio, TX 78229 USA.
[Camargo, Jose F.; Kulkarni, Hemant; Gaitan, Alvaro A.; Beachy, Lisa A.; Srinivas, Sowmya; He, Weijing; Ahuja, Sunil K.] S Texas Vet Hlth Care Syst, Vet Adm Res Ctr AIDS & HIV Infect 1, San Antonio, TX 78229 USA.
[Anderson, Stephanie; Marconi, Vincent C.; Dolan, Matthew J.] Wilford Hall USAF Med Ctr, Infect Dis Serv, Lackland AFB, TX 78236 USA.
[Anderson, Stephanie; Dolan, Matthew J.] Wilford Hall USAF Med Ctr, Henry M Jackson Fdn, Lackland AFB, TX 78236 USA.
[Anderson, Stephanie; Marconi, Vincent C.; Dolan, Matthew J.] San Antonio Mil Med Ctr, Ft Sam Houston, TX USA.
[Anderson, Stephanie; Marconi, Vincent C.; Dolan, Matthew J.] San Antonio Mil Med Ctr, Lackland AFB, TX USA.
[Agan, Brian K.; Anderson, Stephanie; Marconi, Vincent C.] Uniformed Serv Univ Hlth Sci, Infect Dis Clin Res Program, Bethesda, MD 20814 USA.
RP Ahuja, SK (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, 7703 Floyd Curl Dr,Rm 5-009R, San Antonio, TX 78229 USA.
EM mdolan@hjf.org; ahujas@uthscsa.edu
RI Marconi, Vincent/N-3210-2014;
OI Marconi, Vincent/0000-0001-8409-4689; Agan, Brian/0000-0002-5114-1669
FU Veterans Administration Center on AIDS and HIV Infection, South Texas
Veterans Health Care System; National Institutes of Health (NIH)
[R37046326, HU0001-05-2-0011]; Elizabeth Glaser Scientist Award;
Burroughs Wellcome Clinical Scientist Award in Translational Research;
Uniformed Services University of the Health Sciences (USUHS)
FX Veterans Administration Center on AIDS and HIV Infection, South Texas
Veterans Health Care System; National Institutes of Health (NIH; MERIT
award R37046326 to S. K. A.). S. K. A. is a recipient of the Elizabeth
Glaser Scientist Award and the Burroughs Wellcome Clinical Scientist
Award in Translational Research. Support for the Wilford Hall Medical
Center cohort was provided by the Infectious Disease Clinical Research
Program (IDCRP) of the Uniformed Services University of the Health
Sciences (USUHS). The IDCRP is a Department of Defense triservice
program executed through the USUHS and the Henry M. Jackson Foundation
for the Advancement of Military Medicine, in collaboration with the
Department of Health and Human Services/ NIH/National Institute of
Allergy and Infectious Diseases/Division of Clinical Research through
Interagency Agreement HU0001-05-2-0011.
NR 43
TC 36
Z9 37
U1 0
U2 0
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 JUN 15
PY 2009
VL 199
IS 12
BP 1872
EP 1882
DI 10.1086/598858
PG 11
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 448BM
UT WOS:000266236500021
PM 19432535
ER
PT J
AU Raval, MV
Bilimoria, KY
Stewart, AK
Bentrem, DJ
Ko, CY
AF Raval, Mehul V.
Bilimoria, Karl Y.
Stewart, Andrew K.
Bentrem, David J.
Ko, Clifford Y.
TI Using the NCDB for Cancer Care Improvement: An Introduction to Available
Quality Assessment Tools
SO JOURNAL OF SURGICAL ONCOLOGY
LA English
DT Review
DE quality of health care; Health Care Quality Assessment; National Cancer
Database
ID UNITED-STATES; DATA-BASE
AB Improving the quality of cancer care requires high-quality data, mechanisms to feed back information to hospitals, systems to act on the data, and participation of providers. The purpose of this review is to describe how the National Cancer Database (NCDB) can be utilized to improve the quality of cancer care in the United States through a variety of benchmarking reports and data feedback mechanisms available to hospitals approved by the Commission on Cancer (CoC). J. Surg. Oncol. 2009;99:485-490. (C) 2009 Wiley-Liss, Inc.
C1 [Raval, Mehul V.; Bilimoria, Karl Y.; Stewart, Andrew K.; Ko, Clifford Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Canc Programs, Chicago, IL 60611 USA.
[Raval, Mehul V.; Bilimoria, Karl Y.; Bentrem, David J.] Northwestern Univ, Dept Surg, Feinberg Sch Med, Chicago, IL 60611 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 Ko, CY (reprint author), Amer Coll Surg, Div Res & Optimal Patient Care, Canc Programs, 636 N St Clair St,22nd Floor, Chicago, IL 60611 USA.
EM CKo@mednet.ucla.edu
OI Raval, Mehul/0000-0002-1527-2661
NR 16
TC 56
Z9 56
U1 1
U2 3
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0022-4790
J9 J SURG ONCOL
JI J. Surg. Oncol.
PD JUN 15
PY 2009
VL 99
IS 8
BP 488
EP 490
DI 10.1002/jso.21173
PG 3
WC Oncology; Surgery
SC Oncology; Surgery
GA 455DS
UT WOS:000266738200008
PM 19466738
ER
PT J
AU Robertson, SA
Koleva, RI
Argetsinger, LS
Carter-Su, C
Marto, JA
Feener, EP
Myers, MG
AF Robertson, Scott A.
Koleva, Rositsa I.
Argetsinger, Lawrence S.
Carter-Su, Christin
Marto, Jarrod A.
Feener, Edward P.
Myers, Martin G., Jr.
TI Regulation of Jak2 Function by Phosphorylation of Tyr(317) and Tyr(637)
during Cytokine Signaling
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID TYROSINE KINASE TYK2; GROWTH-HORMONE RECEPTOR; LEPTIN RECEPTOR; FERM
DOMAIN; PSEUDOKINASE DOMAIN; CATALYTIC ACTIVITY; ACTIVATION;
AUTOPHOSPHORYLATION; PATHWAYS; SITE
AB Jak2, the cognate tyrosine kinase for numerous cytokine receptors, undergoes multisite phosphorylation during cytokine stimulation. To understand the role of phosphorylation in Jak2 regulation, we used mass spectrometry to identify numerous Jak2 phosphorylation sites and characterize their significance for Jak2 function. Two sites outside of the tyrosine kinase domain, Tyr(317) in the FERM domain and Tyr(637) in the JH2 domain, exhibited strong regulation of Jak2 activity. Mutation of Tyr(317) promotes increased Jak2 activity, and the phosphorylation of Tyr(317) during cytokine signaling requires prior activation loop phosphorylation, which is consistent with a role for Tyr(317) in the feedback inhibition of Jak2 kinase activity after receptor stimulation. Comparison to several previously identified regulatory phosphorylation sites on Jak2 revealed a dominant role for Tyr(317) in the attenuation of Jak2 signaling. In contrast, mutation of Tyr(637) decreased Jak2 signaling and activity and partially suppressed the activating JH2 V617F mutation, suggesting a role for Tyr(637) phosphorylation in the release of JH2 domain-mediated suppression of Jak2 kinase activity during cytokine stimulation. The phosphorylation of Tyr(317) and Tyr(637) act in concert with other regulatory events to maintain appropriate control of Jak2 activity and cytokine signaling.
C1 [Robertson, Scott A.; Myers, Martin G., Jr.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA.
[Robertson, Scott A.; Argetsinger, Lawrence S.; Carter-Su, Christin; Myers, Martin G., Jr.] Univ Michigan, Sch Med, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA.
[Koleva, Rositsa I.; Marto, Jarrod A.] Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Feener, Edward P.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA.
RP Myers, MG (reprint author), Univ Michigan, Sch Med, Div Metab Endocrinol & Diabet, Dept Med, 5560 MSRB 2,MSP5678,1150 W Med Ctr Dr, Ann Arbor, MI 48109 USA.
EM mgmyers@umich.edu
FU NIH [DK57631, D57768, DK20572, P30 CA46592]; Dana Farber Cancer
Institute
FX This study was supported by NIH DK57631 and NIH D57768 (to M. G. M.),
NIH DK34171 (to C. C.-S.), predoctoral fellowships from the American
Diabetes Association and the American Heart Association (to S. A. R.),
and support from the Dana Farber Cancer Institute (to J. A. M.). Support
for peptide synthesis and DNA sequencing was provided by the Biomedical
Research Core facilities at the University of Michigan, which are
supported in part by the Michigan Diabetes Research and Training Center
(NIH P60 DK20572) and the University of Michigan Comprehensive Cancer
Center (NIH P30 CA46592).
NR 39
TC 18
Z9 18
U1 1
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 JUN 15
PY 2009
VL 29
IS 12
BP 3367
EP 3378
DI 10.1128/MCB.00278-09
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 450XW
UT WOS:000266436300012
PM 19364823
ER
PT J
AU Lupien, M
Eeckhoute, J
Meyer, CA
Krum, SA
Rhodes, DR
Liu, XS
Brown, M
AF Lupien, Mathieu
Eeckhoute, Jerome
Meyer, Clifford A.
Krum, Susan A.
Rhodes, Daniel R.
Liu, X. Shirley
Brown, Myles
TI Coactivator Function Defines the Active Estrogen Receptor Alpha Cistrome
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID GENE-EXPRESSION PATTERNS; HUMAN BREAST-CANCER; EMBRYONIC STEM-CELLS;
RNA-POLYMERASE; HUMAN GENOME; CHROMATIN SIGNATURES; HISTOLOGIC GRADE;
BINDING-SITES; CHIP-CHIP; TRANSCRIPTION
AB Proper activation of transcriptional networks in complex organisms is central to the response to stimuli. We demonstrate that the selective activation of a subset of the estrogen receptor alpha (ER alpha) cistrome in MCF7 breast cancer cells provides specificity to the estradiol (E2) response. ER alpha-specific enhancers that are subject to E2-induced coactivator-associated arginine methyltransferase 1 (CARM1) action are critical to E2-stimulated gene expression. This is true for both FoxA1-dependent and independent enhancers. In contrast, a subset of E2-suppressed genes are controlled by FoxA1-independent ER alpha binding sites. Nonetheless, these are sites of E2-induced CARM1 activity. In addition, the MCF7 RNA polymerase II cistrome reveals preferential occupancy of E2-regulated promoters prior to stimulation. Interestingly, E2-suppressed genes tend to lie in otherwise silent genomic regions. Together, our results suggest that the transcriptional response to E2 in breast cancer cells is dependent on the interplay between polymerase II pre-occupied promoters and the subset of the ER alpha cistrome associated with coactivation.
C1 [Lupien, Mathieu; Eeckhoute, Jerome; Krum, Susan A.; Brown, Myles] Dana Farber Canc Inst, Dept Med Oncol, Div Mol & Cellular Oncol, Boston, MA 02115 USA.
[Lupien, Mathieu; Eeckhoute, Jerome; Krum, Susan A.; Brown, Myles] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Lupien, Mathieu; Eeckhoute, Jerome; Krum, Susan A.; Brown, Myles] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Meyer, Clifford A.; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Meyer, Clifford A.; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Rhodes, Daniel R.] Compendia Biosci Inc, Ann Arbor, MI 48104 USA.
RP Brown, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Div Mol & Cellular Oncol, 44 Binney St, Boston, MA 02115 USA.
EM myles_brown@dfci.harvard.edu
RI krum, susan/D-7282-2013;
OI Brown, Myles/0000-0002-8213-1658; Eeckhoute, Jerome/0000-0002-7222-9264
FU NIDDK [R01DK074967]; NCI [P01 CA8011105]; DF/HCC Breast Cancer SPORE;
DFCI Women's Cancers Program; DFCI Women's Cancers Program
[W81XWH-08-1-0214]
FX This study was supported by grants from the NIDDK (R01DK074967 to M.
B.), the NCI (P01 CA8011105) and a DF/HCC Breast Cancer SPORE Grant (to
M. B.), the DFCI Women's Cancers Program, and the U. S. Department of
Defense Breast Cancer Research Program Awards (W81XWH-08-1-0214 to M.
L.).
NR 70
TC 44
Z9 46
U1 0
U2 1
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 JUN 15
PY 2009
VL 29
IS 12
BP 3413
EP 3423
DI 10.1128/MCB.00020-09
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 450XW
UT WOS:000266436300016
PM 19364822
ER
PT J
AU Ehrlich, S
Burghardt, R
Schneider, N
Broecker-Preuss, M
Weiss, D
Merle, JV
Craciun, EM
Pfeiffer, E
Mann, K
Lehmkuhl, U
Hebebrand, J
AF Ehrlich, Stefan
Burghardt, Roland
Schneider, Nora
Broecker-Preuss, Martina
Weiss, Deike
Merle, Julia V.
Craciun, Eugenia Maria
Pfeiffer, Ernst
Mann, Klaus
Lehmkuhl, Ulrike
Hebebrand, Johannes
TI The role of leptin and cortisol in hyperactivity in patients with acute
and weight-recovered anorexia nervosa
SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
LA English
DT Review
DE Anorexia nervosa; Cortisol; Hyperactivity; Leptin
ID CORTICOTROPIN-RELEASING-FACTOR; PITUITARY-ADRENAL AXIS;
PHYSICAL-ACTIVITY; BEHAVIORAL ACTIVATION; RATS; EXERCISE; ADOLESCENTS;
OBESE; RESTLESSNESS; DISORDERS
AB Introduction: In food-restricted rats, leptin as well as corticotropin releasing factor attenuate semistarvation-induced hyperactivity (SIH). Results from studies in patients with anorexia nervosa (AN) showed an association between excessive physical activity (PA) and leptin. One recent report suggests a role for cortisol in PA. In this study, we assessed the relationships between PA and both, cortisol and leptin levels at the same time in patients with acute anorexia nervosa (acAN) in comparison to recovered patients (recAN).
Methods: Plasma leptin, plasma cortisol, body mass index (BMI), and expert-ratings of qualities of PA were assessed in 36 acAN patients, 27 recAN patients and 44 healthy control woman (HCW). Regression analyses were used to predict PA using BMI, leptin and cortisol levels as predictor variables.
Results: Leptin levels but not cortisol significantly contributed to the prediction of PA in acAN. In recAN PA was not elevated and not related to endocrine parameters but correlated positively with core eating disorder symptoms.
Conclusions: Our work lends support to the proposed inverse association between peripheral leptin levels and excessive physical activity in AN. This relationship is specific to the state of semistarvation. The role of additional mediators remains to be clarified. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Ehrlich, Stefan; Burghardt, Roland; Schneider, Nora; Weiss, Deike; Merle, Julia V.; Pfeiffer, Ernst; Lehmkuhl, Ulrike] Charite Univ Med Berlin, Dept Child & Adolescent Psychiat Psychosomat & Ps, CVK, D-13353 Berlin, Germany.
[Ehrlich, Stefan] Charite Univ Med Berlin, Dept Psychiat & Psychotherapy, CCM, D-10117 Berlin, Germany.
[Broecker-Preuss, Martina; Mann, Klaus] Univ Duisburg Essen, Dept Endocrinol, Div Clin Chem & Lab Med, D-45147 Essen, Germany.
[Craciun, Eugenia Maria] Charite Univ Med Berlin, Dept Psychosomat Med, CCM, D-10117 Berlin, Germany.
[Hebebrand, Johannes] Univ Duisburg Essen, Dept Child & Adolescent Psychiat & Psychotherapy, D-45147 Essen, Germany.
RP Ehrlich, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dr R Gollubs Lab, Dept Psychiat,Athinoula A Martinos Ctr Biomed Ima, Bldg 149,13th St,Room 2311, Charlestown, MA 02129 USA.
EM stefan@nmr.mgh.harvard.edu
OI Ehrlich, Stefan/0000-0003-2132-4445
NR 39
TC 10
Z9 10
U1 2
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0278-5846
J9 PROG NEURO-PSYCHOPH
JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry
PD JUN 15
PY 2009
VL 33
IS 4
BP 658
EP 662
DI 10.1016/j.pnpbp.2009.03.007
PG 5
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 455MC
UT WOS:000266763400012
PM 19296912
ER
PT J
AU Medarova, Z
Vallabhajosyula, P
Tena, A
Evgenov, N
Pantazopoulos, P
Tchipashvili, V
Weir, G
Sachs, D
Moore, A
AF Medarova, Zdravka
Vallabhajosyula, Prashanth
Tena, Aseda
Evgenov, Natalia
Pantazopoulos, Pamela
Tchipashvili, Vaja
Weir, Gordon
Sachs, David
Moore, Anna
TI In Vivo Imaging of Autologous Islet Grafts in the Liver and Under the
Kidney Capsule in Non-Human Primates
SO TRANSPLANTATION
LA English
DT Article
DE Islet; Islet labeling; Feridex; Islet transplant; MRI; Non-human primate
ID TRANSPLANTED PANCREATIC-ISLETS; POSITRON-EMISSION-TOMOGRAPHY;
SURFACE-BASED ANALYSIS; EDMONTON PROTOCOL; MRI; CELLS; ENGRAFTMENT;
REJECTION; TRACKING; SURVIVAL
AB Objective. As islet transplantation begins to show promise as a clinical method, there is a critical need for reliable, noninvasive techniques to monitor islet graft survival. Previous work in our laboratory has shown that human islets labeled with a superparamagnetic iron oxide contrast agent and transplanted into mice could be detected by magnetic resonance imaging (MRI). The potential translation of these findings to the clinical situation requires validation of our methodology in a non-human primate model, which we have now carried out in baboons (Papio hamadryas) and reported here.
Research Design and Methods. For islet labeling, we adapted the Food and Drug Administration-approved superparamagnetic iron oxide contrast agent, Feridex, which is used clinically for liver imaging. After partial pancreatectomy, Feridex-labeled islets were prepared and autotransplanted underneath the renal capsule and into the liver. Longitudinal in vivo MRI at days 1, 3, 8, 16, 23, and 30 after transplantation was performed to track the islet grafts.
Results. The renal subcapsular islet graft was easily detectable on T2*-weighted MR images as a pocket of signal loss disrupting the contour of the kidney at the transplantation site. Islets transplanted in the liver appeared as distinct signal voids dispersed throughout the liver parenchyma. A semiautomated computational analysis of our MRI data established the feasibility of monitoring both the renal and intrahepatic grafts during the studied posttransplantation period.
Conclusion. This study establishes a method for the noninvasive, longitudinal detection of pancreatic islets transplanted into non-human primates using a low-field clinical MRI system.
C1 [Medarova, Zdravka; Evgenov, Natalia; Pantazopoulos, Pamela; Moore, Anna] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Radiol,Mol Imaging Lab, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Boston, MA 02129 USA.
[Vallabhajosyula, Prashanth; Tena, Aseda; Sachs, David] Harvard Univ, Sch Med, Transplantat Biol Res Ctr, Massachusetts Gen Hosp, Boston, MA 02129 USA.
[Tchipashvili, Vaja; Weir, Gordon] Harvard Univ, Sch Med, Sect Islet Transplantat & Cell Biol, Joslin Diabet Ctr, Boston, MA 02129 USA.
RP Moore, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Radiol,Mol Imaging Lab, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Room 2301,Bldg 149,13th St, Boston, MA 02129 USA.
EM amoore@helix.mgh.harvard.edu
FU NIH [1RO1 DK078615, 5P30 DK 36836]
FX This study was supported in part by NIH 1RO1 DK078615 (A.M.). Also
supported by NIH 5P30 DK 36836.
NR 31
TC 28
Z9 28
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0041-1337
J9 TRANSPLANTATION
JI Transplantation
PD JUN 15
PY 2009
VL 87
IS 11
BP 1659
EP 1666
DI 10.1097/TP.0b013e3181a5cbc0
PG 8
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA 456YG
UT WOS:000266889900009
PM 19502957
ER
PT J
AU Shah, AA
Sainani, NI
Ramesh, AK
Shah, ZK
Deshpande, V
Hahn, PF
Sahani, DV
AF Shah, Anjuli A.
Sainani, Nisha I.
Ramesh, Avinash Kambadakone
Shah, Zarine K.
Deshpande, Vikram
Hahn, Peter F.
Sahani, Dushyant V.
TI Predictive value of multi-detector computed tomography for accurate
diagnosis of serous cystadenoma: Radiologic-pathologic correlation
SO WORLD JOURNAL OF GASTROENTEROLOGY
LA English
DT Article
DE Pancreas; Serous cystadenoma; Multi-detector computed tomography;
Central scar; Lobulations; Microcystic
ID CYSTIC NEOPLASMS; MUCINOUS CYSTADENOMA; PANCREAS; CT; MANAGEMENT;
ADENOMA; RECOMMENDATIONS; DISCRIMINATION; FEATURES; LESIONS
AB AIM: To identify multi-detector computed tomography (MDCT) features most predictive of serous cystadenomas (SCAs), correlating with histopathology, and to study the impact of cyst size and MDCT technique on reader performance.
METHODS: The MDCT scans of 164 patients with surgically verified pancreatic cystic lesions were reviewed by two readers to study the predictive value of various morphological features for establishing a diagnosis of SCAs. Accuracy in lesion characterization and reader confidence were correlated with lesion size (<= 3 cm or >= 3 cm) and scanning protocols (dedicated vs routine).
RESULTS: 28/164 cysts (mean size, 39 mm; range, 8-92 mm) were diagnosed as SCA on pathology. The MDCT features predictive of diagnosis of SCA were microcystic appearance (22/28, 78.6%), surface lobulations (25/28, 89.3%) and central scar (9/28, 32.4%). Stepwise logistic regression analysis showed that only microcystic appearance was significant for CT diagnosis of SCA (P = 0.0001). The sensitivity, specificity and PPV of central scar and of combined microcystic appearance and lobulations were 32.4%/100%/100% and 68%/100%/100%, respectively. The reader confidence was higher for lesions > 3 cm (P = 0.02) and for MDCT scans performed using thin collimation (1.25-2.5 mm) compared to routine 5 mm collimation exams (P > 0.05).
CONCLUSION: Central scar on MDCT is diagnostic of SCA but is seen in only one third of SCAs. Microcystic morphology is the most significant CT feature in diagnosis of SCA. A combination of microcystic appearance and surface lobulations offers accuracy comparable to central scar with higher sensitivity. (C) 2009 The WIG Press and Baishideng. All rights reserved.
C1 [Shah, Anjuli A.; Sainani, Nisha I.; Ramesh, Avinash Kambadakone; Shah, Zarine K.; Hahn, Peter F.; Sahani, Dushyant V.] Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, Dept Radiol, Boston, MA 02114 USA.
[Deshpande, Vikram] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Sahani, DV (reprint author), Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, Dept Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA.
EM dsahani@partners.org
RI Shah, Zarine/E-4064-2011
OI Shah, Zarine/0000-0002-0354-9678
NR 21
TC 9
Z9 13
U1 0
U2 1
PU W J G PRESS
PI BEIJING
PA APT 1066, YISHOU GARDEN, NO 58, NORTH LANGXINZHUANG RD, PO BOX 2345,
BEIJING 100023, PEOPLES R CHINA
SN 1007-9327
J9 WORLD J GASTROENTERO
JI World J. Gastroenterol.
PD JUN 14
PY 2009
VL 15
IS 22
BP 2739
EP 2747
DI 10.3748/wjg.15.2739
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 460DU
UT WOS:000267169100008
PM 19522024
ER
PT J
AU Woolf, CJ
AF Woolf, Clifford J.
TI Mu and Delta Opioid Receptors Diverge
SO CELL
LA English
DT Editorial Material
ID ANALGESIA; MORPHINE; TOLERANCE; MICE
AB Contrary to current models, Scherrer et al. (2009) provide evidence that mu and delta opioid receptors are not expressed by the same pain-sensing neurons. In mice, agonists for these receptors produce analgesia restricted to either noxious heat or mechanical stimuli, implying that the receptors act on distinct fibers to mediate completely different types of pain relief.
C1 [Woolf, Clifford J.] Massachusetts Gen Hosp, Neural Plast Res Grp, Dept Anesthesia & Crit Care, Boston, MA 02129 USA.
[Woolf, Clifford J.] Harvard Univ, Sch Med, Boston, MA 02129 USA.
RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Neural Plast Res Grp, Dept Anesthesia & Crit Care, Boston, MA 02129 USA.
EM cwoolf@partners.org
NR 9
TC 9
Z9 12
U1 0
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD JUN 12
PY 2009
VL 137
IS 6
BP 987
EP 988
DI 10.1016/j.cell.2009.05.033
PG 2
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 457GL
UT WOS:000266916400007
PM 19524498
ER
PT J
AU Kim, JH
Ellwood, PE
Asher, MI
AF Kim, June-Ho
Ellwood, Philippa E.
Asher, M. Innes
TI Diet and asthma: looking back, moving forward
SO RESPIRATORY RESEARCH
LA English
DT Review
ID GENE-ENVIRONMENT INTERACTIONS; THRIFTY PHENOTYPE HYPOTHESIS; CHILDHOOD
ASTHMA; VITAMIN-D; MEDITERRANEAN DIET; BRONCHIAL HYPERRESPONSIVENESS;
ALLERGIC RHINOCONJUNCTIVITIS; INTESTINAL MICROBIOTA; HYGIENE HYPOTHESIS;
ANTIOXIDANT INTAKE
AB Asthma is an increasing global health burden, especially in the western world. Public health interventions are sought to lessen its prevalence or severity, and diet and nutrition have been identified as potential factors. With rapid changes in diet being one of the hallmarks of westernization, nutrition may play a key role in affecting the complex genetics and developmental pathophysiology of asthma. The present review investigates hypotheses about hygiene, antioxidants, lipids and other nutrients, food types and dietary patterns, breastfeeding, probiotics and intestinal microbiota, vitamin D, maternal diet, and genetics. Early hypotheses analyzed population level trends and focused on major dietary factors such as antioxidants and lipids. More recently, larger dietary patterns beyond individual nutrients have been investigated such as obesity, fast foods, and the Mediterranean diet. Despite some promising hypotheses and findings, there has been no conclusive evidence about the role of specific nutrients, food types, or dietary patterns past early childhood on asthma prevalence. However, diet has been linked to the development of the fetus and child. Breastfeeding provides immunological protection when the infant's immune system is immature and a modest protective effect against wheeze in early childhood. Moreover, maternal diet may be a significant factor in the development of the fetal airway and immune system. As asthma is a complex disease of gene-environment interactions, maternal diet may play an epigenetic role in sensitizing fetal airways to respond abnormally to environmental insults. Recent hypotheses show promise in a biological approach in which the effects of dietary factors on individual physiology and immunology are analyzed before expansion into larger population studies. Thus, collaboration is required by various groups in studying this enigma from epidemiologists to geneticists to immunologists. It is now apparent that this multidisciplinary approach is required to move forward and understand the complexity of the interaction of dietary factors and asthma.
C1 [Kim, June-Ho] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[Ellwood, Philippa E.; Asher, M. Innes] Univ Auckland, Dept Paediat Child & Youth Hlth, Auckland 1, New Zealand.
RP Kim, JH (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
EM juneho.kim@post.harvard.edu; p.ellwood@auckland.ac.nz;
mi.asher@auckland.ac.nz
RI Ellwood, Philippa/G-7555-2015; Asher, Innes/O-2604-2016
OI Ellwood, Philippa/0000-0002-1994-4023; Asher, Innes/0000-0003-1768-3832
NR 94
TC 43
Z9 50
U1 4
U2 16
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1465-9921
J9 RESP RES
JI Respir. Res.
PD JUN 12
PY 2009
VL 10
AR 49
DI 10.1186/1465-9921-10-49
PG 7
WC Respiratory System
SC Respiratory System
GA 475TB
UT WOS:000268382800001
PM 19519921
ER
PT J
AU Corsello, SM
Roti, G
Ross, KN
Chow, KT
Galinsky, I
DeAngelo, DJ
Stone, RM
Kung, AL
Golub, TR
Stegmaier, K
AF Corsello, Steven M.
Roti, Giovanni
Ross, Kenneth N.
Chow, Kwan T.
Galinsky, Ilene
DeAngelo, Daniel J.
Stone, Richard M.
Kung, Andrew L.
Golub, Todd R.
Stegmaier, Kimberly
TI Identification of AML1-ETO modulators by chemical genomics
SO BLOOD
LA English
DT Article
ID ACUTE MYELOID-LEUKEMIA; HIGH-DOSE METHYLPREDNISOLONE; ACUTE
MYELOBLASTIC-LEUKEMIA; ACUTE MONOCYTIC LEUKEMIA; FUSION PROTEIN;
GRANULOCYTIC DIFFERENTIATION; TRANSCRIPTION FACTOR; EXPRESSION PROFILES;
PROSTATE-CANCER; SELF-RENEWAL
AB Somatic rearrangements of transcription factors are common abnormalities in the acute leukemias. With rare exception, however, the resultant protein products have remained largely intractable as pharmacologic targets. One example is AML1-ETO, the most common translocation reported in acute myeloid leukemia (AML). To identify AML1-ETO modulators, we screened a small molecule library using a chemical genomic approach. Gene expression signatures were used as surrogates for the expression versus loss of the translocation in AML1-ETO-expressing cells. The top classes of compounds that scored in this screen were corticosteroids and dihydrofolate reductase (DHFR) inhibitors. In addition to modulating the AML1-ETO signature, both classes induced evidence of differentiation, dramatically inhibited cell viability, and ultimately induced apoptosis via on-target activity. Furthermore, AML1-ETO-expressing cell lines were exquisitely sensitive to the effects of corticosteroids on cellular viability compared with nonexpressers. The corticosteroids diminished AML1-ETO protein in AML cells in a proteasome-and glucocorticoid receptor-dependent manner. Moreover, these molecule classes demonstrated synergy in combination with standard AML chemotherapy agents and activity in an orthotopic model of AML1-ETO-positive AML. This work suggests a role for DHFR inhibitors and corticosteroids in treating patients with AML1-ETO-positive disease. (Blood. 2009; 113: 6193-6205)
C1 [Corsello, Steven M.; Roti, Giovanni; Chow, Kwan T.; Kung, Andrew L.; Golub, Todd R.; Stegmaier, Kimberly] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Corsello, Steven M.; Roti, Giovanni; Chow, Kwan T.; Kung, Andrew L.; Golub, Todd R.; Stegmaier, Kimberly] Harvard Univ, Sch Med, Childrens Hosp Boston, Cambridge, MA 02138 USA.
[Ross, Kenneth N.; Golub, Todd R.; Stegmaier, Kimberly] Harvard Univ, Broad Inst, Cambridge, MA 02138 USA.
[Ross, Kenneth N.; Golub, Todd R.; Stegmaier, Kimberly] MIT, Cambridge, MA 02139 USA.
[Galinsky, Ilene; DeAngelo, Daniel J.; Stone, Richard M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Golub, Todd R.] Howard Hughes Med Inst, Chevy Chase, MD USA.
RP Stegmaier, K (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Dana 322A,44 Binney St, Boston, MA 02115 USA.
EM kimberly_stegmaier@dfci.harvard.edu
OI Kung, Andrew/0000-0002-9091-488X
FU American Society of Hematology (Washington, DC); Sidney Kimmel
Foundation for Cancer Research (Baltimore, MD); National Cancer
Institute (Bethesda, MD); Howard Hughes Medical Institute
FX This work was funded by the American Society of Hematology (Washington,
DC; K. S.), Sidney Kimmel Foundation for Cancer Research (Baltimore, MD;
K. S.), the National Cancer Institute (Bethesda, MD; K. S.), and the
Howard Hughes Medical Institute (K. S., T. R. G., and S. M. C.).
NR 43
TC 22
Z9 29
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 JUN 11
PY 2009
VL 113
IS 24
BP 6193
EP 6205
DI 10.1182/blood-2008-07-166090
PG 13
WC Hematology
SC Hematology
GA 459XS
UT WOS:000267147100024
PM 19377049
ER
PT J
AU Goel, VK
Ibrahim, N
Jiang, G
Singhal, M
Fee, S
Flotte, T
Westmoreland, S
Haluska, FS
Hinds, PW
Haluska, FG
AF Goel, V. K.
Ibrahim, N.
Jiang, G.
Singhal, M.
Fee, S.
Flotte, T.
Westmoreland, S.
Haluska, F. S.
Hinds, P. W.
Haluska, F. G.
TI Melanocytic nevus-like hyperplasia and melanoma in transgenic BRAFV600E
mice
SO ONCOGENE
LA English
DT Article
DE BRAF; p53; CDKN2A; AKT; melanoma; senescence
ID MALIGNANT-MELANOMA; BRAF MUTATIONS; TUMOR SUPPRESSION; IN-VIVO; P53;
SENESCENCE; MDM2; ACTIVATION; PATHWAYS; INK4A
AB BRAF, a cellular oncogene and effector of RAS-mediated signaling, is activated by mutation in similar to 60% of melanomas. Most of these mutations consist of a V600E substitution resulting in constitutive kinase activation. Mutant BRAF thus represents an important therapeutic target in melanoma. In an effort to produce a pre-clinical model of mutant BRAF function in melanoma, we have generated a mouse expressing BRAF V600E targeted to melanocytes. We show that in these transgenic mice, widespread benign melanocytic hyperplasia with histological features of nevi occurs, with biochemical evidence of senescence. Melanocytic hyperplasia progresses to overt melanoma with an incidence dependent on BRAF expression levels. Melanomas show CDKN2A loss, and genetic disruption of the CDKN2A locus greatly enhances melanoma formation, consistent with collaboration between BRAF activation and CDKN2A loss suggested from studies of human melanoma. The development of melanoma also involves activation of the Mapk and Akt signaling pathways and loss of senescence, findings that faithfully recapitulate those seen in human melanomas. This murine model of mutant BRAF-induced melanoma formation thus provides an important tool for identifying further genetic alterations that cooperates with BRAF and that may be useful in enhancing susceptibility to BRAF-targeted therapeutics in melanoma. Oncogene (2009) 28, 2289-2298; doi: 10.1038/onc.2009.95; published online 27 April 2009
C1 [Goel, V. K.; Ibrahim, N.; Jiang, G.; Singhal, M.; Hinds, P. W.; Haluska, F. G.] Tufts Univ New England Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA.
[Fee, S.; Flotte, T.; Haluska, F. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Westmoreland, S.] Harvard Univ, Sch Med, New England Primate Res Ctr, Boston, MA USA.
RP Goel, VK (reprint author), Tufts Univ New England Med Ctr, Mol Oncol Res Inst, 750 Washington St, Boston, MA 02111 USA.
EM vkumargoel@gmail.com; frank.haluska@ARIAD.com
FU NIH [CA095798]
FX This work was supported by NIH grant CA095798 to FGH. We thank Mohammad
Miri for technical assistance, Dr Louis Montoliu for the tyrosinase
promoter, Dr Lynda Chin for the mouse strains, and Dr Philip Tsichlis,
Dr Amit Deshpande and Dr Trevor Pemberton for useful discussions.
NR 36
TC 69
Z9 70
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD JUN 11
PY 2009
VL 28
IS 23
BP 2289
EP 2298
DI 10.1038/onc.2009.95
PG 10
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 456XM
UT WOS:000266886300005
PM 19398955
ER
PT J
AU Sabbisetti, V
Di Napoli, A
Seeley, A
Amato, AM
O'Regan, E
Ghebremichael, M
Loda, M
Signoretti, S
AF Sabbisetti, Venkata
Di Napoli, Arianna
Seeley, Apryle
Amato, Angela M.
O'Regan, Esther
Ghebremichael, Musie
Loda, Massimo
Signoretti, Sabina
TI p63 Promotes Cell Survival through Fatty Acid Synthase
SO PLOS ONE
LA English
DT Article
AB There is increasing evidence that p63, and specifically Delta Np63, plays a central role in both development and tumorigenesis by promoting epithelial cell survival. However, few studies have addressed the molecular mechanisms through which such important function is exerted. Fatty acid synthase (FASN), a key enzyme that synthesizes long-chain fatty acids and is involved in both embryogenesis and cancer, has been recently proposed as a direct target of p53 family members, including p63 and p73. Here we show that knockdown of either total or Delta N-specific p63 isoforms in squamous cell carcinoma (SCC9) or immortalized prostate epithelial (iPrEC) cells caused a decrease in cell viability by inducing apoptosis without affecting the cell cycle. p63 silencing significantly reduced both the expression and the activity of FASN. Importantly, stable overexpression of either FASN or myristoylated AKT (myr-AKT) was able to partially rescue cells from cell death induced by p63 silencing. FASN induced AKT phosphorylation and a significant reduction in cell viability was observed when FASN-overexpressing SCC9 cells were treated with an AKT inhibitor after p63 knockdown, indicating that AKT plays a major role in FASN-mediated survival. Activated AKT did not cause any alteration in the FASN protein levels but induced its activity, suggesting that the rescue from apoptosis documented in the p63-silenced cells expressing myr-AKT cells may be partially mediated by FASN. Finally, we demonstrated that p63 and FASN expression are positively associated in clinical squamous cell carcinoma samples as well as in the developing prostate. Taken together, our findings demonstrate that FASN is a functionally relevant target of p63 and is required for mediating its pro-survival effects.
RP Sabbisetti, V (reprint author), Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp,Dana Farber Canc Inst, Boston, MA 02115 USA.
EM ssignoretti@partners.org
FU NCI NIH HHS [R01 CA131945]; NIDDK NIH HHS [R21 DK72152, R21 DK072152]
NR 65
TC 15
Z9 16
U1 1
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 11
PY 2009
VL 4
IS 6
AR e5877
DI 10.1371/journal.pone.0005877
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 456TJ
UT WOS:000266873100010
PM 19517019
ER
PT J
AU Koreth, J
Schlenk, R
Kopecky, KJ
Honda, S
Sierra, J
Djulbegovic, BJ
Wadleigh, M
DeAngelo, DJ
Stone, RM
Sakamaki, H
Appelbaum, FR
Dohner, H
Antin, JH
Soiffer, RJ
Cutler, C
AF Koreth, John
Schlenk, Richard
Kopecky, Kenneth J.
Honda, Sumihisa
Sierra, Jorge
Djulbegovic, Benjamin J.
Wadleigh, Martha
DeAngelo, Daniel J.
Stone, Richard M.
Sakamaki, Hisashi
Appelbaum, Frederick R.
Doehner, Hartmut
Antin, Joseph H.
Soiffer, Robert J.
Cutler, Corey
TI Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia in First
Complete Remission Systematic Review and Meta-analysis of Prospective
Clinical Trials
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Review
ID BONE-MARROW-TRANSPLANTATION; ACUTE MYELOGENOUS LEUKEMIA; FRENCH AML
INTERGROUP; HIGH-DOSE CYTARABINE; POSTREMISSION THERAPY; CONSOLIDATION
THERAPY; COMORBIDITY INDEX; COOPERATIVE-GROUP; ADULT PATIENTS;
ONCOLOGY-GROUP
AB Context The optimal treatment of acute myeloid leukemia (AML) in first complete remission (CR1) is uncertain. Current consensus, based on cytogenetic risk, recommends myeloablative allogeneic stem cell transplantation (SCT) for poor-risk but not for good-risk AML. Allogeneic SCT, autologous transplantation, and consolidation chemotherapy are considered of equivalent benefit for intermediate-risk AML.
Objective To quantify relapse-free survival (RFS) and overall survival benefit of allogeneic SCT for AML in CR1 overall and also for good-, intermediate-, and poor-risk AML.
Methods Systematic review and meta-analysis of prospective trials evaluating allogeneic SCT vs nonallogeneic SCT therapies for AML in CR1. The search used the combined search terms allogeneic; acut* and leukem*/leukaem*/leucem*/leucaem*/aml; myelo* or nonlympho* in the PubMed, Embase, and Cochrane Registry of Controlled Trials databases in March 2009. The search identified 1712 articles.
