tbuckley/cabot-search huggingface dataset:
Phase III Trial of Observation Versus Six Courses of Paclitaxel in Patients With Advanced Epithelial Ovarian Cancer in Complete Response After Six Courses of Paclitaxel/Platinum-Based Chemotherapy: Final Results of the After-6 Protocol 1
Authors: Sergio Pecorelli, Giuseppe Favalli, Angiolo Gadducci, Dionyssios Katsaros, Pierluigi Benedetti Panici, Amalia Carpi, Giovanni Scambia, Michela Ballardini, Oriana Nanni, PierFranco Conte
Journal: Journal of Clinical Oncology (2009)

To assess whether six courses of paclitaxel are effective as consolidation treatment in patients with advanced epithelial ovarian cancer who are in complete response after first-line paclitaxel/platinum-based chemotherapy.Patients with stages IIb to IV disease in clinical or pathologic complete response after six courses of paclitaxel/platinum-based chemotherapy were randomly allocated to either observation (ie, control) or six courses of paclitaxel 175 mg/m(2) every 3 weeks (ie, maintenance).Two hundred patients were randomly assigned from March 1999 to July 2006. Because of the low accrual rate, an unplanned interim analysis of futility according to the Bayesian approach was performed. Grade 2 or greater motor neurotoxicity and sensory neurotoxicity were reported in 11.3% and 28.0% of the paclitaxel-arm patients, respectively. After a median follow-up of 43.5 months, 107 patients (53%) had experienced relapse, and 48 patients (24%) had died. Two-year progression-free survival rates were 54% (95% CI, 43% to 64%) and 59% (95% CI, 49% to 69%; P = not significant) in the control and maintenance arms, respectively. Corresponding 2-year overall survival rates were 90% (95% CI, 84% to 97%) and 87% (95% CI, 80% to 94%; P = not significant), respectively. The Cox model showed that residual disease after initial surgery (macroscopic v no macroscopic residuum; hazard ratio [HR], 1.91; 95%CI, 1.21 to 3.03) and stage (IIIc to IV v others; HR, 3.10; 95% CI, 1.13 to 8.48) were independent prognostic factors for progression-free survival, whereas the treatment arm (maintenance v control) had no prognostic relevance.A consolidation treatment with six cycles of paclitaxel does not prolong progression-free survival or overall survival in patients in complete response after first-line paclitaxel/platinum-based regimens.
Chronic Active Hepatitis and Severe Hepatic Necrosis Associated with Nitrofurantoin
Authors: JOHN R. SHARP, KAMAL G. ISHAK, HYMAN J. ZIMMERMAN
Journal: Annals of Internal Medicine (1980)

Nitrofurantoin has been associated with an acute hepatocellular and cholestatic injury, but only rarely with a lesion resembling chronic active hepatitis. Death from nitrofurantoin hepatotoxicity after long-term therapy has not been previously described. We report five cases of chronic active hepatitis, including two deaths, associated with nitrofurantoin and discuss previously reported cases. All of the 20 patients were women and had taken the drug from 4 weeks to 11 years. Most patients had a low serum albumin and an elevated gamma globulin; antinuclear antibody was positive in 12 patients. Eighteen patients improved clinically and biochemically when the drug was withdrawn. Cirrhosis occurred in four patients. Both of the patients who died had taken the drug for more than 1 year and had a clinical course of progressive hepatic failure. Severe hepatic necrosis was noted at autopsy in both patients.
Mechanisms of heart failure with well preserved ejection fraction in dogs following limited coronary microembolization
Authors: K HE
Journal: Cardiovascular Research (2004)

