tbuckley/cabot-search huggingface dataset:
Leptin's Role in Lipodystrophic and Nonlipodystrophic Insulin-Resistant and Diabetic Individuals
Authors: Hyun-Seuk Moon, Maria Dalamaga, Sang-Yong Kim, Stergios A. Polyzos, Ole-Petter Hamnvik, Faidon Magkos, Jason Paruthi, Christos S. Mantzoros
Journal: Endocrine Reviews (2013)

Abstract Leptin is an adipocyte-secreted hormone that has been proposed to regulate energy homeostasis as well as metabolic, reproductive, neuroendocrine, and immune functions. In the context of open-label uncontrolled studies, leptin administration has demonstrated insulin-sensitizing effects in patients with congenital lipodystrophy associated with relative leptin deficiency. Leptin administration has also been shown to decrease central fat mass and improve insulin sensitivity and fasting insulin and glucose levels in HIV-infected patients with highly active antiretroviral therapy (HAART)-induced lipodystrophy, insulin resistance, and leptin deficiency. On the contrary, the effects of leptin treatment in leptin-replete or hyperleptinemic obese individuals with glucose intolerance and diabetes mellitus have been minimal or null, presumably due to leptin tolerance or resistance that impairs leptin action. Similarly, experimental evidence suggests a null or a possibly adverse role of leptin treatment in nonlipodystrophic patients with nonalcoholic fatty liver disease. In this review, we present a description of leptin biology and signaling; we summarize leptin's contribution to glucose metabolism in animals and humans in vitro, ex vivo, and in vivo; and we provide insights into the emerging clinical applications and therapeutic uses of leptin in humans with lipodystrophy and/or diabetes.
Studies of Blood Flow in Aorta-to-Coronary Venous Bypass Grafts in Man
Authors: Joseph C. Greenfield, Judith C. Rembert, W. Glenn Young, H. Newland Oldham, James A. Alexander, David C. Sabiston
Journal: Journal of Clinical Investigation (1972)

Pressure-flow measurements were obtained from the vein graft of 57 patients undergoing a single aorta-to-coronary bypass procedure. The flow contour was similar to phasic left coronary artery flow in dogs except for a transient increase during systole possibly related to elongation of the graft. Flow was highest during bypass and decreased to a stable value 30 min after bypass. In 42 patients, flow at this time was 35+/-2 cm(3)/min (mean+/-sem).NO CORRELATIONS WERE DEMONSTRATED BETWEEN FLOW AND THE FOLLOWING: left vs. right grafts, presence or absence of collaterals, total vs. partial block, or the presence or absence of ventricular dyskinesis. In 32 patients, no correlation between these anatomic findings and the presence of reactive hyperemia was demonstrated. In 17 patients, occlusion of the graft for 10 sec resulted in a mean 51.5% flow debt repayment. In nine patients, injection of 0.3 mug of isoproterenol into the graft increased flow from 45+/-6 to 69+/-9 cm(3)/min within 4-7 sec without changes in rate, pressure, time derivative of left ventricular pressure (LV dp/dt), or left ventricular end diastolic pressure (LVEDP). Maximum increases to 87+/-10 cm(3)/min occurred 12-20 sec after injection with concomitant changes in these parameters. Intravenous infusion of norepinephrine did not change vascular resistance, whereas phenylephrine did. In six patients, injection of 0.2 mug of norepinephrine into the graft decreased flow from 49+/-6 to 25+/-5 cm(3)/min within 5-8 sec. Intravenous infusion of 0.15 mg of nitroglycerin decreased coronary vascular resistance from 2.7+/-0.4 to 2.3+/-0.3 mm Hg/cm(3) per min. In five patients, 0.12 mg of nitroglycerin injected into the graft increased flow from 46+/-7 to 71+/-13 cm(3)/min and lasted 20-40 sec.
Fate of bone marrow-derived cultured mast cells after intracutaneous, intraperitoneal, and intravenous transfer into genetically mast cell-deficient W/Wv mice. Evidence that cultured mast cells can give rise to both connective tissue type and mucosal mast cells.