Study Selection Prospective trials assigning adult patients with AML in CR1 to undergo allogeneic SCT vs nonallogeneic SCT treatment(s) based on donor availability and trials reporting RFS and/or overall survival outcomes on an intention-to-treat, donor vs no-donor basis were identified.
Data Extraction Two reviewers independently extracted study characteristics, interventions, and outcomes. Hazard ratios (HRs) with 95% confidence intervals (CIs) were determined.
Data Synthesis Overall, 24 trials and 6007 patients were analyzed (5951 patients in RFS analyses and 5606 patients in overall survival analyses); 3638 patients were analyzed by cytogenetic risk (547, 2499, and 592 with good-, intermediate-, and poor-risk AML, respectively). Interstudy heterogeneity was not significant. Fixed-effects meta-analysis was performed. Compared with nonallogeneic SCT, the HR of relapse or death with allogeneic SCT for AML in CR1 was 0.80 (95% CI, 0.74-0.86). Significant RFS benefit of allogeneic SCT was documented for poor- risk (HR, 0.69; 95% CI, 0.57-0.84) and intermediate- risk AML (HR, 0.76; 95% CI, 0.68-0.85) but not for good- risk AML (HR, 1.06; 95% CI, 0.80-1.42). The HR of death with allogeneic SCT for AML in CR1 was 0.90 ( 95% CI, 0.82-0.97). Significant overall survival benefit with allogeneic SCT was documented for poor- risk (HR, 0.73; 95% CI, 0.59-0.90) and intermediate- risk AML (HR, 0.83; 95% CI, 0.74-0.93) but not for good- risk AML (HR, 1.07; 95% CI, 0.83-1.38).
Conclusion Compared with nonallogeneic SCT therapies, allogeneic SCT has significant RFS and overall survival benefit for intermediate- and poor- risk AML but not for good- risk AML in first complete remission. JAMA. 2009;301(22):2349-2361 www.jama.com
C1 [Koreth, John; Wadleigh, Martha; DeAngelo, Daniel J.; Stone, Richard M.; Antin, Joseph H.; Soiffer, Robert J.; Cutler, Corey] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA.
[Schlenk, Richard; Doehner, Hartmut] Univ Hosp Ulm, Ulm, Germany.
[Kopecky, Kenneth J.; Appelbaum, Frederick R.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Honda, Sumihisa] Nagasaki Univ, Inst Trop Med, Nagasaki 852, Japan.
[Sierra, Jorge] Hosp Santa Creu & Sant Pau, Barcelona, Spain.
[Djulbegovic, Benjamin J.] Univ S Florida, Ctr Evidence Based Med & Hlth Outcomes, Tampa, FL USA.
[Djulbegovic, Benjamin J.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA.
[Sakamaki, Hisashi] Tokyo Metropolitan Komagome Hosp, Tokyo, Japan.
RP Koreth, J (reprint author), Dana Farber Canc Inst, Div Hematol Malignancies, 44 Binney St, Boston, MA 02115 USA.
EM john_koreth@dfci.harvard.edu
RI Djulbegovic, Benjamin/I-3661-2012; Lopez, Dulce/A-7700-2013
OI Djulbegovic, Benjamin/0000-0003-0671-1447;
FU Stem Cell Cyclists of the Pan-Massachusetts Challenge
FX Dr Sakamaki reported serving as a member of the advisory boards of
Bristol-Myers Squibb Co and Wyeth Inc. Dr Cutler reported receiving
partial funding from the Stem Cell Cyclists of the Pan-Massachusetts
Challenge. No other authors reported financial disclosures.
NR 45
TC 346
Z9 363
U1 0
U2 19
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUN 10
PY 2009
VL 301
IS 22
BP 2349
EP 2361
PG 13
WC Medicine, General & Internal
SC General & Internal Medicine
GA 455OT
UT WOS:000266773400028
PM 19509382
ER
PT J
AU Thanassoulis, G
O'Donnell, CJ
AF Thanassoulis, George
O'Donnell, Christopher J.
TI Mendelian Randomization Nature's Randomized Trial in the Post-Genome Era
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID CORONARY-HEART-DISEASE; APOLIPOPROTEIN(A) GENE; PLASMA LIPOPROTEIN(A);
ARTERY-DISEASE; POLYMORPHISM; ASSOCIATION; PREVENTION; VARIANTS; RISK;
MEN
C1 [Thanassoulis, George; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA.
[Thanassoulis, George] Boston Univ, Sch Med, Boston, MA 02118 USA.
[O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA.
RP O'Donnell, CJ (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Ste 2, Framingham, MA 01702 USA.
EM codonnell@nih.gov
FU Intramural NIH HHS [Z99 HL999999]
NR 17
TC 32
Z9 32
U1 1
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUN 10
PY 2009
VL 301
IS 22
BP 2386
EP 2388
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 455OT
UT WOS:000266773400034
PM 19509388
ER
PT J
AU Hoe, HS
Lee, KJ
Carney, RSE
Lee, J
Markova, A
Lee, JY
Howell, BW
Hyman, BT
Pak, DTS
Bu, GJ
Rebeck, GW
AF Hoe, Hyang-Sook
Lee, Kea Joo
Carney, Rosalind S. E.
Lee, Jiyeon
Markova, Alexandra
Lee, Ji-Yun
Howell, Brian W.
Hyman, Bradley T.
Pak, Daniel T. S.
Bu, Guojun
Rebeck, G. William
TI Interaction of Reelin with Amyloid Precursor Protein Promotes Neurite
Outgrowth
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID ALZHEIMERS-DISEASE; HIPPOCAMPAL-NEURONS; F-SPONDIN; SYNAPTIC PLASTICITY;
TAU PHOSPHORYLATION; ACTIN CYTOSKELETON; SIGNALING PATHWAY; RNA
INTERFERENCE; RECEPTOR APOER2; TRANSGENIC MICE
AB The processing of amyloid precursor protein (APP) to A beta is an important event in the pathogenesis of Alzheimer's disease, but the physiological function of APP is not well understood. Our previous work has shown that APP processing and A beta production are regulated by the extracellular matrix protein Reelin. In the present study, we examined whether Reelin interacts with APP, and the functional consequences of that interaction in vitro. Using coimmunoprecipitation, we found that Reelin interacted with APP through the central domain of Reelin (repeats 3-6) and the E1 extracellular domain of APP. Reelin increased cell surface levels of APP and decreased endocytosis of APP in hippocampal neurons in vitro. In vivo, Reelin levels were increased in brains of APP knock-out mice and decreased in APP-overexpressing mice. RNA interference knockdown of APP decreased neurite outgrowth in vitro and prevented Reelin from increasing neurite outgrowth. Knock-out of APP or Reelin decreased dendritic arborization in cortical neurons in vivo, and APP overexpression increased dendritic arborization. APP and Reelin have previously been shown to promote neurite outgrowth through interactions with integrins. We confirmed that APP interacted with alpha 3 beta 1 integrin, and alpha 3 beta 1 integrin altered APP trafficking and processing. Addition of an alpha 3 beta 1 integrin antibody prevented APP and Reelin-induced neurite outgrowth. These findings demonstrate that Reelin interacts with APP, potentially having important effects on neurite development.
C1 [Hoe, Hyang-Sook; Rebeck, G. William] Georgetown Univ, Med Ctr, Dept Neurosci, Washington, DC 20057 USA.
[Lee, Kea Joo; Lee, Ji-Yun; Pak, Daniel T. S.] Georgetown Univ, Med Ctr, Dept Pharmacol, Washington, DC 20057 USA.
[Carney, Rosalind S. E.] Childrens Natl Med Ctr, Ctr Res Neurosci, Washington, DC 20010 USA.
[Lee, Jiyeon; Bu, Guojun] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA.
[Markova, Alexandra; Hyman, Bradley T.] Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Disorders, Charlestown, MA 02129 USA.
[Howell, Brian W.] Natl Inst Neurol Disorders & Stroke, Neurogenet Branch, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Rebeck, GW (reprint author), Georgetown Univ, Med Ctr, Dept Neurosci, 3970 Reservoir Rd NW, Washington, DC 20057 USA.
EM gwr2@georgetown.edu
RI Lee, Ji-Yun/F-8127-2013;
OI Howell, Brian/0000-0002-0204-0773
FU National Institutes of Health [AG014473, R01 AG027924, R37 AG012406,
AG032330]; Alzheimer's Research Fund
FX This work was supported by National Institutes of Health Grants AG014473
( G. W. R.), R01 AG027924 ( G. B.), R37 AG012406 ( B. T. H.), and
AG032330 (H.-S.H.), and the Alzheimer's Research Fund in memory of Bill
and Marie Drach. We thank Drs. Andre Goffinet and Tom Curren for
providing Reelin constructs and Drs. Mary Ann Stepp and Susette Mueller
for integrin antibodies. We thank Drs. Sam Gandy and Paul Mathews for
APP antibodies, and Drs. Yasuji Matsuoka and Baoji Xu for helpful
suggestions. We also thank Ulrike Muller for the APP/APLP1 DKO tissue.
NR 55
TC 110
Z9 111
U1 0
U2 8
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 JUN 10
PY 2009
VL 29
IS 23
BP 7459
EP 7473
DI 10.1523/JNEUROSCI.4872-08.2009
PG 15
WC Neurosciences
SC Neurosciences & Neurology
GA 459SV
UT WOS:000267130800010
PM 19515914
ER
PT J
AU Korngold, EC
Januzzi, JL
Gantzer, ML
Moorthy, MV
Cook, NR
Albert, CM
AF Korngold, Ethan C.
Januzzi, James L., Jr.
Gantzer, Mary Lou
Moorthy, M. V.
Cook, Nancy R.
Albert, Christine M.
TI Amino-Terminal Pro-B-Type Natriuretic Peptide and High-Sensitivity
C-Reactive Protein as Predictors of Sudden Cardiac Death Among Women
SO CIRCULATION
LA English
DT Article
DE death, sudden; epidemiology; natriuretic peptides; risk factors; women
ID CARDIOVASCULAR EVENTS; MYOCARDIAL-INFARCTION; CORONARY DEATH;
UNITED-STATES; RISK; HEART; ARRHYTHMIAS; POPULATION; OUTCOMES; FAILURE
AB Background-Plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) have been found to predict risk of sudden cardiac death (SCD) in patients with known cardiac disease, and C-reactive protein levels have been found to predict risk among apparently healthy men. However, there are no data on SCD risk prediction for either of these markers in a population of women unselected on the basis of cardiovascular disease.
Methods and Results-In a prospective, nested, case-control analysis within the 121 700-participant Nurses' Health Study, 99 cases of definite or probable SCD were identified and matched to 294 controls. In multivariable models that adjusted for coronary heart disease risk factors, glomerular filtration rate, and other biomarkers, the trend across quartiles approached significance for NT-proBNP (rate ratio=2.37 for comparison of the highest and lowest quartile; P for trend=0.05) but not for high-sensitivity C-reactive protein (P for trend=0.60). When examined continuously, both NT-proBNP and high-sensitivity C-reactive protein were significantly associated with SCD risk in age-and fasting-adjusted models (P for linear trend=0.04 and 0.03). Adjustment for coronary heart disease risk factors and other biomarkers strengthened the relationship with NT-proBNP and SCD (relative risk for 1-SD increment=1.49; 95% confidence interval, 1.09 to 2.05; P=0.01) but eliminated the relationship with high-sensitivity C-reactive protein (P=0.34). Women with NT-proBNP levels above the prespecified cut point of 389 pg/mL were at a markedly increased risk of SCD in both models (rate ratio=5.68; 95% confidence interval, 1.78 to 18.2; P=0.003).
Conclusions-In this population of women, baseline levels of NT-proBNP were associated with subsequent risk of SCD. If this association is confirmed in larger prospectively studied populations, these findings might provide another useful marker contributing to efforts to screen and prevent SCD among women. (Circulation. 2009; 119: 2868-2876.)
C1 [Moorthy, M. V.; Albert, Christine M.] Brigham & Womens Hosp, Ctr Arrhythmia Prevent, Div Prevent Med, Boston, MA 02215 USA.
[Albert, Christine M.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02215 USA.
[Korngold, Ethan C.; Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiovasc, Boston, MA 02114 USA.
[Gantzer, Mary Lou] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Gantzer, Mary Lou] Siemens Healthcare Diagnost Inc, Newark, DE USA.
RP Albert, CM (reprint author), Brigham & Womens Hosp, Ctr Arrhythmia Prevent, Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA.
EM calbert@partners.org
FU Siemens Healthcare Diagnostics; National Institutes of Health [CA-87969,
HL-34594, HL-03783]
FX The study was supported by a research grant from Siemens Healthcare
Diagnostics to Dr Albert. The Nurses' Health Study is supported by
grants CA-87969, HL-34594, and HL-03783 from the National Institutes of
Health. The study sponsor did not influence the study design, analysis,
interpretation, and presentation of data.
NR 30
TC 31
Z9 31
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD JUN 9
PY 2009
VL 119
IS 22
BP 2868
EP 2876
DI 10.1161/CIRCULATIONAHA.108.832576
PG 9
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 455QM
UT WOS:000266777900003
PM 19470888
ER
PT J
AU Galie, N
Brundage, BH
Ghofrani, HA
Oudiz, RJ
Simonneau, G
Safdar, Z
Shapiro, S
White, RJ
Chan, M
Beardsworth, A
Frumkin, L
Barst, RJ
AF Galie, Nazzareno
Brundage, Bruce H.
Ghofrani, Hossein A.
Oudiz, Ronald J.
Simonneau, Gerald
Safdar, Zeenat
Shapiro, Shelley
White, R. James
Chan, Melanie
Beardsworth, Anthony
Frumkin, Lyn
Barst, Robyn J.
CA Pulm Arterial Hypertension & Resp
TI Tadalafil Therapy for Pulmonary Arterial Hypertension
SO CIRCULATION
LA English
DT Article
DE hypertension, pulmonary; phosphodiesterase inhibitors; tadalafil
ID DOUBLE-BLIND; NITRIC-OXIDE; INHALED ILOPROST; CONTROLLED-TRIAL;
SILDENAFIL; BOSENTAN; EFFICACY; PROSTACYCLIN; SITAXSENTAN; AMBRISENTAN
AB Background-Treatment options for pulmonary arterial hypertension target the prostacyclin, endothelin, or nitric oxide pathways. Tadalafil, a phosphodiesterase type-5 inhibitor, increases cGMP, the final mediator in the nitric oxide pathway.
Methods and Results-In this 16-week, double-blind, placebo-controlled study, 405 patients with pulmonary arterial hypertension (idiopathic or associated), either treatment-naive or on background therapy with the endothelin receptor antagonist bosentan, were randomized to placebo or tadalafil 2.5, 10, 20, or 40 mg orally once daily. The primary end point was the change from baseline to week 16 in the distance walked in 6 minutes. Changes in World Health Organization functional class, clinical worsening, and health-related quality of life were also assessed. Patients completing the 16-week study could enter a long-term extension study. Tadalafil increased the distance walked in 6 minutes in a dose-dependent manner; only the 40-mg dose met the prespecified level of statistical significance (P<0.01). Overall, the mean placebo-corrected treatment effect was 33 m (95% confidence interval, 15 to 50 m). In the bosentan-naive group, the treatment effect was 44 m (95% confidence interval, 20 to 69 m) compared with 23 m (95% confidence interval, -2 to 48 m) in patients on background bosentan therapy. Tadalafil 40 mg improved the time to clinical worsening (P=0.041), incidence of clinical worsening (68% relative risk reduction; P=0.038), and health-related quality of life. The changes in World Health Organization functional class were not statistically significant. The most common treatment-related adverse events reported with tadalafil were headache, myalgia, and flushing.
Conclusions-In patients with pulmonary arterial hypertension, tadalafil 40 mg was well tolerated and improved exercise capacity and quality of life measures and reduced clinical worsening. (Circulation. 2009; 119: 2894-2903.)
C1 [Galie, Nazzareno] Univ Bologna, Inst Cardiol, I-40138 Bologna, Italy.
[Brundage, Bruce H.] Heart Inst Cascades, Bend, OR USA.
[Ghofrani, Hossein A.] Univ Giessen, Univ Hosp, Giessen, Germany.
[Oudiz, Ronald J.] Univ Calif Los Angeles, Los Angeles Biomed Res Inst Harbor, Torrance, CA USA.
[Simonneau, Gerald] Antoine Beclere Univ Hosp, Clamart, France.
[Safdar, Zeenat] Baylor Coll Med, Div Pulm & Crit Care Med, Houston, TX 77030 USA.
[Shapiro, Shelley] Univ Calif Los Angeles, David Geffen Sch Med, Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA 90095 USA.
[White, R. James] Univ Rochester, Div Pulm & Crit Care Med, Rochester, NY USA.
[Chan, Melanie] Eli Lilly & Co, Toronto, ON, Canada.
[Frumkin, Lyn] ICOS Corp, Bothell, WA USA.
[Barst, Robyn J.] Schneider Childrens Hosp N Shore Long Isl Jewish, New Hyde Pk, NY USA.
RP Galie, N (reprint author), Univ Bologna, Inst Cardiol, Via Massarenti 9, I-40138 Bologna, Italy.
EM nazzareno.galie@unibo.it
RI Reynaud-Gaubert, Martine/P-6958-2016;
OI Galie, Nazzareno/0000-0003-4271-8670
FU Eli Lilly and Company
FX The study was funded by Eli Lilly and Company.
NR 42
TC 418
Z9 450
U1 2
U2 23
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD JUN 9
PY 2009
VL 119
IS 22
BP 2894
EP U65
DI 10.1161/CIRCULATIONAHA.108.839274
PG 12
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 455QM
UT WOS:000266777900006
PM 19470885
ER
PT J
AU Clardy, J
Fischbach, MA
Currie, CR
AF Clardy, Jon
Fischbach, Michael A.
Currie, Cameron R.
TI The natural history of antibiotics
SO CURRENT BIOLOGY
LA English
DT Editorial Material
ID FUNGUS-GROWING ANTS; BACTERIA; MOLECULES
C1 [Clardy, Jon] Harvard Univ, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Fischbach, Michael A.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Currie, Cameron R.] Univ Wisconsin, Dept Bacteriol, Madison, WI 53706 USA.
RP Clardy, J (reprint author), Harvard Univ, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
EM jon_clardy@hms.harvard.edu
FU NCI NIH HHS [R01 CA024487, R01 CA024487-30]; NIGMS NIH HHS [R01
GM086258]
NR 10
TC 39
Z9 40
U1 4
U2 48
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0960-9822
J9 CURR BIOL
JI Curr. Biol.
PD JUN 9
PY 2009
VL 19
IS 11
BP R437
EP R441
DI 10.1016/j.cub.2009.04.001
PG 5
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 456YX
UT WOS:000266891900009
PM 19515346
ER
PT J
AU Yaffe, K
Fiocco, AJ
Lindquist, K
Vittinghoff, E
Simonsick, EM
Newman, AB
Satterfield, S
Rosano, C
Rubin, SM
Ayonayon, HN
Harris, TB
AF Yaffe, K.
Fiocco, A. J.
Lindquist, K.
Vittinghoff, E.
Simonsick, E. M.
Newman, A. B.
Satterfield, S.
Rosano, C.
Rubin, S. M.
Ayonayon, H. N.
Harris, T. B.
CA Hlth ABC Study
TI Predictors of maintaining cognitive function in older adults The Health
ABC Study
SO NEUROLOGY
LA English
DT Article
ID ATTENTIONAL CONTROL; ALZHEIMERS-DISEASE; GLUCOSE-TOLERANCE; LIFE-STYLE;
WOMEN; PLASTICITY; EXERCISE; DECLINE; BRAIN; AGE
AB Background: Although several risk factors for cognitive decline have been identified, much less is known about factors that predict maintenance of cognitive function in advanced age.
Methods: We studied 2,509 well-functioning black and white elders enrolled in a prospective study. Cognitive function was measured using the Modified Mini-Mental State Examination at baseline and years 3, 5, and 8. Random effects models were used to classify participants as cognitive maintainers (cognitive change slope >= 0), minor decliners (slope <0 and >1 SD below mean), or major decliners (slope <= 1 SD below mean). Logistic regression was used to identify domain-specific factors associated with being a maintainer vs a minor decliner.
Results: Over 8 years, 30% of the participants maintained cognitive function, 53% showed minor decline, and 16% had major cognitive decline. In the multivariate model, baseline variables significantly associated with being a maintainer vs a minor decliner were age (odds ratio [OR] = 0.65, 95% confidence interval [CI] 0.55-0.77 per 5 years), white race (OR = 1.72, 95% CI 1.30-2.28), high school education level or greater (OR = 2.75, 95% CI 1.78-4.26), ninth grade literacy level or greater (OR = 4.85, 95% CI 3.00-7.87), weekly moderate/vigorous exercise (OR = 1.31, 95% CI 1.06-1.62), and not smoking (OR = 1.84, 95% CI 1.14-2.97). Variables associated with major cognitive decline compared to minor cognitive decline are reported.
Conclusion: Elders who maintain cognitive function have a unique profile that differentiates them from those with minor decline. Importantly, some of these factors are modifiable and thus may be implemented in prevention programs to promote successful cognitive aging. Further, factors associated with maintenance may differ from factors associated with major cognitive decline, which may impact prevention vs treatment strategies. Neurology (R) 2009; 72: 2029-2035
C1 [Yaffe, K.; Fiocco, A. J.] Univ San Francisco, Sch Med, Dept Psychiat, San Francisco, CA 94117 USA.
[Yaffe, K.; Vittinghoff, E.; Rubin, S. M.; Ayonayon, H. N.] Univ San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA 94117 USA.
[Yaffe, K.] Univ San Francisco, Sch Med, Dept Neurol, San Francisco, CA 94117 USA.
[Lindquist, K.] Univ San Francisco, Sch Med, Dept Med, San Francisco, CA 94117 USA.
[Yaffe, K.] San Francisco VA Med Ctr, San Francisco, CA USA.
[Simonsick, E. M.] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[Harris, T. B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Baltimore, MD 21224 USA.
[Newman, A. B.; Rosano, C.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Satterfield, S.] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA.
RP Fiocco, AJ (reprint author), Univ San Francisco, Sch Med, Dept Psychiat, 4150 Clement St, San Francisco, CA 94117 USA.
EM jazzfiocco@hotmail.com
RI Newman, Anne/C-6408-2013;
OI Newman, Anne/0000-0002-0106-1150; Rosano, Caterina/0000-0002-0909-1506;
Rosano, Caterina/0000-0002-4271-6010
FU Intramural NIH HHS; NIA NIH HHS [AG 031155, AG021918, N01-AG-6-2101,
N01-AG-6-2103, N01-AG-6-2106]
NR 36
TC 112
Z9 118
U1 0
U2 19
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD JUN 9
PY 2009
VL 72
IS 23
BP 2029
EP 2035
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 455QI
UT WOS:000266777500012
PM 19506226
ER
PT J
AU Zhang, Q
Zhou, YF
Zhang, CZ
Zhang, XH
Lu, CF
Springer, TA
AF Zhang, Qing
Zhou, Yan-Feng
Zhang, Cheng-Zhong
Zhang, Xiaohui
Lu, Chafen
Springer, Timothy A.
TI Structural specializations of A2, a force-sensing domain in the
ultralarge vascular protein von Willebrand factor
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID VONWILLEBRAND-FACTOR; DISEASE MUTATIONS; IIA; ISOMERIZATION; ACTIVATION;
SYSTEM
AB The lengths of von Willebrand factor (VWF) concatamers correlate with hemostatic potency. After secretion in plasma, length is regulated by hydrodynamic shear force-dependent unfolding of the A2 domain, which is then cleaved by a specific protease. The 1.9-angstrom crystal structure of the A2 domain demonstrates evolutionary adaptations to this shear sensor function. Unique among VWF A (VWA) domains, A2 contains a loop in place of the alpha 4 helix, and a cis-proline. The central beta 4-strand is poorly packed, with multiple side-chain rotamers. The Tyr-Met cleavage site is buried in the beta 4-strand in the central hydrophobic core, and the Tyr structurally links to the C-terminal alpha 6-helix. The alpha 6-helix ends in 2 Cys residues that are linked by an unusual vicinal disulfide bond that is buried in a hydrophobic pocket. These features may narrow the force range over which unfolding occurs and may also slow refolding. Von Willebrand disease mutations, which presumably lower the force at which A2 unfolds, are illuminated by the structure.
C1 [Springer, Timothy A.] Harvard Univ, Childrens Hosp Boston, Immune Dis Inst, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Springer, TA (reprint author), Harvard Univ, Childrens Hosp Boston, Immune Dis Inst, 3 Blackfan Circle, Boston, MA 02115 USA.
EM springer@idi.harvard.edu
RI Zhou, Yanfeng/B-3792-2012
FU National Institutes of Health [HL48675]
FX We thank Drs. J. Evan Sadler and Wendy Thomas for reviewing the
manuscript. This work was supported by National Institutes of Health
Grant HL48675.
NR 31
TC 90
Z9 92
U1 1
U2 7
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 JUN 9
PY 2009
VL 106
IS 23
BP 9226
EP 9231
DI 10.1073/pnas.0903679106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 456CN
UT WOS:000266817500024
PM 19470641
ER
PT J
AU Guerau-De-Arellano, M
Martinic, M
Benoist, C
Mathis, D
AF Guerau-de-Arellano, Mireia
Martinic, Marianne
Benoist, Christophe
Mathis, Diane
TI Neonatal tolerance revisited: a perinatal window for Aire control of
autoimmunity
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID MEMORY T-CELLS; CUTTING EDGE; MICE; PROLIFERATION; DISEASE; LYMPHOPENIA;
SPECIFICITY; REPERTOIRE; INDUCTION; SELECTION
AB There has long been conceptual and experimental support for, but also challenges to, the notion that the initial period of the immune system's development is particularly important for the establishment of tolerance to self. The display of self-antigens by thymic epithelial cells is key to inducing tolerance in the T lymphocyte compartment, a process enhanced by the Aire transcription factor. Using a doxycycline-regulated transgene to target Aire expression to the thymic epithelium, complementing the Aire knockout in a temporally controlled manner, we find that Aire is essential in the perinatal period to prevent the multiorgan autoimmunity that is typical of Aire deficiency. Surprisingly, Aire could be shut down soon thereafter and remain off for long periods, with few deleterious consequences. The lymphopenic state present in neonates was a factor in this dichotomy because inducing lymphopenia during Aire turnoff in adults recreated the disease, which, conversely, could be ameliorated by supplementing neonates with adult lymphocytes. In short, Aire expression during the perinatal period is both necessary and sufficient to induce long-lasting tolerance and avoid autoimmunity. Aire-controlled mechanisms of central tolerance are largely dispensable in the adult, as a previously tolerized T cell pool can buffer newly generated autoreactive T cells that might emerge.
C1 [Guerau-de-Arellano, Mireia; Martinic, Marianne; Benoist, Christophe; Mathis, Diane] Harvard Univ, Sch Med, Brigham & Womens Hosp, Sect Immunol & Immunogenet,Joslin Diabet Ctr, Boston, MA 02215 USA.
[Guerau-de-Arellano, Mireia; Martinic, Marianne; Benoist, Christophe; Mathis, Diane] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA.
RP Mathis, D (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Sect Immunol & Immunogenet,Joslin Diabet Ctr, Boston, MA 02215 USA.
EM cbdm@hms.harvard.edu; cbdm@hms.harvard.edu
FU R01 DK60027; NIDDK
FX This work was supported by R01 DK60027 and Young Chair funds to D.
Mathis and C. Benoist, and by the Joslin's NIDDK- funded Diabetes and
Endocrinology Research Center.
NR 38
TC 63
Z9 66
U1 1
U2 3
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD JUN 8
PY 2009
VL 206
IS 6
BP 1245
EP 1252
DI 10.1084/jem.20090300
PG 8
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 459TS
UT WOS:000267133700006
PM 19487417
ER
PT J
AU Goonetilleke, N
Liu, MKP
Salazar-Gonzalez, JF
Ferrari, G
Giorgi, E
Ganusov, VV
Keele, BF
Learn, GH
Turnbull, EL
Salazar, MG
Weinhold, KJ
Moore, S
Letvin, N
Haynes, BF
Cohen, MS
Hraber, P
Bhattacharya, T
Borrow, P
Perelson, AS
Hahn, BH
Shaw, GM
Korber, BT
McMichael, AJ
AF Goonetilleke, Nilu
Liu, Michael K. P.
Salazar-Gonzalez, Jesus F.
Ferrari, Guido
Giorgi, Elena
Ganusov, Vitaly V.
Keele, Brandon F.
Learn, Gerald H.
Turnbull, Emma L.
Salazar, Maria G.
Weinhold, Kent J.
Moore, Stephen
Letvin, Norman
Haynes, Barton F.
Cohen, Myron S.
Hraber, Peter
Bhattacharya, Tanmoy
Borrow, Persephone
Perelson, Alan S.
Hahn, Beatrice H.
Shaw, George M.
Korber, Bette T.
McMichael, Andrew J.
CA CHAVI Clin Core B
TI The first T cell response to transmitted/founder virus contributes to
the control of acute viremia in HIV-1 infection
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID ACTIVE ANTIRETROVIRAL THERAPY; CTL ESCAPE MUTATION; IN-VIVO; LYMPHOCYTE
ESCAPE; TYPE-1 INFECTION; PERIPHERAL-BLOOD; RHESUS-MONKEYS; IMMUNE
CONTROL; VIRAL ESCAPE; GAG
AB Identification of the transmitted/founder virus makes possible, for the first time, a genome-wide analysis of host immune responses against the infecting HIV-1 proteome. A complete dissection was made of the primary HIV-1-specific T cell response induced in three acutely infected patients. Cellular assays, together with new algorithms which identify sites of positive selection in the virus genome, showed that primary HIV-1-specific T cells rapidly select escape mutations concurrent with falling virus load in acute infection. Kinetic analysis and mathematical modeling of virus immune escape showed that the contribution of CD8 T cell-mediated killing of productively infected cells was earlier and much greater than previously recognized and that it contributed to the initial decline of plasma virus in acute infection. After virus escape, these first T cell responses often rapidly waned, leaving or being succeeded by T cell responses to epitopes which escaped more slowly or were invariant. These latter responses are likely to be important in maintaining the already established virus set point. In addition to mutations selected by T cells, there were other selected regions that accrued mutations more gradually but were not associated with a T cell response. These included clusters of mutations in envelope that were targeted by NAbs, a few isolated sites that reverted to the consensus sequence, and bystander mutations in linkage with T cell-driven escape.
C1 [Goonetilleke, Nilu; Liu, Michael K. P.; Moore, Stephen; McMichael, Andrew J.] Univ Oxford, Weatherall Inst Mol Med, Med Res Council Human Immunol Unit, Oxford OX3 9DS, England.
[Salazar-Gonzalez, Jesus F.; Keele, Brandon F.; Learn, Gerald H.; Salazar, Maria G.; Hahn, Beatrice H.; Shaw, George M.] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA.
[Ferrari, Guido; Weinhold, Kent J.; Haynes, Barton F.] Duke Univ, Duke Univ Med Res, Durham, NC 27710 USA.
[Giorgi, Elena; Ganusov, Vitaly V.; Hraber, Peter; Bhattacharya, Tanmoy; Perelson, Alan S.; Korber, Bette T.] Los Alamos Natl Lab, Div Theoret, Los Alamos, NM 87545 USA.
[Turnbull, Emma L.; Borrow, Persephone] Univ Oxford, Jenner Inst, Compton RG20 7NN, England.
[Letvin, Norman] Harvard Univ, BIDMC, Boston, MA 02115 USA.
[Cohen, Myron S.] Univ N Carolina, HIV Prevent Trials Unit, Chapel Hill, NC 27599 USA.
[Bhattacharya, Tanmoy; Korber, Bette T.] Santa Fe Inst, Santa Fe, NM 87501 USA.
RP McMichael, AJ (reprint author), Univ Oxford, Weatherall Inst Mol Med, Med Res Council Human Immunol Unit, Oxford OX3 9DS, England.
EM andrew.mcmichael@imm.ox.ac.uk
RI Bhattacharya, Tanmoy/J-8956-2013; Ferrari, Guido/A-6088-2015;
OI Bhattacharya, Tanmoy/0000-0002-1060-652X; Ganusov,
Vitaly/0000-0001-6572-1691; Korber, Bette/0000-0002-2026-5757; Hraber,
Peter/0000-0002-2920-4897
FU HIV/AIDS Vaccine Immunology [A1067854-03]; Medical Research Center Human
Immunology Unit; National Institute for Health Research Oxford
Biomedical Research Center [37874]; Bill and Melinda Gates Foundation;
NIDDK [DK049381]; U. S. Department of Energy [DE-AC52-06NA25396]
FX This work was supported by the Center for HIV/AIDS Vaccine Immunology
grant A1067854-03. Additional support came from the Medical Research
Center Human Immunology Unit, the National Institute for Health Research
Oxford Biomedical Research Center, and grant 37874 from the Bill and
Melinda Gates Foundation. P. Borrow is supported by a Jenner Fellowship
and M. S. Cohen is supported by NIDDK Award DK049381. Portions of this
work were done under the auspices of the U. S. Department of Energy
under contract DE-AC52-06NA25396, and V. V. Ganusov was supported by
their Laboratory Directed Research and Development program.
NR 63
TC 340
Z9 348
U1 5
U2 24
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD JUN 8
PY 2009
VL 206
IS 6
BP 1253
EP 1272
DI 10.1084/jem.20090365
PG 20
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 459TS
UT WOS:000267133700007
PM 19487423
ER
PT J
AU Jinushi, M
Sato, M
Kanamoto, A
Itoh, A
Nagai, S
Koyasu, S
Dranoff, G
Tahara, H
AF Jinushi, Masahisa
Sato, Marimo
Kanamoto, Akira
Itoh, Akihiko
Nagai, Shigenori
Koyasu, Shigeo
Dranoff, Glenn
Tahara, Hideaki
TI Milk fat globule epidermal growth factor-8 blockade triggers tumor
destruction through coordinated cell-autonomous and immune-mediated
mechanisms
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID NF-KAPPA-B; APOPTOTIC CELLS; DENDRITIC CELLS; ANTITUMOR IMMUNITY; CANCER
DEVELOPMENT; GM-CSF; THERAPY; INFLAMMATION; PROGRESSION; DISEASE
AB Carcinogenesis reflects the dynamic interplay of transformed cells and normal host elements, but cancer treatments typically target each compartment separately. Within the tumor micro-environment, the secreted protein milk fat globule epidermal growth factor-8 (MFG-E8) stimulates disease progression through coordinated alpha(v)beta(3) integrin signaling in tumor and host cells. MFG-E8 enhances tumor cell survival, invasion, and angiogenesis, and contributes to local immune suppression. We show that systemic MFG-E8 blockade cooperates with cytotoxic chemotherapy, molecularly targeted therapy, and radiation therapy to induce destruction of various types of established mouse tumors. The combination treatments evoke extensive tumor cell apoptosis that is coupled to efficient dendritic cell cross-presentation of dying tumor cells. This linkage engenders potent antitumor effector T cells but inhibits FoxP3(+) T reg cells, thereby achieving long-term protective immunity. Collectively, these findings suggest that systemic MFG-E8 blockade might intensify the antitumor activities of existing therapeutic regimens through coordinated cell-autonomous and immune-mediated mechanisms.
C1 [Jinushi, Masahisa; Sato, Marimo; Kanamoto, Akira; Itoh, Akihiko; Tahara, Hideaki] Univ Tokyo, Inst Med Sci, Adv Clin Res Ctr, Dept Surg & Bioengn, Tokyo 1088639, Japan.
[Nagai, Shigenori; Koyasu, Shigeo] Keio Univ, Sch Med, Dept Microbiol & Immunol, Tokyo 1608582, Japan.
[Nagai, Shigenori] Japan Sci & Technol Agcy, Core Res Evolut Sci & Technol, Tokyo 1020075, Japan.
[Dranoff, Glenn] Brigham & Womens Hosp, Dept Med Oncol, Boston, MA 02115 USA.
[Dranoff, Glenn] Brigham & Womens Hosp, Canc Vaccine Ctr, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Dranoff, Glenn] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Dranoff, Glenn] Harvard Univ, Sch Med, Boston, MA 02115 USA.
RP Tahara, H (reprint author), Univ Tokyo, Inst Med Sci, Adv Clin Res Ctr, Dept Surg & Bioengn, Tokyo 1088639, Japan.
EM tahara@ims.u-tokyo.ac.jp
RI Jinushi, Masahisa/A-4311-2012; Koyasu, Shigeo/J-5583-2015
OI Koyasu, Shigeo/0000-0001-9585-3038
FU Ministry of Education, Culture, Sports, Science and Technology of Japan
[20015016, 20890050]; Melanoma Research Alliance and the Research
Foundation
FX This study was supported in part by the Grants-in-Aid for Scientific
Research on Priority Areas (20015016 to H. Tahara) and for Young
Scientists (Start-Up; 20890050 to M. Jinushi) from the Ministry of
Education, Culture, Sports, Science and Technology of Japan, as well as
by the Melanoma Research Alliance and the Research Foundation for the
Treatment of Ovarian Cancer (G. Dranoff).
NR 42
TC 40
Z9 40
U1 0
U2 1
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD JUN 8
PY 2009
VL 206
IS 6
BP 1317
EP 1326
DI 10.1084/jem.20082614
PG 10
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 459TS
UT WOS:000267133700011
PM 19433619
ER
PT J
AU Van Rhijn, I
Young, DC
De Jong, A
Vazquez, J
Cheng, TY
Talekar, R
Barral, D
Leon, L
Brenner, MB
Katz, JT
Riese, R
Ruprecht, RM
O'Connor, PB
Costello, CE
Porcelli, SA
Briken, V
Moody, DB
AF Van Rhijn, Ildiko
Young, David C.
De Jong, Annemieke
Vazquez, Jenny
Cheng, Tan-Yun
Talekar, Rahul
Barral, Duarte
Leon, Luis
Brenner, Michael B.
Katz, Joel T.
Riese, Richard
Ruprecht, Ruth M.
O'Connor, Peter B.
Costello, Catherine E.
Porcelli, Steven A.
Briken, Volker
Moody, D. Branch
TI CD1c bypasses lysosomes to present a lipopeptide antigen with 12 amino
acids
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID T-CELL RECOGNITION; MHC CLASS-II; DIFFERENT INTRACELLULAR COMPARTMENTS;
MYCOBACTERIUM-TUBERCULOSIS; LIPID ANTIGENS; CRYSTAL-STRUCTURE;
CATHEPSIN-S; GLYCOLIPID ANTIGENS; CYSTEINE PROTEASES; VIRAL INFECTIVITY
AB The recent discovery of dideoxymycobactin (DDM) as a ligand for CD1a demonstrates how a nonribosomal lipopeptide antigen is presented to T cells. DDM contains an unusual acylation motif and a peptide sequence present only in mycobacteria, but its discovery raises the possibility that ribosomally produced viral or mammalian proteins that commonly undergo lipidation might also function as antigens. To test this, we measured T cell responses to synthetic acylpeptides that mimic lipoproteins produced by cells and viruses. CD1c presented an N-acyl glycine dodecamer peptide (lipo-12) to human T cells, and the response was specific for the acyl linkage as well as the peptide length and sequence. Thus, CD1c represents the second member of the CD1 family to present lipopeptides. lipo-12 was efficiently recognized when presented by intact cells, and unlike DDM, it was inactivated by proteases and augmented by protease inhibitors. Although lysosomes often promote antigen presentation by CD1, rerouting CD1c to lysosomes by mutating CD1 tail sequences caused reduction in lipo-12 presentation. Thus, although certain antigens require antigen processing in lysosomes, others are destroyed there, providing a hypothesis for the evolutionary conservation of large CD1 families containing isoforms that survey early endosomal pathways.