It has been suggested that in some settings, heart failure (HF) may occur with normal ejection fraction (EF) as a consequence of undetected systolic dysfunction. However, others have argued that this can only occur in the presence of diastolic dysfunction. We therefore sought to determine the contribution of diastolic dysfunction in an animal model of HF with normal EF.Limited myocardial injury was induced in 21 dogs chronically instrumented to measure hemodynamics and LV properties by daily coronary microembolization ( approximately 115 microm beads) until LV end diastolic pressure (LVEDP) was > or =16 mm Hg. Nine dogs developed HF within 16+/-6 days (LVEDP 12+/-2 vs. 21+/-2 mm Hg, p<0.001) with no significant change in dP/dt(max) (2999+/-97 vs. 2846+/-189 mm Hg/s), mean arterial pressure (103+/-4 vs. 100+/-4 mm Hg), EF (57+/-5% vs. 53+/-4%) or E(es) (end-systolic elastance, 3.1+/-0.9 vs. 2.9+/-0.8 mm Hg/ml) but with an approximately 10 ml increase in V(o) (14+/-12 vs. 25+/-16 ml; p<0.01). The EDPVR and time constant of relaxation (tau, 25+/-3 vs. 28+/-3 ms) did not change significantly. These animals were hemodynamically stable out to 3 1/2 months. Neurohormonal activation occurred (elevations of NE, AngII, BNP) and there was intravascular volume expansion by approximately 16% (p<0.05).A small amount of myocardial injury can lead to neurohormonal activation with intravascular volume expansion and elevation of LVEDP in the absence of reductions in dP/dt(max) or EF and without diastolic dysfunction. Thus, HF with preserved EF does not a priori equate with diastolic heart failure.
Acceleration of thrombin-antithrombin complex formation in rat hindquarters via heparinlike molecules bound to the endothelium.
Authors: J A Marcum, J B McKenney, R D Rosenberg
Journal: Journal of Clinical Investigation (1984)

We have examined the role of heparinlike molecules in the regulation of coagulation by perfusing rat hindquarters with purified human thrombin and with its plasma inhibitor, antithrombin. Our data indicate that contact of the hemostatic components with the endothelium enhances the rate of thrombin-antithrombin complex formation by as much as 19-fold over the uncatalyzed rate of enzyme-inhibitor interaction. Heparinlike molecules are responsible for the antithrombin accelerating activity. The amount of thrombin-antithrombin complex generated within the hindlimb preparation after pretreatment of the vasculature with purified Flavobacterium heparinase or with addition of platelet Factor IV to the hemostatic components, was equal to the uncatalyzed levels. These heparinlike molecules appear to be tightly bound to the luminal surface of the endothelium, since they could not be detected within the physiologic buffer that was perfused through the animal. The above mucopolysaccharides function in a manner similar to commercial heparin, since modification of antithrombin at a site critical for heparin-dependent acceleration of the protease inhibitor resulted in a level of interaction product identical to the uncatalyzed amount. Finally, addition of diisofluorophosphate-thrombin to the enzyme perfusion stream reduced the amount of thrombin-antithrombin complex formed in the animal by 30-40%, which suggested that thrombin bound to the endothelium as well as enzyme free in solution are accessible to antithrombin that has interacted with heparinlike molecules present on the endothelium.
α <sub>v</sub> β <sub>3</sub> Integrin Expression in Normal and Atherosclerotic Artery
Authors: Masaaki Hoshiga, Charles E. Alpers, Laura L. Smith, Cecilia M. Giachelli, Stephen M. Schwartz
Journal: Circulation Research (1995)

Abstract Recent evidence suggests that α v β 3 integrin is a critical molecule in several processes involved in atherosclerosis progression and in restenosis, eg, smooth muscle cell (SMC) migration and angiogenesis. While several ligands for this integrin are known to be present in atherosclerotic plaque, little is known about the presence of α v β 3 integrin at this site. In the present study, we have examined α v β 3 expression in normal and atherosclerotic arteries. Thirty-six coronary artery segments from the recipient hearts of 24 patients undergoing heart transplantation were classified into two groups: nonatherosclerotic diffuse intimal thickening (DIT) and atherosclerotic plaques. Serial frozen sections were examined immunohistochemically with four different monoclonal antibodies directed against human α v β 3 complex or the β 3 subunit and with cell markers for SMCs, macrophages, and endothelial cells. The endothelium along the lumen of both DIT and plaque arteries showed high expression of α v β 3 . The media of both DIT and plaque arteries showed less intense but extensive expression of α v β 3 . Immunoprecipitation and reverse-transcribed polymerase chain reaction (RT-PCR) analyses performed on extracts from the aortic media confirmed the presence of α v β 3 in the media. In the intima of both DIT and plaque arteries, α v β 3 expression generally colocalized with SMCs but rarely with macrophages. The microvessels in the adventitia as well as in the plaque showed prominent expression of α v β 3 , in contrast to low expression in similar-sized microvessels of the skin. These results suggest that α v β 3 is present both in the normal artery and in sites of SMC accumulation and angiogenesis in atherosclerotic plaques.
GATA4 and GATA6 control mouse pancreas organogenesis
Authors: Manuel Carrasco, Irene Delgado, Bernat Soria, Francisco Martín, Anabel Rojas
Journal: Journal of Clinical Investigation (2012)