Authors: T Nakano, T Sonoda, C Hayashi, A Yamatodani, Y Kanayama, T Yamamura, H Asai, T Yonezawa, Y Kitamura, S J Galli
Journal: The Journal of Experimental Medicine (1985)

Both connective tissue mast cells and mast cells grown in vitro are derived from multipotential hematopoietic stem cells, but these two mast cell populations exhibit many differences in morphology, biochemistry, and function. We investigated whether the phenotype of cultured mast cells or their progeny was altered when the cells were transferred into different locations in vivo. Cultured mast cells were immature by ultrastructure, and stained with alcian blue but with neither safranin or berberine sulfate, a fluorescent dye that binds to the heparin of connective tissue mast cell granules. By contrast, mast cells recovered from the peritoneal cavity of congenitally mast cell-deficient (WB X C57BL/6)F1-W/Wv (WBB6F1-W/Wv) mice 10 wk after intraperitoneal injection of cultured WBB6F1-+/+ or C57BL/6-bgJ/bgJ mast cells stained with both safranin and berberine sulfate. Staining with berberine sulfate was prevented by treatment of the cells with heparinase but not chondroitinase ABC, suggesting that the adoptively transferred mast cell population had acquired the ability to synthesize and store heparin. Furthermore, the recovered mast cells were indistinguishable by ultrastructure from the normal mature peritoneal mast cells of WBB6F1-+/+ mice, and contained substantially more histamine than mast cells studied directly from culture. Intravenous injection of cultured mast cells resulted in the development of safranin-and berberine sulfate-positive mast cells in the peritoneal cavity, spleen, skin, and glandular stomach muscularis propria. Mast cells also developed on the glandular stomach mucosa, but these cells stained with alcian blue rather than safranin, and did not stain with berberine sulfate. This result suggests that cultured mast cells can give rise to mast cells of either the connective tissue type or mucosal phenotype, depending on anatomical location. Furthermore, transplantation of cultured mast cells into WBB6F1-W/Wv mice had no measurable effect on the anemia of the recipient mice, suggesting a possible strategy for repairing the mast cell deficiency of WBB6F1-W/Wv mice without affecting other bone marrow-derived populations such as erythrocytes. Intravenous injection of representative connective tissue type mast cells (30-50% pure peritoneal mast cells derived from WBB6F1-+/+ mice) gave results similar to those obtained with cultured mast cells: mast cells developing in the peritoneal cavity, skin, spleen, and glandular stomach muscularis propria of WBB6F1-W/Wv recipients stained with safranin and berberine sulfate, whereas mast cells developing in the mucosa of the glandular stomach stained only with alcian blue.(ABSTRACT TRUNCATED AT 400 WORDS)
Proliferation accurately identifies the high-risk patients among small, low-grade, lymph node-negative invasive breast cancers
Authors: J.P.A. Baak, P.J. van Diest, E.A.M. Janssen, E. Gudlaugsson, F.J. Voorhorst, E. van der Wall, J.B. Vermorken
Journal: Annals of Oncology (2007)
Coffee, Tea, and Caffeine Consumption and Incidence of Colon and Rectal Cancer
Authors: K. B. Michels, W. C. Willett, C. S. Fuchs, E. Giovannucci
Journal: JNCI Journal of the National Cancer Institute (2005)

Background: Frequent coffee consumption has been associated with a reduced risk of colorectal cancer in a number of case–control studies. Cohort studies have not revealed such an association but were limited in size. We explored the association between consumption of coffee and tea and the incidence of colorectal cancer in two large prospective cohorts of women and men. Methods: We used data from the Nurses' Health Study (women) and the Health Professionals' Follow-up Study (men). Consumption of coffee and tea and total caffeine intake were assessed and updated in 1980, 1984, 1986, 1990, and 1994 among women and in 1986, 1990, and 1994 among men. The incidence of cancer of the colon or rectum was ascertained through 1998. Hazard ratios were calculated using Cox proportional hazards models that adjusted for potential confounders. All tests of statistical significance were two-sided. Results: During almost 2 million person-years of follow-up, 1438 cases of colorectal cancer were observed. Consumption of caffeinated coffee or tea with caffeine or caffeine intake was not associated with the incidence of colon or rectal cancer in either cohort. For both cohorts combined, the covariate-adjusted hazard ratio for colorectal cancer associated with consumption of each additional cup of caffeinated coffee was 0.99 (95% confidence interval [CI] = 0.96 to 1.03). However, participants who regularly consumed two or more cups of decaffeinated coffee per day had a 52% (95% CI = 19% to 71%) lower incidence of rectal cancer than those who never consumed decaffeinated coffee. Conclusions: Consumption of caffeinated coffee, tea with caffeine, or caffeine was not associated with incidence of colon of rectal cancer, whereas regular consumption of decaffeinated coffee was associated with a reduced incidence of rectal cancer.