C1 [Van Rhijn, Ildiko; Young, David C.; De Jong, Annemieke; Cheng, Tan-Yun; Talekar, Rahul; Barral, Duarte; Leon, Luis; Brenner, Michael B.; Moody, D. Branch] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA.
[Katz, Joel T.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Infect Dis, Boston, MA 02115 USA.
[Riese, Richard] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pulm Med, Boston, MA 02115 USA.
[Vazquez, Jenny; O'Connor, Peter B.; Costello, Catherine E.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Ruprecht, Ruth M.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Immunol & AIDS, Boston, MA 02115 USA.
[Porcelli, Steven A.] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA.
[Briken, Volker] Univ Maryland, Maryland Pathogen Res Inst, College Pk, MD 20742 USA.
[Briken, Volker] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA.
RP Moody, DB (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA.
EM i.vanrhijn@uu.nl; bmoody@rics.bwh.harvard.edu
RI OConnor, Peter/C-2117-2009; Barral, Duarte/E-7548-2013;
OI de Jong, Annemieke/0000-0001-6707-6585; Briken,
Volker/0000-0001-5830-6107; OConnor, Peter/0000-0002-6588-6274; Barral,
Duarte/0000-0001-8867-2407; Costello, Catherine/0000-0003-1594-5122
FU National Institute of Allergy and Infectious Diseases [R01 AI049313,
AI45889]; National Institute of Arthritis and Musculoskeletal and Skin
Diseases [R01 AR048632]; American Lung Association [RT-95-N]; National
Institutes of Health/National Center for Research Resources [P41
RR10888]; Pew Foundation Scholars in the Biomedical Sciences
FX This work was supported by the National Institute of Allergy and
Infectious Diseases (grant R01 AI049313 to D. B. Moody and grant AI45889
to S. A. Porcelli), the National Institute of Arthritis and
Musculoskeletal and Skin Diseases (grant R01 AR048632 to D. B. Moody),
the American Lung Association (grant RT-95-N to I. Van Rhijn), the
National Institutes of Health/National Center for Research Resources
(grant P41 RR10888 to C. E. Costello), the Pew Foundation Scholars in
the Biomedical Sciences,
NR 66
TC 37
Z9 37
U1 1
U2 6
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD JUN 8
PY 2009
VL 206
IS 6
BP 1409
EP 1422
DI 10.1084/jem.20082480
PG 14
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 459TS
UT WOS:000267133700018
PM 19468063
ER
PT J
AU Nohadani, O
Seco, J
Martin, BC
Bortfeld, T
AF Nohadani, Omid
Seco, Joao
Martin, Benjamin C.
Bortfeld, Thomas
TI Dosimetry robustness with stochastic optimization
SO PHYSICS IN MEDICINE AND BIOLOGY
LA English
DT Article
ID INTENSITY-MODULATED RADIOTHERAPY; IMRT OPTIMIZATION; MONTE-CARLO;
THERAPY; MOTION
AB All radiation therapy treatment planning relies on accurate dose calculation. Uncertainties in dosimetric prediction can significantly degrade an otherwise optimal plan. In this work, we introduce a robust optimization method which handles dosimetric errors and warrants for high-quality IMRT plans. Unlike other dose error estimations, we do not rely on the detailed knowledge about the sources of the uncertainty and use a generic error model based on random perturbation. This generality is sought in order to cope with a large variety of error sources. We demonstrate the method on a clinical case of lung cancer and show that our method provides plans that are more robust against dosimetric errors and are clinically acceptable. In fact, the robust plan exhibits a two-fold improved equivalent uniform dose compared to the non-robust but optimized plan. The achieved speedup will allow computationally extensivemulti-criteria or beam-angle optimization approaches to warrant for dosimetrically relevant plans.
C1 [Nohadani, Omid; Seco, Joao; Martin, Benjamin C.; Bortfeld, Thomas] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Nohadani, Omid; Seco, Joao; Martin, Benjamin C.; Bortfeld, Thomas] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Nohadani, Omid] MIT, Ctr Operat Res, Cambridge, MA 02139 USA.
RP Nohadani, O (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
EM nohadani@mit.edu; jseco@partners.org; ben.martin@alum.bu.edu;
tbortfeld@partners.org
RI Seco, Joao/J-4451-2012; Nohadani, Omid/N-8177-2013
FU National Cancer Institute of the United States; NIH [R01 CA 111590];
[R01-CA118200]; [R01-CA103904]
FX We would like to thank D Craft and G Sharp for fruitful discussions. We
are also very grateful to H Paganetti for his insights as well as
computation time. We would also like to thank N Choi for providing the
lung patient data. This work was supported by the National Cancer
Institute of the United States under grants R01-CA118200 and
R01-CA103904. JS also acknowledges support from NIH grant R01 CA 111590.
NR 20
TC 9
Z9 9
U1 0
U2 0
PU IOP PUBLISHING LTD
PI BRISTOL
PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND
SN 0031-9155
J9 PHYS MED BIOL
JI Phys. Med. Biol.
PD JUN 7
PY 2009
VL 54
IS 11
BP 3421
EP 3432
DI 10.1088/0031-9155/54/11/010
PG 12
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA 447QZ
UT WOS:000266208200010
PM 19436100
ER
PT J
AU Raskind, WH
Matsushita, M
Peter, B
Biberston, J
Wolff, J
Lipe, H
Burbank, R
Bird, TD
AF Raskind, Wendy H.
Matsushita, Mark
Peter, Beate
Biberston, Jeffrey
Wolff, John
Lipe, Hillary
Burbank, Ruben
Bird, Thomas D.
TI Familial Dyskinesia and Facial Myokymia (FDFM): Follow-Up of a Large
Family and Linkage to Chromosome 3p21-3q21
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
LA English
DT Article
DE chorea; movement disorder; episodic disorder
ID EPISODIC ATAXIA; CHANNEL; MUTATION; GENE; EPILEPSY; PROTEIN; KCNA1
AB We previously reported a five-generation family manifesting an autosomal dominant disorder of facial myokymia and dystonic/choreic movements (FDFM). The dyskinetic episodes are initially paroxysmal but may become constant. With increasing age they may lessen or even disappear. The previous study excluded nine candidate genes chosen for their association with myokymia or chorea and two regions containing single or clustered ion channel genes. We now report identification by whole genome linkage analysis of a broad region on chromosome 3p21-3q21 that segregates with the disease in all 10 affected members in three generations who participated in the study. GENEHUNTER-MODSCORE Version 2.0.1 provided a maximum multipoint LOD score of 3.099. No other disorders primarily characterized by myokymia, dystonia, or chorea are known to map to this region. Identification of additional families with FDFM may narrow the critical region and facilitate the choice of candidate genes for further analysis. (C) 2008 Wiley-Liss, Inc.
C1 [Raskind, Wendy H.; Matsushita, Mark; Biberston, Jeffrey; Wolff, John; Burbank, Ruben] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA.
[Raskind, Wendy H.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[Raskind, Wendy H.; Matsushita, Mark] Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA.
[Peter, Beate] Univ Washington, Sch Med, Dept Speech & Hearing Sci, Seattle, WA 98195 USA.
[Wolff, John; Lipe, Hillary; Bird, Thomas D.] Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA.
[Bird, Thomas D.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98195 USA.
RP Raskind, WH (reprint author), Univ Washington, Sch Med, Dept Med, Box 35-7720, Seattle, WA 98195 USA.
EM wendyrun@u.washington.edu
FU Department of Veterans Affairs; NIH [2 T32 DC000033]
FX The authors wish to thank the members of the family whose cooperation
with, and interest in, the research is essential. The research was
supported in part by funds from the Department of Veterans Affairs
(W.H.R., M.M., J.W., H.L., and T.D.B.) and NIH 2 T32 DC000033 (B.P.).
NR 25
TC 8
Z9 8
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4841
J9 AM J MED GENET B
JI Am. J. Med. Genet. B
PD JUN 5
PY 2009
VL 150B
IS 4
BP 570
EP 574
DI 10.1002/ajmg.b.30879
PG 5
WC Genetics & Heredity; Psychiatry
SC Genetics & Heredity; Psychiatry
GA 452CD
UT WOS:000266516400016
PM 18980218
ER
PT J
AU Hofmann, I
Stover, EH
Cullen, DE
Mao, J
Morgan, KJ
Lee, BH
Kharas, MG
Miller, PG
Cornejo, MG
Okabe, R
Armstrong, SA
Ghilardi, N
Gould, S
de Sauvage, FJ
McMahon, AP
Gilliland, DG
AF Hofmann, Inga
Stover, Elizabeth H.
Cullen, Dana E.
Mao, Junhao
Morgan, Kelly J.
Lee, Benjamin H.
Kharas, Michael G.
Miller, Peter G.
Cornejo, Melanie G.
Okabe, Rachel
Armstrong, Scott A.
Ghilardi, Nico
Gould, Stephen
de Sauvage, Frederic J.
McMahon, Andrew P.
Gilliland, D. Gary
TI Hedgehog Signaling Is Dispensable for Adult Murine Hematopoietic Stem
Cell Function and Hematopoiesis
SO CELL STEM CELL
LA English
DT Article
ID ACUTE MYELOID-LEUKEMIA; SONIC HEDGEHOG; HUMAN HOMOLOG; BCR-ABL; CANCER;
GENE; DIFFERENTIATION; MEDULLOBLASTOMA; PROLIFERATION; MAINTENANCE
AB We report the unexpected finding that loss of Hh signaling through conditional deletion of Smoothened (Smo) in the adult hematopoietic compartment has no apparent effect on adult hematopoiesis, including peripheral blood count, number or cell-cycle status of stem or progenitor cells, hematopoietic colony-forming potential, long-term repopulating activity in competitive repopulation assays, or stress response to serial 5-fluorouracil treatment. Furthermore, pharmacologic inhibition of Hh signaling with a potent and selective small molecule antagonist has no substantive effect on hematopoiesis in the mouse. In addition, Hh signaling is not required for the development of MLL-AF9-mediated acute myeloid leukemia (AML). Taken together, these data demonstrate that Hh signaling is dispensable for normal hematopoietic development and hematopoietic stem cell function, indicating that targeting of Hh signaling in solid tumors is not likely to result in hematopoietic toxicity. Furthermore, the Hh pathway may not be a compelling target in certain hematopoietic malignancies.
C1 [Hofmann, Inga; Stover, Elizabeth H.; Cullen, Dana E.; Morgan, Kelly J.; Lee, Benjamin H.; Kharas, Michael G.; Miller, Peter G.; Cornejo, Melanie G.; Okabe, Rachel; Gilliland, D. Gary] Brigham & Womens Hosp, Div Hematol, Dept Med, Boston, MA 02115 USA.
[Hofmann, Inga; Armstrong, Scott A.; Gilliland, D. Gary] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Hofmann, Inga; Stover, Elizabeth H.; Miller, Peter G.; Cornejo, Melanie G.; Armstrong, Scott A.; Gilliland, D. Gary] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Gilliland, D. Gary] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
[Gilliland, D. Gary] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
[Mao, Junhao; McMahon, Andrew P.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
[Hofmann, Inga; Armstrong, Scott A.] Childrens Hosp, Boston, MA 02115 USA.
[Ghilardi, Nico; Gould, Stephen; de Sauvage, Frederic J.] Genentech Inc, San Francisco, CA 94080 USA.
RP Gilliland, DG (reprint author), Brigham & Womens Hosp, Div Hematol, Dept Med, 75 Francis St, Boston, MA 02115 USA.
EM ggilliland@rics.bwh.harvard.edu
OI Ghilardi, Nico/0000-0003-4945-3097
FU Leukemia and Lymphoma Society; National Institutes of Health (NIH);
NIH/National Institute of Neurological Disorders and Stroke (NINDS)
[R37NS033642]
FX We thank Emily Chan, Leslie Lee, and Maria Pitsiouni from Genentech and
Allison Coburn, Elizabeth McDowell, and Sandra Moore from the Gilliland
lab for technical support; and Thomas Mercher, Glen Raffel, Zuzanna
Tothova, Claudia Scholl, and Stefan Frohling for valuable discussion.
This work was supported in part by the Leukemia and Lymphoma Society and
by National Institutes of Health (NIH) grants (D.G.G., E.H.S.). D.G.G is
an Investigator of the Howard Hughes Medical Institute. Work in A.P.M.'s
laboratory was supported in part by a grant from the NIH/National
Institute of Neurological Disorders and Stroke (NINDS), R37NS033642.
E.H.S. and I.H.Z. designed and performed research, analyzed data, and
wrote the manuscript. F.J.d.S., N.G., and S.G. designed and performed
research and analyzed data on the pharmacological experiments,
participated in interpretation of data, and reviewed the manuscript.
J.M. and A.P.M. generated the Smo mice, participated in design and
interpretation of experiments, and reviewed the manuscript. S.A.A.
participated in design and interpretation of experiments involving the
MLL-AF9 fusion. D.G.G. designed research, analyzed data, and revised the
paper. F.J.d.S., N.G., and S.G. are employees of Genentech, Inc. A.P.M.
is a consultant for Merck.
NR 36
TC 96
Z9 101
U1 1
U2 5
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 JUN 5
PY 2009
VL 4
IS 6
BP 559
EP 567
DI 10.1016/j.stem.2009.03.016
PG 9
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA 455UY
UT WOS:000266793600018
PM 19497284
ER
PT J
AU Zhang, XH
Halvorsen, K
Zhang, CZ
Wong, WP
Springer, TA
AF Zhang, Xiaohui
Halvorsen, Kenneth
Zhang, Cheng-Zhong
Wong, Wesley P.
Springer, Timothy A.
TI Mechanoenzymatic Cleavage of the Ultralarge Vascular Protein von
Willebrand Factor
SO SCIENCE
LA English
DT Article
ID FACTOR A2 DOMAIN; VONWILLEBRAND-FACTOR; FACTOR MULTIMERS; SHEAR-STRESS;
PLASMA; ADAMTS13; SUBSTRATE; ADHESION; DISEASE; CONFORMATION
AB Von Willebrand factor (VWF) is secreted as ultralarge multimers that are cleaved in the A2 domain by the metalloprotease ADAMTS13 to give smaller multimers. Cleaved VWF is activated by hydrodynamic forces found in arteriolar bleeding to promote hemostasis, whereas uncleaved VWF is activated at lower, physiologic shear stresses and causes thrombosis. Single-molecule experiments demonstrate that elongational forces in the range experienced by VWF in the vasculature unfold the A2 domain, and only the unfolded A2 domain is cleaved by ADAMTS13. In shear flow, tensile force on a VWF multimer increases with the square of multimer length and is highest at the middle, providing an efficient mechanism for homeostatic regulation of VWF size distribution by force-induced A2 unfolding and cleavage by ADAMTS13, as well as providing a counterbalance for VWF-mediated platelet aggregation.
C1 [Zhang, Xiaohui; Zhang, Cheng-Zhong; Springer, Timothy A.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
[Halvorsen, Kenneth; Wong, Wesley P.] Harvard Univ, Rowland Inst Harvard, Cambridge, MA 02142 USA.
[Zhang, Xiaohui] Chinese Acad Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, Shanghai 200031, Peoples R China.
RP Springer, TA (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
EM wong@rowland.harvard.edu; springer@idi.harvard.edu
FU NIH [HL-48675]; Rowland Junior Fellows; American Heart Association
[525918T]
FX Supported by NIH HL-48675 (T.A.S.), the Rowland Junior Fellows (W.P.W.),
and American Heart Association 525918T (X.Z.). The authors thank C.
Bustamante, S. Marqusee, and C. Cecconi for protocols for DNA-protein
coupling; J. E. Sadler, D. Schaak, J. Kim, J. Seog, C. Lu, and A.
Alexander-Katz for reagents and insightful discussions; and G. Dempsey
for work on the early stages of this project.
NR 32
TC 213
Z9 215
U1 3
U2 46
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD JUN 5
PY 2009
VL 324
IS 5932
BP 1330
EP 1334
DI 10.1126/science.1170905
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 453TF
UT WOS:000266635100047
PM 19498171
ER
PT J
AU Sundrud, MS
Koralov, SB
Feuerer, M
Calado, DP
Kozhaya, AE
Rhule-Smith, A
Lefebvre, RE
Unutmaz, D
Mazitschek, R
Waldner, H
Whitman, M
Keller, T
Rao, A
AF Sundrud, Mark S.
Koralov, Sergei B.
Feuerer, Markus
Calado, Dinis Pedro
Kozhaya, Aimee ElHed
Rhule-Smith, Ava
Lefebvre, Rachel E.
Unutmaz, Derya
Mazitschek, Ralph
Waldner, Hanspeter
Whitman, Malcolm
Keller, Tracy
Rao, Anjana
TI Halofuginone Inhibits T(H)17 Cell Differentiation by Activating the
Amino Acid Starvation Response
SO SCIENCE
LA English
DT Article
ID UNFOLDED PROTEIN RESPONSE; REGULATORY T-CELLS; NF-KAPPA-B;
GENE-EXPRESSION; ROR-GAMMA; STRESS; INFLAMMATION; GENERATION;
INITIATION; INDUCTION
AB A central challenge for improving autoimmune therapy is preventing inflammatory pathology without inducing generalized immunosuppression. T helper 17 (T(H)17) cells, characterized by their production of interleukin-17, have emerged as important and broad mediators of autoimmunity. Here we show that the small molecule halofuginone (HF) selectively inhibits mouse and human T(H)17 differentiation by activating a cytoprotective signaling pathway, the amino acid starvation response (AAR). Inhibition of T(H)17 differentiation by HF is rescued by the addition of excess amino acids and is mimicked by AAR activation after selective amino acid depletion. HF also induces the AAR in vivo and protects mice from T(H)17-associated experimental autoimmune encephalomyelitis. These results indicate that the AAR pathway is a potent and selective regulator of inflammatory T cell differentiation in vivo.
C1 [Whitman, Malcolm; Keller, Tracy] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA.
[Sundrud, Mark S.; Koralov, Sergei B.; Calado, Dinis Pedro; Lefebvre, Rachel E.; Rao, Anjana] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Sundrud, Mark S.; Koralov, Sergei B.; Calado, Dinis Pedro; Lefebvre, Rachel E.; Rao, Anjana] Immune Dis Inst, Boston, MA 02115 USA.
[Feuerer, Markus] Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA.
[Kozhaya, Aimee ElHed; Unutmaz, Derya] NYU, Sch Med, Dept Microbiol, New York, NY 10016 USA.
[Kozhaya, Aimee ElHed; Unutmaz, Derya] NYU, Sch Med, Microbial Pathogenesis Program, New York, NY 10016 USA.
[Rhule-Smith, Ava; Waldner, Hanspeter] Penn State Univ, Dept Microbiol & Immunol, Coll Med, Hershey, PA 17033 USA.
[Mazitschek, Ralph] Broad Inst, Chem Biol Program, Cambridge, MA 02142 USA.
[Mazitschek, Ralph] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02142 USA.
RP Whitman, M (reprint author), Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA.
EM whitman@hms.harvard.edu; tkeller@hms.harvard.edu; arao@idi.harvard.edu
RI Mazitschek, Ralph/E-3741-2013
OI Mazitschek, Ralph/0000-0002-1105-689X
FU NIH [T32, P01]; Juvenile Diabetes Research Foundation; Irvington
Institute fellowship program of the Cancer Research Institute;
Portuguese Foundation for Science and Technology fellowship
FX D. Littman and A. Rudensky provided reagents for this work, and K.
Otipoby prepared recombinant TAT-Cre. We thank J. Hill and K. Leatherbee
for technical assistance with microarray data analysis and members of
the Rao lab for critical discussion. This work was supported by grants
from NIH (to A.R., D.U., and M.W.) and the Juvenile Diabetes Research
Foundation (to A.R.). M.S.S. was supported by the Irvington Institute
fellowship program of the Cancer Research Institute. D.P.C. was
supported by a fellowship from the Portuguese Foundation for Science and
Technology. S.K. was supported by an NIH training grant (T32). Further
support was provided by a P01 grant to K Rajewsky. M.S.S., A.R., T.K.,
and M.W. have filed patent applications concerning the use of HF and its
derivatives to inhibit TH17 cell differentiation. Array data can be
found at www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE15624 with the
accession number of GSE15624 [NCBI GEO] .
NR 29
TC 161
Z9 173
U1 2
U2 16
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD JUN 5
PY 2009
VL 324
IS 5932
BP 1334
EP 1338
DI 10.1126/science.1172638
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 453TF
UT WOS:000266635100048
PM 19498172
ER
PT J
AU Burns, CE
Galloway, JL
Smith, ACH
Keefe, MD
Cashman, TJ
Paik, EJ
Mayhall, EA
Amsterdam, AH
Zon, LI
AF Burns, Caroline E.
Galloway, Jenna L.
Smith, Alexandra C. H.
Keefe, Matthew D.
Cashman, Timothy J.
Paik, Elizabeth J.
Mayhall, Elizabeth A.
Amsterdam, Adam H.
Zon, Leonard I.
TI Agenetic screen in zebrafish defines a hierarchical network of pathways
required for hematopoietic stem cell emergence
SO BLOOD
LA English
DT Article
ID ENDOTHELIAL-GROWTH-FACTOR; GONAD-MESONEPHROS REGION; DIAMOND-BLACKFAN
ANEMIA; DEFINITIVE HEMATOPOIESIS; ARTERIAL DEVELOPMENT; NOTCH; GENE;
DIFFERENTIATION; EXPRESSION; SPADETAIL
AB Defining the genetic pathways essential for hematopoietic stem cell (HSC) development remains a fundamental goal impacting stem cell biology and regenerative medicine. To genetically dissect HSC emergence in the aorta-gonad-mesonephros (AGM) region, we screened a collection of insertional zebrafish mutant lines for expression of the HSC marker, c-myb. Nine essential genes were identified, which were subsequently binned into categories representing their proximity to HSC induction. Using overexpression and loss-of-function studies in zebrafish, we ordered these signaling pathways with respect to each other and to the Vegf, Notch, and Runx programs. Overexpression of vegf and notch is sufficient to induce HSCs in the tbx16 mutant, despite a lack of axial vascular organization. Although embryos deficient for artery specification, such as the phospholipase C gamma-1 (plc gamma 1) mutant, fail to specify HSCs, overexpression of notch or runx1 can rescue their hematopoietic defect. The most proximal HSC mutants, such as hdac1, were found to have no defect in vessel or artery formation. Further analysis demonstrated that hdac1 acts downstream of Notch signaling but upstream or in parallel to runx1 to promote AGM hematopoiesis. Together, our results establish a hierarchy of signaling programs required and sufficient for HSC emergence in the AGM. (Blood. 2009; 113: 5776-5782)
C1 [Burns, Caroline E.; Galloway, Jenna L.; Smith, Alexandra C. H.; Keefe, Matthew D.; Paik, Elizabeth J.; Mayhall, Elizabeth A.; Zon, Leonard I.] Harvard Univ, Sch Med, Stem Cell Program, Boston, MA 02115 USA.
[Burns, Caroline E.; Galloway, Jenna L.; Smith, Alexandra C. H.; Keefe, Matthew D.; Paik, Elizabeth J.; Mayhall, Elizabeth A.; Zon, Leonard I.] Harvard Univ, Sch Med, Div Hematol Oncol, Childrens Hosp, Boston, MA 02115 USA.
[Burns, Caroline E.; Galloway, Jenna L.; Smith, Alexandra C. H.; Keefe, Matthew D.; Paik, Elizabeth J.; Mayhall, Elizabeth A.; Zon, Leonard I.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Burns, Caroline E.; Cashman, Timothy J.] Harvard Univ, Cardiovasc Res Ctr, Massachusetts Gen Hosp, Sch Med, Charlestown, MA USA.
[Amsterdam, Adam H.] MIT, Ctr Canc Res, Cambridge, MA 02139 USA.
RP Zon, LI (reprint author), Harvard Univ, Sch Med, Stem Cell Program, 320 Longwood Ave,Enders Bldg Rm 761, Boston, MA 02115 USA.
EM zon@enders.tch.harvard.edu
FU National Heart, Lung, and Blood Institute [5 R01 HL48801]; National
Institute of Diabetes and Digestive and Kidney Diseases [1 K01
DK067179]; National Institutes of Health grant from the National Center
for Research Resources [2 R01 RR012589]; Howard Hughes Medical Institute
FX This work was supported by the National Heart, Lung, and Blood Institute
(grant 5 R01 HL48801). C. E. B. is supported by the National Institute
of Diabetes and Digestive and Kidney Diseases ( Research Career Award 1
K01 DK067179). A. H. A. is supported by a National Institutes of Health
grant from the National Center for Research Resources (2 R01 RR012589).
L. I. Z. is supported by Howard Hughes Medical Institute.
NR 48
TC 48
Z9 49
U1 0
U2 3
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 JUN 4
PY 2009
VL 113
IS 23
BP 5776
EP 5782
DI 10.1182/blood-2008-12-193607
PG 7
WC Hematology
SC Hematology
GA 454BH
UT WOS:000266656100017
PM 19332767
ER
PT J
AU Kisucka, J
Chauhan, AK
Zhao, BQ
Patten, IS
Yesilaltay, A
Krieger, M
Wagner, DD
AF Kisucka, Janka
Chauhan, Anil K.
Zhao, Bing-Qiao
Patten, Ian S.
Yesilaltay, Ayce
Krieger, Monty
Wagner, Denisa D.
TI Elevated levels of soluble P-selectin in mice alter blood-brain barrier
function, exacerbate stroke, and promote atherosclerosis
SO BLOOD
LA English
DT Article
ID OBSTRUCTIVE SLEEP-APNEA; VASCULAR ENDOTHELIAL-CELLS; DEFICIENT MICE;
ISCHEMIC-STROKE; PLATELET ACTIVATION; ALZHEIMERS-DISEASE; CYTOPLASMIC
DOMAIN; APOLIPOPROTEIN-E; TISSUE FACTOR; IN-VIVO
AB Cerebrovascular and cardiovascular diseases are a major cause of morbidity and mortality. Soluble P-selectin (sP-selectin) is a biomarker for platelet/endothelial activation and is considered a risk factor for vascular disease. sP-selectin enhances procoagulant activity by inducing leukocyte-derived microparticle production and promotes activation of leukocyte integrins. However, it is not known whether it directly contributes to vascular complications. We investigated the effect of in-creased levels of sP-selectin on blood-brain barrier (BBB) function, stroke outcome, and atherosclerosis by comparing wild-type mice with P-sel(Delta CT/Delta CT) mice in which the endogenous P-selectin gene was replaced with a mutant that produces abnormally high plasma levels of sP-selectin. P-sel(Delta CT/Delta CT) mice presented several abnormalities, including (1) higher BBB permeability, with 25% of the animals showing differential permeability between the right and left hemispheres; (2) altered social behavior with increased aggression; (3) larger infarcts in the middle cerebral artery occlusion ischemic stroke model; and (4) increased susceptibility to atherosclerotic, macrophage-rich lesion development in both male and female mice on the apoE(-/-) genetic background. Thus, elevated sP-selectin is not only a biomarker for vascular disease, but also may contribute directly to atherosclerosis and cerebrovascular complications. (Blood. 2009; 113: 6015-6022)
C1 [Kisucka, Janka; Chauhan, Anil K.; Zhao, Bing-Qiao; Patten, Ian S.; Wagner, Denisa D.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
[Kisucka, Janka; Chauhan, Anil K.; Zhao, Bing-Qiao; Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Yesilaltay, Ayce; Krieger, Monty] MIT, Dept Biol, Cambridge, MA 02139 USA.
RP Wagner, DD (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, 3 Blackfan Circle,3rd Floor, Boston, MA 02115 USA.
EM wagner@idi.harvard.edu
FU National Heart, Lung, and Blood Institute of the National Institutes of
Health (Bethesda, MD) [HL056949, HL066105]
FX This work was supported by grants HL056949 (to D. D. W.) and HL066105
(to M. K. and D. D. W.) from the National Heart, Lung, and Blood
Institute of the National Institutes of Health (Bethesda, MD).
NR 56
TC 34
Z9 41
U1 2
U2 3
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 JUN 4
PY 2009
VL 113
IS 23
BP 6015
EP 6022
DI 10.1182/blood-2008-10-186650
PG 8
WC Hematology
SC Hematology
GA 454BH
UT WOS:000266656100044
PM 19349621
ER
PT J
AU Wilson, D
Hurtado, RM
Digumarthy, S
AF Wilson, Douglas
Hurtado, Rocio M.
Digumarthy, Subba
TI A Woman with AIDS and Tuberculosis with Progressive Cough, Dyspnea, and
Wasting Extensively drug-resistant Mycobacterium tuberculosis infection
in a patient with HIV/AIDS.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article; Proceedings Paper
CT 2nd Annual Workshop on Advanced Clinical Care - Aids
CT IEEE International Conference on Computer Design
CY OCT 02, 2008
CY OCT 12-15, 2008
CL Durban, SOUTH AFRICA
CL Lake Tahoe, CA
SP IEEE, IEEE Circuits & Syst Soc, IEEE Comp Soc
ID MULTIDRUG-RESISTANT; PULMONARY TUBERCULOSIS; TREATMENT OUTCOMES;
SOUTH-AFRICA; THERAPY; LIMA; PERU; DIAGNOSIS; STRAINS
C1 [Wilson, Douglas] Edendale Hosp, Dept Med, Pietermaritzburg, South Africa.
[Wilson, Douglas] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Dept Med, Durban, South Africa.
[Hurtado, Rocio M.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Digumarthy, Subba] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Hurtado, Rocio M.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Digumarthy, Subba] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
RP Wilson, D (reprint author), Edendale Hosp, Dept Med, Pietermaritzburg, South Africa.
NR 29
TC 0
Z9 0
U1 0
U2 2
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUN 4
PY 2009
VL 360
IS 23
BP 2456
EP 2464
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 453DN
UT WOS:000266590500013
PM 19494222
ER
PT J
AU Masaki, K
Gu, JW
Ghaffari, R
Chan, G
Smith, RJH
Freeman, DM
Aranyosi, AJ
AF Masaki, Kinuko
Gu, Jianwen Wendy
Ghaffari, Roozbeh
Chan, Gary
Smith, Richard J. H.
Freeman, Dennis M.
Aranyosi, A. J.
TI Col11a2 Deletion Reveals the Molecular Basis for Tectorial Membrane
Mechanical Anisotropy
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID ARTICULAR-CARTILAGE; HEARING-LOSS; MOTION; COLLAGEN; MOUSE; ORGAN;
MODEL; CORTI; LOCALIZATION; ORGANIZATION
AB The tectorial membrane (TM) has a significantly larger stiffness in the radial direction than other directions, a prominent mechanical anisotropy that is believed to be critical for the proper functioning of the cochlea. To determine the molecular basis of this anisotropy, we measured material properties of TMs from mice with a targeted deletion of Col11a2, which encodes for collagen XI. In light micrographs, the density of TM radial collagen fibers was lower in Col11a2-/- mice than wild-types. Tone-evoked distortion product otoacoustic emission and auditory brainstem response measurements in Col11a2-/- mice were reduced by 30-50 dB independent of frequency as compared with wild-types, showing that the sensitivity loss is cochlear in origin. Stress-strain measurements made using osmotic pressure revealed no significant dependence of TM bulk compressibility on the presence of collagen XI. Charge measurements made by placing the TM as an electrical conduit between two baths revealed no change in the density of charge affixed to the TM matrix in Col11a2-/- mice. Measurements of mechanical shear impedance revealed a 5.5 +/- 0.8 dB decrease in radial shear impedance and a 3.3 +/- 0.3 dB decrease in longitudinal shear impedance resulting from the Col11a2 deletion. The ratio of radial to longitudinal shear impedance fell from 1.8 +/- 0.7 for TMs from wild-type mice to 1.0 +/- 0.1 for those from Col11a2-/- mice. These results show that the organization of collagen into radial fibrils is responsible for the mechanical anisotropy of the TM. This anisotropy can be attributed to increased mechanical coupling provided by the collagen fibrils. Mechanisms by which changes in TM material properties may contribute to the threshold elevation in Col11a2-/- mice are discussed.
C1 [Masaki, Kinuko; Gu, Jianwen Wendy; Ghaffari, Roozbeh; Freeman, Dennis M.; Aranyosi, A. J.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Masaki, Kinuko; Gu, Jianwen Wendy; Ghaffari, Roozbeh; Freeman, Dennis M.; Aranyosi, A. J.] MIT, Elect Res Lab, Cambridge, MA 02139 USA.
[Chan, Gary; Freeman, Dennis M.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA.
[Masaki, Kinuko; Gu, Jianwen Wendy; Ghaffari, Roozbeh; Freeman, Dennis M.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA.
[Smith, Richard J. H.] Univ Iowa, Dept Otolaryngol Head & Neck Surg, Iowa City, IA 52242 USA.
RP Aranyosi, AJ (reprint author), MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
EM aja@mit.edu
OI Aranyosi, Alexander/0000-0002-8133-5026
FU National Institutes of Health (NIH) [R01-DC00238]; NIH-NIDCD [R01
DC03544]
FX G.C., A.J.A., and D.M.F. were Supported by National Institutes of Health
(NIH) grant No. R01-DC00238. J.W.G. and R.G. Were Supported by in NIH
training grant to the Harvard-MIT Speech and Hearing Biosciences and
Technology Program. K.M. and R.J.H.S. were Supported in part by
NIH-NIDCD grant No. R01 DC03544.
NR 43
TC 10
Z9 10
U1 0
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
J9 BIOPHYS J
JI Biophys. J.
PD JUN 3
PY 2009
VL 96
IS 11
BP 4717
EP 4724
DI 10.1016/j.bpj.2009.02.056
PG 8
WC Biophysics
SC Biophysics
GA 453ZC
UT WOS:000266650400036
PM 19486694
ER
PT J
AU Mortensen, EM
Copeland, LA
Pugh, MJV
Restrepo, MI
de Molina, RM
Nakashima, B
Anzueto, A
AF Mortensen, Eric M.
Copeland, Laurel A.
Pugh, Mary Jo V.
Restrepo, Marcos I.
de Molina, Rosa Malo
Nakashima, Brandy
Anzueto, Antonio
TI Impact of statins and ACE inhibitors on mortality after COPD
exacerbations
SO RESPIRATORY RESEARCH
LA English
DT Article
ID OBSTRUCTIVE PULMONARY-DISEASE; C-REACTIVE PROTEIN; AIRWAY INFLAMMATION;
PROPENSITY SCORE; HEALTH-STATUS; VALIDATION; PROTECTION; PNEUMONIA;
MORBIDITY; INFLUENZA
AB Background: The purpose of our study was to examine the association of prior outpatient use of statins and angiotensin converting enzyme (ACE) inhibitors on mortality for subjects >= 65 years of age hospitalized with acute COPD exacerbations.
Methods: We conducted a retrospective national cohort study using Veterans Affairs administrative data including subjects >= 65 years of age hospitalized with a COPD exacerbation. Our primary analysis was a multilevel model with the dependent variable of 90-day mortality and hospital as a random effect, controlling for preexisting comorbid conditions, demographics, and other medications prescribed.
Results: We identified 11,212 subjects with a mean age of 74.0 years, 98% were male, and 12.4% of subjects died within 90-days of hospital presentation. In this cohort, 20.3% of subjects were using statins, 32.0% were using ACE inhibitors or angiotensin II receptor blockers (ARB). After adjusting for potential confounders, current statin use (odds ratio 0.51, 95% confidence interval 0.40-0.64) and ACE inhibitor/ARB use (0.55, 0.46-0.66) were significantly associated with decreased 90-day mortality.
Conclusion: Use of statins and ACE inhibitors prior to admission is associated with decreased mortality in subjects hospitalized with a COPD exacerbation. Randomized controlled trials are needed to examine whether the use of these medications are protective for those patients with COPD exacerbations.
C1 [Mortensen, Eric M.; Copeland, Laurel A.; Pugh, Mary Jo V.; Restrepo, Marcos I.; de Molina, Rosa Malo; Nakashima, Brandy; Anzueto, Antonio] S Texas Vet Hlth Care Syst, VERDICT Res Unit, San Antonio, TX USA.
[Mortensen, Eric M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Gen Internal Med, San Antonio, TX 78229 USA.
[Copeland, Laurel A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA.
[Pugh, Mary Jo V.] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA.
[Restrepo, Marcos I.; de Molina, Rosa Malo; Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Pulm & Crit Care Med, San Antonio, TX 78229 USA.
RP Mortensen, EM (reprint author), S Texas Vet Hlth Care Syst, VERDICT Res Unit, San Antonio, TX USA.
EM mortensene@uthscsa.edu; copelandl@uthscsa.edu; pughm@uthsca.edu;
restrepom@uthscsa.edu; rmm02004@yahoo.es; nakashima@uthscsa.edu;
anzueto@uthsa.edu
RI Restrepo, Marcos/H-4442-2014;
OI Pugh, Mary Jo/0000-0003-4196-7763; Mortensen, Eric/0000-0002-3880-5563;
Copeland, Laurel/0000-0002-9478-0209
FU Department of Veterans Affairs [IIR 02-076, MREP 02-267, MREP 05-145]
FX Dr. Pugh received funding from the Department of Veterans Affairs IIR
02-076 and MREP 02-267. Dr. Copeland was supported by Department of
Veterans Affairs MREP 05-145. This material is the result of work
supported with resources and the use of facilities at the South Texas
Veterans Health Care System. The funding agencies had no role in
conducting the study, or role in the preparation, review, or approval of
the manuscript.
NR 38
TC 62
Z9 65
U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1465-9921
J9 RESP RES
JI Respir. Res.
PD JUN 3
PY 2009
VL 10
AR 45
DI 10.1186/1465-9921-10-45
PG 9
WC Respiratory System
SC Respiratory System
GA 462BR
UT WOS:000267320800001
PM 19493329
ER
PT J
AU Singh, A
Greninger, P
Rhodes, D
Koopman, L
Violette, S
Bardeesy, N
Settleman, J
AF Singh, Anurag
Greninger, Patricia
Rhodes, Daniel
Koopman, Louise
Violette, Sheila
Bardeesy, Nabeel
Settleman, Jeff
TI A Gene Expression Signature Associated with "K-Ras Addiction" Reveals
Regulators of EMT and Tumor Cell Survival
SO CANCER CELL
LA English
DT Article
ID PANCREATIC DUCTAL ADENOCARCINOMA; FACTOR RECEPTOR INHIBITION;
TO-MESENCHYMAL TRANSITION; TYROSINE KINASE; LUNG-CANCER; SENSITIVITY;
GROWTH; AMPLIFICATION; PROGRESSION; GENOME
AB K-ras mutations occur frequently in epithelial cancers. Using short hairpin RNAs to deplete K-Ras in lung and pancreatic cancer cell lines harboring K-ras mutations, two classes were identified-lines that do or do not require K-Ras to maintain viability. Comparing these two classes of cancer cells revealed a gene expression signature in K-Ras-dependent cells, associated with a well-differentiated epithelial phenotype, which was also seen in primary tumors. Several of these genes encode pharmacologically tractable proteins, such as Syk and Ron kinases. and integrin beta 6, depletion of which induces epithelial-mesenchymal transformation (EMT) and apoptosis specifically in K-Ras-dependent cells. These findings indicate that epithelial differentiation and tumor cell viability are associated, and that EMT regulators in "K-Ras-addicted" cancers represent candidate therapeutic targets.
C1 [Singh, Anurag; Greninger, Patricia; Bardeesy, Nabeel; Settleman, Jeff] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
[Singh, Anurag; Greninger, Patricia; Bardeesy, Nabeel; Settleman, Jeff] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
[Rhodes, Daniel] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA.
[Rhodes, Daniel] Univ Michigan, Sch Med, Dept Bioinformat, Ann Arbor, MI 48109 USA.