Recently, heterozygous mutations in GATA6 have been found in neonatal diabetic patients with failed pancreatic organogenesis. To investigate the roles of GATA4 and GATA6 in mouse pancreas organogenesis, we conditionally inactivated these genes within the pancreas. Single inactivation of either gene did not have a major impact on pancreas formation, indicating functional redundancy. However, double Gata4/Gata6 mutant mice failed to develop pancreata, died shortly after birth, and displayed hyperglycemia. Morphological defects in Gata4/Gata6 mutant pancreata were apparent during embryonic development, and the epithelium failed to expand as a result of defects in cell proliferation and differentiation. The number of multipotent pancreatic progenitors, including PDX1+ cells, was reduced in the Gata4/Gata6 mutant pancreatic epithelium. Remarkably, deletion of only 1 Gata6 allele on a Gata4 conditional knockout background severely reduced pancreatic mass. In contrast, a single WT allele of Gata4 in Gata6 conditional knockout mice was sufficient for normal pancreatic development, indicating differential contributions of GATA factors to pancreas formation. Our results place GATA factors at the top of the transcriptional network hierarchy controlling pancreas organogenesis.
Association of the Dopamine D<sub>4</sub> Receptor Gene 7-Repeat Allele With Neuropsychological Test Performance of Children With ADHD
Authors: Kate Langley, Lucy Marshall, Marianne van den Bree, Hollie Thomas, Michael Owen, Michael O’Donovan, Anita Thapar
Journal: American Journal of Psychiatry (2004)

Association between attention deficit hyperactivity disorder (ADHD) and the 7-repeat allele of a variant (a 48 bp variable number of tandem repeats) in the dopamine D4 receptor gene (DRD4) has been widely documented. A meta-analysis of 21 studies revealed evidence of significant association. In this article the authors examine whether the DRD4 7-repeat allele is associated with performance on a variety of neuropsychological tasks in children with ADHD.The presence or absence of the 7-repeat allele was determined in 133 drug-naive children 6 to 13 years of age who fulfilled diagnostic criteria for ADHD. These children were then assessed on several neuropsychological tests known to be associated with attention, impulse control, and response inhibition (the Continuous Performance Test, Matching Familiar Figures Test, Go/No Go Task, and Stop Task). Activity levels were assessed with an actigraph. Children with and without at least one 7-repeat allele were compared with each other and with children in a previous population-based study.Children who had the 7-repeat allele had significantly more incorrect responses on the Matching Familiar Figures Test (16.1 versus 14.3) than children who did not have the allele. Children with the allele also had shorter mean reaction times for incorrect responses on the Matching Familiar Figures Test (846.1 versus 1103.7 msec) and on the Stop Task (116.6 versus 134.1 msec) than children without the allele. Children with the allele also displayed higher activity levels. The children with and without the allele did not differ significantly in number of ADHD symptoms when the symptoms were split into the areas of inattention and hyperactivity/impulsivity. Both groups of children with ADHD were more neuropsychologically impaired than the nonpatient comparison group.In children with ADHD, possession of the DRD4 7-repeat allele appears to be associated with an inaccurate, impulsive response style on neuropsychological tasks that is not explained by ADHD symptom severity.
Novel MRI Contrast Agent for Molecular Imaging of Fibrin
Authors: Sebastian Flacke, Stefan Fischer, Michael J. Scott, Ralph J. Fuhrhop, John S. Allen, Mark McLean, Patrick Winter, Gregorio A. Sicard, Patrick J. Gaffney, Samuel A. Wickline, Gregory M. Lanza
Journal: Circulation (2001)