Identifying outcome reporting bias in randomised trials on PubMed: review of publications and survey of authors
Authors: An-Wen Chan, Douglas G Altman
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objective</b> To examine the extent and nature of outcome reporting bias in a broad cohort of published randomised trials. <b>Design</b> Retrospective review of publications and follow up survey of authors. <b>Cohort</b> All journal articles of randomised trials indexed in PubMed whose primary publication appeared in December 2000. <b>Main outcome measures</b> Prevalence of incompletely reported outcomes per trial; reasons for not reporting outcomes; association between completeness of reporting and statistical significance. <b>Results</b> 519 trials with 553 publications and 10 557 outcomes were identified. Survey responders (response rate 69%) provided information on unreported outcomes but were often unreliable—for 32% of those who denied the existence of such outcomes there was evidence to the contrary in their publications. On average, over 20% of the outcomes measured in a parallel group trial were incompletely reported. Within a trial, such outcomes had a higher odds of being statistically non-significant compared with fully reported outcomes (odds ratio 2.0 (95% confidence interval 1.6 to 2.7) for efficacy outcomes; 1.9 (1.1 to 3.5) for harm outcomes). The most commonly reported reasons for omitting efficacy outcomes included space constraints, lack of clinical importance, and lack of statistical significance. <b>Conclusions</b> Incomplete reporting of outcomes within published articles of randomised trials is common and is associated with statistical non-significance. The medical literature therefore represents a selective and biased subset of study outcomes, and trial protocols should be made publicly available.
The specific inhibitor of RORγt transcriptional activity and Th17 polarisation digoxin reduces the severity of adjuvant-induced arthritis
Authors: Rita Cascão, Bruno Vidal, João Eurico Fonseca, Luis Ferreira Moita
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> The authors have previously reported an increase of interleukin (IL)-17 levels during the first weeks of rheumatoid arthritis onset. <h3>Objectives</h3> Our main goal here was to investigate whether administration of digoxin, a specific inhibitor of Th17 cells polarisation, is able to attenuate inflammation in a rat model of adjuvant-induced arthritis (AIA). <h3>Materials and methods</h3> Digoxin was administered to AIA rats in the early phase (4 days after disease induction) or in the established phase of arthritis (11 days after disease induction). The inflammatory score, paw perimeter and body weight were evaluated during the period of treatment. Rats were killed after 19 days of disease evolution and paw samples were collected for histological and immunohistochemical evaluation. <h3>Results</h3> The authors found that digoxin administration significantly suppressed joint inflammation if administrated in the early phase of disease course. The histological and immunohistochemical evaluation revealed that digoxin treatment was not efficient in inhibiting the infiltration of immune cells within the joint, but it was able to reduce local immune cells proliferation, if administrated in the early phase of arthritis. <h3>Conclusions</h3> Early inhibition of Th17 polarisation ameliorates AIA but does not inhibit immune cell infiltration into the joints.
PI3Kδ Inhibition by Idelalisib in Patients with Relapsed Indolent Lymphoma
Authors: Ajay K. Gopal, Brad S. Kahl, Sven de Vos, Nina D. Wagner-Johnston, Stephen J. Schuster, Wojciech J. Jurczak, Ian W. Flinn, Christopher R. Flowers, Peter Martin, Andreas Viardot, Kristie A. Blum, Andre H. Goy, Andrew J. Davies, Pier Luigi Zinzani, Martin Dreyling, Dave Johnson, Langdon L. Miller, Leanne Holes, Daniel Li, Roger D. Dansey, Wayne R. Godfrey, Gilles A. Salles
Journal: New England Journal of Medicine (2014)

Phosphatidylinositol-3-kinase delta (PI3Kδ) mediates B-cell receptor signaling and microenvironmental support signals that promote the growth and survival of malignant B lymphocytes. In a phase 1 study, idelalisib, an orally active selective PI3Kδ inhibitor, showed antitumor activity in patients with previously treated indolent non-Hodgkin's lymphomas.