[Koopman, Louise] Biogen Idec, Dept Discovery Oncol, Cambridge, MA 02142 USA.
[Violette, Sheila] Stromedix Inc, Cambridge, MA 02141 USA.
RP Settleman, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, 149 13th St, Charlestown, MA 02129 USA.
EM settleman@helix.mgh.harvard.edu
RI Singh, Anurag/C-7347-2014
OI Singh, Anurag/0000-0003-4705-8683
FU NRSA T32 postdoctoral fellowship; NIH [R01 CA109447]; Lustgarten
Foundation
FX A.S. was supported by a NRSA T32 postdoctoral fellowship. The studies
were supported by NIH R01 CA109447 and a Lustgarten Foundation grant (to
J.S.). We thank Marie Classon, Jeff Engelman, and Rushika Perara for
comments on the manuscript. We thank Michael Rothenberg for construction
of the pWPI-K-Ras(12V) expression vector and for advice regarding
lentiviral use. We thank Maria Varadi for technical assistance. We thank
Nathanael Gray for providing the R406 Syk inhibitor. We thank Sridhar
Ramaswamy and Andrew Yee for advice with the application of gene
expression signatures as predictive tools. We thank Vikram Deshpande for
assistance with IHC analysis. S.V. and L.K. have been or are in the
employ of Biogen Idec. S.V. is currently employed by Stromedix Inc.
These companies currently have an anti-integrin alpha V beta 6
monoclonal antibody in clinical development.
NR 42
TC 317
Z9 323
U1 1
U2 16
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 JUN 2
PY 2009
VL 15
IS 6
BP 489
EP 500
DI 10.1016/j.ccr.2009.03.022
PG 12
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 454MP
UT WOS:000266686500007
PM 19477428
ER
PT J
AU Fu, J
Kim, DH
Knoll, W
AF Fu, Jun
Kim, Dong Ha
Knoll, Wolfgang
TI Aqueous Networks and Toroids of Amphiphilic Block Copolymer with
Non-ionic Surfactants
SO CHEMPHYSCHEM
LA English
DT Article
DE block copolymers; morphological transformation; responsive;
self-assembly; surfactants
ID POLYSTYRENE-BLOCK-POLY(ETHYLENE OXIDE); PHASE-SEPARATION;
TERNARY-SYSTEM; DRUG-DELIVERY; MICELLES; ASSEMBLIES; TRANSITION; ACID);
MICELLIZATION; COMPLEXATION
C1 [Fu, Jun; Knoll, Wolfgang] Max Planck Inst Polymer Res, D-55128 Mainz, Germany.
[Kim, Dong Ha] Ewha Womans Univ, Dept Chem & Nano Sci, Seoul 120750, South Korea.
RP Fu, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 55 Fruit St,GRJ 1227, Boston, MA 02114 USA.
EM jfu1@partners.org
RI Fu, Jun/C-1648-2012; Kim, Dong Ha/B-3778-2008
OI Fu, Jun/0000-0002-8723-1439; Kim, Dong Ha/0000-0003-0444-0479
FU Korea government (MEST) [R11-2005-008-00000-0]
FX J.F thanks the Max Planck Society (MPG) and the Chinese Academy of
Sciences (CAS) for the Max Planck Society Fellowship under the
Cooperative Program of Science and Technology between CAS and MPG. D.H.K
thanks the Korea Science and Engineering Foundation (KOSEF) for a grant
funded by the Korea government (MEST) (No. R11-2005-008-00000-0).
NR 39
TC 7
Z9 7
U1 0
U2 9
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY
SN 1439-4235
J9 CHEMPHYSCHEM
JI ChemPhysChem
PD JUN 2
PY 2009
VL 10
IS 8
BP 1190
EP 1194
DI 10.1002/cphc.200900081
PG 5
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 457SV
UT WOS:000266954500004
PM 19334021
ER
PT J
AU Morrow, DA
Wiviott, SD
White, HD
Nicolau, JC
Bramucci, E
Murphy, SA
Bonaca, MP
Ruff, CT
Scirica, BM
McCabe, CH
Antman, EM
Braunwald, E
AF Morrow, David A.
Wiviott, Stephen D.
White, Harvey D.
Nicolau, Jose C.
Bramucci, Ezio
Murphy, Sabina A.
Bonaca, Marc P.
Ruff, Christian T.
Scirica, Benjamin M.
McCabe, Carolyn H.
Antman, Elliott M.
Braunwald, Eugene
TI Effect of the Novel Thienopyridine Prasugrel Compared With Clopidogrel
on Spontaneous and Procedural Myocardial Infarction in the Trial to
Assess Improvement in Therapeutic Outcomes by Optimizing Platelet
Inhibition With Prasugrel-Thrombolysis in Myocardial Infarction 38 An
Application of the Classification System From the Universal Definition
of Myocardial Infarction
SO CIRCULATION
LA English
DT Article
DE angioplasty; myocardial infarction; platelets; prasugrel; unstable
angina
ID PERCUTANEOUS CORONARY INTERVENTION; CARDIAC ENZYME ELEVATION;
RANDOMIZED-TRIAL; ADVERSE OUTCOMES; ISCHEMIC EVENTS; AGGREGATION;
DISEASE
AB Background-Prasugrel is a novel thienopyridine that reduces new or recurrent myocardial infarctions (MIs) compared with clopidogrel in patients with acute coronary syndrome undergoing percutaneous coronary intervention. This effect must be balanced against an increased bleeding risk. We aimed to characterize the effect of prasugrel with respect to the type, size, and timing of MI using the universal classification of MI.
Methods and Results-We studied 13 608 patients with acute coronary syndrome undergoing percutaneous coronary intervention randomized to prasugrel or clopidogrel and treated for 6 to 15 months in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial Infarction (TRITON-TIMI 38). Each MI underwent supplemental classification as spontaneous, secondary, or sudden cardiac death (types 1, 2, and 3) or procedure related (Types 4 and 5) and examined events occurring early and after 30 days. Prasugrel significantly reduced the overall risk of MI (7.4% versus 9.7%; hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.67 to 0.85; P < 0.0001). This benefit was present for procedure-related MIs (4.9% versus 6.4%; HR, 0.76; 95% CI, 0.66 to 0.88; P = 0.0002) and nonprocedural (type 1, 2, or 3) MIs (2.8% versus 3.7%; HR, 0.72; 95% CI, 0.59 to 0.88; P = 0.0013) and consistently across MI size, including MIs with a biomarker peak >= 5 times the reference limit (HR. 0.74; 95% CI, 0.64 to 0.86; P = 0.0001). In landmark analyses starting at 30 days, patients treated with prasugrel had a lower risk of any MI (2.9% versus 3.7%; HR, 0.77; P = 0.014), including nonprocedural MI (2.3% versus 3.1%; HR, 0.74; 95% CI, 0.60 to 0.92; P = 0.0069).
Conclusion-Treatment with prasugrel compared with clopidogrel for up to 15 months in patients with acute coronary syndrome undergoing percutaneous coronary intervention significantly reduces the risk of MIs that are procedure related and spontaneous and those that are small and large, including new MIs occurring during maintenance therapy. (Circulation. 2009; 119: 2758-2764.)
C1 [Morrow, David A.; Wiviott, Stephen D.; Murphy, Sabina A.; Bonaca, Marc P.; Ruff, Christian T.; Scirica, Benjamin M.; McCabe, Carolyn H.; Antman, Elliott M.; Braunwald, Eugene] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Dept Med, Boston, MA 02115 USA.
[White, Harvey D.] Auckland City Hosp, Auckland, New Zealand.
[Nicolau, Jose C.] Univ Sao Paulo, Sch Med, Heart Inst InCor, Sao Paulo, Brazil.
[Bramucci, Ezio] Policlin San Matteo, IRCCS, Div Cardiol, I-27100 Pavia, Italy.
RP Morrow, DA (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Dept Med, 75 Francis St, Boston, MA 02115 USA.
EM dmorrow@partners.org
RI Nicolau, Jose/E-1487-2012
FU Daiichi Sankyo Co, Ltd; Eli Lilly and Co
FX This study was supported by a grant from Daiichi Sankyo Co, Ltd, and Eli
Lilly and Co.
NR 12
TC 85
Z9 91
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD JUN 2
PY 2009
VL 119
IS 21
BP 2758
EP 2764
DI 10.1161/CIRCULATIONAHA.108.833665
PG 7
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 452DY
UT WOS:000266521400003
PM 19451347
ER
PT J
AU Chirinos, JA
Segers, P
Gupta, AK
Swillens, A
Rietzschel, ER
De Buyzere, ML
Kirkpatrick, JN
Gillebert, TC
Wang, Y
Keane, MG
Townsend, R
Ferrari, VA
Wiegers, SE
Sutton, MSJ
AF Chirinos, Julio A.
Segers, Patrick
Gupta, Amit Kumar
Swillens, Abigail
Rietzschel, Ernst R.
De Buyzere, Marc L.
Kirkpatrick, James N.
Gillebert, Thierry C.
Wang, Yan
Keane, Martin G.
Townsend, Raymond
Ferrari, Victor A.
Wiegers, Susan E.
Sutton, Martin St John
TI Time-Varying Myocardial Stress and Systolic Pressure-Stress Relationship
Role in Myocardial-Arterial Coupling in Hypertension
SO CIRCULATION
LA English
DT Article
DE hypertension; myocardium; hemodynamics
ID LEFT-VENTRICULAR GEOMETRY; WAVE REFLECTION; HEART-FAILURE; WALL STRESS;
HYPERTROPHY; ECHOCARDIOGRAPHY; QUANTIFICATION; DISEASE
AB Background-Myocardial afterload depends on left ventricular (LV) cavity size, pressure, and wall thickness, all of which change markedly throughout ejection. We assessed the relationship between instantaneous ejection-phase pressure and myocardial stress and the effect of arterial wave reflections on myocardial stress in hypertensive and normotensive adults.
Methods and Results-We studied 42 untreated hypertensive, 42 treated hypertensive, and 42 normotensive adults with normal LV ejection fraction. Time-resolved central pressure, flow, and LV geometry were measured with carotid tonometry, Doppler, and speckle-tracking echocardiography for computation of arterial load and time-varying circumferential and longitudinal myocardial stress. In all 3 groups, peak myocardial stress typically occurred in early systole (within the first 100 milliseconds of ejection), followed by a marked midsystolic shift in the pressure-stress relationship, which favored lower late systolic stress values (P < 0.001) relative to pressure. The mean magnitude of this midsystolic shift was quantitatively important in all 3 groups (circumferential stress, 144 to 148 kdynes/cm(2)) and was independently predicted by a higher LV ejection fraction and ratio of LV end-diastolic cavity to wall volume. Time of peak myocardial stress independently correlated with time of the first systolic but not with time of the second systolic central pressure peak.
Conclusions-Peak myocardial stress occurs in early systole, before important contributions of reflected waves to central pressure. In the presence of normal LV ejection fraction, a midsystolic shift in the pressure-stress relationship protects cardiomyocytes against excessive late systolic stress (despite pressure augmentation associated with wave reflections), a coupling mechanism that may be altered in various disease states. (Circulation. 2009; 119:2798-2807.)
C1 [Chirinos, Julio A.; Gupta, Amit Kumar; Kirkpatrick, James N.; Wang, Yan; Keane, Martin G.; Townsend, Raymond; Ferrari, Victor A.; Wiegers, Susan E.; Sutton, Martin St John] Univ Penn, Philadelphia, PA 19104 USA.
[Chirinos, Julio A.] Philadelphia VA Med Ctr, Philadelphia, PA USA.
[Segers, Patrick; Swillens, Abigail] Univ Ghent, Cardiovasc Mech & Biofluid Dynam Res Unit, IBiTech, B-9000 Ghent, Belgium.
[Rietzschel, Ernst R.; De Buyzere, Marc L.; Gillebert, Thierry C.] Ghent Univ Hosp, Dept Cardiovasc Dis, B-9000 Ghent, Belgium.
RP Chirinos, JA (reprint author), Childrens Hosp Philadelphia, Div Cardiol, Room 8B111,3900 Woodland Ave, Philadelphia, PA 19104 USA.
EM julio.chirinos@uphs.upenn.edu
RI Gupta, amit/B-3831-2012;
OI Gillebert, Thierry/0000-0002-3832-919X
NR 19
TC 32
Z9 32
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD JUN 2
PY 2009
VL 119
IS 21
BP 2798
EP U100
DI 10.1161/CIRCULATIONAHA.108.829366
PG 20
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 452DY
UT WOS:000266521400008
PM 19451350
ER
PT J
AU Breitner, JCS
Haneuse, SJPA
Walker, R
Dublin, S
Crane, PK
Gray, SL
Larson, EB
AF Breitner, J. C. S.
Haneuse, S. J. P. A.
Walker, R.
Dublin, S.
Crane, P. K.
Gray, S. L.
Larson, E. B.
TI Risk of dementia and AD with prior exposure to NSAIDs in an elderly
community-based cohort
SO NEUROLOGY
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; ALZHEIMERS-DISEASE; APOLIPOPROTEIN-E;
ANTIINFLAMMATORY DRUGS; CACHE COUNTY; ONSET; AGE; ROFECOXIB; NAPROXEN
AB Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) may prevent Alzheimer dementia (AD).
Methods: We analyzed the association of prior NSAID exposure with incident dementia and AD in the Adult Changes in Thought population-based cohort aged >= 65 years (median 74.8) at enrollment. Participants were members of Group Health, which provided computerized pharmacy dispensing records from 1977 onward. We studied 2,736 dementia-free enrollees with extensive prior pharmacy data, following them biennially for up to 12 years to identify dementia and AD. Cox proportional hazards regression assessed association of dementia or AD with NSAID use graded in standard daily doses (SDD) dispensed over 2 years (e.g., heavy use = 500 + SDD), with some analyses also adding consecutive biennial self-reports of NSAID use.
Results: Pharmacy records identified 351 participants (12.8%) with history of heavy NSAID use at enrollment. Another 107 became heavy users during follow-up. Some 476 individuals developed incident dementia, 356 with AD (median onset ages 83.5 and 83.8 years). Contrary to the hypothesis that NSAIDs protect against AD, pharmacy-defined heavy NSAID users showed increased incidence of dementia and AD, with adjusted hazard ratios of 1.66 (95% confidence interval, 1.24-2.24) and 1.57 (95% confidence interval, 1.10-2.23). Addition of self-reported exposure data did not alter these results.
Conclusions: These findings differ from those of other studies with younger cohorts. The results observed elsewhere may reflect delayed onset of Alzheimer dementia (AD) in nonsteroidal anti-inflammatory drug (NSAID) users. Conceivably, such delay could result in increased AD incidence in late old age. The relation of NSAID use and AD pathogenesis needs further investigation. Neurology (R) 2009; 72: 1899-1905
C1 [Breitner, J. C. S.] Geriatr Res Educ & Clin Ctr, Dept Vet Affairs Med Ctr, Seattle, WA USA.
[Breitner, J. C. S.; Crane, P. K.] Univ Washington, Sch Med, Seattle, WA USA.
[Haneuse, S. J. P. A.; Walker, R.; Dublin, S.; Larson, E. B.] Ctr Hlth Studies, Grp Hlth Cooperat, Seattle, WA USA.
[Dublin, S.] Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA.
[Gray, S. L.] Univ Washington, Sch Pharm, Seattle, WA 98195 USA.
RP Breitner, JCS (reprint author), VA Puget Sound Hlth Care Syst, GRECC S182, 1660 S Columbian Way, Seattle, WA 98108 USA.
EM jcsb@u.washington.edu
RI Crane, Paul/C-8623-2014;
OI Crane, Paul/0000-0003-4278-7465
FU NIA NIH HHS [U01-AG-15477, K23 AG028954, K23 AG028954-01A1,
K23-AG-28954, R01-AG-24010, U01 AG006781, U01 AG006781-13, U01-AG-06781]
NR 28
TC 99
Z9 102
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD JUN 2
PY 2009
VL 72
IS 22
BP 1899
EP 1905
DI 10.1212/WNL.0b013e3181a18691
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 452FD
UT WOS:000266524600005
PM 19386997
ER
PT J
AU Kivisakk, P
Healy, BC
Viglietta, V
Quintana, FJ
Hootstein, MA
Weiner, HL
Khoury, SJ
AF Kivisakk, P.
Healy, B. C.
Viglietta, V.
Quintana, F. J.
Hootstein, M. A.
Weiner, H. L.
Khoury, S. J.
TI Natalizumab treatment is associated with peripheral sequestration of
proinflammatory T cells
SO NEUROLOGY
LA English
DT Article
ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; PROGRESSIVE MULTIFOCAL
LEUKOENCEPHALOPATHY; MULTIPLE-SCLEROSIS PATIENTS;
CENTRAL-NERVOUS-SYSTEM; TRANSCRIPTION FACTOR; REGULATORY CELLS;
EXPRESSION; INTEGRIN; BRAIN; ANTIBODIES
AB Background: Natalizumab is an antibody directed against integrin alpha 4 that reduces disease activity in patients with multiple sclerosis (MS) by blocking migration of T and B cells into the CNS. The goal of this study was to characterize the effects of natalizumab treatment on cytokine production and expression of activation markers, costimulatory molecules, and trafficking determinants on CD4(+) and CD8(+) T cells.
Methods: In a longitudinal study, we investigated the expression of surface makers and cytokine expression on peripheral blood lymphocytes from 28 patients with MS who started natalizumab treatment and were followed for 1 year. A mixed effects model was used to compare pretreatment to on-treatment measurements.
Results: The frequency of CD4(+) T cells producing interferon-gamma, tumor necrosis factor, and interleukin (IL)-17 upon anti-CD3 stimulation increased 6 months after initiation of natalizumab treatment and remained elevated throughout the follow-up. The frequency of CD4(+) T cells expressing CD25, HLA-DR, and CCR6 ex vivo was increased at one or more time points during treatment. Among CD8(+) T cells, the frequency of cells producing IL-2 and IL-17 after stimulation was increased during natalizumab treatment, as was the frequency of CD8(+) T cells expressing CD58 and CCR5 ex vivo. The increase in the frequency of activated cells could not be replicated by in vitro exposure to natalizumab.
Conclusion: Natalizumab treatment increases the percentage of activated leukocytes producing proinflammatory cytokines in blood, presumably due to sequestration of activated cells in the peripheral circulation. Neurology (R) 2009; 72:1922-1930
C1 [Khoury, S. J.] Harvard Univ, Brigham & Womens Hosp, Ctr Neurol Dis, Dept Neurol,Partners MS Ctr,Sch Med,Harvard Inst, Boston, MA 02115 USA.
[Healy, B. C.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA.
RP Khoury, SJ (reprint author), Harvard Univ, Brigham & Womens Hosp, Ctr Neurol Dis, Dept Neurol,Partners MS Ctr,Sch Med,Harvard Inst, Room 710,77 Ave Louis Pasteur, Boston, MA 02115 USA.
EM skhoury@rics.bwh.harvard.edu
OI khoury, samia/0000-0003-3198-6063
FU NIAID NIH HHS [N01 AI05411, U19 AI46130]
NR 40
TC 70
Z9 71
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD JUN 2
PY 2009
VL 72
IS 22
BP 1922
EP 1930
DI 10.1212/WNL.0b013e3181a8266f
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA 452FD
UT WOS:000266524600008
PM 19487650
ER
PT J
AU Landers, JE
Melki, J
Meininger, V
Glass, JD
van den Berg, LH
van Es, MA
Sapp, PC
van Vught, PWJ
McKenna-Yasek, DM
Blauw, HM
Cho, TJ
Polak, M
Shi, LJ
Wills, AM
Broom, WJ
Ticozzi, N
Silani, V
Ozoguz, A
Rodriguez-Leyva, I
Veldink, JH
Ivinson, AJ
Saris, CGJ
Hosler, BA
Barnes-Nessa, A
Couture, N
Wokke, JHJ
Kwiatkowski, TJ
Ophoff, RA
Cronin, S
Hardiman, O
Diekstra, FP
Leigh, PN
Shaw, CE
Simpson, CL
Hansen, VK
Powell, JF
Corcia, P
Salachas, F
Heath, S
Galan, P
Georges, F
Horvitz, HR
Lathrop, M
Purcell, S
Al-Chalabi, A
Brown, RH
AF Landers, John E.
Melki, Judith
Meininger, Vincent
Glass, Jonathan D.
van den Berg, Leonard H.
van Es, Michael A.
Sapp, Peter C.
van Vught, Paul W. J.
McKenna-Yasek, Diane M.
Blauw, Hylke M.
Cho, Ting-Jan
Polak, Meraida
Shi, Lijia
Wills, Anne-Marie
Broom, Wendy J.
Ticozzi, Nicola
Silani, Vincenzo
Ozoguz, Aslihan
Rodriguez-Leyva, Ildefonso
Veldink, Jan H.
Ivinson, Adrian J.
Saris, Christiaan G. J.
Hosler, Betsy A.
Barnes-Nessa, Alayna
Couture, Nicole
Wokke, John H. J.
Kwiatkowski, Thomas J., Jr.
Ophoff, Roel A.
Cronin, Simon
Hardiman, Orla
Diekstra, Frank P.
Leigh, P. Nigel
Shaw, Christopher E.
Simpson, Claire L.
Hansen, Valerie K.
Powell, John F.
Corcia, Philippe
Salachas, Francois
Heath, Simon
Galan, Pilar
Georges, Franck
Horvitz, H. Robert
Lathrop, Mark
Purcell, Shaun
Al-Chalabi, Ammar
Brown, Robert H., Jr.
TI Reduced expression of the Kinesin-Associated Protein 3 (KIFAP3) gene
increases survival in sporadic amyotrophic lateral sclerosis
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE genome-wide association study; single nucleotide polymorphism
ID GENOME-WIDE ASSOCIATION; MOTOR-NEURON DISEASE; MULTIPLE-SCLEROSIS;
INTERLEUKIN-7 RECEPTOR; SUPEROXIDE-DISMUTASE; AXONAL-TRANSPORT; RISK
LOCI; MUTATIONS; ALS; SUSCEPTIBILITY
AB Amyotrophic lateral sclerosis is a degenerative disorder of motor neurons that typically develops in the 6th decade and is uniformly fatal, usually within 5 years. To identify genetic variants associated with susceptibility and phenotypes in sporadic ALS, we performed a genome-wide SNP analysis in sporadic ALS cases and controls. A total of 288,357 SNPs were screened in a set of 1,821 sporadic ALS cases and 2,258 controls from the U. S. and Europe. Survival analysis was performed using 1,014 deceased sporadic cases. Top results for susceptibility were further screened in an independent sample set of 538 ALS cases and 556 controls. SNP rs1541160 within the KIFAP3 gene (encoding a kinesin-associated protein) yielded a genome-wide significant result ( P = 1.84 x 10(-8)) that withstood Bonferroni correction for association with survival. Homozygosity for the favorable allele (CC) conferred a 14.0 months survival advantage. Sequence, genotypic and functional analyses revealed that there is linkage disequilibrium between rs1541160 and SNP rs522444 within the KIFAP3 promoter and that the favorable alleles of rs1541160 and rs522444 correlate with reduced KIFAP3 expression. No SNPs were associated with risk of sporadic ALS, site of onset, or age of onset. We have identified a variant within the KIFAP3 gene that is associated with decreased KIFAP3 expression and increased survival in sporadic ALS. These findings support the view that genetic factors modify phenotypes in this disease and that cellular motor proteins are determinants of motor neuron viability.
C1 [Landers, John E.; Sapp, Peter C.; McKenna-Yasek, Diane M.; Cho, Ting-Jan; Shi, Lijia; Wills, Anne-Marie; Broom, Wendy J.; Ticozzi, Nicola; Rodriguez-Leyva, Ildefonso; Hosler, Betsy A.; Barnes-Nessa, Alayna; Couture, Nicole; Kwiatkowski, Thomas J., Jr.; Brown, Robert H., Jr.] Massachusetts Gen Hosp E, Cecil B Day Neuromuscular Res Lab, Charlestown, MA 02129 USA.
[Melki, Judith; Georges, Franck] Univ Evry & Paris 11, Mol Neurogenet Lab, Inst Natl Sante & Rech Med, U798, F-91057 Evry, France.
[Meininger, Vincent; Salachas, Francois] Hop La Pitie Salpetriere, Assistance Publ Hop Paris, F-75651 Paris, France.
[Glass, Jonathan D.; Polak, Meraida] Emory Univ, Dept Neurol, Atlanta, GA 30322 USA.
[van den Berg, Leonard H.; van Es, Michael A.; van Vught, Paul W. J.; Blauw, Hylke M.; Veldink, Jan H.; Saris, Christiaan G. J.; Wokke, John H. J.] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Dept Neurol, NL-3584 CX Utrecht, Netherlands.
[Ophoff, Roel A.] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Dept Med Genet, NL-3584 CX Utrecht, Netherlands.
[Sapp, Peter C.; Horvitz, H. Robert] MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02139 USA.
[Ticozzi, Nicola; Silani, Vincenzo] Univ Milan, Sch Med, Dept Neurol,Ist Auxol Italiano, Dino Ferrari Ctr,Ist Di Ricovero & Cura Carattere, I-20149 Milan, Italy.
[Ticozzi, Nicola; Silani, Vincenzo] Univ Milan, Sch Med, Lab Neurosci,Ist Auxol Italiano, Dino Ferrari Ctr,Ist Di Ricovero & Cura Carattere, I-20149 Milan, Italy.
[Ozoguz, Aslihan] Bogazici Univ, Dept Mol Biol & Genet, Neurodegenerat Res Lab, Istanbul, Turkey.
[Rodriguez-Leyva, Ildefonso] Univ Autonoma San Luis Potosi, Fac Med, San Luis Potosi 78210, Mexico.
[Ivinson, Adrian J.] Harvard Univ, Sch Med, Harvard NeuroDiscovery Ctr, Boston, MA 02115 USA.
[Ophoff, Roel A.] Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90024 USA.
[Cronin, Simon; Hardiman, Orla] Beaumont Hosp, Dept Neurol, Dublin 9, Ireland.
[Diekstra, Frank P.; Leigh, P. Nigel; Shaw, Christopher E.; Simpson, Claire L.; Hansen, Valerie K.; Powell, John F.; Al-Chalabi, Ammar] Kings Coll London, Dept Clin Neurosci, MRC, Ctr Neurodegenerat Res,Inst Psychiat, London SE5 8AF, England.
[Corcia, Philippe] CHU Bretonneau, Serv Neurol, F-37044 Tours, France.
[Heath, Simon; Lathrop, Mark] CEA, Ctr Natl Genotypage, Inst Genom, F-91057 Evry, France.
[Galan, Pilar] UFR Sante Med & Biol Humaine, Unite Rech Epidemiol Nutr, F-93017 Bobigny, France.
[Purcell, Shaun] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
RP Landers, JE (reprint author), Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01605 USA.
EM john.landers@umassmed.edu
RI Al-Chalabi, Ammar/E-5361-2010; Powell, John/G-4412-2011; Ticozzi,
Nicola/K-8094-2016;
OI Al-Chalabi, Ammar/0000-0002-4924-7712; Powell, John/0000-0001-6124-439X;
Ticozzi, Nicola/0000-0001-5963-7426; Silani,
Vincenzo/0000-0002-7698-3854; Hardiman, Orla/0000-0003-2610-1291
FU The Netherlands Organisation for Scientific Research; Adessium
Foundation; Howard Hughes Medical Institute; Packard Center for ALS
Research; Muscular Dystrophy Association; National Center for Research
Resources [U54 RR020278-01]; Howard Hughes Medical Institute
Investigator; ALS Family Charitable Foundation; Al-Athel ALS Research
Foundation; Pierre L. de Bourgknecht ALS Research Foundation; Angel
Fund; ALS Therapy Alliance; National Institute of Neurological Disorders
and Stroke; American Academy of Neurology Foundation/ALS Association;
Harvard Business School Class of 2007; Medical Research Council;
Wellcome Trust; Psychiatry Research Trust
FX We dedicate this article to the memories of Frieda R. Abraham, Donna
Roberts, and Jennifer Estess. We thank Daniel Mirel ( Broad Institute)
for all of his assistance, all of the clinicians who assisted in
recruiting cases and controls, particularly to clients with ALS and
their families, and Jerry Xu and Dennis Gurgul of the Enterprise
Research IS group at Partners Healthcare for support and use of the
Hewlett-Packard computing facilities. The Boston- based investigations
were supported by the ALS Therapy Alliance, Project ALS, the Angel Fund,
the Pierre L. de Bourgknecht ALS Research Foundation, the Al-Athel ALS
Research Foundation ( R. H. B., J. E. L., D. M. M.- Y., I. R.- L, T. J.
K.), the ALS Family Charitable Foundation, the American Academy of
Neurology Foundation/ALS Association ( A.-M. W.), the National Institute
of Neurological Disorders and Stroke ( R. H. B., T. J. K.), the Harvard
Business School Class of 2007, the Yamner family, Avichai Kremer, Guy
Yamen, Nate Boaz, and Professor Robert S. Kaplan. London-based
investigations were supported by the Motor Neurone Disease Association
of Great Britain and Northern Ireland ( A. A.- C.), the Medical Research
Council ( A. A.- C.), the Wellcome Trust ( P. N. L. and C. E. S.), and
Psychiatry Research Trust ( Tim Perkins Fund) ( P. N. L., A. A.-. C.,
and C. E. S.). The investigations in France were supported by Assistance
Publique, Hopitaux de Paris, Institut National de la Santeet de la
Recherche Medicale, GIS-Institut des Maladies Rares and the Ministere de
l'Enseignement Superieur et de la Recherche. V. S. was partially
suported by a donation of the Peviani Family. We thank DNA banks
maintained by the Coriell Institute ( with support from the National
Institute of Neurological DisordersandStroke) andGenethon. This study
used data from the SNP Database at the National Institute of
Neurological Disorders and Stroke Human Genetics Resource CenterDNAand
Cell Line Repository (http://ccr.coriell.org/ninds). Investigations in
The Netherlands were supported by The Netherlands Organisation for
Scientific Research, the "Prinses Beatrix Fonds,'' the Kersten
Foundation, the Adessium Foundation, J. R. van Dijk and VSB Fonds ( L.
H. v. d. B.). This work was supported by Howard Hughes Medical Institute
( P. S. and H. R. H.), the Packard Center for ALS Research ( J. D. G.
and M. P.), The Muscular Dystrophy Association ( U. S.) ( S. C. and O.
H.), and National Center for Research Resources Grant U54 RR020278-01 (
to The Broad Institute Center for Genotyping and Analysis). H. R. H. is
Howard Hughes Medical Institute Investigator.
NR 48
TC 92
Z9 93
U1 0
U2 8
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 JUN 2
PY 2009
VL 106
IS 22
BP 9004
EP 9009
DI 10.1073/pnas.0812937106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 452ZU
UT WOS:000266580500042
PM 19451621
ER
PT J
AU Song, LK
Sun, ZYJ
Coleman, KE
Zwick, MB
Gach, JS
Wang, JH
Reinherz, EL
Wagner, G
Kim, M
AF Song, Likai
Sun, Zhen-Yu J.
Coleman, Kate E.
Zwick, Michael B.
Gach, Johannes S.
Wang, Jia-huai
Reinherz, Ellis L.
Wagner, Gerhard
Kim, Mikyung
TI Broadly neutralizing anti-HIV-1 antibodies disrupt a hinge-related
function of gp41 at the membrane interface
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE membrane-proximal ectodomain region; neutralizing antibody; vaccine
design; AIDS; fusion
ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODY; PROXIMAL
EXTERNAL REGION; ENVELOPE GLYCOPROTEIN; MEDIATED FUSION; HIV-1 GP41;
EPITOPE; 2F5; RECOGNITION; CONFORMATION
AB A vaccine capable of stimulating protective antiviral antibody responses is needed to curtail the global AIDS epidemic caused by HIV-1. Although rarely elicited during the course of natural infection or upon conventional vaccination, the membrane-proximal ectodomain region (MPER) of the HIV-1 glycoprotein of M(r) 41,000 (gp41) envelope protein subunit is the target of 3 such human broadly neutralizing antibodies (BNAbs): 4E10, 2F5, and Z13e1. How these BNAbs bind to their lipid-embedded epitopes and mediate antiviral activity is unclear, but such information might offer important insight into a worldwide health imperative. Here, EPR and NMR techniques were used to define the manner in which these BNAbs differentially recognize viral membrane-encrypted residues configured within the L-shaped helix-hinge-helix MPER segment. Two distinct modes of antibody-mediated interference of viral infection were identified. 2F5, like 4E10, induces large conformational changes in the MPER relative to the membrane. However, although 4E10 straddles the hinge and extracts residues W672 and F673, 2F5 lifts up residues N-terminal to the hinge region, exposing L669 and W670. In contrast, Z13e1 effects little change in membrane orientation or conformation, but rather immobilizes the MPER hinge through extensive rigidifying surface contacts. Thus, BNAbs disrupt HIV-1MPERfusogenic functions critical for virus entry into human CD4 T cells and macrophages either by preventing hinge motion or by perturbing MPER orientation. HIV-1 MPER features important for targeted vaccine design have been revealed, the implications of which extend to BNAb targets on other viral fusion proteins.
C1 [Song, Likai; Coleman, Kate E.; Reinherz, Ellis L.] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA.
[Song, Likai; Reinherz, Ellis L.; Kim, Mikyung] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Sun, Zhen-Yu J.; Wang, Jia-huai; Wagner, Gerhard] Harvard Univ, Sch Med, Dept Mol Pharmacol & Biochem, Boston, MA 02115 USA.
[Zwick, Michael B.; Gach, Johannes S.] Scripps Res Inst, Dept Immunol & Microbiol Sci, La Jolla, CA 92037 USA.
[Wang, Jia-huai; Reinherz, Ellis L.; Kim, Mikyung] Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA.
[Wang, Jia-huai; Reinherz, Ellis L.; Kim, Mikyung] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Wang, Jia-huai] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
RP Reinherz, EL (reprint author), Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA.
EM ellis_reinherz@dfci.harvard.edu; mikyung_kim@dfci.harvard.edu
OI Gach, Johannes/0000-0002-5043-5710
FU National Institutes of Health [AI43649, AI69993]; Austrian Science Fund
[J2845-B13]
FX We thank Drs. Barton Haynes (Duke University Human Vaccine Institute)
and Munir S. Alam (Duke University Human Vaccine Institute) for
providing 13H11 mAb and SP62 peptide, and Kyoung Joon Oh and Piotr G.
Fajer for helpful discussions. This work was supported by National
Institutes of Health Grants AI43649 (to E. L. R. and G. W.) and AI69993
(to M. B. Z.), as well as Austrian Science Fund Grant J2845-B13 (to J.
S. G.).
NR 40
TC 78
Z9 78
U1 0
U2 10
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 JUN 2
PY 2009
VL 106
IS 22
BP 9057
EP 9062
DI 10.1073/pnas.0901474106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 452ZU
UT WOS:000266580500051
PM 19458040
ER
PT J
AU Caterino, JM
Weed, SG
Espinola, JA
Camargo, CA
AF Caterino, Jeffrey M.
Weed, Sarah Grace
Espinola, Janice A.
Camargo, Carlos A., Jr.
TI National Trends in Emergency Department Antibiotic Prescribing for
Elders with Urinary Tract Infection, 1996-2005
SO ACADEMIC EMERGENCY MEDICINE
LA English
DT Article; Proceedings Paper
CT Scientific Research Forum of the
American-College-of-Emergency-Physicians
CY OCT 24-28, 2008
CL Chicago, IL
SP Amer Coll Emergency Phys
DE urinary tract infection; aged; emergency department; antibiotic; elderly
ID VENTILATOR-ASSOCIATED PNEUMONIA; INADEQUATE ANTIMICROBIAL TREATMENT;
TERM-CARE FACILITY; ESCHERICHIA-COLI; PATIENT OUTCOMES; SEPTIC SHOCK;
RISK-FACTORS; WOMEN; MANAGEMENT; THERAPY
AB Given reported increases in antibiotic resistance among elders with urinary tract infection (UTI) and pyelonephritis, the authors identified national rates and trends in emergency department (ED) trimethoprim-sulfamethoxazole (TMP-SMX) and fluoroquinolone prescribing for older adults from 1996 to 2005.
This was a retrospective analysis utilizing the ED component of the 1996-2005 National Hospital Ambulatory Medical Care Survey (NHAMCS). The authors included NHAMCS ED entries aged >= 18 years with a diagnosis of UTI or pyelonephritis; pregnancy was excluded. Records were divided into 18-64 years ("adults") and >= 65 years ("elders"). Primary outcome measures were prescription of TMP-SMX monotherapy, fluoroquinolone monotherapy, and combination therapy with two or more antibiotics. Estimated visit totals and rates were calculated and trends analyzed.
From 1996 to 2005, there were 5 million elder ED visits for UTI or pyelonephritis. Approximately 9.4% (95% confidence interval [CI] = 7.9% to 11%) of elders received TMP-SMX monotherapy with rates decreasing over time (p-value for trend = 0.031). Overall, 35% (95% CI = 32% to 38%) of elders received fluoroquinolone monotherapy, which increased from 21% (95% CI = 14% to 27%) in 1996 to 45% (95% CI = 39% to 50%) in 2005 (p-value for trend < 0.001). Therapy with a fluoroquinolone plus a second antibiotic was used in only 4.2% (95% CI = 3.1% to 5.3%) of older patients.
From 1996 to 2005, TMP-SMX monotherapy in elder ED patients decreased while fluoroquinolone therapy increased. The majority of older patients receiving fluoroquinolone therapy received a single agent. Given the continued prevalence of monotherapy for elder ED patients with UTI or pyelonephritis, antibiotic resistance patterns in these patients should be better characterized to ensure institution of appropriate empiric therapy.
C1 [Caterino, Jeffrey M.] Ohio State Univ, Dept Emergency Med, Columbus, OH 43210 USA.
[Caterino, Jeffrey M.] Ohio State Univ, Dept Internal Med, Columbus, OH 43210 USA.
[Weed, Sarah Grace] Duke Univ, Coll Med, Durham, NC USA.
[Espinola, Janice A.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
RP Caterino, JM (reprint author), Ohio State Univ, Dept Emergency Med, Columbus, OH 43210 USA.
EM jeffrey.caterino@osumc.edu
NR 42
TC 12
Z9 12
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1069-6563
EI 1553-2712
J9 ACAD EMERG MED
JI Acad. Emerg. Med.
PD JUN
PY 2009
VL 16
IS 6
BP 500
EP 507
DI 10.1111/j.1553-2712.2009.00353.x
PG 8
WC Emergency Medicine
SC Emergency Medicine
GA 453FB
UT WOS:000266594600004
PM 19245373
ER
PT J
AU Grudzen, CR
Timmermans, S
Koenig, WJ
Torres, JM
Hoffman, JR
Lorenz, KA
Asch, SM
AF Grudzen, Corita R.
Timmermans, Stefan
Koenig, William J.
Torres, Jacqueline M.
Hoffman, Jerome R.
Lorenz, Karl A.
Asch, Steven M.
TI Paramedic and Emergency Medical Technicians Views on Opportunities and
Challenges When Forgoing and Halting Resuscitation in the Field
SO ACADEMIC EMERGENCY MEDICINE
LA English
DT Article
DE resuscitation; ethics; emergency medical services; prehospital care;
cardiac arrest
ID CARDIAC-ARREST; QUALITY; DEATH
AB The objective was to assess paramedic and emergency medical technicians (EMT) perspectives and decision-making after a policy change that allows forgoing or halting resuscitation in prehospital atraumatic cardiac arrest.
Five semistructured focus groups were conducted with 34 paramedics and 2 EMTs from emergency medical services (EMS) agencies within Los Angeles County (LAC), 6 months after a policy change that allowed paramedics to forgo or halt resuscitation in the field under certain circumstances.