Background Molecular imaging of thrombus within fissures of vulnerable atherosclerotic plaques requires sensitive detection of a robust thrombus-specific contrast agent. In this study, we report the development and characterization of a novel ligand-targeted paramagnetic molecular imaging agent with high avidity for fibrin and the potential to sensitively detect active vulnerable plaques. Methods and Results The nanoparticles were formulated with 2.5 to 50 mol% Gd-DTPA-BOA, which corresponds to &gt;50 000 Gd 3+ atoms/particle. Paramagnetic nanoparticles were characterized in vitro and evaluated in vivo. In contradistinction to traditional blood-pool agents, T1 relaxation rate as a function of paramagnetic nanoparticle number was increased monotonically with Gd-DTPA concentration from 0.18 mL · s −1 · pmol −1 (10% Gd-DTPA nanoparticles) to 0.54 mL · s −1 · pmol −1 for the 40 mol% Gd-DTPA formulations. Fibrin clots targeted in vitro with paramagnetic nanoparticles presented a highly detectable, homogeneous T1-weighted contrast enhancement that improved with increasing gadolinium level (0, 2.5, and 20 mol% Gd). Higher-resolution scans and scanning electron microscopy revealed that the nanoparticles were present as a thin layer over the clot surface. In vivo contrast enhancement under open-circulation conditions was assessed in dogs. The contrast-to-noise ratio between the targeted clot (20 mol% Gd-DTPA nanoparticles) and blood was ≈118±21, and that between the targeted clot and the control clot was 131±37. Conclusions These results suggest that molecular imaging of fibrin-targeted paramagnetic nanoparticles can provide sensitive detection and localization of fibrin and may allow early, direct identification of vulnerable plaques, leading to early therapeutic decisions.
Deletion of the Insulin Receptor in the Proximal Tubule Promotes Hyperglycemia
Authors: Swasti Tiwari, Ravi Shankar Singh, Lijun Li, Susanna Tsukerman, Madan Godbole, Gaurav Pandey, Carolyn M. Ecelbarger
Journal: Journal of the American Society of Nephrology (2013)

Nearly all renal tubular epithelial cells express insulin receptor. The insulin receptor in the distal tubule appears to modulate BP, but the role of the insulin receptor in the proximal tubule is unknown. Here, we selectively knocked out the insulin receptor from the proximal tubules of mice. Western blotting confirmed a two- to three-fold reduction in renal cortical homogenate insulin receptor-β among knockout mice compared with wild-type littermates. Young knockout mice exhibited a mildly diabetic phenotype, evidenced by higher fasting plasma glucose levels than wild-type mice. Assessments by hyperinsulinemic-euglycemic clamp and a glucose tolerance test revealed no differences in insulin sensitivity or overt pancreatic function, respectively. Renal cortical mRNA expression and enzyme activity of glucose-6-phosphatase, which catalyzes the final step of glucose production, were significantly higher in knockout mice. Taken together, these results support a role for insulin receptor in the proximal tubule in the modulation of systemic glucose levels. Downregulation of the insulin receptor in the proximal tubule, which occurs in insulin-resistant states, may promote hyperglycemia through enhanced gluconeogenesis.
Experimental Subendocardial Ischemia in Dogs with Normal Coronary Arteries
Authors: GERALD D. BUCKBERG, DAVID E. FIXLER, JOSEPH P. ARCHIE, JULIEN I.E. HOFFMAN
Journal: Circulation Research (1972)

Subendocardial ischemia without anatomic coronary artery obstruction may result from a discrepancy between metabolic needs and available blood supply. We studied this in open-chest anesthetized dogs and measured pressures in aorta and left ventricle (LV), phasic left coronary arterial blood flow (CBF) by electromagnetic flowmeter, total CBF and LV subendocardial (endo) and subepicardial (epi) flow with radioactive microspheres 8-10µ, in diameter. Since LV Subendocardial flow is mainly or entirely diastolic, it should depend on coronary driving pressure and duration of diastole (i.e., the area between aortic and left ventricular diastolic pressures). This diastolic pressure time index (DPTI) was varied by opening arteriovenous fistulas to lower aortic diastolic pressure, constricting the ascending aorta to raise LV diastolic pressure and pacing to shorten diastole. Myocardial oxygen needs were estimated from the tension time index (TTI). Normal endo-epi flow ratios per gram (1:1) fell to 0.1:1 with these procedures and paralleled a fall in diastolic flow fraction (often nearly zero) and postischemic coronary reactive hyperemic responses. These changes occurred despite normal or raised mean CBF and 300-500% increase in systolic CBF. The altered flow ratios were best predicted by relating them to the ratio of DPTI (supply) to TTI (demand).
Cataracts associated with long-term topical steroids
Authors: C. Costagliola, B. Cati-Giovannelli, A. Piccirillo, M. Delfino
Journal: British Journal of Dermatology (1989)

