tbuckley/cabot-search huggingface dataset:
Ultrasonographic hepatic steatosis increases prediction of mortality risk from elevated serum gamma-glutamyl transpeptidase levels
Authors: Robin Haring, Henri Wallaschofski, Matthias Nauck, Marcus Dörr, Sebastian E. Baumeister, Henry Völzke
Journal: Hepatology (2009)

Abstract The aim of the present study was to investigate the association of serum gamma-glutamyltransferase (GGT) levels with all-cause mortality and to assess the impact of ultrasonographic findings of hepatic hyperechogenicity in that association. We used data from 4,160 subjects (2,044 men and 2,116 women) recruited for the population-based Study of Health in Pomerania (SHIP) without baseline hepatitis B and C infections or liver cirrhosis. GGT was divided into age- and sex-dependent quintiles to calculate overall and sex-specific crude incidence mortality rates. Hepatic steatosis was defined by elevated GGT levels (&gt;80%) and the presence of hyperechogenic liver ultrasound. We used multiple-adjusted Cox proportional hazards regression models, first, to assess the direct effect of GGT on all-cause mortality, second, to stratify according to the ultrasonographic finding, and third, to investigate potential mediating effects of cardiometabolic risk factors. During 29,810 person-years (7.3 years, median) of follow-up, 307 individuals (7.5%) died, resulting in a death rate of 0.86 deaths per 1000 person-years. Elevated GGT levels were associated with increased risk of mortality in men (hazard ratio [HR] 1.49; 95% confidence interval [CI], 1.08–2.05), but not in women (HR 1.30; 95% CI, 0.80–2.12). This association was even stronger in men with hepatic steatosis (HR 1.98; 95% CI, 1.21–3.27). Cause-specific mortality analysis by cardiovascular disease deaths confirmed the sex-specific association. Adjustment for cardiometabolic risk factors did not affect the estimates. Conclusion: In the case of increased GGT levels, liver ultrasound should be performed, not only for diagnosis, but also for further risk stratification. (Hepatology 2009.)
Partial vs Single Aortic Clamping
Authors: Michael D. Crittenden
Journal: JAMA Surgery (2015)

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Foretinib (GSK1363089), an Orally Available Multikinase Inhibitor of c-Met and VEGFR-2, Blocks Proliferation, Induces Anoikis, and Impairs Ovarian Cancer Metastasis
Authors: Marion Zillhardt, Sun-Mi Park, Iris L. Romero, Kenjiro Sawada, Anthony Montag, Thomas Krausz, S. Diane Yamada, Marcus E. Peter, Ernst Lengyel
Journal: Clinical Cancer Research (2011)

Currently, there are no approved targeted therapies for the treatment of ovarian cancer, despite the fact that it is the most lethal gynecological malignancy. One proposed target is c-Met, which has been shown to be an important prognostic indicator in a number of malignancies, including ovarian cancer. The objective of this study was to determine whether an orally available multikinase inhibitor of c-Met and vascular endothelial growth factor receptor-2 (foretinib, GSK1363089) blocks ovarian cancer growth.The effect of foretinib was tested in a genetic mouse model of endometrioid ovarian cancer, several ovarian cancer cell lines, and an organotypic 3D model of the human omentum.In the genetic mouse model, treatment with foretinib prevented the progression of primary tumors to invasive adenocarcinoma. Invasion through the basement membrane was completely blocked in treated mice, whereas in control mice, invasive tumors entirely replaced the normal ovary. In 2 xenograft mouse models using human ovarian cancer cell lines, the inhibitor reduced overall tumor burden (86% inhibition, P < 0.0001) and metastasis (67% inhibition, P < 0.0001). The mechanism of inhibition by foretinib involved (a) inhibition of c-Met activation and downstream signaling, (b) reduction of ovarian cancer cell adhesion, (c) a block in migration and invasion, (d) reduced proliferation mediated by a G(2)-M cell-cycle arrest, and (e) induction of anoikis.This study shows that foretinib blocks tumorigenesis and reduces invasive tumor growth in different models of ovarian cancer by affecting several critical tumor functions. We believe that it provides a rationale for the further clinical development of foretinib for the treatment of ovarian cancer.
Increased deoxycholic acid absorption and gall stones in acromegalic patients treated with octreotide: more evidence for a connection between slow transit constipation and gall stones
Authors: A F Hofmann
Journal: Gut (2005)

Acromegalic patients treated with octreotide have prolonged colonic transit, increased bacterial formation, and subsequent absorption of deoxycholic acid that is indicated by an increased proportion of deoxycholic acid in plasma bile acids. Enrichment of deoxycholic acid in the circulating bile acid pool leads to supersaturated bile and cholesterol gall stones.

Thomas and colleagues,1 in this issue of Gut , extend previous work from the laboratory of R Hermon Dowling by showing that acromegalic patients treated with octreotide have an increase in faecal anaerobic bacteria that convert cholic acid, the major primary bile acid in humans, to deoxycholic acid, the major secondary bile acid (see page 630) . The paper also confirms previous reports from the Dowling laboratory2,3 that octreotide treatment increases colonic transit time in acromegalic patients. In addition, the paper of Thomas et al shows that octreotide treatment results in enrichment of deoxycholic acid in fasting state plasma bile acids. 