Participants had an overwhelmingly positive view of the policy; felt it empowered their decision-making abilities; and thought the benefits to patients, family, EMS, and the public outweighed the risks. Except under certain circumstances, such as when the body was in public view or when family members did not appear emotionally prepared to have the body left on scene, they felt the policy improved care. Assuming that certain patient characteristics were present, decisions by paramedics about implementing the policy in the field involve many factors, including knowledge and comfort with the new policy, family characteristics (e.g., agreement), and logistics regarding the place of arrest (e.g., size of space). Paramedic and EMT experiences with and attitudes toward forgoing resuscitation, as well as group dynamics among EMS leadership, providers, police, and ED staff, also play a role.
Participants view the ability to forgo or halt resuscitation in the field as empowering and do not believe it presents harm to patients or families under most circumstances. Factors other than patient clinical characteristics, such as knowledge and attitudes toward the policy, family emotional preparedness, and location of arrest, affect whether paramedics will implement it.
C1 [Grudzen, Corita R.] Mt Sinai Sch Med, Dept Emergency Med, New York, NY 10029 USA.
[Timmermans, Stefan] Univ Calif Los Angeles, Dept Sociol, Los Angeles, CA 90024 USA.
[Koenig, William J.] Los Angeles Cty, Emergency Med Serv Agcy, Los Angeles, CA USA.
[Torres, Jacqueline M.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA.
[Hoffman, Jerome R.] Univ Calif Los Angeles, Dept Emergency Med, Los Angeles, CA USA.
[Lorenz, Karl A.] Vet Integrated Palliat Care Program, Los Angeles, CA USA.
[Lorenz, Karl A.; Asch, Steven M.] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA.
[Grudzen, Corita R.] Univ Calif Los Angeles, Robert Wood Johnson Clin Scholars Program, Los Angeles, CA USA.
RP Grudzen, CR (reprint author), Mt Sinai Sch Med, Dept Emergency Med, New York, NY 10029 USA.
EM corita.grudzen@mountsinai.org
OI Grudzen, Corita/0000-0003-3039-8497
FU California Health Care Foundation [07-1155]
FX This study was funded with a grant from the California Health Care
Foundation, Grant 07-1155.
NR 14
TC 9
Z9 9
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1069-6563
J9 ACAD EMERG MED
JI Acad. Emerg. Med.
PD JUN
PY 2009
VL 16
IS 6
BP 532
EP 538
DI 10.1111/j.1553-2712.2009.00427.x
PG 7
WC Emergency Medicine
SC Emergency Medicine
GA 453FB
UT WOS:000266594600009
PM 19438412
ER
PT J
AU Lebedev, AY
Cheprakov, AV
Sakadzic, S
Boas, DA
Wilson, DF
Vinogradov, SA
AF Lebedev, Artem Y.
Cheprakov, Andrei V.
Sakadzic, Sava
Boas, David A.
Wilson, David F.
Vinogradov, Sergei A.
TI Dendritic Phosphorescent Probes for Oxygen Imaging in Biological Systems
SO ACS APPLIED MATERIALS & INTERFACES
LA English
DT Review
DE phosphorescence; oxygen; porphyrins; dendrimers; quenching; imaging
ID ELECTRON-TRANSFER REACTIONS; NEAR-INFRARED PHOSPHORS; IN-VIVO;
PHOTOPHYSICAL PROPERTIES; PEGYLATED DENDRIMERS; OPTICAL NANOSENSORS;
MOLECULAR-OXYGEN; O-2 UPTAKE; PORPHYRINS; COMPLEXES
AB Oxygen levels in biological systems can be measured by the phosphorescence quenching method using probes with controllable quenching parameters and defined biodistributions. We describe a general approach to the construction of phosphorescent nanosensors with tunable spectral characteristics, variable degrees of quenching, and a high selectivity for oxygen. The probes are based on bright phosphorescent Pt and Pd complexes of porphyrins and symmetrically pi-extended porphyrins (tetrabenzoporphyrins and tetranaphthoporphyrins). pi-Extension of the core macrocycle allows tuning of the spectral parameters of the probes in order to meet the requirements of a particular imaging application (e.g., oxygen tomography versus planar microscopic imaging). Metalloprophyrins are encapsulated into poly(arylglycine) dendrimers, which fold in aqueous environments and create diffusion barriers for oxygen, making it possible to regulate the sensitivity and the dynamic range of the method. The periphery of the dendrimers is modified with poly(ethylene glycol) residues, which enhance the probe's solubility, diminish toxicity, and help prevent interactions of the probes with the biological environment. The probe's parameters were measured under physiological conditions and shown to be unaffected by the presence of biomacromolecules. The performance of the probes was demonstrated in applications, including in vivo microscopy of vascular pO(2) in the rat brain.
C1 [Lebedev, Artem Y.; Wilson, David F.; Vinogradov, Sergei A.] Univ Penn, Dept Biochem & Biophys, Philadelphia, PA 19104 USA.
[Cheprakov, Andrei V.] Moscow MV Lomonosov State Univ, Dept Chem, Moscow, Russia.
[Sakadzic, Sava; Boas, David A.] Harvard Univ, Sch Med, Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Charlestown, MA 02129 USA.
RP Vinogradov, SA (reprint author), Univ Penn, Dept Biochem & Biophys, Philadelphia, PA 19104 USA.
EM vinograd@mail.med.upenn.edu
RI Cheprakov, Andrey/D-7255-2015;
OI Cheprakov, Andrey/0000-0001-9589-4104; Wilson, David
F/0000-0002-2626-5838; Lebedev, Artem/0000-0001-5366-9793
FU NHLBI NIH HHS [R01 HL081273-04, HL081273, R01 HL081273]; NIBIB NIH HHS
[EB007279, R01 EB007279, R01 EB007279-03]; NINDS NIH HHS [NS031465, R01
NS031465, R01 NS031465-16]
NR 100
TC 118
Z9 119
U1 4
U2 39
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1944-8244
J9 ACS APPL MATER INTER
JI ACS Appl. Mater. Interfaces
PD JUN
PY 2009
VL 1
IS 6
BP 1292
EP 1304
DI 10.1021/am9001698
PG 13
WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary
SC Science & Technology - Other Topics; Materials Science
GA 464NX
UT WOS:000267513100024
PM 20072726
ER
PT J
AU De Witte, PB
Wijffels, M
Jupiter, JB
Ring, D
AF De Witte, Pieter Bas
Wijffels, Mathieu
Jupiter, Jesse B.
Ring, David
TI The Darrach procedure for post-traumatic reconstruction
SO ACTA ORTHOPAEDICA BELGICA
LA English
DT Article
DE distal ulna resection; Darrach
ID DISTAL RADIOULNAR JOINT; SAUVE-KAPANDJI PROCEDURE; ULNAR IMPINGEMENT;
FOLLOW-UP; RESECTION; HEMIRESECTION
AB Over a 6-year-period, 15 women and It men with a mean age of 53 years (range, 24 to 80 years) had resection of the distal part of the ulna (Darrach's procedure) to address stiffness, instability, non-union, or substantial radioulnar length discrepancy after trauma. At an average follow-up of 21 months (range, 4 to 60 months), the improvement in total arc of forearm rotation averaged 87 degrees (range, 0 degrees to 160 degrees), from an average of 49 degrees to an average of 136 degrees (p < 0.001). The proportion of patients with occasional or continuous pain after the Darrach procedure (7 after vs. 16 prior; p = 0.04) was significantly reduced. Only two patients had reoperation related to the residual ulna.
In this study, the Darrach procedure improved forearm rotation and pain in patients with posttraumatic stiffness, instability, nonunion, or substantial radio-ulnar length discrepancy with a low complication and re-operation rate.
C1 [De Witte, Pieter Bas; Wijffels, Mathieu; Jupiter, Jesse B.; Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Dept Orthopaed Surg, Boston, MA 02114 USA.
RP Ring, D (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Dept Orthopaed Surg, Yawkey Ctr Suite 2100,55 Fruit St, Boston, MA 02114 USA.
EM dring@partners.org
NR 28
TC 11
Z9 11
U1 0
U2 1
PU ACTA MEDICA BELGICA
PI BRUSSELS
PA AVENUE WINSTON CHURCHILL, WINSTON CHURCHILL-LAAN, 11 BOX 30, B-1180
BRUSSELS, BELGIUM
SN 0001-6462
J9 ACTA ORTHOP BELG
JI Acta Orthop. Belg.
PD JUN
PY 2009
VL 75
IS 3
BP 316
EP 322
PG 7
WC Orthopedics
SC Orthopedics
GA 465SV
UT WOS:000267608600005
PM 19681316
ER
PT J
AU Henderson, DC
Fan, X
Sharma, B
Copeland, PM
Borba, CP
Boxill, R
Freudenreich, O
Cather, C
Evins, AE
Goff, DC
AF Henderson, D. C.
Fan, X.
Sharma, B.
Copeland, P. M.
Borba, C. P.
Boxill, R.
Freudenreich, O.
Cather, C.
Evins, A. Eden
Goff, D. C.
TI A double-blind, placebo-controlled trial of rosiglitazone for
clozapine-induced glucose metabolism impairment in patients with
Schizophrenia
SO ACTA PSYCHIATRICA SCANDINAVICA
LA English
DT Article
DE clozapine; rosiglitazone; metabolic syndrome; lipids
ID TYPE-2 DIABETES-MELLITUS; CORONARY-ARTERY-DISEASE; DENSITY-LIPOPROTEIN
CHOLESTEROL; INSULIN-RESISTANCE SYNDROME; MINIMAL MODEL ANALYSIS;
INTRAVENOUS GLUCOSE; WEIGHT-GAIN; PEROXISOME-PROLIFERATOR;
BLOOD-PRESSURE; TOLERANCE TEST
AB Henderson DC, Fan X, Sharma B, Copeland PM, Borba CP, Boxill R, Freudenreich O, Cather C, Eden Evins A, Goff DC. A double-blind, placebo-controlled trial of rosiglitazone for clozapine-induced glucose metabolism impairment in patients with Schizophrenia.
The primary purpose of this 8-week double-blind, placebo-controlled trial of rosiglitazone 4 mg/day was to examine its effect on insulin sensitivity index (SI) and glucose utilization (SG) in clozapine-treated subjects with schizophrenia with insulin resistance.
Eighteen subjects were randomized and accessed with a Frequently Sampled Intravenous Glucose Tolerance Test (FSIVGTT) at baseline and at week 8 to estimate SG and SI.
Controlling for the baseline, comparing the rosiglitazone group with placebo group, there was a non-significant improvement in SG (0.016 +/- 0.006-0.018 +/- 0.008, effect size = 0.23, P = 0.05) with a trend of improvement in SI in the rosiglitazone group (4.6 +/- 2.8-7.8 +/- 6.7, effect size = 0.18, P = 0.08). There was a significant reduction in small low-density lipoprotein cholesterol (LDL-C) particle number (987 +/- 443-694 +/- 415, effect size = 0.30, P = 0.04).
Rosiglitazone may have a role in addressing insulin resistance and lipid abnormalities associated with clozapine.
C1 [Henderson, D. C.; Fan, X.; Sharma, B.; Borba, C. P.; Boxill, R.; Freudenreich, O.; Cather, C.; Evins, A. Eden; Goff, D. C.] Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA 02114 USA.
[Henderson, D. C.; Fan, X.; Copeland, P. M.; Boxill, R.; Freudenreich, O.; Cather, C.; Evins, A. Eden; Goff, D. C.] Harvard Univ, Sch Med, Boston, MA USA.
RP Henderson, DC (reprint author), Freedom Trail Clin, 25 Staniford St, Boston, MA USA.
EM dchenderson@partners.org
FU Stanley Foundation; National Institute of Health (NIH/NCRR)
[5MO1RR01066-24]; NARSAD New Investigator Award
FX This study was funded by Stanley Foundation, National Institute of
Health (NIH/NCRR) Grant 5MO1RR01066-24 (General Clinical Research
Center) and a NARSAD New Investigator Award (DCH).
NR 63
TC 21
Z9 21
U1 3
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0001-690X
J9 ACTA PSYCHIAT SCAND
JI Acta Psychiatr. Scand.
PD JUN
PY 2009
VL 119
IS 6
BP 457
EP 465
DI 10.1111/j.1600-0447.2008.01325.x
PG 9
WC Psychiatry
SC Psychiatry
GA 447CR
UT WOS:000266169700006
PM 19183127
ER
PT J
AU Watkins, LE
O'Farrell, TJ
Suvak, MK
Murphy, CM
Taft, CT
AF Watkins, Laura E.
O'Farrell, Timothy J.
Suvak, Michael K.
Murphy, Christopher M.
Taft, Casey T.
TI Parenting satisfaction among fathers with alcoholism
SO ADDICTIVE BEHAVIORS
LA English
DT Article
DE Parenting satisfaction; Alcohol use; Alcoholism
AB This study examined parenting satisfaction among a clinical sample of 88 men with alcoholism at baseline and 6-month and 12-month follow-up. Findings indicated no overall improvements in parenting satisfaction from the outset of treatment across assessments. Alcohol consumption variables were associated with parenting satisfaction at the bivariate level, and changes in alcohol consumption from pre to post treatment emerged as a significant predictor of changes in parenting satisfaction over the course of the study. Greater decreases in alcohol consumption were associated with greater improvement in parenting satisfaction. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [O'Farrell, Timothy J.] Harvard Univ, Sch Med, Families & Addict Program, Dept Psychiat,VA Boston Healthcare Syst,VAMC, Brockton, MA 02301 USA.
[Watkins, Laura E.; Suvak, Michael K.; Taft, Casey T.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA.
[Suvak, Michael K.] Boston Univ, Dept Psychol, Boston, MA 02215 USA.
[Taft, Casey T.] Boston Univ, Dept Psychiat, Sch Med, Boston, MA 02215 USA.
[Murphy, Christopher M.] Univ Maryland Baltimore Cty, Dept Psychol, Baltimore, MD 21250 USA.
RP O'Farrell, TJ (reprint author), Harvard Univ, Sch Med, Families & Addict Program, Dept Psychiat,VA Boston Healthcare Syst,VAMC, 116B-1,940 Belmont St, Brockton, MA 02301 USA.
EM timothy_ofarrell@hms.harvard.edu
FU National Institute on Alcohol Abuse and Alcoholism [R01AA10796,
K02AA00234]; Department of Veterans Affairs
FX This research was supported by grants to Timothy O'Farrell from the
National Institute on Alcohol Abuse and Alcoholism (R01AA10796 and
K02AA00234) and by the Department of Veterans Affairs.
NR 11
TC 1
Z9 1
U1 0
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4603
J9 ADDICT BEHAV
JI Addict. Behav.
PD JUN-JUL
PY 2009
VL 34
IS 6-7
BP 610
EP 612
DI 10.1016/j.addbeh.2009.01.006
PG 3
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA 455DU
UT WOS:000266738400020
PM 19232833
ER
PT J
AU Lee, S
Van Remmen, H
Csete, M
AF Lee, Sukkyoo
Van Remmen, Holly
Csete, Marie
TI Sod2 overexpression preserves myoblast mitochondrial mass and function,
but not muscle mass with aging
SO AGING CELL
LA English
DT Article
DE hydrogen peroxide; mitochondria; muscle aging; myoblast; PI3 kinase-Akt
signaling; superoxide
ID MANGANESE SUPEROXIDE-DISMUTASE; FOXO TRANSCRIPTION FACTORS;
PROTEIN-KINASE B; DNA COPY NUMBER; SKELETAL-MUSCLE; SATELLITE-CELL;
MUTANT MICE; DILATED CARDIOMYOPATHY; OXIDATIVE STRESS; COMPLEX I
AB Mice lacking superoxide dismutase-2 (SOD2 or MnSOD) die during embryonic or early neonatal development, with diffuse superoxide-induced mitochondrial damage. Although stem and progenitor cells are exquisitely sensitive to oxidant stress, they have not been well studied in MnSOD2-manipulated mouse models. Patterns of proliferation and differentiation of cultured myoblasts (muscle progenitor cells), PI3-Akt signaling during differentiation, and the maintenance of mitochondrial mass with aging using myoblasts from young (3-4 week old) and aged (27-29 months old) MnSOD2-overexpressing (Sod2-Tg) and heterozygote (Sod2(+/-)) mice were characterized by us. Overexpression of MnSOD2 in myoblasts had a protective effect on mitochondrial DNA abundance and some aspects of mitochondrial function with aging, and preservation of differentiation potential. Sod2 deficiency resulted in defective signaling in the PI3-Akt pathway, specifically impaired phosphorylation of Akt at Ser473 and Thr308 in young myoblasts, and decreased differentiation potential. Compared with young myoblasts, aged myoblast Akt was constitutively phosphorylated, unresponsive to mitogen signaling, and indifferent to MnSOD2 levels. These data suggest that specific sites in the PI3K-Akt pathway are more sensitive to increased superoxide levels than to the increased hydrogen peroxide levels generated in Sod2-transgenic myoblasts. In wild-type myoblasts, aging was associated with significant loss of mitochondrial DNA relative to chromosomal DNA, but MnSOD2 overexpression was associated with maintained myoblast mitochondrial DNA with aging.
C1 [Lee, Sukkyoo; Csete, Marie] Emory Univ, Sch Med, Dept Anesthesiol, Atlanta, GA 30322 USA.
[Lee, Sukkyoo; Csete, Marie] Emory Univ, Sch Med, Program Biochem Cell & Dev Biol, Atlanta, GA 30322 USA.
[Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA.
[Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA.
[Van Remmen, Holly] S Texas Vet Hlth Care Syst, San Antonio, TX USA.
RP Csete, M (reprint author), Calif Inst Regenerat Med, 210 King St, San Francisco, CA 94107 USA.
EM mcsete@cirm.ca.gov
FU Emory Anesthesiology; [PO1 NIA 1-386003609]
FX The authors thank Dr Charles Epstein for supplying mice for these
studies. The authors acknowledge Drs Russ Price (Emory), David Lambeth
(Emory), Tom Burkholder (GaTech) and Karl Saxe (American Cancer Society)
for helpful discussions. This work was supported by PO1 NIA 1-386003609
(MC, HVR), and Emory Anesthesiology.
NR 63
TC 10
Z9 10
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1474-9718
J9 AGING CELL
JI Aging Cell
PD JUN
PY 2009
VL 8
IS 3
BP 296
EP 310
DI 10.1111/j.1474-9726.2009.00477.x
PG 15
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA 450RE
UT WOS:000266417700009
PM 19627269
ER
PT J
AU Gardner, EM
Burman, WJ
Steiner, JF
Anderson, PL
Bangsberg, DR
AF Gardner, Edward M.
Burman, William J.
Steiner, John F.
Anderson, Peter L.
Bangsberg, David R.
TI Antiretroviral medication adherence and the development of
class-specific antiretroviral resistance
SO AIDS
LA English
DT Editorial Material
DE adherence; antiretroviral resistance; antiretroviral therapy; genetic
barrier to resistance; HIV; potency; replication capacity
ID HIV DRUG-RESISTANCE; REVERSE-TRANSCRIPTASE INHIBITORS;
IMMUNODEFICIENCY-VIRUS TYPE-1; TREATMENT-NAIVE PATIENTS; VIROLOGICAL
FAILURE; VIRAL LOAD; COMBINATION THERAPY; PROTEASE INHIBITORS; INITIAL
TREATMENT; INFECTED PATIENTS
AB Objective: To assess the association between antiretroviral adherence and the development of class-specific antiretroviral medication resistance.
Design and methods: Literature and conference abstract review of studies assessing the association between adherence to antiretroviral therapy and the development of antiretroviral medication resistance.
Results: Factors that determine class-specific adherence-resistance relationships include antiretroviral regimen potency, viral fitness or, more specifically, the interplay between the fold-change in resistance and fold-change in fitness caused by drug resistance mutations, and the genetic barrier to antiretroviral resistance. During multidrug therapy, differential drug exposure increases the likelihood of developing resistance. In addition, antiretroviral medications with higher potency and higher genetic barriers to resistance decrease the incidence of resistance for companion antiretroviral medications at all adherence levels.
Conclusion: Knowledge of class-specific adherence-resistance relationships may help clinicians and patients tailor therapy to match individual patterns of adherence in order to minimize the development of resistance at failure. In addition, this information may guide the selection of optimal drug combinations and regimen sequences to improve the durability of antiretroviral therapy. (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
C1 [Gardner, Edward M.; Burman, William J.] Denver Publ Hlth, Denver, CO 80204 USA.
[Gardner, Edward M.; Burman, William J.] Univ Colorado Denver, Dept Med, Aurora, CO USA.
[Anderson, Peter L.] Univ Colorado Denver, Dept Pharmaceut Sci, Aurora, CO USA.
[Bangsberg, David R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harvard Initiat Global Hlth, Boston, MA USA.
RP Gardner, EM (reprint author), Denver Publ Hlth, 605 Bannock St, Denver, CO 80204 USA.
EM edward.m.gardner@dhha.org
FU NIAID NIH HHS [K01 AI067063, K01 AI067063-05, R01 AI 64029, R01
AI064029]; NIMH NIH HHS [R01 MH054907]; PHS HHS [NIAAA 015287, NIMH
54907]
NR 57
TC 70
Z9 72
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD JUN 1
PY 2009
VL 23
IS 9
BP 1035
EP 1046
DI 10.1097/QAD.0b013e32832ba8ec
PG 12
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 452VN
UT WOS:000266569400001
PM 19381075
ER
PT J
AU Gonzalez, JS
Hendriksen, ES
Collins, EM
Duran, RE
Safren, SA
AF Gonzalez, Jeffrey S.
Hendriksen, Ellen Setsuko
Collins, Erin Marie
Duran, Ron E.
Safren, Steven A.
TI Latinos and HIV/AIDS: Examining Factors Related to Disparity and
Identifying Opportunities for Psychosocial Intervention Research
SO AIDS AND BEHAVIOR
LA English
DT Review
DE HIV/AIDS; Latino/Hispanic; Treatment adherence; Mental health; Substance
abuse; Disparities
ID HUMAN-IMMUNODEFICIENCY-VIRUS; BEHAVIORAL STRESS-MANAGEMENT;
SELF-REPORTED ADHERENCE; ILLICIT DRUG-USE; ACTIVE ANTIRETROVIRAL
THERAPY; HIV-SEROPOSITIVE WOMEN; PRIMARY-CARE PATIENTS; QUALITY-OF-LIFE;
HEALTH LITERACY; SOCIAL SUPPORT
AB Latinos maintain an AIDS case rate more than 3 times higher than whites, a greater rate of progression to AIDS, and a higher rate of HIV/AIDS-related deaths. Three broad areas are reviewed related to these disparities: (1) relevant demographic, socioeconomic, and socio-cultural factors among Latinos; (2) drug abuse and mental health problems in Latinos relevant to HIV/AIDS outcomes; and (3) opportunities for psychosocial intervention. Latinos living with HIV are a rapidly growing group, are more severely impacted by HIV than whites, and confront unique challenges in coping with HIV/AIDS. A body of research suggests that depression, substance abuse, treatment adherence, health literacy, and access to healthcare may be fruitful targets for intervention research in this population. Though limited, the current literature suggests that psychosocial interventions that target these factors could help reduce HIV/AIDS disparities between Latinos and whites and could have important public health value.
C1 [Gonzalez, Jeffrey S.; Hendriksen, Ellen Setsuko; Collins, Erin Marie; Safren, Steven A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Gonzalez, Jeffrey S.; Hendriksen, Ellen Setsuko; Safren, Steven A.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Duran, Ron E.] Alliant Int Univ, Dept Psychol, Los Angeles, CA USA.
RP Gonzalez, JS (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,ACC 812, Boston, MA 02114 USA.
EM jsgonzalez@partners.org
FU NIDA NIH HHS [R01DA018603, R01 DA018603]
NR 149
TC 32
Z9 32
U1 9
U2 20
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1090-7165
J9 AIDS BEHAV
JI AIDS behav.
PD JUN
PY 2009
VL 13
IS 3
BP 582
EP 602
DI 10.1007/s10461-008-9402-4
PG 21
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA 449NI
UT WOS:000266336900021
PM 18498050
ER
PT J
AU Byakika-Tusiime, J
Crane, J
Oyugi, JH
Ragland, K
Kawuma, A
Musoke, P
Bangsberg, DR
AF Byakika-Tusiime, Jayne
Crane, Johanna
Oyugi, Jessica H.
Ragland, Kathleen
Kawuma, Annet
Musoke, Philippa
Bangsberg, David R.
TI Longitudinal Antiretroviral Adherence in HIV plus Ugandan Parents and
Their Children Initiating HAART in the MTCT-Plus Family Treatment Model:
Role of Depression in Declining Adherence Over Time
SO AIDS AND BEHAVIOR
LA English
DT Article; Proceedings Paper
CT Conference on Switching Gears in HIV Research
CY APR 21-23, 2008
CL Soweto, SOUTH AFRICA
DE Uganda; Adherence; Antiretroviral therapy; Household; MTCT-Plus
ID FIXED-DOSE COMBINATION; HIV-1-INFECTED ADULTS; POSITIVE INDIVIDUALS;
SOUTHWEST ETHIOPIA; THERAPY; NEVIRAPINE; BARRIERS; AFRICA; DETERMINANTS;
FACILITATORS
AB We conducted a study to assess the effect of family-based treatment on adherence amongst HIV-infected parents and their HIV-infected children attending the Mother-To-Child-Transmission Plus program in Kampala, Uganda. Adherence was assessed using home-based pill counts and self-report. Mean adherence was over 94%. Depression was associated with incomplete adherence on multivariable analysis. Adherence declined over time. Qualitative interviews revealed lack of transportation money, stigma, clinical response to therapy, drug packaging, and cost of therapy may impact adherence. Our results indicate that providing ART to all eligible HIV-infected members in a household is associated with excellent adherence in both parents and children. Adherence to ART among new parents declines over time, even when patients receive treatment at no cost. Depression should be addressed as a potential barrier to adherence. Further study is necessary to assess the long-term impact of this family treatment model on adherence to ART in resource-limited settings.
C1 [Byakika-Tusiime, Jayne] Univ Calif Berkeley, Sch Publ Hlth, Dept Epidemiol, Berkeley, CA 94720 USA.
[Crane, Johanna] Cornell Univ, Dept Sci & Technol Studies, Ithaca, NY USA.
[Oyugi, Jessica H.] Infect Dis Inst, Kampala, Uganda.
[Ragland, Kathleen] Univ Calif San Francisco, San Francisco Gen Hosp, Epidemiol & Prevent Intervent Ctr, Div Infect Dis, San Francisco, CA USA.
[Kawuma, Annet] Mbarara Univ Sci & Technol, Dept Community Hlth, Mbarara, Uganda.
[Musoke, Philippa] Makerere Univ, Dept Pediat & Child Hlth, Kampala, Uganda.
[Musoke, Philippa] Makerere Univ Johns Hopkins Univ Res Collaborat, Kampala, Uganda.
[Bangsberg, David R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harvard Initiat Global Hlth, Boston, MA USA.
RP Byakika-Tusiime, J (reprint author), Univ Calif Berkeley, Sch Publ Hlth, Dept Epidemiol, Berkeley, CA 94720 USA.
EM tusiimej@berkeley.edu
FU FIC NIH HHS [1D43 TW00003]; NIAAA NIH HHS [K24 AA015287, R21 AA015897];
NIMH NIH HHS [K24 MH087227, R0-1 MH54907, R01 MH054907]
NR 53
TC 71
Z9 71
U1 0
U2 5
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1090-7165
J9 AIDS BEHAV
JI AIDS behav.
PD JUN
PY 2009
VL 13
BP S82
EP S91
DI 10.1007/s10461-009-9546-x
PG 10
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA 473CG
UT WOS:000268181900012
PM 19301113
ER
PT J
AU Kaida, A
Lima, VD
Andia, I
Kabakyenga, J
Mbabazi, P
Emenyonu, N
Patterson, TL
Hogg, RS
Bangsberg, DR
AF Kaida, Angela
Lima, Viviane Dias
Andia, Irene
Kabakyenga, Jerome
Mbabazi, Pamela
Emenyonu, Nneka
Patterson, Thomas L.
Hogg, Robert S.
Bangsberg, David R.
TI The WHOMEN's Scale (Women's HAART Optimism Monitoring and EvaluatioN
Scale v.1) and the Association with Fertility Intentions and Sexual
Behaviours Among HIV-Positive Women in Uganda
SO AIDS AND BEHAVIOR
LA English
DT Article; Proceedings Paper
CT Conference on Switching Gears in HIV Research
CY APR 21-23, 2008
CL Soweto, SOUTH AFRICA
DE HIV; HAART; Uganda; Scale; HAART optimism; Women; Fertility intentions;
Sexual behaviour; HAART optimism scale
ID ACTIVE ANTIRETROVIRAL THERAPY; RISK BEHAVIOR; COMBINATION THERAPIES;
BISEXUAL MEN; GAY MEN; PREVENTION; MORTALITY; MORBIDITY; SURVIVAL;
CONTEXT
AB The objective of this study was to develop a reliable HAART optimism scale among HIV-positive women in Uganda and to test the scale's validity against measures of fertility intentions, sexual activity, and unprotected sexual intercourse. We used cross-sectional survey data of 540 women (18-50 years) attending Mbarara University's HIV clinic in Uganda. Women were asked how much they agreed or disagreed with 23 statements about HAART. Data were subjected to a principal components and factor analyses. Subsequently, we tested the association between the scale and fertility intentions and sexual behaviour using Wilcoxon rank sum test. Factor analysis yielded three factors, one of which was an eight-item HAART optimism scale with moderately high internal consistency (alpha = 0.70). Women who reported that they intended to have (more) children had significantly higher HAART optimism scores (median = 13.5 [IQR: 12-16]) than women who did not intend to have (more) children (median = 10.5 [IQR: 8-12]; P < 0.0001). Similarly, women who were sexually active and who reported practicing unprotected sexual intercourse had significantly higher HAART optimism scores than women who were sexually abstinent or who practiced protected sexual intercourse. Our reliable and valid scale, termed the Women's HAART Optimism Monitoring and EvaluatioN scale (WHOMEN's scale), may be valuable to broader studies investigating the role of HAART optimism on reproductive intentions and sexual behaviours of HIV-positive women in high HIV prevalence settings.
C1 [Kaida, Angela; Lima, Viviane Dias; Hogg, Robert S.] BC Ctr Excellence HIV AIDS, Vancouver, BC, Canada.
[Kaida, Angela] Univ British Columbia, Sch Populat & Publ Hlth, Vancouver, BC V5Z 1M9, Canada.
[Andia, Irene; Kabakyenga, Jerome; Mbabazi, Pamela] MUST, Mbarara, Uganda.
[Emenyonu, Nneka] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Patterson, Thomas L.] Univ Calif San Diego, San Diego, CA 92103 USA.
[Hogg, Robert S.] Simon Fraser Univ, Burnaby, BC V5A 1S6, Canada.
[Bangsberg, David R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
RP Kaida, A (reprint author), BC Ctr Excellence HIV AIDS, 608-1081 Burrard St, Vancouver, BC, Canada.
EM akaida@interchange.ubc.ca
RI Hogg, Robert/B-2783-2012;
OI Hogg, Robert/0000-0003-3463-5488
FU NIMH NIH HHS [R01 MH054907]; PHS HHS [NIAAA 015287, NIMH 54907]
NR 46
TC 10
Z9 10
U1 1
U2 1
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1090-7165
J9 AIDS BEHAV
JI AIDS behav.
PD JUN
PY 2009
VL 13
BP S72
EP S81
DI 10.1007/s10461-009-9553-y
PG 10
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA 473CG
UT WOS:000268181900011
PM 19387819
ER
PT J
AU Kaida, A
Bangsberg, DR
Gray, G
Hogg, RS
King, R
Miller, CL
AF Kaida, Angela
Bangsberg, David R.
Gray, Glenda
Hogg, Robert S.
King, Rachel
Miller, Cari L.
TI Editorial: Introduction to the Supplement on HIV, HAART, and Fertility
in sub-Saharan Africa
SO AIDS AND BEHAVIOR
LA English
DT Editorial Material
C1 [Kaida, Angela; Hogg, Robert S.] BC Ctr Excellence HIV AIDS, Vancouver, BC, Canada.
[Kaida, Angela] Univ British Columbia, Sch Populat & Publ Hlth, Vancouver, BC V5Z 1M9, Canada.
[Bangsberg, David R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Gray, Glenda] Univ Witwatersrand, Perinatal HIV Res Unit, Johannesburg, South Africa.
[Hogg, Robert S.; Miller, Cari L.] Simon Fraser Univ, Burnaby, BC V5A 1S6, Canada.
[King, Rachel] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[King, Rachel] Karolinska Inst, Stockholm, Sweden.
RP Kaida, A (reprint author), BC Ctr Excellence HIV AIDS, 608-1081 Burrard St, Vancouver, BC, Canada.
EM akaida@interchange.ubc.ca
RI Hogg, Robert/B-2783-2012;
OI Hogg, Robert/0000-0003-3463-5488
FU NIMH NIH HHS [K24 MH087227, R01 MH054907]
NR 3
TC 6
Z9 6
U1 0
U2 1
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1090-7165
J9 AIDS BEHAV
JI AIDS behav.
PD JUN
PY 2009
VL 13
BP S1
EP S4
DI 10.1007/s10461-009-9568-4
PG 4
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA 473CG
UT WOS:000268181900001
PM 19434488
ER
PT J
AU Crothers, K
Goulet, JL
Rodriguez-Barradas, MC
Gibert, CL
Oursler, KAK
Goetz, MB
Crystal, S
Leaf, DA
Butt, AA
Braithwaite, RS
Peck, R
Justice, AC
AF Crothers, Kristina
Goulet, Joseph L.
Rodriguez-Barradas, Maria C.
Gibert, Cynthia L.
Oursler, Kris Ann K.
Goetz, Matthew Bidwell
Crystal, Stephen
Leaf, David A.
Butt, Adeel A.
Braithwaite, R. Scott
Peck, Robin
Justice, Amy C.
TI IMPACT OF CIGARETTE SMOKING ON MORTALITY IN HIV-POSITIVE AND
HIV-NEGATIVE VETERANS
SO AIDS EDUCATION AND PREVENTION
LA English
DT Article; Proceedings Paper
CT Workshop on Current Issues in Cigarette Smoking and HIV/AIDS
CY OCT 08, 2007
CL Bethesda, MD
SP Natl Inst Hlth
ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEALTH-CARE-SYSTEM; QUALITY-OF-LIFE;
BACTERIAL PNEUMONIA; RANDOMIZED-TRIAL; ALCOHOL-USE; INFECTION;
CESSATION; OUTCOMES; DISEASE
AB It is unknown whether smoking confers similar mortality risk in HIV-positive as in HIV-negative patients. We compared overall mortality stratified by HIV and smoking of 1,034 HIV-positive block-matched to 739 HIV-negative veterans, enrolled 2001-2002 in the Veterans Aging Cohort 5 Site Study. Adjusted incidence rate ratios (IRR) for mortality were calculated using Poisson regression. Mortality was significantly increased in HIV-positive veterans according to both smoking status and pack-years in unadjusted and adjusted analyses (adjusted IRR 2.31, 95% confidence interval [CI] 1.53-3.49 for HIV-positive current smokers and IRR 1.32, 95% CI 0.67-2.61 for HIV-negative current smokers). Comorbid diseases were also significantly increased according to smoking status and pack-years. Current smoking is associated with poor outcomes; even lower levels of exposure appear to be detrimental in HIV-infected veterans. These findings support the need for improvements in smoking cessation and for studies of mechanisms and diseases underlying increased mortality in smokers with HIV.
C1 [Crothers, Kristina; Goulet, Joseph L.; Rodriguez-Barradas, Maria C.; Justice, Amy C.] VA Connecticut Healthcare Syst, Dept Internal Med, New Haven, CT USA.
[Crothers, Kristina; Goulet, Joseph L.; Rodriguez-Barradas, Maria C.; Justice, Amy C.] Yale Univ, Sch Med, New Haven, CT USA.
[Rodriguez-Barradas, Maria C.] Michael E DeBakey VA Med Ctr, Med Serv, Houston, TX USA.
[Rodriguez-Barradas, Maria C.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
[Gibert, Cynthia L.; Peck, Robin] George Washington Univ, Dept Med, Washington, DC USA.
[Gibert, Cynthia L.; Peck, Robin] VA Med Ctr, Washington, DC USA.
[Oursler, Kris Ann K.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Oursler, Kris Ann K.] Baltimore VA Med Ctr, Ctr Geriatr Res Educ & Clin, Baltimore, MD USA.
[Goetz, Matthew Bidwell; Leaf, David A.] VA Greater Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA.
[Goetz, Matthew Bidwell; Leaf, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Crystal, Stephen] Rutgers State Univ, Ctr Pharmacotherapy Chron Dis Management & Outcom, New Brunswick, NJ 08903 USA.
[Crystal, Stephen] Rutgers State Univ, Inst Hlth, New Brunswick, NJ 08903 USA.
[Crystal, Stephen] Rutgers State Univ, Sch Social Work, New Brunswick, NJ 08903 USA.
[Butt, Adeel A.] VA Pittsburgh Healthcare Syst, Dept Internal Med, Pittsburgh, PA USA.
[Butt, Adeel A.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
RP Crothers, K (reprint author), VA Connecticut Healthcare Syst, 950 Campbell Ave,11 ACSLG, West Haven, CT 06516 USA.
EM kristina.crothers@yale.edu
OI Goetz, Matthew/0000-0003-4542-992X; Goulet, Joseph/0000-0002-0842-804X;
Crothers, Kristina/0000-0001-9702-0371
FU AHRQ HHS [U18 HS016097, U18-HS016097]; NCRR NIH HHS [1KL2 RR024138, KL2
RR024138]; NHLBI NIH HHS [1R01 HL090342, R01 HL090342]; NIAAA NIH HHS
[3U01AA13566, U01 AA013566, U10 AA013566, U10 AA013566-08]; NIMH NIH HHS
[MH058984, R01 MH058984]
NR 37
TC 53
Z9 54
U1 0
U2 1
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 JUN
PY 2009
VL 21
IS 3
BP 40
EP 53
PG 14
WC Education & Educational Research; Public, Environmental & Occupational
Health
SC Education & Educational Research; Public, Environmental & Occupational
Health
GA 456XT
UT WOS:000266888500005
PM 19537953
ER
PT J
AU Applebaum, AJ
Reilly, LC
Gonzalez, JS
Richardson, MA
Leveroni, CL
Safren, SA
AF Applebaum, Allison J.
Reilly, Laura C.
Gonzalez, Jeffrey S.
Richardson, Mark A.
Leveroni, Catherine L.
Safren, Steven A.
TI The Impact of Neuropsychological Functioning on Adherence to HAART in
HIV-Infected Substance Abuse Patients
SO AIDS PATIENT CARE AND STDS
LA English
DT Article
ID ACTIVE ANTIRETROVIRAL THERAPY; METHADONE-MAINTENANCE PATIENTS;
PSYCHOMOTOR SPEED PERFORMANCE; INJECTING DRUG-USERS; COGNITIVE
IMPAIRMENT; NEUROCOGNITIVE IMPAIRMENT; MEDICATION ADHERENCE; VIRAL LOAD;
PREDICTORS; ADULTS
AB This study assessed the frequency of neuropsychological impairment and its relationship to adherence in a sample of HIV-infected injection drug users (IDUs) in treatment. One hundred eight participants recruited between September 2006 and October 2008 completed psychodiagnostic and neuropsychological assessments and monitored HAART adherence over a 2-week period via the use of Medication Event Monitoring System (MEMS) electronic pill caps and self-report. Assessment of concurrent functioning included clinician-rated scales of depression and substance use severity, and a battery of neuropsychological tests. Findings from individual neuropsychological tests were converted to Z scores relative to standard norms and averaged to form a composite score (NPZ). NPZ was generally poor (mean = -1.505, standard deviation = 1.120), with 76.9% of the sample being classified as highly impaired. Self-reported adherence was significantly higher than MEMS cap adherence. In contrast with previous studies, overall neuropsychological functioning was not a significant predictor of electronically monitored or self-reported adherence. However, examiner-rated current global severity of substance use and delayed word list recall emerged as significant predictors of self-reported adherence. Additionally, estimated premorbid verbal intelligence emerged as a significant predictor of the discrepancy between electronically monitored and self-reported adherence. Given the extent of neuropsychological impairment in this sample, future studies should examine the degree to which the impact of neuropsychological impairment may moderate interventions for this population, and the extent to which skills to cope with neuropsychological problems may boost the potential efficacy of such interventions.