HIGH INCIDENCE OF CARDIAC MAGNETIC RESONANCE IMAGING FINDINGS IN PATIENTS WITH HIGH GRADE VENTRICULAR ARRHYTHMIAS WITHOUT PREVIOUSLY KNOWN HEART DISEASE
Authors: Jutta Weisser-Thomas, Claas Naehle, Victor Ferrari, Lars Lickfett, Georg Nickenig, Hans Schild, Daniel Thomas
Journal: Journal of the American College of Cardiology (2011)
The Association between Phthalates in Dust and Allergic Diseases among Bulgarian Children
Authors: Barbara Kolarik, Kiril Naydenov, Malin Larsson, Carl-Gustaf Bornehag, Jan Sundell
Journal: Environmental Health Perspectives (2007)

BackgroundRecent studies have identified associations between the concentration of phthalates in indoor dust and allergic symptoms in the airways, nose, and skin.ObjectivesOur goal was to investigate the associations between allergic symptoms in children and the concentration of phthalate esters in settled dust collected from children's homes in Sofia and Burgas, Bulgaria.MethodsDust samples from the child's bedroom were collected. A total of 102 children (2–7 years of age) had symptoms of wheezing, rhinitis, and/or eczema in preceding 12 months (cases), and 82 were nonsymptomatic (controls). The dust samples were analyzed for their content of dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DnBP), butyl benzyl phthalate (BBzP), di(2-ethylhexyl) phthalate (DEHP), and di-n-octyl phthalate (DnOP).ResultsA higher concentration of DEHP was found in homes of case children than in those of controls (1.24 vs. 0.86 mg/g dust). The concentration of DEHP was significantly associated with wheezing in the preceding 12 months (p = 0.035) as reported by parents. We found a dose–response relationship between DEHP concentration and case status and between DEHP concentration and wheezing in the preceding 12 months.ConclusionsThis study shows an association between concentration of DEHP in indoor dust and wheezing among preschool children in Bulgaria.
Atenolol: once-daily cardioselective beta blockade for angina pectoris.
Authors: G Jackson, J Schwartz, R E Kates, M Winchester, D C Harrison
Journal: Circulation (1980)

The physiology, pharmacokinetics and efficacy of atenolol, a cardioselective beta-adrenergic blocking agent, were evaluated in 10 patients with stable angina pectoris in a single-blind, dose-ranging study. After a 1-month control placebo period, atenolol was administered once daily at dosages of 25, 50, 100 and 200 mg for 2-week periods. All patients had fewer anginal attacks and consumed fewer nitroglycerin tablets than mg for 2-week periods. All patients had fewer anginal attacks and consumed fewer nitroglycerin tablets than during the placebo period. Twenty-four-hour ambulatory ECG recordings showed a decrease in mean hourly heart rate throughout the dosing period, with preservation of diurnal variation. Maximal, symptom-limited, treadmill exercise tests performed 3 hours after drug ingestion showed significantly increased exercise time and decreased double products for all doses, but especially with 100-mg and 200-mg doses. Exercise time 24 hours after drug ingestion continued to show a decrease in maximum heart rate and double product, with 100-mg and 200-mg doses again being most effective. Atenolol serum levels correlated with percent reduction in exercise heart rate and increased exercise time. Serum levels rose linearly, with an average elimination half-life of about 10 hours after chronic oral dosing. Thus, atenolol was an effective antianginal agent and suppressed resting and exercise-stressed heart rate for 24 hours after ingestion when given in a 100-mg or 200-mg dose once daily.