Journal Article Cataracts associated with long‐term topical steroids Get access C. Costagliola, C. Costagliola Eye Clinic, 1st School of Medicine, University of Naples, Naples, Italy. Search for other works by this author on: Oxford Academic Google Scholar B. Cati‐Giovannelli, B. Cati‐Giovannelli Rieti General Hospital, Rieti, Italy. Search for other works by this author on: Oxford Academic Google Scholar A. Piccirillo, A. Piccirillo Department of Dermatology, 2nd School of Medicine, University of Naples, Naples, Italy. Search for other works by this author on: Oxford Academic Google Scholar M. Delfino M. Delfino Department of Dermatology, 2nd School of Medicine, University of Naples, Naples, Italy. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 120, Issue 3, 1 March 1989, Pages 472–473, https://doi.org/10.1111/j.1365-2133.1989.tb04181.x Published: 01 March 1989
Reoxygenation of Hypoxic Human Umbilical Vein Endothelial Cells Activates the Classic Complement Pathway
Authors: Charles D. Collard, Antti Väkevä, Cüneyt Büküsoglu, Gregor Zünd, C. John Sperati, Sean P. Colgan, Gregory L. Stahl
Journal: Circulation (1997)

Background Ischemia-reperfusion injury leads to the activation and endothelial deposition of complement. We investigated whether exposure of human umbilical vein endothelial cells (HUVECs) to hypoxia and/or reoxygenation activates complement and decreases HUVEC-surface expression of the C3 regulatory proteins CD46 and CD55. Methods and Results HUVECs were subjected to 0, 12, or 24 hours of hypoxia (O 2 =1%) and then reoxygenated for 3 hours (O 2 =21%) in the presence of 30% human serum. C3 deposition and HUVEC-surface expression of CD46 and CD55 were evaluated by ELISA and flow cytometry. C3 deposition on HUVECs subjected to 12 or 24 hours of hypoxia followed by 3 hours of reoxygenation was significantly greater than normoxic HUVECs. Inhibition of the classic but not the alternative complement pathway during reoxygenation attenuated C3 deposition. Western blot analysis of HUVEC lysates under reducing conditions demonstrated significantly increased iC3b deposition in hypoxic/reoxygenated HUVECs compared with normoxic HUVECs. FACS analysis confirmed iC3b deposition. HUVEC-surface expression of CD46 and CD55 increased after hypoxia and/or reoxygenation. Conclusions We conclude that (1) hypoxia and reoxygenation of HUVECs significantly increases iC3b deposition on HUVECs, (2) C3 deposition after hypoxia and reoxygenation is largely mediated by the classic complement pathway, and (3) HUVEC-surface expression of CD46 and CD55 increases after hypoxia and reoxygenation. These data demonstrate that hypoxia and reoxygenation of human endothelial cells activates the classic complement pathway despite an increase in complement C3 regulatory proteins.
705 PEGINTERFERON ALFA-2A [40KD] PLUS ADEFOVIR FOR 96 WEEKS IN HBEAG-NEGATIVE CHB RESULTS IN HIGH RATES OF HBSAG CLEARANCE/SEROCONVERSION
Authors: Z. Cao, H. Yu, L. Ma, Y. Zhang, Y. Liu, B. Ma, H. Wu, X. Chen
Journal: Journal of Hepatology (2011)
Activity limitations and participation restrictions in women with hand osteoarthritis: patients' descriptions and associations between dimensions of functioning
Authors: I Kjeken
Journal: Annals of the Rheumatic Diseases (2005)

To describe the functional consequences of hand osteoarthritis, and analyse associations between personal factors, hand impairment, activity limitations, and participation restrictions within the framework of the International Classification of Functioning (ICF).87 women with hand osteoarthritis completed a clinical examination including recording of sociodemographic data, measures of hand impairment, and completion of self reported health status measures. The function subscale of the AUSCAN Osteoarthritis Hand Index was used as a measure of hand related activity limitations, while the Canadian Occupational Performance Measure (COPM) was used to describe and measure activity limitations and participation restrictions as perceived by the individual. The study variables were categorised using the dimensions in the ICF framework and analysed using bivariate and multivariate statistical approaches.The patients described problems in many domains of activity and participation. The most frequently described hand related problems were activities requiring considerable grip strength combined with twisting of the hands. On the impairment level, the patients had reduced grip force and joint mobility in the hands, and resisted motion was painful. Regression analyses showed that hand related activity limitations were associated with measures of hand impairment, while activity and participation (as measured by the COPM) were more strongly associated with personal factors than with hand impairment.Hand osteoarthritis has important functional consequences in terms of pain, reduced hand mobility and grip force, activity limitations, and participation restrictions. Rehabilitation programmes should therefore be multidisciplinary and multidimensional, focusing on hand function, occupational performance, and coping strategies.