C1 [Applebaum, Allison J.; Reilly, Laura C.; Gonzalez, Jeffrey S.; Leveroni, Catherine L.; Safren, Steven A.] Massachusetts Gen Hosp, Behav Med Serv, Boston, MA 02114 USA.
[Applebaum, Allison J.; Richardson, Mark A.] Boston Univ, Dept Psychol, Boston, MA 02215 USA.
[Richardson, Mark A.] Boston Univ, Sch Med, Div Psychiat, Boston, MA 02215 USA.
[Gonzalez, Jeffrey S.; Leveroni, Catherine L.; Safren, Steven A.] Harvard Univ, Sch Med, Boston, MA USA.
[Gonzalez, Jeffrey S.] Yeshiva Univ, Bronx, NY USA.
RP Safren, SA (reprint author), Massachusetts Gen Hosp, Behav Med Serv, 1 Bowdoin Sq,BS07-B, Boston, MA 02114 USA.
EM ssafren@partners.org
OI Richardson, Mark/0000-0003-4730-3431
FU National Institute of Drug Abuse [DA018603-03]
FX This project was funded by grant number DA018603-03 from the National
Institute of Drug Abuse to Dr. Steven Safren.
NR 72
TC 16
Z9 17
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1087-2914
J9 AIDS PATIENT CARE ST
JI Aids Patient Care STDS
PD JUN
PY 2009
VL 23
IS 6
BP 455
EP 462
DI 10.1089/apc.2008.0181
PG 8
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 457GB
UT WOS:000266915400008
PM 19519229
ER
PT J
AU Denmark, DL
Buck, KJ
AF Denmark, D. L.
Buck, K. J.
TI A POSSIBLE ROLE FOR THE MITOCHONDRIAL RESPIRATORY CHAIN IN GENETIC
VULNERABILITY TO SEVERE ALCOHOL WITHDRAWAL
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA.
Oregon Hlth & Sci Univ, Portland Alcohol Res Ctr, Portland, OR 97239 USA.
Portland VA Med Ctr, Portland, OR 97239 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
BP 18A
EP 18A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335100030
ER
PT J
AU Hashimoto, JG
Forquer, MR
Wiren, KM
AF Hashimoto, J. G.
Forquer, M. R.
Wiren, K. M.
TI SEXUALLY DIMORPHIC HORMONE PROFILES AFTER CHRONIC ALCOHOL EXPOSURE IN
WSP AND WSR MICE: TESTOSTERONE LEVELS DROP IN MALES BUT INCREASE IN
FEMALES
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 Portland VA Med Ctr, Res Serv, Portland, OR 97239 USA.
Oregon Hlth & Sci Univ, Portland, OR 97239 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
BP 32A
EP 32A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335100086
ER
PT J
AU Kelly, JF
Stout, RL
Tonigan, JS
Magill, M
AF Kelly, J. F.
Stout, R. L.
Tonigan, J. S.
Magill, M.
TI NEGATIVE AFFECT, RELAPSE, AND ALCOHOLICS ANONYMOUS: DOES AA WORK BY
REDUCING DEPRESSIVE SYMPTOMS?
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Kelly, J. F.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Kelly, J. F.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Tonigan, J. S.] Univ New Mexico, Albuquerque, NM 87131 USA.
[Magill, M.] Brown Univ, Sch Med, Providence, RI 02912 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
BP 47A
EP 47A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335100147
ER
PT J
AU Kelly, JF
Magill, M
Stout, RL
AF Kelly, J. F.
Magill, M.
Stout, R. L.
TI HOW DO PEOPLE RECOVER FROM ALCOHOL DEPENDENCE? A SYSTEMATIC REVIEW OF
THE RESEARCH ON MECHANISMS OF BEHAVIOR CHANGE IN ALCOHOLICS ANONYMOUS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Kelly, J. F.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Kelly, J. F.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Magill, M.] Brown Univ, Sch Med, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA.
NR 0
TC 1
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PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
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SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
BP 48A
EP 48A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335100150
ER
PT J
AU Hawkins, EH
Malte, CA
Baer, JS
Kivlahan, DR
AF Hawkins, E. H.
Malte, C. A.
Baer, J. S.
Kivlahan, D. R.
TI PREVALENCE AND CHARACTERISTICS OF PATIENTS WITH MULTIPLE ALCOHOL USE
DISORDER TREATMENT EPISODES
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Hawkins, E. H.; Malte, C. A.; Baer, J. S.; Kivlahan, D. R.] VA Puget Sound Hlth Care Syst, Seattle, WA USA.
NR 0
TC 0
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U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
BP 57A
EP 57A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335100188
ER
PT J
AU Gazdzinski, S
Mon, A
Durazzo, TC
Meyerhoff, DJ
AF Gazdzinski, S.
Mon, A.
Durazzo, T. C.
Meyerhoff, D. J.
TI ELEVATED BODY MASS INDEX IS ASSOCIATED WITH BRAIN INJURY IN ALCOHOL
DEPENDENCE - A MAGNETIC RESONANCE STUDY
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 Univ Calif San Francisco, San Francisco VA Med Ctr, CIND, San Francisco, CA 94121 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
BP 90A
EP 90A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335100321
ER
PT J
AU Batki, SL
Dimmock, JA
Ploutz-Snyder, R
Meszaros, ZS
Canfield, K
AF Batki, S. L.
Dimmock, J. A.
Ploutz-Snyder, R.
Meszaros, Z. S.
Canfield, K.
TI DIRECTLY MONITORED NALTREXONE REDUCES HEAVY DRINKING IN SCHIZOPHRENIA:
PRELIMINARY ANALYSIS OF A CONTROLLED TRIAL
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 UCSF, Dept Psychiat, San Francisco, CA 94121 USA.
San Francisco VA Med Ctr, San Francisco, CA 94121 USA.
SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
BP 113A
EP 113A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335100412
ER
PT J
AU Hahn, JA
Dobkin, LM
Mayanja, B
Emenyonu, N
Kigozi, IM
Bangsberg, DR
Weinmann, W
Yegles, M
Wurst, FM
AF Hahn, Judith A.
Dobkin, Loren M.
Mayanja, Bernard
Emenyonu, Nneka
Kigozi, Isaac M.
Bangsberg, David R.
Weinmann, Wolfgang
Yegles, Michel
Wurst, Friedrich M.
TI VALIDATION OF DIRECT METABOLITES OF ALCOHOL CONSUMPTION IN HIV POSITIVES
IN UGANDA
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Emenyonu, Nneka; Bangsberg, David R.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Weinmann, Wolfgang] Univ Hosp Freiburg, Freiburg, Germany.
[Yegles, Michel] Univ Luxembourg, Luxembourg, Luxembourg.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
BP 126A
EP 126A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335100462
ER
PT J
AU Kelly, JF
Dow, SJ
AF Kelly, J. F.
Dow, S. J.
TI STIGMA IN ADDICTION: DOES IT MATTER HOW WE REFER TO INDIVIDUALS WITH
SUBSTANCE-RELATED CONDITIONS?
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Kelly, J. F.; Dow, S. J.] Massachusetts Gen Hosp, Ctr Addict Med, Boston, MA 02114 USA.
[Kelly, J. F.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
BP 129A
EP 129A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335100475
ER
PT J
AU Milner, LC
Giardino, W
Buck, KJ
AF Milner, L. C.
Giardino, W.
Buck, K. J.
TI DEVELOPMENT OF A NOVEL MURINE BEHAVIORAL BATTERY: EFFECTS OF ETHANOL
WITHDRAWAL AND KCNJ9 ALLELIC STATUS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 Portland VA Med Ctr, Portland, OR 97239 USA.
Oregon Hlth & Sci Univ, Portland Alcohol Res Ctr, Dept Behav Neurosci, Portland, OR 97239 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
BP 141A
EP 141A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335100525
ER
PT J
AU Rasmussen, DD
Federoff, D
Froehlich, JC
AF Rasmussen, D. D.
Federoff, D.
Froehlich, J. C.
TI PRAZOSIN REDUCES ALCOHOL DRINKING IN AN ANIMAL MODEL OF ALCOHOL RELAPSE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Rasmussen, D. D.] VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA.
[Rasmussen, D. D.] Univ Washington, Seattle, WA 98195 USA.
[Federoff, D.; Froehlich, J. C.] Indiana Univ, Sch Med, Indianapolis, IN 46202 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
BP 146A
EP 146A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335100543
ER
PT J
AU Dou, X
Menkari, CE
Charness, ME
AF Dou, X.
Menkari, C. E.
Charness, M. E.
TI ALCOHOL BINDING SITES ON L1 REGULATE L1-MEDIATED CELL ADHESION
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Dou, X.; Menkari, C. E.; Charness, M. E.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, W Roxbury, MA 02132 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
BP 165A
EP 165A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335100621
ER
PT J
AU Pedrelli, P
Shyu, I
Kelly, J
Farabaugh, A
Fava, M
AF Pedrelli, P.
Shyu, I.
Kelly, J.
Farabaugh, A.
Fava, M.
TI GENDER, DEPRESSIVE SYMPTOMS AND ALCOHOL CONSUMPTION AMONG COLLEGE
STUDENTS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Pedrelli, P.; Shyu, I.; Kelly, J.; Farabaugh, A.; Fava, M.] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
BP 184A
EP 184A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335100694
ER
PT J
AU Mckay, JR
Lynch, KG
Van Horn, D
Ivey, M
Oslin, D
Drapkin, M
AF McKay, J. R.
Lynch, K. G.
Van Horn, D.
Ivey, M.
Oslin, D.
Drapkin, M.
TI EFFECTIVENESS OF EXTENDED TELEPHONE CONTINUING CARE: 18 MONTH OUTCOMES
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
Vet Affairs Med Ctr, Philadelphia, PA 19104 USA.
NR 0
TC 2
Z9 2
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
BP 197A
EP 197A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335100747
ER
PT J
AU Leite-Morris, KA
Kerestes, HB
Colombo, G
AF Leite-Morris, K. A.
Kerestes, H. B.
Colombo, G.
TI INTRA-VENTRAL TEGMENTAL AREA INJECTION OF THE GABA B RECEPTOR POSITIVE
ALLOSTERIC MODULATOR GS39783 INHIBITS ETHANOL SEEKING BEHAVIOR IN RATS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 Boston Univ, Sch Med & Res Serv, Boston VA Healthcare Syst, Div Psychiat, Boston, MA 02130 USA.
Boston Univ, Sch Med & Res Serv, Boston VA Healthcare Syst, Dept Pharmacol & Expt Therapeut, Boston, MA 02130 USA.
NR 0
TC 4
Z9 4
U1 0
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
BP 226A
EP 226A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335100863
ER
PT J
AU Durazzo, TC
Pathik, V
Gazdzinski, S
Mon, A
Meyerhoff, DJ
AF Durazzo, T. C.
Pathik, V.
Gazdzinski, S.
Mon, A.
Meyerhoff, D. J.
TI METABOLITE LEVELS IN THE BRAIN REWARD PATHWAY AT TREATMENT ENTRY
DIFFERENTIATE FUTURE ABSTAINERS AND RELAPERS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Durazzo, T. C.; Pathik, V.; Gazdzinski, S.; Mon, A.; Meyerhoff, D. J.] Univ Calif San Francisco, San Francisco VA Med Ctr, Ctr Neuroimaging Neurodegenerat Dis, San Francisco, CA 94143 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
BP 231A
EP 231A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335100883
ER
PT J
AU Kelly, JF
Stout, RL
Tonigan, S
Magill, M
Pagano, ME
AF Kelly, John F.
Stout, Robert L.
Tonigan, Scott
Magill, Molly
Pagano, Maria E.
TI DOES AA WORK BY REDUCING ANGER?
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Kelly, John F.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA.
[Tonigan, Scott] Univ New Mexico, Albuquerque, NM 87131 USA.
[Magill, Molly] Brown Univ, Providence, RI 02912 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
BP 302A
EP 302A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335101160
ER
PT J
AU Raskind, MA
AF Raskind, M. A.
TI SUSTAINED RECOVERY FROM CHRONIC ALCOHOL DEPENDENCE WITH PRAZOSIN
TREATMENT OF PTSD
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Raskind, M. A.] Univ Washington, Mental Hlth Serv, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA.
[Raskind, M. A.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98108 USA.
NR 0
TC 2
Z9 2
U1 3
U2 4
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
BP 311A
EP 311A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335101195
ER
PT J
AU Walker, B
Rasmussen, D
Raskind, M
Koob, G
AF Walker, B.
Rasmussen, D.
Raskind, M.
Koob, G.
TI THE EFFECT OF ALPHA-1 ADRENERGIC RECEPTOR ANTAGONISM ON EXCESSIVE
ALCOHOL SELF-ADMINISTRATION DURING ACUTE WITHDRAWAL IN DEPENDENT
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Walker, B.] Washington State Univ, Pullman, WA 99164 USA.
[Rasmussen, D.; Raskind, M.] VA Puget Sound Hlth Care Syst, Seattle, WA USA.
[Rasmussen, D.; Raskind, M.] Univ Washington, Seattle, WA 98195 USA.
[Koob, G.] Scripps Res Inst, La Jolla, CA 92037 USA.
RI koob, george/P-8791-2016
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
BP 311A
EP 311A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335101196
ER
PT J
AU Rasmussen, DD
Federoff, D
Froehlich, JC
AF Rasmussen, D. D.
Federoff, D.
Froehlich, J. C.
TI PRAZOSIN REDUCES VOLUNTARY ALCOHOL DRINKING IN BOTH NON-DEPRIVED AND
ALCOHOL-DEPRIVED RATS SELECTIVELY BRED FOR ALCOHOL PREFERENCE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Rasmussen, D. D.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA.
[Federoff, D.; Froehlich, J. C.] Indiana Univ, Sch Med, Indianapolis, IN 46202 USA.
NR 0
TC 2
Z9 2
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
BP 312A
EP 312A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335101197
ER
PT J
AU Simpson, TL
Saxon, AJ
Meredith, CW
Malte, CA
McBride, B
Ferguson, LC
Gross, CA
Hart, KL
Raskind, M
AF Simpson, T. L.
Saxon, A. J.
Meredith, C. W.
Malte, C. A.
McBride, B.
Ferguson, L. C.
Gross, C. A.
Hart, K. L.
Raskind, M.
TI A PILOT TRIAL OF THE ALPHA-1 ADRENERGIC ANTAGONIST, PRAZOSIN, FOR
ALCOHOL DEPENDENCE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Simpson, T. L.; Saxon, A. J.; Meredith, C. W.; Malte, C. A.; McBride, B.; Ferguson, L. C.; Gross, C. A.; Hart, K. L.; Raskind, M.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
BP 312A
EP 312A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335101198
ER
PT J
AU Gheorghiade, M
Adams, KF
Cleland, JGF
Cotter, G
Felker, GM
Filippatos, GS
Fonarow, GC
Greenberg, BH
Hernandez, AF
Khan, S
Komajda, M
Konstam, MA
Liu, PP
Maggioni, AP
Massie, BM
McMurray, JJ
Mehra, M
Metra, M
O'Connell, J
O'Connor, CM
Pang, PS
Pina, IL
Sabbah, HN
Teerlink, JR
Udelson, JE
Yancy, CW
Zannad, F
Stockbridge, N
AF Gheorghiade, Mihai
Adams, Kirkwood F.
Cleland, John G. F.
Cotter, Gad
Felker, G. Michael
Filippatos, Gerasimos S.
Fonarow, Gregg C.
Greenberg, Barry H.
Hernandez, Adrian F.
Khan, Sadiya
Komajda, Michel
Konstam, Marvin A.
Liu, Peter P.
Maggioni, Aldo P.
Massie, Barry M.
McMurray, John J.
Mehra, Mandeep
Metra, Marco
O'Connell, John
O'Connor, Christopher M.
Pang, Peter S.
Pina, Ileana L.
Sabbah, Hani N.
Teerlink, John R.
Udelson, James E.
Yancy, Clyde W.
Zannad, Faiez
Stockbridge, Norman
CA Acute Heart Failure Syndromes Int
TI Phase III clinical trial end points in acute heart failure syndromes: A
virtual roundtable with the acute heart failure syndromes international
working group
SO AMERICAN HEART JOURNAL
LA English
DT Editorial Material
C1 [Gheorghiade, Mihai; Khan, Sadiya; O'Connell, John; Pang, Peter S.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Adams, Kirkwood F.] Univ N Carolina, Chapel Hill, NC USA.
[Cleland, John G. F.] Univ Hull, Castle Hill Hosp, Kingston Upon Hull, Yorks, England.
[Cotter, Gad] Momentum Res Inc, Durham, NC USA.
[Felker, G. Michael; Hernandez, Adrian F.; O'Connor, Christopher M.] Duke Univ, Med Ctr, Durham, NC USA.
[Filippatos, Gerasimos S.] Univ Athens, Athens, Greece.
[Fonarow, Gregg C.] Univ Calif Los Angeles, Los Angeles Med Ctr, Los Angeles, CA USA.
[Greenberg, Barry H.] Univ Calif San Diego, San Diego, CA 92103 USA.
[Komajda, Michel] Univ Paris 06, Paris, France.
[Komajda, Michel] Hosp Pitie Salpetriere, Paris, France.
[Konstam, Marvin A.] Tufts Med Ctr, Boston, MA USA.
[Liu, Peter P.] UHN, Toronto Gen Hosp, Toronto, ON, Canada.
[Maggioni, Aldo P.] Assoc Nazl Med Cardiol Osped, Florence, Italy.
[Massie, Barry M.] San Francisco VA Med Ctr, San Francisco, CA USA.
[McMurray, John J.] Univ Glasgow, British Heart Fdn, Glasgow Cardiovasc Res Ctr, Glasgow, Lanark, Scotland.
[Mehra, Mandeep] Univ Maryland, Med Ctr, Baltimore, MD 21201 USA.
[Metra, Marco] Univ Brescia, Brescia, Italy.
[Pina, Ileana L.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Sabbah, Hani N.] Henry Ford Hosp, Henry Ford Heart & Vasc Inst, Detroit, MI 48202 USA.
[Teerlink, John R.] Univ Calif San Francisco, Vet Adm Med Ctr, San Francisco, CA USA.
[Yancy, Clyde W.] Baylor Heart & Vasc Inst, Dallas, TX USA.
[Zannad, Faiez] INSERM, Nancy, France.
[Stockbridge, Norman] US FDA, Silver Spring, MD USA.
RP Gheorghiade, M (reprint author), Northwestern Univ, Feinberg Sch Med, 676 N St Clair St,Suite 600, Chicago, IL 60611 USA.
EM m-gheorghiade@northwestern.edu
RI Teerlink, John/D-2986-2012; Lainscak, Mitja/F-3237-2015; Hernandez,
Adrian F./A-7818-2016;
OI Mehra, Mandeep/0000-0001-8683-7044; Hernandez, Adrian
F./0000-0003-3387-9616; Cleland, John/0000-0002-1471-7016; Metra,
Marco/0000-0001-6691-8568; mcmurray, john/0000-0002-6317-3975
NR 0
TC 37
Z9 37
U1 0
U2 0
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 JUN
PY 2009
VL 157
IS 6
BP 957
EP 970
DI 10.1016/j.ahj.2009.04.010
PG 14
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 454GD
UT WOS:000266669500002
PM 19464405
ER
PT J
AU Dokholyan, RS
Muhlbaier, LH
Falletta, JM
Jacobs, JP
Shahian, D
Haan, CK
Peterson, ED
AF Dokholyan, Rachel S.
Muhlbaier, Lawrence H.
Falletta, John M.
Jacobs, Jeffrey P.
Shahian, David
Haan, Constance K.
Peterson, Eric D.
TI Regulatory and ethical considerations for linking clinical and
administrative databases
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID HEALTH-CARE; IMPROVEMENT; QUALITY; PRIVACY; HIPAA
AB Clinical data registries are valuable tools that support evidence development, performance assessment, comparative effectiveness studies, and the adoption of new treatments into routine clinical practice. Although these registries do not have important information on long-term therapies or clinical events, administrative claims databases offer a potentially valuable complement. This article focuses on the regulatory and ethical considerations that arise from the use of registry data for research, including linkage of clinical and administrative data sets. (1) Are such activities primarily designed for quality assessment and improvement, research, or both, as this determines the appropriate ethical and regulatory standards? (2) Does the submission of data to a central registry, which may subsequently be linked to other data sources, require review by the institutional review board (IRB) of each participating organization? (3) What levels and mechanisms of IRB oversight are appropriate for the existence of a linked central data repository and the specific studies that may subsequently be developed using it? (4) Under what circumstances are waivers of informed consent and Health Insurance Portability and Accountability Act authorization required? (5) What are the requirements for a limited data set that would qualify a research activity as not involving human subjects and thus not subject to further IRB review? The approaches outlined in this article represent a local interpretation of the regulations in the context of several clinical data registry projects and focuses on a specific case study of the Society of Thoracic Surgeons National Database. (Am Heart J 2009;157:971-82.)
C1 [Dokholyan, Rachel S.; Muhlbaier, Lawrence H.; Peterson, Eric D.] Duke Clin Res Inst, Durham, NC 27705 USA.
[Falletta, John M.] Duke Univ, Sch Med, Durham, NC USA.
[Jacobs, Jeffrey P.] CHIF, St Petersburg, FL USA.
[Jacobs, Jeffrey P.] CHIF, Tampa, FL USA.
[Shahian, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
[Haan, Constance K.] Univ Florida, Coll Med, Jacksonville, FL USA.
RP Dokholyan, RS (reprint author), Duke Clin Res Inst, Room 0311 Terrace Level,2400 Pratt St, Durham, NC 27705 USA.
EM rachel.dokholyan@duke.edu
NR 20
TC 45
Z9 45
U1 2
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 JUN
PY 2009
VL 157
IS 6
BP 971
EP 982
DI 10.1016/j.ahj.2009.03.023
PG 12
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 454GD
UT WOS:000266669500003
PM 19464406
ER
PT J
AU Forman, DE
Cannon, CP
Hernandez, AF
Liang, L
Yancy, C
Fonarow, GC
AF Forman, Daniel E.
Cannon, Christopher P.
Hernandez, Adrian F.
Liang, Li
Yancy, Clyde
Fonarow, Gregg C.
CA Get Guidelines Steering Comm Hosp
TI Influence of age on the management of heart failure: Findings from Get
With the Guidelines-Heart Failure (GWTG-HF)
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS; INITIATE LIFESAVING TREATMENT;
ACUTE MYOCARDIAL-INFARCTION; EARLY INVASIVE MANAGEMENT; ACUTE CORONARY
SYNDROMES; QUALITY-OF-CARE; HOSPITALIZED-PATIENTS; ORGANIZED PROGRAM;
OPTIMIZE-HF; PART II
AB Background Heart failure (HF) is common among elderly adults. Although multiple studies demonstrate age-related declines in the utilization of evidence-based therapies for coronary artery disease, there are few analyses of HF patients to distinguish possible age-related management differences.
Methods We analyzed 57,937 HF admissions from January 2005 through April 2007 in 257 hospitals participating in the American Heart Association's Get With The Guidelines-Heart Failure program. Patient characteristics and management were stratified by age groups <= 65, 66-75, 76-85, and >85 years. Multivariable regression analyses were used to assess the influence of age on use of therapies and inhospital mortality.
Results The mean patient age was 73 +/- 14 years; 18.7% were >85 years of age. Prescriptions of most HF therapies were relatively reduced with age but still remained high overall. Although 88.6% of patients <= 65 years of age with left ventricular systolic dysfunction were prescribed angiotensin-converting enzyme inhibitor or angiotensin receptor blacker and 90.9% were prescribed beta-blockers, among those >85 years of age with left ventricular systolic dysfunction, 79% were prescribed angiotensin-converting enzyme inhibitor or angiotensin receptor blacker and 82.7% were prescribed beta-blockers. Regression analysis that accounted for typical confounders demonstrated that older age was associated with diminished utilization of most evidence-based treatment measures as well as increased mortality.
Conclusions Get With The Guidelines-Heart Failure data demonstrate that guidelines recommended therapies are frequently utilized for older patients with HF, including patients >85 years old. Nonetheless, age-related differences in therapy persist, suggesting that opportunities to improve care still remain. (Am Heart J 2009; 157:1010-7.)
C1 [Forman, Daniel E.; Cannon, Christopher P.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.
[Forman, Daniel E.] VA Boston Healthcare Syst, Boston, MA USA.
[Hernandez, Adrian F.] Duke Univ, Med Ctr, Durham, NC USA.
[Liang, Li] Duke Clin Res Inst, Durham, NC USA.
[Yancy, Clyde] Baylor Univ, Med Ctr, Baylor Heart & Vasc Inst, Dallas, TX USA.
[Fonarow, Gregg C.] Univ Calif Los Angeles, Ahmanson UCLA Cardiomyopathy Ctr, Los Angeles, CA USA.
RP Forman, DE (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA.
EM deforman@partners.org
RI Hernandez, Adrian F./A-7818-2016
OI Hernandez, Adrian F./0000-0003-3387-9616
NR 28
TC 30
Z9 31
U1 0
U2 1
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 JUN
PY 2009
VL 157
IS 6
BP 1010
EP 1017
DI 10.1016/j.ahj.2009.03.010
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 454GD
UT WOS:000266669500008
PM 19464411
ER
PT J
AU Sorensen, SV
Dewilde, S
Singer, DE
Goldhaber, SZ
Monz, BU
Plumb, JM
AF Sorensen, Sonja V.
Dewilde, Sarah
Singer, Daniel E.
Goldhaber, Samuel Z.
Monz, Brigitta U.
Plumb, Jonathan M.
TI Cost-effectiveness of warfarin: Trial versus "real-world" stroke
prevention in atrial fibrillation
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID ANTITHROMBOTIC THERAPY; ISCHEMIC-STROKE; ORAL ANTICOAGULATION;
CLINICAL-PRACTICE; HEART-DISEASE; RISK; METAANALYSIS; ASPIRIN;
INTENSITY; PROPHYLAXIS
AB Background and Purpose Previous cost-effectiveness analyses analyzed warfarin for stroke prevention in randomized trial settings. Given the complexities of warfarin treatment, cost-effectiveness should be examined within a real-world setting.
Methods Our model followed patients with atrial fibrillation at moderate to high risk of stroke through primary and recurrent ischemic stroke, hemorrhages-intracranial and extracranial, and the resulting disability. Four scenarios were examined: (1) all patients start on warfarin with perfect control, that is, international normalized ratio (INR) values always within range; (2) all patients start on warfarin with trial-like control, where INR can fall outside the recommended range; (3) all patients start on warfarin with real-world INR control; and (4) real-world prescription (and control) of warfarin, aspirin, or neither for warfarin-eligible patients. Reported warfarin discontinuation rates were used. Main outcomes were total number of events, quality adjusted life years, and costs in a US setting.
Results The total number of primary and recurrent ischemic strokes in a 1000-patient cohort (age 70 years, lifetime analysis) was 626, 832, 984, and 1,171 in scenarios 1 to 4, respectively. The corresponding mean quality adjusted life years per patient were 7.21, 6.92, 6.75, and 6.67 for scenarios 1 to 4, respectively. Costs per patient were $68,039, $77,764, $84,518, and $87,248 in scenarios 1 to 4, respectively. If "perfect" adherence to warfarin was assumed, except for discontinuations for clinical reasons, strokes would decrease to 503, 737, 909, and 1,120 in scenarios 1 to 4, respectively.
Conclusions Clinical and cost outcomes are strongly dependent on the quality of anticoagulation and rates of warfarin discontinuation. Clinicians should work to improve both. Policy makers should use real-world INR control and warfarin discontinuation rates when assessing cost-effectiveness. (Am Heart J 2009; 157:1064-73.)
C1 [Sorensen, Sonja V.] United BioSource Corp, Bethesda, MD USA.
[Dewilde, Sarah] United BioSource Corp, Brussels, Belgium.
[Singer, Daniel E.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Singer, Daniel E.; Goldhaber, Samuel Z.] Harvard Univ, Sch Med, Boston, MA USA.
[Goldhaber, Samuel Z.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Monz, Brigitta U.; Plumb, Jonathan M.] Boehringer Ingelheim GmbH & Co KG, Ingelheim, Germany.
RP Sorensen, SV (reprint author), 7101 Wisconsin Ave,Suite 600, Bethesda, MD 20814 USA.
EM sonja.sorensen@unitedbiosource.com
NR 55
TC 40
Z9 41
U1 0
U2 1
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 JUN
PY 2009
VL 157
IS 6
BP 1064
EP 1073
DI 10.1016/j.ahj.2009.03.022
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 454GD
UT WOS:000266669500015
PM 19464418
ER
PT J
AU Mendez, MF
McMurtray, AM
Licht, EA
Saul, RE
AF Mendez, Mario F.
McMurtray, Aaron M.
Licht, Eliot A.
Saul, Ronald E.
TI Frontal-executive Versus Posterior-perceptual Mental Status Deficits in
Early-onset Dementias
SO AMERICAN JOURNAL OF ALZHEIMERS DISEASE AND OTHER DEMENTIAS
LA English
DT Article
DE dementia; Alzheimer's disease; vascular dementia; frontotemporal
dementia; frontal-executive functions; perceptual disturbances
ID FRONTOTEMPORAL LOBAR DEGENERATION; DIAGNOSED PRESENILE-DEMENTIA;
ISCHEMIC VASCULAR DEMENTIA; ALZHEIMERS-DISEASE; ASSESSMENT BATTERY;
NEUROPSYCHOLOGICAL FEATURES; CLINICAL CHARACTERISTICS; COGNITIVE
IMPAIRMENT; PREVALENCE; MEMORY
AB Background: Compared to late-onset dementias, early-onset dementias (EODs) may have greater focal cognitive involvement with differences in frontal-executive compared to posterior-perceptual deficits. Objective: This study evaluated whether mental status screening based on this frontal-posterior axis can distinguish EODs. Methods: Twenty-three patients each with early-onset Alzheimer's disease (eAD), frontotemporal dementia (FTD), or subcortical ischemic vascular disease (SIVD), and 20 normal controls underwent the Frontal Assessment Battery (FAB) and the Perceptual Assessment Battery (PAB). Results: Compared to controls, SIVD and FTD groups were impaired on the FAB whereas eAD and SIVD groups were impaired on the PAB. The FAB/PAB ratio further differentiated the groups (F(3,85) = 26.49, P < .001). For sensitivities and specificities of 93%, a cut-off score of 1.25 on the FAB/PAB distinguished eAD, and a cut-off of 0.83 distinguishing FTD. Conclusion: Although preliminary, this study indicates that mental status screening based on frontal versus posterior cortical functions may help clinicians diagnose EODs.
C1 [Mendez, Mario F.; McMurtray, Aaron M.; Licht, Eliot A.] VA Greater Los Angeles Healthcare Syst, Dept Neurol, Neurobehav Unit, Los Angeles, CA 90073 USA.
[Mendez, Mario F.; McMurtray, Aaron M.; Saul, Ronald E.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
RP Mendez, MF (reprint author), VA Greater Los Angeles Healthcare Syst, Neurobehav Unit 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
EM mmendez@ucla.edu
NR 56
TC 5
Z9 5
U1 1
U2 4
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1533-3175
J9 AM J ALZHEIMERS DIS
JI Am. J. Alzheimers Dis. Other Dement.
PD JUN-JUL
PY 2009
VL 24
IS 3
BP 220
EP 227
DI 10.1177/1533317509332626
PG 8
WC Geriatrics & Gerontology; Clinical Neurology
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 464NL
UT WOS:000267511700005
PM 19329784
ER
PT J
AU Baruch, L
Agarwal, S
Gupta, B
Haynos, A
Eng, C
AF Baruch, Lawrence
Agarwal, Sanjay
Gupta, Bhanu
Haynos, Ann
Eng, Calvin
TI Effect on Serum Lipid Levels of Switching Dose of Ezetimibe from 10 to 5
mg
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID CHOLESTEROL ABSORPTION INHIBITOR; TREATMENT PANEL-III; PRIMARY
HYPERCHOLESTEROLEMIA; CLINICAL-TRIALS; TOLERABILITY
AB Although during its initial development, lower doses of ezetimibe reduced low-density lipoprotein (LDL) significantly, ezetimibe is available only in 10-mg form. Compliant patients receiving ezetimibe 10 mg were randomized in a blinded fashion to continue therapy with ezetimibe 10 mg or to convert to a split-tablet 5-mg dose. Lipid panels were collected at baseline and after 4 weeks of therapy. The impact of the 2 ezetimibe dosing strategies on LDL and the achievement of the Adult Treatment Panel III LDL goal was evaluated. One hundred thirty patients receiving ezetimibe 10 mg were screened for eligibility. Thirty-nine of the 130 patients were randomized; 36 patients successfully completed the study. All patients who had achieved their Adult Treatment Panel III LDL goals at baseline remained at their LDL goals after conversion to 5 mg. In conclusion, conversion to the lower dose of ezetimibe did not result in any clinically meaningful or statistically significant changes in any lipid parameter. (C) 2009 Published by Elsevier Inc. (Am J Cardiol 2009;103:1568-1571)
C1 [Baruch, Lawrence; Agarwal, Sanjay; Gupta, Bhanu; Haynos, Ann; Eng, Calvin] James J Peters Vet Affairs Med Ctr, Bronx, NY USA.
[Baruch, Lawrence; Agarwal, Sanjay; Gupta, Bhanu; Eng, Calvin] Mt Sinai Sch Med, New York, NY USA.
RP Baruch, L (reprint author), James J Peters Vet Affairs Med Ctr, Bronx, NY USA.
EM lawrence.baruch@va.gov
NR 10
TC 1
Z9 1
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 JUN 1
PY 2009
VL 103
IS 11
BP 1568
EP 1571
DI 10.1016/j.amjcard.2009.01.365
PG 4
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 456ZR
UT WOS:000266894300015
PM 19463517
ER
PT J
AU Aizer, A
Gaziano, JM
Cook, NR
Manson, JE
Buring, JE
Albert, CM
AF Aizer, Anthony
Gaziano, J. Michael
Cook, Nancy R.
Manson, Joann E.
Buring, Julie E.
Albert, Christine M.
TI Relation of Vigorous Exercise to Risk of Atrial Fibrillation
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID LONG-DISTANCE RUNNERS; PHYSICAL-ACTIVITY; SPORT PRACTICE; FOLLOW-UP;
ABLATION; ASPIRIN; TONE; MEN
AB Limited data suggest that athletes may have a higher risk of developing atrial fibrillation (AF); however, there has been no large prospective assessment of the relation between vigorous exercise and AF. Logistic regression analyses stratified by time were used to assess the association between frequency of vigorous exercise and risk of developing AF in 16,921 apparently healthy men in the Physicians' Health Study. During 12 years of follow-up, 1,661 men reported developing AF. With increasing frequency of vigorous exercise (0, 1, 1 to 2, 3 to 4, 5 to 7 days/week), multivariate relative risks for the full cohort were 1.0 (referent), 0.90, 1.09, 1.04, and 1.20 (p = 0.04). This risk was not significantly increased when exercise habits were updated or in models excluding variables that may be in the biological pathway through which exercise influences AF risk. In subgroup analyses, this increased risk was observed only in men <50 years of age (1.0, 0.94, 1.20, 1.05, 1.74, p <0.01) and joggers (1.0, 0.91, 1.03, 1.30, 1.53, p <0.01), where risks remained increased in all analyses. In conclusion, frequency of vigorous exercise was associated with an increased risk of developing AF in young men and joggers. This risk decreased as the population aged and was offset by known beneficial effects of vigorous exercise on other AF risk factors. (C) 2009 Elsevier Inc. (Am J Cardiol 2009;103:1572-1577)
C1 [Aizer, Anthony; Albert, Christine M.] Brigham & Womens Hosp, Dept Med, Ctr Arrhythmia Prevent, Boston, MA 02115 USA.
[Aizer, Anthony; Gaziano, J. Michael; Cook, Nancy R.; Manson, Joann E.; Buring, Julie E.; Albert, Christine M.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA.
[Gaziano, J. Michael; Albert, Christine M.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02115 USA.
[Gaziano, J. Michael; Buring, Julie E.] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA.
[Gaziano, J. Michael] MAVERIC, VA Boston Healthcare Syst, Boston, MA USA.
[Buring, Julie E.] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA.
[Cook, Nancy R.; Manson, Joann E.; Buring, Julie E.; Albert, Christine M.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Aizer, Anthony] NYU, Med Ctr, Dept Med, Leon H Charney Div Cardiol, New York, NY 10016 USA.
RP Aizer, A (reprint author), Brigham & Womens Hosp, Dept Med, Ctr Arrhythmia Prevent, 75 Francis St, Boston, MA 02115 USA.
EM anthony.aizer@nyumc.org
OI Aizer, Anthony/0000-0001-6550-0178
FU NCI NIH HHS [R01 CA097193, CA097193, CA34944, CA40360, R01 CA040360, R01
CA040360-17, R01 CA047988, R01 CA097193-07]; NHLBI NIH HHS [HL26490,
HL34595, R01 HL043851]
NR 23
TC 120
Z9 125
U1 2
U2 12
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 JUN 1
PY 2009
VL 103
IS 11
BP 1572
EP 1577
DI 10.1016/j.amjcard.2009.01.374
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 456ZR
UT WOS:000266894300016
PM 19463518
ER
PT J
AU Shea, MK
O'Donnell, CJ
Hoffmann, U
Dallal, GE
Dawson-Hughes, B
Ordovas, JM
Price, PA
Williamson, MK
Booth, SL
AF Shea, M. Kyla
O'Donnell, Christopher J.
Hoffmann, Udo
Dallal, Gerard E.
Dawson-Hughes, Bess
Ordovas, Jose M.
Price, Paul A.
Williamson, Matthew K.
Booth, Sarah L.
TI Vitamin K supplementation and progression of coronary artery calcium in
older men and women
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID MATRIX GLA PROTEIN; GAMMA-CARBOXYGLUTAMIC ACID; VASCULAR CALCIFICATION;
ASYMPTOMATIC SUBJECTS; POSTMENOPAUSAL WOMEN; ATHEROSCLEROSIS MESA;
COMPUTED-TOMOGRAPHY; RISK-FACTORS; WARFARIN; ATORVASTATIN
AB Background: Coronary artery calcification (CAC) is an independent predictor of cardiovascular disease. A preventive role for vitamin K in CAC progression has been proposed on the basis of the properties of matrix Gla protein (MGP) as a vitamin K-dependent calcification inhibitor.
Objective: The objective was to determine the effect of phylloquinone (vitamin K1) supplementation on CAC progression in older men and women.
Design: CAC was measured at baseline and after 3 y of follow-up in 388 healthy men and postmenopausal women; 200 received a multivitamin with 500 mu g phylloquinone/d (treatment), and 188 received a multivitamin alone (control).