The American Heart Association's Recommendations for Expanding the Applications of Existing and Future Clinical Registries
Authors: Vincent J. Bufalino, Frederick A. Masoudi, Steven K. Stranne, Katie Horton, Nancy M. Albert, Craig Beam, Robert O. Bonow, Roger L. (Vern) Davenport, Meighan Girgus, Gregg C. Fonarow, Harlan M. Krumholz, Mark W. Legnini, William R. Lewis, Graham Nichol, Eric D. Peterson, Wayne Rosamond, John S. Rumsfeld, Lee H. Schwamm, David M. Shahian, John A. Spertus, Pamela K. Woodard, Clyde W. Yancy
Journal: Circulation (2011)
Risk of deep venous thrombosis and pulmonary embolism in individuals with polymyositis and dermatomyositis: a general population-based study
Authors: Erin C Carruthers, Hyon K Choi, Eric C Sayre, J Antonio Aviña-Zubieta
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background/objective</h3> Patients with polymyositis (PM) and dermatomyositis (DM) may have an increased risk of venous thromboembolism (VTE); however, no general population data are available to date. The purpose of this study was to estimate the future risk and time trends of new VTE (deep venous thrombosis (DVT) or pulmonary embolism (PE)) in individuals with incident PM/DM at the general population level. <h3>Methods</h3> We assembled a retrospective cohort of all patients with incident PM/DM in British Columbia and a corresponding comparison cohort of up to 10 age-matched, sex-matched and entry-time-matched individuals from the general population. We calculated incidence rate ratios (IRR) for VTE, DVT and PE and stratified by disease duration. We calculated HRs adjusting for relevant confounders. <h3>Results</h3> Among 752 cases with inflammatory myopathies, 443 had PM (58% female, mean age 60 years) and 355 had DM (65% female, mean age 56 years); 46 subjects developed both diseases. The corresponding IRRs (95% CI) for VTE, DVT and PE in PM were 8.14 (4.62 to 13.99), 6.16 (2.50 to 13.92) and 9.42 (4.59 to 18.70), respectively. Overall, the highest IRRs for VTE, DVT and PE were observed in the first year after PM diagnosis (25.25, 9.19 and 38.74, respectively). Fully adjusted HRs for VTE, DVT and PE remained statistically significant (7.0 (3.34 to 14.64), 6.16 (2.07 to 18.35), 7.23 (2.86 to 18.29), respectively). Similar trends were seen in DM. <h3>Conclusions</h3> These findings provide the first general population-based evidence that patients with PM/DM have an increased risk of VTE. Increased vigilance of this serious but preventable complication is recommended.
High plasma levels of atrial natriuretic peptide in preascitic cirrhosis: Indirect evidence of reduced natriuretic effectiveness of the peptide
Authors: Franco Trevisani, Alessandra Colantoni, Giuseppe Sica, Antonio Gasbarrini, Paola Emanuela D'Intino, Stefania De Notariis, Rosaria De Jaso, Annarita Barbieri, Antonello Morselli, Giovanni Gasbarrini, Mauro Bernardi
Journal: Hepatology (1995)

Controversial results come from spot measurements of plasma atrial natriuretic peptide (ANP) in compensated cirrhotic patients. Moreover, either blunted or exaggerated natriuresis has been described after maneuvers increasing plasma ANP. This does not make it possible to delineate the ANP effectiveness. Plasma ANP, renin activity (PRA) and aldosterone and hematocrit were serially measured (7 AM, 9 AM, 6 PM, and 11 PM) in nine preascitic cirrhotic outpatients and in nine healthy subjects on normal sodium diet (150 mmol/day) and carrying on their usual activities (mobile from 7 AM to 10 PM). Daily natriuresis was monitored the day before and during the study. In both groups, ANP peaked at the end of the recumbence period (7 AM) and declined on the assumption of the upright position, so that both ANP values of the standing period were significantly lower than the mean daily level. These fluctuations were reciprocal to PRA and hematocrit changes. Patients showed steadily elevated plasma ANP and reduced PRA (ANP mean daily level: 33.3 ± 3.8 vs. 15.5 ± 3.2 pg/mL, P = .004; PRA: 0.76 ± 0.23 vs. 1.66 ± 0.21 ng/mL/hr, P = .003). Aldosterone fluctuations and mean daily level were similar in the two groups (mean daily level: 122 ± 11 vs. 119 ± 9 pg/mL). Natriuresis was well adapted to the sodium intake and similar in healthy subjects (day 1: 152 ± 11 mmol; day 2: 138 ± 12.5 mmol) and patients (143 ± 15 mmol; 148 ± 29 mmol). Preascitic cirrhotic patients on a normal salt intake and carrying on their usual activities develop a new steady state requiring increased ANP levels to maintain a sodium balance. In addition to a reduced renal sensitivity to ANP, several subtle abnormalities of the antinatriuretic forces may yield the renal hyporesponsiveness to the peptide. (Hepatology 1995; 22:132-137.)