The present paper is the 11th and could well be the last in a series of papers spanning more than a decade from the Dowling laboratory that have dealt with the pathogenesis of gall stones in acromegalic patients treated with octreotide, a potent somatostatin agonist. Octreotide is a synthetic peptide whose amide bonds are resistant to hydrolysis by plasma peptidases, thus resulting in its having a much longer duration of action than that of somatostatin.4 In acromegalic patients, octreotide administration suppresses the release of growth hormone and insulin growth factor by the pituitary and results in clinical improvement.5

The initial paper in this series showed that such patients have an increased prevalence of gall stones.6 The gall stones were shown to be rich in cholesterol7 and, as would be expected, bile was found to be supersaturated in cholesterol8 and to …
Soy Protein Intake, Cardiorenal Indices, and C-Reactive Protein in Type 2 Diabetes With Nephropathy
Authors: Leila Azadbakht, Shahnaz Atabak, Ahmad Esmaillzadeh
Journal: Diabetes Care (2008)

Several short-term trials on the effect of soy consumption on cardiovascular risks are available, but little evidence exists regarding the impact of long-term soy protein consumption among type 2 diabetic patients with nephropathy. To determine the effects of long-term soy consumption on cardiovascular risks, we measured C-reactive protein (CRP) and kidney function indexes among type 2 diabetic patients with nephropathy.This longitudinal randomized clinical trial was conducted among 41 type 2 diabetic patients with nephropathy (18 men and 23 women). Twenty patients in the soy protein group consumed a diet containing 0.8 g protein/kg body weight (35% animal proteins, 35% textured soy protein, and 30% vegetable proteins) and 21 patients in the control group consumed a similar diet containing 70% animal proteins and 30% vegetable proteins for 4 years.Soy protein consumption significantly affected cardiovascular risks such as fasting plasma glucose (mean change in the soy protein versus control groups: -18 +/- 3 vs. 11 +/- 2 mg/dl; P = 0.03), total cholesterol (-23 +/- 5 vs. 10 +/- 3 mg/dl; P = 0.01), LDL cholesterol (-20 +/- 5 vs. 6 +/- 2 mg/dl; P = 0.01), and serum triglyceride (-24 +/- 6 vs. -5 +/- 2 mg/dl; P = 0.01) concentrations. Serum CRP levels were significantly decreased by soy protein intake compared with those in the control group (1.31 +/- 0.6 vs. 0.33 +/- 0.1 mg/l; P = 0.02). Significant improvements were also seen in proteinuria (-0.15 +/- 0.03 vs. 0.02 +/- 0.01 g/day; P = 0.001) and urinary creatinine (-1.5 +/- 0.9 vs. 0.6 +/- 0.3 mg/dl, P = 0.01) by consumption of soy protein.Longitudinal soy protein consumption significantly affected cardiovascular risk factors and kidney-related biomarkers among type 2 diabetic patients with nephropathy.
Video-assisted thoracic surgery and extramedullary haematopoiesis
Authors: C. S. H. Ng
Journal: European Respiratory Journal (2006)

Importantly, K. Challen and co-workers fail to mention that PMEWS is a graded score for each parameter, rather than the categorical scores used in CURB, making PMEWS inherently more complex to use, especially outside the hospital.In addition, CRB-65 can be calculated without any laboratory or oximetric results.The medical early warning score has the potential advantages of not being disease specific, and familiarity of use in some UK hospitals at least, for the assessment of patients already admitted to hospital.However, we know of no studies reporting its use as a tool for the hospital admission decision.
Failure to Maintain a Low ADP Concentration Impairs Diastolic Function in Hypertrophied Rat Hearts
Authors: Rong Tian, Luigino Nascimben, Joanne S. Ingwall, Beverly H. Lorell
Journal: Circulation (1997)

Background Mechanisms in addition to diastolic calcium overload may contribute to diastolic dysfunction in hypertrophied hearts. In this study, we tested the hypothesis that failure to maintain a low ADP concentration in hypertrophied hearts contributes to diastolic dysfunction by inhibiting the rate of cross-bridge cycling. Methods and Results By perfusing isolated rat hearts with pyruvate and 2-deoxyglucose (2DG), we were able to perturb [ADP] with minimal changes in [ATP] and [inorganic phosphate] or the contribution of glycolytic ATP to ATP synthesis. The effects of 2DG were compared in aortic-banded (LVH, n=5) and sham-operated (control, n=5) rat hearts. 31 P NMR spectroscopy was used to measure the concentrations of phosphorus-containing compounds. We found a threefold increase of left ventricular end-diastolic pressure (LVEDP) in LVH during 2DG perfusion, and this increase was concomitant with a threefold increase in intracellular free [ADP]. The [ADP] in the control hearts was maintained &lt;40 μmol/L, and no change in LVEDP was observed. A linear relationship between increases in [ADP] and LVEDP was found ( r 2 =.66, P =.001). Furthermore, the capacity of the creatine kinase reaction, a major mechanism for maintaining a low [ADP], was decreased in LVH ( P =.0001). Conclusions Increased [ADP] contributes to diastolic dysfunction in LVH, possibly due to slowed cross-bridge cycling. Decreased capacity of the creatine kinase reaction to rephosphorylate ADP is a likely contributing mechanism to the failure to maintain a low [ADP] in LVH.
Relationship between reduced forced expiratory volume in one second and the risk of lung cancer: a systematic review and meta-analysis
Authors: S Wasswa-Kintu
Journal: Thorax (2005)