Results: In an intention-to-treat analysis, there was no difference in CAC progression between the phylloquinone group and the control group; the mean (+/- SEM) changes in Agatston scores were 27 +/- 6 and 37 +/- 7, respectively. In a subgroup analysis of participants who were >= 85% adherent to supplementation (n = 367), there was less CAC progression in the phylloquinone group than in the control group (P = 0.03). Of those with preexisting CAC (Agatston score > 10), those who received phylloquinone supplements had 6% less progression than did those who received the multivitamin alone (P = 0.04). Phylloquinone-associated decreases in CAC progression were independent of changes in serum MGP. MGP carboxylation status was not determined.
Conclusions: Phylloquinone supplementation slows the progression of CAC in healthy older adults with preexisting CAC, independent of its effect on total MGP concentrations. Because our data are hypothesis-generating, further studies are warranted to clarify this mechanism. This trial was registered at clinicaltrials. gov as NCT00183001. Am J Clin Nutr 2009; 89: 1799-807.
C1 [Shea, M. Kyla; Dawson-Hughes, Bess; Ordovas, Jose M.; Booth, Sarah L.] Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
[O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Bethesda, MD USA.
[O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Hoffmann, Udo] Massachusetts Gen Hosp, CIMIT, Boston, MA 02114 USA.
[Price, Paul A.; Williamson, Matthew K.] Univ Calif San Diego, Div Biol Sci, San Diego, CA 92103 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 Ordovas, Jose/0000-0002-7581-5680
FU US Department of Agriculture, Agricultural Research Service
[58-1950-7-707]; National Institutes of Health [AG14759, HL69272,
T32HL69772]; American Heart Association [0515605T]
FX Supported by the US Department of Agriculture, Agricultural Research
Service, under Cooperative Agreement no. 58-1950-7-707; National
Institutes of Health (AG14759, HL69272, and T32HL69772); and the
American Heart Association (0515605T).
NR 37
TC 65
Z9 67
U1 0
U2 1
PU AMER SOC CLINICAL NUTRITION
PI BETHESDA
PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998
USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD JUN 1
PY 2009
VL 89
IS 6
BP 1799
EP 1807
DI 10.3945/ajcn.2008.27338
PG 9
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 448EI
UT WOS:000266245500014
PM 19386744
ER
PT J
AU Shaikh, S
Van Cott, EM
AF Shaikh, Salima
Van Cott, Elizabeth M.
TI The Effect of Argatroban on Activated Protein C Resistance
SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY
LA English
DT Article
DE Argatroban; Anticoagulation; Activated protein C resistance;
Interference
ID FACTOR-V-LEIDEN; LUPUS ANTICOAGULANTS; THROMBOSIS; THERAPY; RISK
AB Activated protein C (APC) resistance is commonly tested in hypercoagulation evaluations, and argatroban is an anticoagulant therapy used in hypercoagulable patients. The effect of argatroban on APC resistance testing is unknown. We studied 100 ex vivo specimens from 44 patients treated with argatroban. Argatroban increased the APC resistance ratio in all but 1 patient. The effect was seen even in the specimens containing subtherapeutic argatroban levels. For patients without APC resistance, the mean APC resistance ratio significantly increased from 2.43 without argatroban to 3.10 with argatroban. For patients with APC resistance due to factor V Leiden, argatroban significantly increased the mean ratio from 1.73 to 2.13, falsely raising it into the normal range (> 2). Argatroban increases the APC resistance ratio, which can mask a diagnosis of APC resistance and, therefore, factor V Leiden. Clinicians should be advised that APC resistance testing for patients receiving argatroban is not valid.
C1 [Van Cott, Elizabeth M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Van Cott, EM (reprint author), Massachusetts Gen Hosp, Dept Pathol, Gray Jackson 235,55 Fruit St, Boston, MA 02114 USA.
NR 13
TC 8
Z9 8
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 JUN
PY 2009
VL 131
IS 6
BP 828
EP 833
DI 10.1309/AJCPVMUS77ZMBEHJ
PG 6
WC Pathology
SC Pathology
GA 448CB
UT WOS:000266238600012
PM 19461089
ER
PT J
AU de Fucio, SBP
Puppin-Rontani, RM
de Carvalho, FG
Mattos-Graner, RD
Correr-Sobrinho, L
Garcia-Godoy, F
AF Portugal de Fucio, Suzana Beatriz
Puppin-Rontani, Regina Maria
de Carvalho, Fabiola Galbiatti
Mattos-Graner, Renata de Oliveira
Correr-Sobrinho, Lourenco
Garcia-Godoy, Franklin
TI Analyses of biofilms accumulated on dental restorative materials
SO AMERICAN JOURNAL OF DENTISTRY
LA English
DT Article
ID LASER-SCANNING MICROSCOPY; GLASS-IONOMER CEMENTS; STREPTOCOCCUS-MUTANS;
IN-VITRO; ANTIBACTERIAL ACTIVITY; SPATIAL-DISTRIBUTION; CONFOCAL
MICROSCOPY; PLAQUE-FORMATION; BACTERIA; COMPOSITE
AB Purpose: To qualitatively and quantitatively assess the architectural arrangement of microorganisms in biofilm developed on the surface of different restorative materials: ceramic (C), resin composite (RC), conventional (CGIC) and resin-modified glass-ionomer cements (RMGIC). Methods: Streptococcus mutans was used to develop a biofilm that adhered to the surfaces of the selected material disks in 30 days. The specimens were stained and analyzed by confocal laser scanning microscopy and COMSTAT. Among biofilm properties, mean thickness, total bio-volume, roughness coefficient and surface-to-volume ratio were investigated, as well as characteristics of the distribution and architecture of viable/nonviable cells in the biofilm. Results: Only the mean biofilm thickness was statistically significantly different among the restorative materials tested. C and RC accumulated the thickest biofilms. Qualitative analysis showed cellular aggregates and fluid-filled channels penetrating to a considerable depth of the biofilm. In addition, images demonstrated a progression of more viable cells in superficial regions of the biofilm to proportionally more nonviable cells in the deeper regions of the biofilms near the disk. (Am J Dent 2009;22:131-136).
C1 [Puppin-Rontani, Regina Maria] Univ Estadual Campinas, Piracicaba Dent Sch, Dept Pediat Dent, UNICAMP, BR-13414018 Piracicaba, SP, Brazil.
[Puppin-Rontani, Regina Maria] Univ Estadual Campinas, Piracicaba Dent Sch, Pre & Postgrad Program Dent Mat, BR-13414018 Piracicaba, SP, Brazil.
[Portugal de Fucio, Suzana Beatriz; de Carvalho, Fabiola Galbiatti] Univ Estadual Campinas, Piracicaba Dent Sch, Dent Mat Program, BR-13414018 Piracicaba, SP, Brazil.
[Mattos-Graner, Renata de Oliveira] Univ Estadual Campinas, Piracicaba Dent Sch, Dept Microbiol & Immunol, BR-13414018 Piracicaba, SP, Brazil.
[Correr-Sobrinho, Lourenco] Univ Estadual Campinas, Piracicaba Dent Sch, Dept Operat Dent, BR-13414018 Piracicaba, SP, Brazil.
[Garcia-Godoy, Franklin] Univ Tennessee, Coll Dent, Biosci Res Ctr, Memphis, TN USA.
[Garcia-Godoy, Franklin] Forsyth Inst, Boston, MA USA.
RP Puppin-Rontani, RM (reprint author), Univ Estadual Campinas, Piracicaba Dent Sch, Dept Pediat Dent, UNICAMP, Av Limeira 901, BR-13414018 Piracicaba, SP, Brazil.
EM rmpuppin@fop.unicamp.br
RI PUPPIN-RONTANI, regina/C-3994-2012; Mattos-Graner, Renata/C-9410-2012
OI PUPPIN-RONTANI, regina/0000-0002-1218-5159; Mattos-Graner,
Renata/0000-0001-8309-8135
FU CAPES (Coordenacao de Aperfeicoamento Profissional de Nivel Superior)
FX The research was Supported by CAPES (Coordenacao de Aperfeicoamento
Profissional de Nivel Superior). All authors claim no conflict of
interest.
NR 42
TC 9
Z9 9
U1 0
U2 7
PU MOSHER & LINDER, INC
PI WESTON
PA 318 INDIAN TRACE SUITE 500, WESTON, FL 33326 USA
SN 0894-8275
J9 AM J DENT
JI Am. J. Dent.
PD JUN
PY 2009
VL 22
IS 3
BP 131
EP 136
PG 6
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 475FM
UT WOS:000268344000001
PM 19650591
ER
PT J
AU Aspinall, SL
Good, CB
Metlay, JP
Mor, MK
Fine, MJ
AF Aspinall, Sherrie L.
Good, Chester B.
Metlay, Joshua P.
Mor, Maria K.
Fine, Michael J.
TI Antibiotic prescribing for presumed nonbacterial acute respiratory tract
infections
SO AMERICAN JOURNAL OF EMERGENCY MEDICINE
LA English
DT Article
CT National Annual Meeting of the
US-Department-of-Veterans-Affairs-Health-Services-Research-and-Developme
nt-Service
CY FEB, 2005
CL Baltimore, MD
SP US Dept Vet Affairs Hlth Serv Res & Dev Serv
ID ACUTE BRONCHITIS; STREPTOCOCCUS-PNEUMONIAE; EMERGENCY-DEPARTMENTS;
AMBULATORY PRACTICE; CARE PHYSICIANS; UNITED-STATES; ADULTS; TRENDS;
PREDICTORS; MANAGEMENT
AB Objective: The objective of the study was to identify patient and provider factors associated with prescribing antibiotics for outpatients with acute respiratory tract infections of likely nonbacterial etiology.
Methods: We identified outpatients who were diagnosed in the emergency department with nonspecific upper respiratory tract infections (URIs) and acute bronchitis at the VA Pittsburgh Healthcare System from June 15, 2003, to June 14, 2004, and the Philadelphia VA Medical Center from November 30, 2003, to March 31, 2004. Stepwise logistic regression was used to identify factors independently associated with antibiotic prescribing.
Results: Overall, 26% of the 667 eligible patients with URIs and/or acute bronchitis received antibiotics. Antibiotics were prescribed significantly more frequently for acute bronchitis at one site (97% vs 65%, P < .001). Using multivariable analysis, the following factors were independently associated with antibiotic prescribing (odds ratio, 95% confidence interval): presence of I or more comorbidities (2.1, 1.2-3.5), fever (2.5, 1.4-4.4), purulent sputum (2.5, 1.5-4.4), shortness of breath (2.8, 1.4-5.4), altered breath sounds (4.6, 2.4-8.6), diagnosis of acute bronchitis (15.9, 8.0-31.8), provider age >= 30 years (2.6, 1.1-6.3), and noninternal medicine specialty (2.7, 1.2-6.0).
Conclusions: Antibiotic use was high and varied substantially for URN and acute bronchitis. Specific signs and symptoms, a diagnosis of acute bronchitis, and provider age and specialty were associated with antibiotic prescribing. Interventions to decrease inappropriate prescribing should address the perceived utility of antibiotics in acute bronchitis and the accuracy of signs and symptoms in diagnosing a bacterial respiratory infection. Published by Elsevier Inc.
C1 [Aspinall, Sherrie L.; Good, Chester B.; Mor, Maria K.; Fine, Michael J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA.
[Aspinall, Sherrie L.; Good, Chester B.] VA Ctr Medicat Safety, Hines VA, Hines, IL 60141 USA.
[Aspinall, Sherrie L.] Univ Pittsburgh, Sch Pharm, Pittsburgh, PA 15261 USA.
[Good, Chester B.; Fine, Michael J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15261 USA.
[Metlay, Joshua P.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 19104 USA.
[Metlay, Joshua P.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Mor, Maria K.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA.
RP Aspinall, SL (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, 151C-H, Pittsburgh, PA 15206 USA.
EM sherrie.aspinall@va.gov
FU PHS HHS [5K24 A101769]
NR 31
TC 12
Z9 12
U1 2
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 0735-6757
J9 AM J EMERG MED
JI Am. J. Emerg. Med.
PD JUN
PY 2009
VL 27
IS 5
BP 544
EP 551
DI 10.1016/j.ajem.2008.04.015
PG 8
WC Emergency Medicine
SC Emergency Medicine
GA 457OH
UT WOS:000266940800005
PM 19497459
ER
PT J
AU Levin, SK
Metlay, JP
Maselli, JH
Kersey, AS
Camargo, CA
Gonzales, R
AF Levin, Sara K.
Metlay, Joshua P.
Maselli, Judith H.
Kersey, Ayanna S.
Camargo, Carlos A., Jr.
Gonzales, Ralph
CA IMPAACT Project Investigators
TI Perceived social support among adults seeking care for acute respiratory
tract infections in US EDs
SO AMERICAN JOURNAL OF EMERGENCY MEDICINE
LA English
DT Article
ID MULTIDIMENSIONAL SCALE; MEDICAL-CARE; COMMON COLD; EMERGENCY;
EXPERIENCE; ILLNESS; STRESS; HEALTH
AB Emergency departments (EDs) provide a disproportionate amount of care to disenfranchised and vulnerable populations. We examined social support levels among a diverse population of adults seeking ED care for acute respiratory tract infections. A convenience sample of adults seeking care in I of 15 US EDs was telephone interviewed 1 to 6 weeks postvisit. The Multidimensional Scale of Perceived Social Support (7-point Likert) assessed social support across 3 domains: friends, family, and significant others. Higher scores indicate higher support. Of 1104 subjects enrolled, 704 (64%) completed the follow-up interview. Factor analysis yielded 3 factors. Mean social support score was 5.54 (SD 1.04). Female sex, greater household income, and better health status were independently associated with higher levels of social support. Social support levels among adults seeking care in the ED for acute respiratory tract infections are similar to general population cohorts, suggesting that social support is not a strong determinant of health care seeking in EDs. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Levin, Sara K.; Maselli, Judith H.; Gonzales, Ralph] Univ Calif San Francisco, Dept Med, San Francisco, CA 94118 USA.
[Metlay, Joshua P.] Univ Penn, Sch Med, Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot,Dept Med, Philadelphia, PA 19104 USA.
[Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
RP Gonzales, R (reprint author), Univ Calif San Francisco, Dept Med, San Francisco, CA 94118 USA.
EM ralphg@medicine.ucsf.edu
FU Translating Research Into Practice Initiative; Agency for Healthcare
Research and Quality [1 R01 HS013915]; Health Services Research and
Development Service of the Department of Veteran Affairs [AVA-03-239]
FX This project was supported by the Translating Research Into Practice
Initiative, jointly sponsored by the Agency for Healthcare Research and
Quality (grant 1 R01 HS013915) and the Health Services Research and
Development Service of the Department of Veteran Affairs (AVA-03-239).
NR 18
TC 0
Z9 0
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 0735-6757
J9 AM J EMERG MED
JI Am. J. Emerg. Med.
PD JUN
PY 2009
VL 27
IS 5
BP 582
EP 587
DI 10.1016/j.ajem.2008.05.013
PG 6
WC Emergency Medicine
SC Emergency Medicine
GA 457OH
UT WOS:000266940800011
PM 19497465
ER
PT J
AU Freedland, SJ
Aronson, WJ
AF Freedland, Stephen J.
Aronson, William J.
TI Invited Commentary: Lower Urinary Tract Symptoms and Inflammation -
Weighing the Evidence
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Editorial Material
DE inflammation; prostate; urinary tract physiological phenomena
ID MEN
AB Lower urinary tract symptoms (LUTS) are a common condition, particularly among older men. The etiology of these symptoms is often obscure and not always clearly related to prostatic enlargement or benign prostatic hyperplasia. St. Sauver et al. (Am J Epidemiol. 2009;169(11):1281-1290) hypothesized that systemic inflammation may be associated with LUTS and benign prostatic hyperplasia. Using a well-defined cohort, they found that, in general, inflammation was not related to LUTS or to benign prostatic hyperplasia progression. However, men with the highest amount of systemic inflammation, as measured by C-reactive protein levels, were at increased risk of a rapid change in irritative voiding symptoms and decreased urinary flow but not obstructive voiding symptoms or prostate size. To what degree systemic inflammation relates to inflammation within the urinary system and specifically the bladder and/or prostate is unclear. Furthermore, to what degree inflammation within the urinary system contributes to LUTS is unclear. Given that clinical trials of antiinflammatory drugs for LUTS have been largely unsuccessful, the role of inflammation as a contributor to LUTS remains an interesting hypothesis that requires further study.
C1 [Freedland, Stephen J.] Durham VA Med Ctr, Dept Surg, Durham, NC USA.
[Freedland, Stephen J.] Duke Prostate Ctr, Durham, NC USA.
[Freedland, Stephen J.] Duke Univ, Med Ctr, Div Urol Surg, Dept Surg, Durham, NC 27710 USA.
[Freedland, Stephen J.] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA.
[Aronson, William J.] Greater Los Angeles VA Hlth Syst, Dept Surg, Los Angeles, CA USA.
[Aronson, William J.] Univ Calif Los Angeles, Med Ctr, Dept Urol, Los Angeles, CA 90024 USA.
RP Freedland, SJ (reprint author), Duke Univ, Med Ctr, Div Urol Surg, Dept Surg, Box 2626, Durham, NC 27710 USA.
EM steve.freedland@duke.edu
NR 8
TC 4
Z9 4
U1 0
U2 0
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 JUN 1
PY 2009
VL 169
IS 11
BP 1291
EP 1293
DI 10.1093/aje/kwp084
PG 3
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 446GF
UT WOS:000266109400002
PM 19395692
ER
PT J
AU Hassanein, T
Blei, AT
Perry, W
Hilsabeck, R
Stange, J
Larsen, FS
Brown, RS
Caldwell, S
McGuire, B
Nevens, F
Fontana, R
AF Hassanein, Tarek
Blei, Andres T.
Perry, William
Hilsabeck, Robin
Stange, Jan
Larsen, Fin S.
Brown, Robert S., Jr.
Caldwell, Stephen
McGuire, Brendan
Nevens, Frederik
Fontana, Robert
TI Performance of the Hepatic Encephalopathy Scoring Algorithm in a
Clinical Trial of Patients With Cirrhosis and Severe Hepatic
Encephalopathy
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Article
ID PORTAL-SYSTEMIC ENCEPHALOPATHY; DOUBLE-BLIND; ALBUMIN DIALYSIS;
FLUMAZENIL; PLACEBO; MULTICENTER; LACTULOSE; NEOMYCIN; COMA
AB OBJECTIVES: The grading of hepatic encephalopathy (HE) is based on a combination of indicators that reflect the state of consciousness, intellectual function, changes in behavior, and neuromuscular alterations seen in patients with liver failure.
METHODS: We modified the traditional West Haven criteria (WHC) to provide an objective assessment of the cognitive parameters to complement the subjective clinical ratings for the performance of extracorporeal albumin dialysis (ECAD) using a molecular adsorption recirculating system in patients with cirrhosis and severe (grade III/IV) encephalopathy. The HE Scoring Algorithm (HESA) combined clinical indicators with those derived from simple neuropsychological tests, the latter more often used in milder grades of HE (I/II). The performance of each indicator was compared across grades and sites.
RESULTS: Results of HESA were also compared with the Glasgow Coma Scale. A total of 597 evaluations were performed in patients randomized to ECAD plus standard medical therapy or the latter only. Most parameters exhibited significant separation between grades; the most effective indicators were lack of verbal, eye, and motor response (grade IV), somnolence and disorientation to place (grade III), and lethargy and disorientation to time (grade II). Two clinical and four neuropsychological indicators were useful to classify patients as grade I. The Glasgow Coma Scale differed among the four stages of the WHC, but the differences between grades I and II were small and not clinically useful.
CONCLUSION: HESA extends the traditional WHC for grading HE. In the absence of a "gold" standard, the most useful indicators noted in this trial should be further validated.
C1 [Hassanein, Tarek] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA.
[Blei, Andres T.] Northwestern Univ, Dept Med, Chicago, IL 60611 USA.
[Perry, William; Hilsabeck, Robin] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA.
[Hilsabeck, Robin] S Texas Vet Hlth Care Syst, Psychol Serv, San Antonio, TX USA.
[Hilsabeck, Robin] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA.
[Stange, Jan] Univ Rostock, Dept Internal Med, D-2500 Rostock, Germany.
[Larsen, Fin S.] Univ Copenhagen Hosp, Rigshosp, Dept Hepatol, DK-2100 Copenhagen, Denmark.
[Brown, Robert S., Jr.] Columbia Univ, Dept Med, New York, NY USA.
[Caldwell, Stephen] Univ Virginia, Dept Med, Charlottesville, VA USA.
[McGuire, Brendan] Univ Alabama, Dept Med, Birmingham, AL 35294 USA.
[Nevens, Frederik] Univ Hosp Gasthuisberg, Dept Hepatol, B-3000 Louvain, Belgium.
[Fontana, Robert] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.
RP Hassanein, T (reprint author), Univ Calif San Diego, Dept Med, 200 W Arbor Dr,MC 8423, San Diego, CA 92103 USA.
EM thassanein@ucsd.edu
OI Larsen, Fin Stolze/0000-0003-2205-8265
FU Teraklin
FX The authors acknowledge Dr Je C Gornbein from the Department of
Biostatistics at the University of California at Los Angeles for
invaluable statistical assistance. The authors also thank Fatma Barakat
and Deanna L. Oliver for their support in preparation of the manuscript.
This study was supported by research grants from Teraklin.
NR 29
TC 28
Z9 29
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0002-9270
J9 AM J GASTROENTEROL
JI Am. J. Gastroenterol.
PD JUN
PY 2009
VL 104
IS 6
BP 1392
EP 1400
DI 10.1038/ajg.2009.160
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 457DR
UT WOS:000266906900017
PM 19455117
ER
PT J
AU Khandwalla, HE
Fasakin, Y
El-Serag, HB
AF Khandwalla, Hashim E.
Fasakin, Yemi
El-Serag, Hashem B.
TI The Utility of Evaluating Low Serum Albumin Gradient Ascites in Patients
With Cirrhosis
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Article
ID PERITONITIS; DIAGNOSIS; PROTEIN; FLUID
AB OBJECTIVES: Serum-ascites albumin gradient (SAAG) has been used extensively in the diagnostic workup of patients with ascites. A SAAG level of <1.1 g/dl is usually thought of as a result of nonportal hypertension etiologies, including malignancies, tuberculous peritonitis, and nephrotic syndrome. However, the predictive value of a low SAAG in patients with existing cirrhosis in whom the pretest probability of portal hypertension is high is not clear.
METHODS: We identified all patients with a SAAG of <1.1 g/dl during a 5-year period at a single large veterans affairs medical center. Cirrhosis was defined by clinical, histological, and radiological features. Nonportal hypertension causes of low SAAG were identified, including bacterial peritonitis, peritoneal carcinomatosis, nephrogenous ascites, tuberculous peritonitis, chylous ascites, and pancreatic ascites.
RESULTS: We identified 92 patients (76 with cirrhosis and 16 with no cirrhosis) with ascites and a SAAG of <1.1 g/dl. Of the 76 patients with cirrhosis, only 29 (38%) had an identifiable cause, most commonly primary bacterial peritonitis (11, 38%), followed by peritoneal carcinomatosis or malignant ascites (8, 28%) and nephrotic syndrome (5, 17%). There were 47 patients with cirrhosis and a low SAAG for whom no etiology was identified. Thirty-three patients underwent a repeat paracentesis, 24 (73%) of whom changed to a high SAAG. On the other hand, the 16 patients with no cirrhosis had significantly lower SAAG (0.66 vs. 0.81), and most (12, 75 %) had an identifiable cause of ascites.
CONCLUSIONS: Evaluation of a SAAG <1.1 g/dl in patients with known cirrhosis has low yield and is less likely to be helpful than that in patients without cirrhosis. A repeat paracentesis as part of the workup is recommended. Further studies of low SAAG cutoffs are needed.
C1 [El-Serag, Hashem B.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX 77030 USA.
[Khandwalla, Hashim E.; Fasakin, Yemi; El-Serag, Hashem B.] Michael E DeBakey Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston, TX USA.
RP El-Serag, HB (reprint author), Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Gastroenterol Sect, 2002 Holcombe Blvd, Houston, TX 77030 USA.
EM hasheme@bcm.tmc.edu
FU Houston VA HSR&D Center of Excellence [HFP90-020]; NIH/NIDDK Center [P30
DK56338]; Dr El-Serag [K24DK078154-03]
FX This is work was supported in part by the Houston VA HSR&D Center of
Excellence (HFP90-020) and NIH/NIDDK Center Grant P30 DK56338. Dr
El-Serag is supported by NIH K24DK078154-03.
NR 15
TC 7
Z9 8
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0002-9270
J9 AM J GASTROENTEROL
JI Am. J. Gastroenterol.
PD JUN
PY 2009
VL 104
IS 6
BP 1401
EP 1405
PG 5
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 457DR
UT WOS:000266906900018
PM 19491852
ER
PT J
AU Lembo, AJ
Conboy, L
Kelley, JM
Schnyer, RS
McManus, CA
Quilty, MT
Kerr, CE
Drossman, D
Jacobson, EE
Davis, RB
Kaptchuk, TJ
AF Lembo, Anthony J.
Conboy, Lisa
Kelley, John M.
Schnyer, Rosa S.
McManus, Claire A.
Quilty, Mary T.
Kerr, Catherine E.
Drossman, Doug
Jacobson, Eric E.
Davis, Roger B.
Kaptchuk, Ted J.
TI A Treatment Trial of Acupuncture in IBS Patients
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Article
ID IRRITABLE-BOWEL-SYNDROME; RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE;
PLACEBO RUN-IN; LOW-BACK-PAIN; CLINICAL-TRIALS; ALTERNATIVE MEDICINE;
DIARRHEA-PREDOMINANT; END-POINT; ADEQUATE RELIEF
AB OBJECTIVES: This study aimed to compare the effects of true and sham acupuncture in relieving symptoms of irritable bowel syndrome (IBS).
METHODS: A total of 230 adult IBS patients (75% females, average age: 38.4 years) were randomly assigned to 3 weeks of true or sham acupuncture (6 treatments) after a 3-week "run-in" with sham acupuncture in an "augmented" or "limited" patient-practitioner interaction. A third arm of the study included a waitlist control group. The primary outcome was the IBS Global Improvement Scale (IBS-GIS) (range: 1-7); secondary outcomes included the IBS Symptom Severity Scale (IBS-SSS), the IBS Adequate Relief (IBS-AR), and the IBS Quality of Life (IBS-QOL).
RESULTS: Although there was no statistically significant difference between acupuncture and sham acupuncture on the IBS-GIS (41 vs. 32%, P=0.25), both groups improved significantly compared with the waitlist control group (37 vs. 4%, P=0.001). Similarly, small differences that were not statistically significant favored acupuncture over the other three outcomes: IBS-AR (59 vs. 57%, P=0.83), IBS-SSS (31 vs. 21%, P=0.18), and IBS-QOL (17 vs. 13%, P=0.56). Eliminating responders during the run-in period did not substantively change the results. Side effects were generally mild and only slightly greater in the acupuncture group.
CONCLUSIONS: This study did not find evidence to support the superiority of acupuncture compared with sham acupuncture in the treatment of IBS.
C1 [Lembo, Anthony J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Conboy, Lisa; Schnyer, Rosa S.; McManus, Claire A.; Quilty, Mary T.; Kerr, Catherine E.; Davis, Roger B.; Kaptchuk, Ted J.] Harvard Univ, Sch Med, Osher Res Ctr, Boston, MA USA.
[Kelley, John M.] Massachusetts Gen Hosp, Dept Psychol, Boston, MA 02114 USA.
[Kelley, John M.] Endicott Coll, Dept Math & Psychol, Beverly, MA USA.
[Drossman, Doug] Harvard Univ, Sch Med, Dept Social Med, Boston, MA 02115 USA.
[Jacobson, Eric E.] Univ N Carolina, Ctr Funct GI & Motil Disorders, Chapel Hill, NC USA.
RP Lembo, AJ (reprint author), 330 Brookline Ave,Rabb Rose 1, Boston, MA 02215 USA.
EM alembo@bidmc.harvard.edu
RI Kerr, Catherine/D-3299-2009
FU NCCIH NIH HHS [R21 AT002860, 1 R21 AT 002564, 1K24 AT 004095, 1R01 AT
001414-01, 1R21 AT 002860-01, K24 AT004095, R01 AT001414, R21
AT002860-02]; NCRR NIH HHS [M01 RR001032, RR 01032]
NR 47
TC 46
Z9 50
U1 1
U2 12
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0002-9270
EI 1572-0241
J9 AM J GASTROENTEROL
JI Am. J. Gastroenterol.
PD JUN
PY 2009
VL 104
IS 6
BP 1489
EP 1497
DI 10.1038/ajg.2009.156
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 457DR
UT WOS:000266906900030
PM 19455132
ER
PT J
AU Kastrinos, F
Allen, JI
Stockwell, DH
Stoffel, EM
Cook, EF
Mutinga, ML
Balmana, J
Syngal, S
AF Kastrinos, Fay
Allen, John I.
Stockwell, David H.
Stoffel, Elena M.
Cook, Earl F.
Mutinga, Muthoka L.
Balmana, Judith
Syngal, Sapna
TI Development and Validation of a Colon Cancer Risk Assessment Tool for
Patients Undergoing Colonoscopy
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Article
ID NONPOLYPOSIS COLORECTAL-CANCER; REVISED BETHESDA GUIDELINES; REGRESSION
TREE ANALYSIS; LYNCH-SYNDROME; MICROSATELLITE INSTABILITY;
FAMILY-HISTORY; COST-EFFECTIVENESS; SCORING SYSTEM; CHEST PAIN;
SURVEILLANCE
AB OBJECTIVES: Diagnostic criteria for hereditary colorectal cancer (CRC) are complex. "Open-access" colonoscopy makes it challenging to identify who needs genetic evaluation, intensive surveillance, and screening for extracolonic tumors. Our aim was to develop a simple, preprocedural risk assessment tool to identify who may be at highest risk for CRC.
METHODS: A total of 631 outpatients undergoing colonoscopy at two academic practices completed a questionnaire assessing personal and family histories of CRC, polyps, and Lynch syndrome (LS)-associated malignancies. Subjects were considered to be high-risk if one of the nine prespecified characteristics of hereditary CRC syndromes was met. Through recursive partitioning analysis, an algorithm of fewest questions needed to capture the most high-risk individuals was developed. The results were validated in 5,335 individuals undergoing colonoscopy at five private endoscopy centers and tested in 285 carriers of mismatch repair mutations associated with LS.
RESULTS: About 17.7% and 20.0% of individuals were classified as high-risk in the development and validation cohorts, respectively. Recursive partitioning revealed three questions that were most informative for identifying high-risk patients: (i) "Do you have a first-degree relative with CRC or LS-related cancer diagnosed before age 50?" (ii) "Have you had CRC or polyps diagnosed before age 50?" (iii) "Do you have >= 3 relatives with CRC?" When asked successively, these questions identified 77% of high-risk individuals in both cohorts and 271 of 285 (95%) of mutation carriers.
CONCLUSIONS: Approximately one in five individuals undergoing colonoscopy would benefit from further risk assessment. We developed a simple, three-question CRC Risk Assessment Tool to identify the majority of patients who require additional assessment and possible genetic evaluation.
C1 [Kastrinos, Fay; Stockwell, David H.; Stoffel, Elena M.; Syngal, Sapna] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA.
[Kastrinos, Fay] Columbia Univ, Med Ctr, Div Digest & Liver Dis, New York, NY USA.
[Allen, John I.] Minnesota Gastroenterol, Minneapolis, MN USA.
[Stockwell, David H.; Stoffel, Elena M.; Cook, Earl F.; Mutinga, Muthoka L.; Syngal, Sapna] Harvard Univ, Sch Med, Boston, MA USA.
[Stockwell, David H.; Mutinga, Muthoka L.] Faulkner Hosp, Div Gastroenterol, Boston, MA USA.
[Stoffel, Elena M.; Syngal, Sapna] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA.
[Cook, Earl F.] Harvard Univ, Sch Publ Hlth, Div Epidemiol, Boston, MA 02115 USA.
[Balmana, Judith] Univ Autonoma Barcelona, Hosp Vall Hebron, Dept Med Oncol, E-08193 Barcelona, Spain.
RP Syngal, S (reprint author), Dana Farber Canc Inst, Div Populat Sci, 1 Jimmy Fund Way,SM 209, Boston, MA 02115 USA.
EM fk18@columbia.edu; ssyngal@partners.org
FU NCI NIH HHS [K07 CA120448, K07 CA 120448-01A1, K24 CA 113433, K24
CA113433]
NR 42
TC 24
Z9 24
U1 1
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0002-9270
J9 AM J GASTROENTEROL
JI Am. J. Gastroenterol.
PD JUN
PY 2009
VL 104
IS 6
BP 1508
EP 1518
DI 10.1038/ajg.2009.135
PG 11
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 457DR
UT WOS:000266906900032
PM 19491864
ER
PT J
AU Castle, NG
Hanlon, JT
Handler, SM
AF Castle, Nicholas G.
Hanlon, Joseph T.
Handler, Steven M.
TI Results of a Longitudinal Analysis of National Data to Examine
Relationships Between Organizational and Market Characteristics and
Changes in Antipsychotic Prescribing in US Nursing Homes From 1996
Through 2006
SO AMERICAN JOURNAL OF GERIATRIC PHARMACOTHERAPY
LA English
DT Article
DE aged; antipsychotics; elderly; nursing homes; prescribing patterns
ID QUALITY-OF-CARE; RANDOMIZED-TRIAL; DRUG-USE; DEMENTIA; RESIDENTS;
PLACEBO; RISK; REGULATIONS; MEDICATIONS; RISPERIDONE
AB Objective: The aim of this work was to examine the association between organizational characteristics, market characteristics, and changes in antipsychotic medication use in US nursing homes over time.
Methods: This was a longitudinal study comparing antipsychotic use in US nursing homes from 1996 through 2006 using Medicare and Medicaid data (the Online Survey Certification And Reporting system) and US Department of Health and Human Resources Health Resources and Services Administration data (the Area Resource File). The 3 outcomes of interest were increasing, decreasing, or stable use of antipsychotic medications. The primary independent variables were organizational characteristics (eg, for-profit status, chain membership) and market characteristics (eg, Medicaid reimbursement, levels of competition).
Results: Antipsychotic use increased from 16.4% in 1996 to 25.9% in 2006 (P < 0.05). A multinomial generalized estimating equations model, controlling for facility, staffing, and resident factors, suggested that increased antipsychotic use was associated with for-profit facilities (adjusted odds ratio [AOR], 1.58; 95% CI, 1.51-1.65; P <= 0.001). Decreased antipsychotic use was associated with chain membership (AOR, 0.82; 95% CI, 0.79-0.85; P <= 0.001), higher levels of competition (AOR, 1.22; 95% CI, 1.16-1.29; P <= 0.001), and a higher Medicaid reimbursement rate (AOR, 0.88; 95% CI, 0.85-0.92; P <= 0.001).
Conclusions: Antipsychotic use increased in US nursing homes from 1996 through 2006 and was associated with certain organizational characteristics and market characteristics. Future interventions to reduce antipsychotic use in nursing homes will have to focus Oil these factors. (Am J Geriatr Pharmacother. 2009;7:143-150) (C) 2009 Excerpta Medica Inc.
C1 [Castle, Nicholas G.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy & Management, Pittsburgh, PA 15213 USA.
[Hanlon, Joseph T.; Handler, Steven M.] Univ Pittsburgh, Sch Med, Dept Med, Div Geriatr Med, Pittsburgh, PA 15213 USA.
[Hanlon, Joseph T.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15213 USA.
[Handler, Steven M.] Univ Pittsburgh, Sch Med, Dept Biomed Informat, Pittsburgh, PA 15213 USA.
[Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA.
[Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA.
RP Castle, NG (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy & Management, Pittsburgh, PA 15213 USA.
EM castlen@pitt.edu
OI Handler, Steven/0000-0002-3940-3224
FU National Institute of Aging [R01AG027896, R01AG027017, P30AG024827,
5KL2RR024154]; Agency for Health Care Research and Quality grants
[R01HS016808, R03HS016547]; Veterans Administration Health Services
Research grant [IIR-06-062]
FX This study was supported by National Institute of Aging grants (R01
AG027896,R01AG027017,P30AG024827, 5KL2RR024154), Agency for Health Care
Research and Quality grants (R01HS016808, R03HS016547), and a Veterans
Administration Health Services Research grant (IIR-06-062).
NR 36
TC 17
Z9 17
U1 2
U2 3
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 1543-5946
J9 AM J GERIATR PHARMAC
JI Am. J. Geriatr. Pharmacother.
PD JUN
PY 2009
VL 7
IS 3
BP 143
EP 150
DI 10.1016/j.amjopharm.2009.05.001
PG 8
WC Geriatrics & Gerontology; Pharmacology & Pharmacy
SC Geriatrics & Gerontology; Pharmacology & Pharmacy
GA 470MF
UT WOS:000267978100001
PM 19616182
ER
PT J
AU LoboPrabhu, SM
Molinari, VA
Hamilton, JD
Lomax, JW
AF LoboPrabhu, Sheila M.
Molinari, Victor A.
Hamilton, Joseph D.
Lomax, James W.
TI The Aging Physician With Cognitive Impairment: Approaches to Oversight,
Prevention, and Remediation
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Article
DE Aging; physician; dementia; dyscompetence; impairment
AB There are many important unanswered issues regarding the occurrence of cognitive impairment in physicians, such as detection of deficits, remediation efforts, policy implications for safe medical practice, and the need to safeguard quality patient care. The authors review existing literature on these complex issues and derive heuristic formulations regarding how to help manage the professional needs of the aging physician with dementia. To ensure safe standards of medical care while also protecting the needs of physicians and their families, state regulatory or licensing agencies in collaboration with state medical associations and academic medical centers should generate evaluation guidelines to assure continued high levels of functioning. The authors also raise the question of whether age should be considered as a risk factor that merits special screening for adequate functioning. Either age-related screening for cognitive impairment should be initiated or rigorous evaluation after lapses in standard of care should be the norm regardless of age. Ultimately, competence rather than mandatory retirement due to age per se should be the deciding factor regarding whether physicians should be able to continue their practice. Finally, the authors issue a call for an expert consensus panel to convene to make recommendations concerning aging physicians with cognitive impairment who are at risk for medical errors. (Am J Geriatr Psychiatry 2009; 17: 445-454)
C1 [LoboPrabhu, Sheila M.] Michael E DeBakey Dept Vet Affairs Med Ctr, Mental Hlth Care Line & MIRECC, Houston, TX 77030 USA.
[LoboPrabhu, Sheila M.; Hamilton, Joseph D.; Lomax, James W.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA.
[Molinari, Victor A.] Univ S Florida, Dept Aging & Mental Hlth Dispar, Louis de la Parte Florida Mental Hlth Inst, Tampa, FL USA.
RP LoboPrabhu, SM (reprint author), Michael E DeBakey Dept Vet Affairs Med Ctr, Mental Hlth Care Line & MIRECC, 2002 Holcombe Blvd, Houston, TX 77030 USA.
EM SheilaM.Loboprabhu@med.va.gov
NR 37
TC 7
Z9 7
U1 2
U2 5
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 JUN
PY 2009
VL 17
IS 6
BP 445
EP 454
DI 10.1097/JGP.0b013e31819e2d7e
PG 10
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA V21XU
UT WOS:000208241100001
PM 19461256
ER
PT J
AU Wetherell, JL
Ayers, CR
Sorrell, JT
Thorp, SR
Nuevo, R
Belding, W
Gray, E
Stanley, MA
Arean, PA
Donohue, M
Unutzer, J
Ramsdell, J
Xu, RH
Patterson, TL
AF Wetherell, Julie Loebach
Ayers, Catherine R.
Sorrell, John T.
Thorp, Steven R.
Nuevo, Roberto
Belding, Wendy
Gray, Emily
Stanley, Melinda A.
Arean, Patricia A.
Donohue, Michael
Unutzer, Jurgen
Ramsdell, Joe
Xu, Ronghui
Patterson, Thomas L.
TI Modular Psychotherapy for Anxiety in Older Primary Care Patients
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Article
DE Aged; elderly; generalized anxiety disorder; cognitive-behavioral
therapy
ID LATE-LIFE ANXIETY; COGNITIVE-BEHAVIORAL TREATMENT; GENERALIZED ANXIETY;
ELDERLY-PATIENTS; INVENTORY-II; OPEN TRIAL; DISORDER; ADULTS;
DEPRESSION; HEALTH
AB Objective: To develop and test a modular psychotherapy protocol in older primary care patients with anxiety disorders. Design: Randomized, controlled pilot study. Setting: University-based geriatric medicine clinics. Participants: Thirty-one elderly primary care patients with generalized anxiety disorder or anxiety disorder not otherwise specified. Intervention: Modular form of psychotherapy compared with enhanced community treatment. Measurements: Self-reported, interviewer-rated, and qualitative assessments of anxiety, worry, depression, and mental health-related quality of life. Results: Both groups showed substantial improvements in anxiety symptoms, worry, depressive symptoms, and mental health-related quality of life. Most individuals in the enhanced community treatment condition reported receiving medications or some other form of professional treatment for anxiety. Across both conditions, individuals who reported major life events or stressors and those who used involvement in activities as a coping strategy made smaller gains than those who did not. Conclusions: Results suggest that modular psychotherapy and other treatments can be effective for anxiety in older primary care patients. Results further suggest that life events and coping through increased activity may play a role in the maintenance of anxiety in older adults. (Am J Geriatr Psychiatry 2009; 17:483-492)
C1 [Wetherell, Julie Loebach; Ayers, Catherine R.; Thorp, Steven R.; Belding, Wendy; Gray, Emily; Patterson, Thomas L.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA.
[Wetherell, Julie Loebach; Ayers, Catherine R.; Thorp, Steven R.; Belding, Wendy; Gray, Emily] VA San Diego Healthcare Syst, Psychol Serv, San Diego, CA USA.
[Sorrell, John T.] San Mateo Med Ctr, San Mateo, CA USA.
[Nuevo, Roberto] Hosp Univ Princesa, Dept Psychiat, Madrid, Spain.
[Stanley, Melinda A.] Baylor Coll Med, Dept Psychiat & Behav Sci, Houston, TX 77030 USA.
[Stanley, Melinda A.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA.
[Arean, Patricia A.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA.
[Donohue, Michael; Xu, Ronghui] Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA.
[Unutzer, Jurgen] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[Ramsdell, Joe] Univ Calif San Diego, Dept Internal Med, San Diego, CA 92103 USA.
RP Wetherell, JL (reprint author), Univ Calif San Diego, Dept Psychiat, 9500 Gilman Dr,Dept 9116B, La Jolla, CA 92093 USA.
EM jwetherell@ucsd.edu
OI Nuevo, Roberto/0000-0003-3385-2747
FU NIMH [MH067643]
FX The authors gratefully acknowledge the contributions of Georgia
Birchler, Debora Goodman, Dilip V. Jeste, M. D., Laura Otis, Ph. D., and
Murray B. Stein, M. D., M. P. H. This research was supported by NIMH
grant MH067643.
NR 41
TC 31
Z9 31
U1 2
U2 12
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 JUN
PY 2009
VL 17
IS 6
BP 483
EP 492
DI 10.1097/JGP.0b013e3181a31fb5
PG 10
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA 451YC
UT WOS:000266505800005
PM 19461257
ER
PT J
AU Nathan, DG
AF Nathan, David G.
TI The rewards of patience in bone marrow transplantation
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Editorial Material
C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
RP Nathan, DG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
EM david_nathan@dfci.harvard.edu
NR 2
TC 0
Z9 0
U1 0
U2 0
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 JUN
PY 2009
VL 84
IS 6
BP 319
EP 319
DI 10.1002/ajh.21430
PG 1
WC Hematology
SC Hematology
GA 452VW
UT WOS:000266570300001
PM 19425069
ER
PT J
AU Cheng, S
Wang, TJ
AF Cheng, Susan
Wang, Thomas J.
TI Predicting Incident CKD
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Editorial Material
ID CHRONIC KIDNEY-DISEASE; POPULATION
C1 [Wang, Thomas J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Cheng, Susan] Massachusetts Gen Hosp, Brigham & Womens Hosp, Boston, MA 02114 USA.
[Cheng, Susan; Wang, Thomas J.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
RP Wang, TJ (reprint author), Massachusetts Gen Hosp, Div Cardiol, GRB 800,55 Fruit St, Boston, MA 02114 USA.
EM tjwang@partners.org
NR 13
TC 0
Z9 0
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 0272-6386
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD JUN
PY 2009
VL 53
IS 6
BP 936
EP 939
DI 10.1053/j.ajkd.2009.04.004
PG 4
WC Urology & Nephrology
SC Urology & Nephrology
GA 456RY
UT WOS:000266866600008
PM 19463762
ER
PT J
AU Coca, SG
Yusuf, B
Shlipak, MG
Garg, AX
Parikh, CR
AF Coca, Steven G.
Yusuf, Bushra
Shlipak, Michael G.
Garg, Amit X.
Parikh, Chirag R.
TI Long-term Risk of Mortality and Other Adverse Outcomes After Acute
Kidney Injury: A Systematic Review and Meta-analysis
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Article
DE Acute renal failure; chronic kidney disease; prognosis
ID ACUTE-RENAL-FAILURE; CRITICALLY-ILL PATIENTS; QUALITY-OF-LIFE;
PERCUTANEOUS CORONARY INTERVENTION; INTENSIVE-CARE-UNIT; CONTINUOUS
VENOVENOUS HEMODIALYSIS; ACUTE TUBULAR-NECROSIS; REPLACEMENT THERAPY;
HOSPITAL MORTALITY; PERITUBULAR CAPILLARIES
AB Background: Acute kidney injury (AKI) is common in hospitalized patients. The impact of AKI on long-term outcomes is controversial.
Study Design: Systematic review and meta-analysis.
Setting & Participants: Persons with AKI.
Selection Criteria for Studies: MEDLINE and EMBASE databases were searched from 1985 through October 2007. Original studies describing outcomes of AKI for patients who survived hospital discharge were included. Studies were excluded from review when participants were followed up for less than 6 months.
Predictor: AKI, defined as acute changes in serum creatinine level or acute need for renal replacement therapy.
Outcomes: Chronic kidney disease (CKD), cardiovascular disease, and mortality.
Results: 48 studies that contained a total of 47,017 participants were reviewed; 15 studies reported long-term data for patients without AKI. The incidence rate of mortality was 8.9 deaths/100 person-years in survivors of AKI and 4.3 deaths/100 patient-years in survivors without AKI (rate ratio [RR], 2.59; 95% confidence interval, 1.97 to 3.42). AKI was associated independently with mortality risk in 6 of 6 studies that performed multivariate adjustment (adjusted RR, 1.6 to 3.9) and with myocardial infarction in 2 of 2 studies (RR, 2.05; 95% confidence interval, 1.61 to 2.61). The incidence rate of CKD after an episode of AKI was 7.8 events/100 patient-years, and the rate of end-stage renal disease was 4.9 events/100 patient-years.
Limitations: The relative risk for CKD and end-stage renal disease after AKI was unattainable because of lack of follow-up of appropriate controls without AKI.
Conclusions: The development of AKI, defined as acute changes in serum creatinine level, characterizes hospitalized patients at increased risk of long-term adverse outcomes. Am J Kidney Dis 53:961-973. Published by Elsevier Inc on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use.
C1 [Coca, Steven G.; Yusuf, Bushra; Parikh, Chirag R.] Yale Univ, Nephrol Sect, West Haven, CT 06516 USA.
[Coca, Steven G.; Yusuf, Bushra; Parikh, Chirag R.] Vet Affairs Med Ctr, West Haven, CT USA.
[Shlipak, Michael G.] San Francisco VA Med Ctr, San Francisco, CA USA.
[Shlipak, Michael G.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Garg, Amit X.] Univ Western Ontario, London, ON, Canada.
RP Parikh, CR (reprint author), Yale Univ, Nephrol Sect, 950 Campbell Ave,Mail Code 151B,Bldg 35 A,Rm 219, West Haven, CT 06516 USA.
EM chirag.parikh@yale.edu
FU National Institutes of Health [K23DK08013, DK082185]; Canadian
Institutes of Health Research; AKI [RO1 HL085757]
FX Support: Dr Coca is funded by the career development grant K23DK08013
from the National Institutes of Health and is Supported by the American
Heart Association's Established investigator Award. Dr Garg is funded by
the Clinical Scientist Award from the Canadian Institutes of Health
Research. Dr Parikh is Supported by the AKI grants RO1 HL085757 and
UOI-DK082185 from the National Institutes of Health.
NR 77
TC 359
Z9 390
U1 2
U2 16
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0272-6386
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD JUN
PY 2009
VL 53
IS 6
BP 961
EP 973
DI 10.1053/j.ajkd.2008.11.034
PG 13
WC Urology & Nephrology
SC Urology & Nephrology
GA 456RY
UT WOS:000266866600011
PM 19346042
ER
PT J
AU Anderka, MT
Lin, AE
Abuelo, DN
Mitchell, AA
Rasmussen, SA
AF Anderka, Marlene T.
Lin, Angela E.
Abuelo, Dianne N.
Mitchell, Allen A.
Rasmussen, Sonja A.
TI Reviewing the Evidence for Mycophenolate Mofetil as a New Teratogen:
Case Report and Review of the Literature
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE CellCept (R); cleft lip and palate; coloboma; malformation; microtia;
mycophenolate mofetil; teratogenesis
ID ACROFACIAL DYSOSTOSIS; PREGNANCY; EXPOSURE; IMMUNOSUPPRESSION;
TRANSPLANTATION; MALFORMATIONS; EMBRYOPATHY; RECIPIENTS; OUTCOMES;
EDITORS
AB Mycophenolate mofetil (MMF) (CellCept (R)) is an immunosuppressant drug that is teratogenic in rats and rabbits. Reports of malformations in 13 offspring of women exposed to MMF in pregnancy raise concern that MMF is also a human teratogen. We report an additional child with malformations following prenatal exposure to MMF and review the other 13 reports. We identified a Cambodian male born at 31 weeks' gestation to a mother who had been treated for lupus nephritis with MMF from before conception to 12 weeks' gestational age. He had bilateral moderate-to-severe microtia, external auditory canal atresia, bilateral conductive hearing loss, mild microcephaly, and apparently normal development. Among the 14 MMF-exposed offspring now reported, the underlying maternal conditions were kidney transplantation (7), lupus nephritis (4), liver transplantation (1), heart transplantation (1), and recurrent erythema. multiforme (1). All were exposed in early pregnancy. The most distinctive malformation was moderate-to-severe microtia. or anotia (12), with external auditory canal atresia in 9. Other common craniofacial malformations and minor anomalies included orofacial clefts (7), hypertelorism (3), coloboma (3), and micrognathia (3). Six had cardiovascular malformations, of which three were either conotruncal or aortic arch defects. MMF dose, reported in 12 patients, was <1 g/day in 4 and 1 g or more/day in 8; no correlation between dose and phenotype severity was apparent. While case reports have limited value in identifying human teratogens, the unusual distribution of malformations among the 14 reported exposed offspring identifies a phenotype suggesting that MMF is likely a human teratogen. (C) 2009 Wiley-Liss, Inc.
C1 [Anderka, Marlene T.; Lin, Angela E.] Massachusetts Ctr Birth Defects Res & Prevent, Massachusetts Dept Publ Hlth, Boston, MA 02108 USA.
[Lin, Angela E.] MassGen Hosp Children, Genet Unit, Boston, MA USA.
[Abuelo, Dianne N.] Rhode Isl Hosp, Div Genet, Providence, RI USA.
[Abuelo, Dianne N.] Hasbro Childrens Hosp, Providence, RI USA.
[Abuelo, Dianne N.] Brown Univ, Warren Alpert Sch Med, Providence, RI 02912 USA.
[Mitchell, Allen A.] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA.
[Rasmussen, Sonja A.] Ctr Dis Control & Prevent, Atlanta, GA USA.
RP Anderka, MT (reprint author), Massachusetts Ctr Birth Defects Res & Prevent, Massachusetts Dept Publ Hlth, 250 Washington St,5th Floor, Boston, MA 02108 USA.
EM marlene.anderka@state.ma.us
OI Mitchell, Allen/0000-0003-0950-6799
NR 43
TC 95
Z9 101
U1 0
U2 3
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4825
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD JUN
PY 2009
VL 149A
IS 6
BP 1241
EP 1248
DI 10.1002/ajmg.a.32685
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 454LT
UT WOS:000266684200019
PM 19441125
ER
PT J
AU Lehman, SJ
Abbara, S
Cury, RC
Nagurney, JT
Hsu, J
Goela, A
Schlett, CL
Dodd, JD
Brady, TJ
Bamberg, F
Hoffmann, U
AF Lehman, Sam J.
Abbara, Suhny
Cury, Ricardo C.
Nagurney, John T.
Hsu, Joe
Goela, Aashish
Schlett, Christopher L.
Dodd, Jonathan D.
Brady, Thomas J.
Bamberg, Fabian
Hoffmann, Udo
TI Significance of Cardiac Computed Tomography Incidental Findings in Acute
Chest Pain
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Article
DE Chest pain; Computed tomography; Incidental findings
ID EMERGENCY-DEPARTMENT PATIENTS; ACUTE CORONARY SYNDROMES; NONCARDIAC
FINDINGS; COST-EFFECTIVENESS; CT ANGIOGRAPHY; CARE-UNIT; PREVALENCE;
SCANS; MDCT
AB BACKGROUND: Coronary computed tomography angiography might improve the management of patients presenting to the emergency department with acute chest pain; however, noncoronary incidental findings are frequently detected. The prevalence and clinical significance of these findings have not been well described.
METHODS: Consecutive patients presenting to the emergency department with acute chest pain and inconclusive initial evaluation between May 2005 and May 2007 underwent 64-slice coronary computed tomography angiography before hospital admission with noncoronary incidental findings immediately reported. An expert panel adjudicated which incidental findings changed in-hospital patient management, and projections for additional testing were based on standard medical practice.
RESULTS: Among 395 patients (37.0% were female, mean age 53 +/- 12 years), incidental findings were detected in 44.8% (n = 177): noncalcified pulmonary nodules (n = 94, 23.8%), simple liver cysts (n = 26, 6.6%), calcified pulmonary nodules (n = 16, 4.1%), and contrast-enhancing liver lesions (n = 9, 2.3%). In-hospital management was changed because of incidental finding reporting in 5 patients (1.3%), and a potential alternative diagnosis was offered in another 16 patients (4.1%). Subsequent diagnostic imaging tests were recommended in 81 patients (20.5%), including 74 chest computed tomography scans. After 6 months, biopsy was performed in 3 patients, revealing cancer in 2 (0.5%) who underwent successful tumor resection.
CONCLUSION: Clinically important findings are detected in up to 5% of patients with a lead symptom of acute chest pain and low to intermediate likelihood of acute coronary syndrome, but only few directly change patient management; 21% are recommended for further imaging tests, resulting in invasive procedures and detection of cancer in few patients. (C) 2009 Elsevier Inc. All rights reserved. The American Journal of Medicine (2009) 122, 543-549
C1 [Lehman, Sam J.; Abbara, Suhny; Cury, Ricardo C.; Hsu, Joe; Schlett, Christopher L.; Dodd, Jonathan D.; Brady, Thomas J.; Bamberg, Fabian; Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA.
[Lehman, Sam J.; Abbara, Suhny; Cury, Ricardo C.; Nagurney, John T.; Hsu, Joe; Schlett, Christopher L.; Dodd, Jonathan D.; Brady, Thomas J.; Bamberg, Fabian; Hoffmann, Udo] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Lehman, Sam J.] Flinders Univ S Australia, Dept Cardiol, Adelaide, SA, Australia.
[Abbara, Suhny; Cury, Ricardo C.; Hsu, Joe; Goela, Aashish; Dodd, Jonathan D.; Brady, Thomas J.; Bamberg, Fabian; Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Nagurney, John T.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, 165 Charles River Plaza,Suite 400, Boston, MA 02114 USA.
EM uhoffmann@partners.org
NR 26
TC 51
Z9 51
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 JUN
PY 2009
VL 122
IS 6
BP 543
EP 549
DI 10.1016/j.amjmed.2008.10.039
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 451XG
UT WOS:000266503600012
PM 19486717
ER
PT J
AU Cruz-Gonzalez, I
Sanchez-Ledesma, M
Sanchez, PL
Martin-Moreiras, J
Jneid, H
Rengifo-Moreno, P
Inglessis-Azuaje, I
Maree, AO
Palacios, IF
AF Cruz-Gonzalez, Ignacio
Sanchez-Ledesma, Maria
Sanchez, Pedro L.
Martin-Moreiras, Javier
Jneid, Hani
Rengifo-Moreno, Pablo
Inglessis-Azuaje, Ignacio
Maree, Andrew O.
Palacios, Igor F.
TI Predicting Success and Long-Term Outcomes of Percutaneous Mitral
Valvuloplasty: A Multifactorial Score
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Article
DE Percutaneous mitral valvuloplasty; Prognosis; Score
ID BALLOON VALVOTOMY; FOLLOW-UP; COMMISSUROTOMY; IMMEDIATE; STENOSIS;
DISEASE; COMPLICATIONS; DILATATION; VARIABLES; VALVE
AB BACKGROUND: Percutaneous mitral valvuloplasty (PMV) success depends on appropriate patient selection. A multifactorial score derived from clinical, anatomic/echocardiographic, and hemodynamic variables would predict procedural success and clinical outcome.
METHODS: Demographic data, echocardiographic parameters (including echocardiographic score), and procedure-related variables were recorded in 1085 consecutive PMVs. Long-term clinical follow-up (death, mitral valve replacement, redo PMV) was performed. Multivariate regression analysis of the first 800 procedures was performed to identify independent predictors of procedural success. Significant variables were formulated into a risk score and validated prospectively.
RESULTS: Six independent predictors of PMV success were identified: age less than 55 years, New York Heart Association classes I and II, pre-PMV mitral area of 1 cm(2) or greater, pre-PMV mitral regurgitation grade less than 2, echocardiographic score of 8 or greater, and male sex. A score was constructed from the arithmetic sum of variables present per patient. Procedural success rates increased incrementally with increasing score (0% for 0/6, 39.7% for 1/6, 54.4% for 2/6, 77.3% for 3/6, 85.7% for 4/6, 95% for 5/6, and 100% for 6/6; P < .001). In a validation cohort (n = 285 procedures), the multifactorial score remained a significant predictor of PMV success (P < .001). Comparison between the new score and the echocardiographic score confirmed that the new index was more sensitive and specific (P < .001). This new score also predicts long-term outcomes (P < .001).
CONCLUSION: Clinical, anatomic, and hemodynamic variables predict PMV success and clinical outcome and may be formulated in a scoring system that would help to identify the best candidates for PMV. (C) 2009 Elsevier Inc. All rights reserved. The American Journal of Medicine (2009) 122, 581.e11-581.e19
C1 [Cruz-Gonzalez, Ignacio] Harvard Univ, Cardiac Catheterizat Lab, Massachusetts Gen Hosp, Cardiol Div,Med Sch, Boston, MA 02114 USA.
[Sanchez, Pedro L.] Hosp Univ Gregorio Maranon, Serv Cardiol, Madrid, Spain.
[Martin-Moreiras, Javier] Hosp Univ Salamanca, Serv Cardiol, Salamanca, Spain.
RP Cruz-Gonzalez, I (reprint author), Harvard Univ, Cardiac Catheterizat Lab, Massachusetts Gen Hosp, Cardiol Div,Med Sch, GRB 800,55 Fruit St, Boston, MA 02114 USA.
EM i-cruz@secardiologia.es
RI 2009, Secribsal/A-1266-2012;
OI Sanchez, Pedro L/0000-0002-4288-345X
NR 24
TC 1
Z9 1
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 JUN
PY 2009
VL 122
IS 6
AR 581.e11
DI 10.1016/j.amjmed.2008.10.038
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 451XG
UT WOS:000266503600018
PM 19486721
ER
PT J
AU Roukoz, H
Bavry, AA
Sarkees, ML
Mood, GR
Kumbhani, DJ
Rabbat, MG
Bhatt, DL
AF Roukoz, Henri
Bavry, Anthony A.
Sarkees, Michael L.
Mood, Girish R.
Kumbhani, Dharam J.
Rabbat, Mark G.
Bhatt, Deepak L.
TI Comprehensive Meta-Analysis on Drug-Eluting Stents versus Bare-Metal
Stents during Extended Follow-up
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Article
DE Bare-metal stent; Drug-eluting stent; Percutaneous coronary
intervention; Stent thrombosis
ID ACUTE MYOCARDIAL-INFARCTION; RANDOMIZED CLINICAL-TRIALS; CORONARY-ARTERY
LESIONS; DOUBLE-BLIND TRIAL; DIABETIC-PATIENTS; UNCOATED STENTS;
STANDARD STENT; SLOW-RELEASE; CANADIAN MULTICENTER; LATE THROMBOSIS
AB BACKGROUND: Several observational reports have documented both increased and decreased cardiac mortality or Q-wave myocardial infarction with drug-eluting stents compared with bare-metal stents.
METHODS: We sought to evaluate the safety and efficacy of drug-eluting stents compared with bare-metal stents early after intervention (<1 year) and late (>1 year) among a broad population of patients, using a meta-analysis of randomized clinical trials.
RESULTS: We identified 28 trials with a total of 10,727 patients and a mean follow-up of 29.6 months. For early outcomes (<1 year), all-cause mortality for drug-eluting stents versus bare-metal stents was 2.1% versus 2.4% (risk ratio [RR] 0.91, [95% confidence interval (CI), 0.70-1.18]; P = .47), non-Q-wave myocardial infarction was 3.3% versus 4.4% (RR 0.78 [95% CI, 0.61-1.00]; P = .055), target lesion revascularization was 5.8% versus 18.4% (RR 0.28 [95% CI, 0.21-0.38]; P = .001), and stent thrombosis was 1.1% versus 1.3% (RR 0.87 [95% CI, 0.60-1.26]; P = .47). For late outcomes (>1 year), all-cause mortality for drug-eluting stents versus bare-metal stents was 5.9% versus 5.7% (RR 1.03 [95% CI, 0.83-1.28]; P = .79), target lesion revascularization was 4.0% versus 3.3% (RR 1.22 [95% CI, 0.92-1.60]; P = .16), non-Q-wave myocardial infarction was 1.6% versus 1.2% (RR 1.36 [95% CI, 0.74-2.53]; P = .32) and stent thrombosis was 0.7% versus 0.1% (RR 4.57 [95% CI, 1.54-13.57]; P = .006).
CONCLUSIONS: There was no excess mortality with drug-eluting stents. Within 1 year, drug-eluting stents appear to be safe and efficacious with possibly decreased non-Q-wave myocardial infarction compared with bare-metal stents. After 1 year, drug-eluting stents still have similar mortality, despite increased stent thrombosis. The reduction in target lesion revascularization with drug-eluting stents mainly happens within 1 year, but is sustained thereafter. Published by Elsevier Inc. The American Journal of Medicine (2009) 122, 581.e1-581.e10
C1 [Bhatt, Deepak L.] Brigham & Womens Hosp, Integrated Intervent Cardiovasc Program, VA Boston Healthcare Syst, Boston, MA 02115 USA.
[Roukoz, Henri] Univ Minnesota, Dept Cardiovasc Med, Minneapolis, MN USA.
[Bavry, Anthony A.] Univ Florida, Div Cardiovasc Med, Gainesville, FL USA.
[Sarkees, Michael L.] Cleveland Clin, Dept Internal Med, Cleveland, OH 44106 USA.
[Mood, Girish R.; Kumbhani, Dharam J.] Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44106 USA.
[Rabbat, Mark G.] Loyola Univ, Med Ctr, Cardiovasc Inst, Maywood, IL 60153 USA.
RP Bhatt, DL (reprint author), Brigham & Womens Hosp, Integrated Intervent Cardiovasc Program, VA Boston Healthcare Syst, 75 Francis St,PBB-146, Boston, MA 02115 USA.
EM dlbhattmd@alum.mit.edu
NR 80
TC 9
Z9 10
U1 0
U2 2
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 JUN
PY 2009
VL 122
IS 6
AR 581.e1
DI 10.1016/j.amjmed.2008.12.019
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 451XG
UT WOS:000266503600017
PM 19486720
ER
PT J
AU Almandoz, JED
Schaefer, PW
Forero, NP
Falla, JR
Gonzalez, RG
Romero, JM
AF Almandoz, J. E. Delgado
Schaefer, P. W.
Forero, N. P.
Falla, J. R.
Gonzalez, R. G.
Romero, J. M.
TI Diagnostic Accuracy and Yield of Multidetector CT Angiography in the
Evaluation of Spontaneous Intraparenchymal Cerebral Hemorrhage
SO AMERICAN JOURNAL OF NEURORADIOLOGY
LA English
DT Article; Proceedings Paper
CT 45th Annual Meeting of the American-Society-of-Neuroradiology
CY JUN 09-11, 2007
CL Chicago, IL
SP Amer Soc Neuroradiol
ID INTRACEREBRAL HEMORRHAGE; ARTERIOVENOUS-MALFORMATIONS; AMYLOID
ANGIOPATHY; RISK-FACTORS; INTRACRANIAL HEMORRHAGE; COMPUTED-TOMOGRAPHY;
NATURAL-HISTORY; ANEURYSMS; BRAIN; HEMATOMA
AB BACKGROUND AND PURPOSE: Multidetector CT angiography (MDCTA) is emerging as the favored initial diagnostic examination in the evaluation of patients presenting with spontaneous intraparenchymal hemorrhage (IPH). This study aims to evaluate the diagnostic accuracy and yield of MDCTA for the detection of vascular etiologies in adult patients presenting to the emergency department with IPH.
MATERIALS AND METHODS: We conducted a retrospective study of 623 consecutive adult patients presenting to the emergency department with IPH, who were evaluated with MDCTA during a 9-year period. CT angiograms were reviewed by 2 neuroradiologists to determine the IPH site and the presence of a vascular etiology. Patients with associated subarachnoid hemorrhage in the basal cisterns were excluded from the study. Medical records were reviewed for risk factors and correlation with final diagnosis. The diagnostic accuracy of MDCTA compared with conventional angiography, intraoperative evaluation, and pathologic findings was determined, when available. Multiple-variable logistic regression analysis was performed to determine clinical and radiologic factors that predict a higher yield of MDCTA.
RESULTS: MDCTA demonstrated a vascular etiology in 91 patients (14.6%), with a sensitivity of 96%, specificity of 99%, and diagnostic accuracy of 98%. We found independent, statistically significant higher yields of MDCTA in patients with the following characteristics: 1) age younger than 46 years (47%); 2) lobar (20%) or infratentorial (16%) IPH, especially lobar IPH with associated intraventricular hemorrhage (25%); 3) female sex (18%); or 4) neither known hypertension nor impaired coagulation at presentation (33%).
CONCLUSIONS: MDCTA is an accurate diagnostic examination in the evaluation of adult patients presenting with spontaneous IPH and should be performed in all patients with the aforementioned clinical and radiologic characteristics.
C1 [Almandoz, J. E. Delgado; Schaefer, P. W.; Forero, N. P.; Falla, J. R.; Gonzalez, R. G.; Romero, J. M.] Massachusetts Gen Hosp, Dept Radiol, Div Neuroradiol, Boston, MA 02114 USA.
RP Almandoz, JED (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Neuroradiol, Founders 216,55 Fruit St, Boston, MA 02114 USA.
EM jdelgadoalmandoz@partners.org
NR 27
TC 40
Z9 41
U1 0
U2 0
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 JUN-JUL
PY 2009
VL 30
IS 6
BP 1213
EP 1221
DI 10.3174/ajnr.A1546
PG 9
WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 461IL
UT WOS:000267258400025
ER
PT J
AU Stefancyk, AL
AF Stefancyk, Amanda L.
TI Improving Processes of Care
SO AMERICAN JOURNAL OF NURSING
LA English
DT Editorial Material
C1 Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA.
RP Stefancyk, AL (reprint author), Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA.
EM astefancyk@partners.org
NR 2
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0002-936X
J9 AM J NURS
JI Am. J. Nurs.
PD JUN
PY 2009
VL 109
IS 6
BP 36
EP 37
PG 2
WC Nursing
SC Nursing
GA 453XW
UT WOS:000266647200015
PM 19478603
ER
PT J
AU Ohishi, M
Chiusaroli, R
Ominsky, M
Asuncion, F
Thomas, C
Khatri, R
Kostenuik, P
Schipani, E
AF Ohishi, Masanobu
Chiusaroli, Riccardo
Ominsky, Michael
Asuncion, Frank
Thomas, Clare
Khatri, Richa
Kostenuik, Paul
Schipani, Ernestina
TI Osteoprotegerin Abrogated Cortical Porosity and Bone Marrow Fibrosis in
a Mouse Model of Constitutive Activation of the PTH/PTHrP Receptor
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID MCCUNE-ALBRIGHT-SYNDROME; GROWTH-FACTOR-BETA; PRIMARY
HYPERPARATHYROIDISM; PARATHYROID-HORMONE; IN-VIVO; CYNOMOLGUS MONKEYS;
TARGETED DELETION; CANCELLOUS BONE; MEDICAL THERAPY; TRABECULAR BONE
AB Intracortical porosities and marrow fibrosis are hallmarks of hyperparathyroidism and are present in bones of transgenic mice expressing constitutively active parathyroid hormone/parathyroid hormone-related protein receptors (PPR*Tg). Cortical porosity is the result of osteoclast activity; however, the etiology of marrow fibrosis is poorly understood. While osteoclast numbers and activity are regulated by osteoprotegerin (OPG), bisphosphonates suppress osteoclast activity but not osteoclast numbers. We therefore used OPG and bisphosphonates to evaluate the extent to which osteoclasts, as opposed to bone resorption, regulate marrow fibrosis in PPR*Tg mice after treatment of animals with vehicle, OPG, alendronate, or zoledronate. All three agents similarly increased trabecular bone volume in both PPR*Tg and control mice, suggesting that trabecular bone resorption was comparably suppressed by these agents. However, the number of trabecular osteoclasts was greatly decreased by OPG but not by either alendronate or zoledronate. Furthermore, intracortical porosity and marrow fibrosis were virtually abolished by OPG treatment, whereas alendronate and zoledronate only partially reduced these two parameters. The greater reductions in cortical porosity and increments in cortical bone mineral density with OPG in PPR*Tg mice were associated with greater improvements in bone strength. The differential effect of OPG versus bisphosphonates on marrow fibrosis, despite similar effects on trabecular bone volume, suggests that marrow fibrosis was related not only to bone resorption but also to the presence of osteoclasts. (Am J Pathol 2009, 174:2160-2171; DOI:10.2353/ajpath.2009.081026)
C1 [Ohishi, Masanobu; Chiusaroli, Riccardo; Thomas, Clare; Khatri, Richa; Kostenuik, Paul; Schipani, Ernestina] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA USA.
[Ominsky, Michael; Asuncion, Frank; Kostenuik, Paul] Amgen Inc, Metab Disorders, Thousand Oaks, CA 91320 USA.
RP Schipani, E (reprint author), Thier 11-MGH,50 Blossom St, Boston, MA 02114 USA.
EM paulk@amgen.com
FU Amgen Inc
FX Supported by a grant from Amgen Inc to E.S.
NR 54
TC 16
Z9 16
U1 1
U2 1
PU AMER SOC INVESTIGATIVE PATHOLOGY, INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD JUN
PY 2009
VL 174
IS 6
BP 2160
EP 2171
DI 10.2353/ajpath.2009.081026
PG 12
WC Pathology
SC Pathology
GA 449ZT
UT WOS:000266370600020
PM 19389927
ER
PT J
AU Ponnuswamy, P
Ostermeier, E
Schrottle, A
Chen, J
Huang, PL
Ertl, G
Nieswandt, B
Kuhlencordt, PJ
AF Ponnuswamy, Padmapriya
Ostermeier, Eva
Schroettle, Angell
Chen, Jiqiu
Huang, Paul L.
Ertl, Georg
Nieswandt, Bernhard
Kuhlencordt, Peter J.
TI Oxidative Stress and Compartment of Gene Expression Determine
Proatherosclerotic Effects of Inducible Nitric Oxide Synthase
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID VASCULAR SMOOTH-MUSCLE; E-DEFICIENT MICE; DIET-INDUCED ATHEROSCLEROSIS;
TRAUMATIC BRAIN-INJURY; E-KNOCKOUT MICE; IN-VIVO; SUPEROXIDE GENERATION;
NO-SYNTHASE; TETRAHYDROBIOPTERIN; 17-BETA-ESTRADIOL
AB Genetic and pharmacological inhibition of inducible nitric oxide synthase (iNOS) decreases atherosclerosis development. Potential proatherogenic effects of iNOS include iNOS mediated oxidative stress and iNOS expression in different cellular compartments. Lesional iNOS can potentially produce nitric oxide radicals (NO), superoxide radicals (O(2)(-)), or both; these radicals may then react to form peroxynitrite. Alternatively, O(2)(-) radicals from oxidases co-expressed with iNOS could react with NO to produce peroxynitrite. Therefore, the expression profiles of the genes that modulate the redox system in different iNOS-expressing cell compartments may determine the role of iNOS in atherosclerosis. We used apoE (apoE(-/-)) and apoE/iNOS double knockout (apoE(-/-)/iNOS(-/-)) mice to assess vascular NO, O(2)(-), and peroxynitrite formation by electron spin resonance spectroscopy, high performance liquid chromatography, and 3-nitrotyrosine staining. The relevance of the iNOS expressing cell compartment was tested by bone marrow transplantation. We show that iNOS significantly contributes to vascular NO production and itself produces O(2)(-), leading to peroxynitrite formation in atherosclerotic lesions. Our bone marrow transplantation experiments show that bone marrow derived cells exclusively mediate the proatherosclerotic effects of iNOS in mates, while both parenchymal and bone marrow derived iNOS equally contribute to atherosclerosis in females. Moreover, iNOS expression affects vascular remodeling. These findings establish for the first time that the proatherosclerotic effects of iNOS vary with sex in addition to the compartment of its expression. (Am J Pathol 2009, 174;2400-2410; DOI: 10.2353/ajpath.2009.080730)
C1 [Kuhlencordt, Peter J.] Univ Munich, Med Poliklin, D-80336 Munich, Germany.
[Chen, Jiqiu; Huang, Paul L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
[Nieswandt, Bernhard] Univ Wurzburg, Inst Clin Biochem & Pathobiochem, Wurzburg, Germany.
[Ponnuswamy, Padmapriya; Ostermeier, Eva; Schroettle, Angell; Ertl, Georg] Univ Wurzburg, DFG Res Ctr Expt Biomed, Rudolf Virchow Ctr, Herz Kreislaufzentrum,Med Klin 1, Wurzburg, Germany.
RP Kuhlencordt, PJ (reprint author), Univ Munich, Med Poliklin, Pettenkoferstr 8A, D-80336 Munich, Germany.
EM peter.kuhlencordt@med.uni-muenchen.de
FU Deutsche-Forschungsgemeinschaft [KU-1206, 1206]; IZKF-Wurzburg
FX Supported by grants from the Deutsche-Forschungsgemeinschaft (KU-1206(1)
and 1206(2) and the IZKF-Wurzburg to P.K.
NR 55
TC 26
Z9 28
U1 2
U2 8
PU AMER SOC INVESTIGATIVE PATHOLOGY, INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD JUN
PY 2009
VL 174
IS 6
BP 2400
EP 2410
DI 10.2353/ajpath.2009.080730
PG 11
WC Pathology
SC Pathology
GA 449ZT
UT WOS:000266370600042
PM 19465644
ER
PT J
AU Van Hoek, AN
Bouley, R
Lu, YX
Silberstein, C
Brown, D
Wax, MB
Patil, RV
AF Van Hoek, Alfred N.
Bouley, Richard
Lu, YingXian
Silberstein, Claudia
Brown, Dennis
Wax, Martin B.
Patil, Rajkumar V.
TI Vasopressin-induced differential stimulation of AQP4 splice variants
regulates the in-membrane assembly of orthogonal arrays
SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
LA English
DT Article
DE hydrophobic plasma membrane protein; osmotic water transport
ID INSENSITIVE WATER CHANNEL; PLASMA-MEMBRANES; COLLECTING DUCTS;
EPITHELIAL-CELLS; M23 ISOFORMS; AQUAPORIN-4; EXPRESSION; KIDNEY;
PROTEIN; BRAIN
AB Van Hoek AN, Bouley R, Lu YX, Silberstein C, Brown D, Wax MB, Patil RV. Vasopressin-induced differential stimulation of AQP4 splice variants regulates the in-membrane assembly of orthogonal arrays. Am J Physiol Renal Physiol 296: F1396-F1404, 2009. First published March 18, 2009; doi: 10.1152/ajprenal.00018.2009.-Aquaporin-4 (AQP4) is a basolateral water channel in collecting duct principal cells and assembles into orthogonal array particles (OAPs), the size of which appears to depend on relative expression levels of AQP4 splice variants. Because the higher-order organization of AQP4 was perturbed by vasopressin in Brattleboro rats and phosphorylation sites have been identified on AQP4, we investigated whether vasopressin and forskolin (Fk) affect AQP4 assembly and/or expression in LLC-PK1 cells stably transfected with the AQP4 splice variant M23, which is responsible for formation of OAPs, and/or the splice variant M1, which does not form OAPs. Our data show that [lys(8)]-vasopressin (LVP) and Fk treatment led to differential increases in expression levels of M23-AQP4 and M1-AQP4 that varied as a function of incubation time. At early time points (day 1) expression of M1 was significantly stimulated (4.5-fold), over that of M23 (1.6-fold), but after 3 days the expression of M23 became predominant (4.1-fold) over that of M1 (1.9-fold). This pattern of stimulation was dependent on an intact AQP4 residue serine 111 and required protein synthesis. In cells expressing both M1 and M23 (M1/M23 similar to 1), with small sized OAPs at the membrane, the LVP/Fk-induced stimulation of M23 was modified and mimicked that of M1 when expressed alone, suggesting a dominant role for M1. In Brattleboro kidney inner medulla, an 8-day chronic exposure to the vasopressin agonist (dDAVP) led to reduction in M1 and a significant increase in M23 immunoblot staining (M1/M23 = 2/3 -> 1/4). These results indicate that AQP4 organization and expression are regulated by vasopressin in vivo and in vitro and demonstrate that the dominant role for M1 is restricted to a one-to-one interaction between AQP4 splice variants that regulates the membrane expression of OAPs.
C1 [Van Hoek, Alfred N.; Bouley, Richard; Lu, YingXian; Brown, Dennis] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[Van Hoek, Alfred N.; Bouley, Richard; Lu, YingXian; Brown, Dennis] Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02114 USA.
[Van Hoek, Alfred N.; Bouley, Richard; Lu, YingXian; Brown, Dennis] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA.
[Van Hoek, Alfred N.; Bouley, Richard; Lu, YingXian; Brown, Dennis] Harvard Univ, Sch Med, Boston, MA USA.
[Silberstein, Claudia] Univ Buenos Aires, Fac Med, Dept Fisiol, Lab Fisiopatogenia, RA-1425 Buenos Aires, DF, Argentina.
[Wax, Martin B.; Patil, Rajkumar V