<b>Background:</b> Individuals with severely impaired lung function have an increased risk of lung cancer. Whether milder reductions in forced expiratory volume in 1 second (FEV<sub>1</sub>) also increase the risk of lung cancer is controversial. Moreover, there is little consensus on whether men and women have similar risks for lung cancer for similar decreases in FEV<sub>1</sub>. <b>Methods:</b> A search was conducted of PubMed and EMBASE from January 1966 to January 2005 and studies that examined the relationship between FEV<sub>1</sub> and lung cancer were identified. The search was limited to studies that were population based, employed a prospective design, were large in size (⩾5000 participants), and adjusted for cigarette smoking status. <b>Results:</b> Twenty eight abstracts were identified, six of which did not report FEV<sub>1</sub> and eight did not adjust for smoking. Included in this report are four studies that reported FEV<sub>1</sub> in quintiles. The risk of lung cancer increased with decreasing FEV<sub>1</sub>. Compared with the highest quintile of FEV<sub>1</sub> (&gt;100% of predicted), the lowest quintile of FEV<sub>1</sub> (&lt;∼70% of predicted) was associated with a 2.23 fold (95% confidence interval (CI) 1.73 to 2.86) increase in the risk for lung cancer in men and a 3.97 fold increase in women (95% CI 1.93 to 8.25). Even relatively small decrements in FEV<sub>1</sub> (∼90% of predicted) increased the risk for lung cancer by 30% in men (95% CI 1.05 to 1.62) and 2.64 fold in women (95% CI 1.30 to 5.31). <b>Conclusion:</b> Reduced FEV<sub>1</sub> is strongly associated with lung cancer. Even a relatively modest reduction in FEV<sub>1</sub> is a significant predictor of lung cancer, especially among women.
Intestinal permeability in patients with Crohn's disease and their first degree relatives.
Authors: K Teahon, P Smethurst, A J Levi, I S Menzies, I Bjarnason
Journal: Gut (1992)

It has been reported that intestinal permeability to polyethylene glycol 400 is increased in patients with Crohn's disease and their apparently unaffected first degree relatives. Because of the implications that these findings have for the aetiology of Crohn's disease these studies were repeated. Patients with Crohn's disease (n = 28) and 32 first degree relatives from 11 families underwent a polyethylene glycol 400 (PEG400) intestinal permeability test and a hyperosmotic (1500 mosmol/l) absorption/permeability test using 3-0-methyl-D-glucose, D-xylose, L-rhamnose, lactulose, and 51chromium labelled ethylenediamine-tetraacetate. The five hour urine excretion of polyethylene glycol 400 did not differ significantly between controls (n = 25) and first degree relatives, 25.5 (3.3)% v 24.6% (4)% (mean(SD)) p greater than 0.1, respectively. Patients with small bowel involvement excreted significantly less (p less than 0.01) polyethylene glycol 400 (16.3 (4.6)% than controls while those with Crohn's colitis did not (26.4 (3.9)% p greater than 0.1). The permeation of the monosaccharides in patients with Crohn's disease and their first degree relatives did not differ from normal subjects. The permeation of lactulose and 51chromium ethylenediaminetetraacetate was not significantly altered in first degree relatives but was significantly increased in the patients, as was the lactulose/L-rhamnose urine excretion ratio which is a specific measure of small intestinal permeability. These studies show normal absorption and permeability in first degree relatives of patients with Crohn's disease. A genetically determined abnormality of intestinal permeability is not likely to be an important aetiological factor in Crohn's disease.
Oral Bisphosphonate Use and Risk of Postmenopausal Endometrial Cancer
Authors: Polly A. Newcomb, Michael N. Passarelli, Amanda I. Phipps, Garnet L. Anderson, Jean Wactawski-Wende, Gloria Y.F. Ho, Mary Jo O'Sullivan, Rowan T. Chlebowski
Journal: Journal of Clinical Oncology (2015)

Purpose Bisphosphonates are common medications used for the treatment of osteoporosis and are also used to reduce metastases to bone in patients with cancer. Several studies, including the Women's Health Initiative (WHI), have found that use of bisphosphonates is associated with reduced risk of developing breast cancer, but less is known about associations with other common malignancies. This study was aimed at examining the effects of bisphosphonates on the risk of endometrial cancer. Methods We evaluated the relationship between use of oral bisphosphonates and endometrial cancer risk in a cohort of 89,918 postmenopausal women participating in the WHI. A detailed health interview was conducted at baseline, and bisphosphonate use was ascertained from an inventory of regularly used medications at baseline and over follow-up. All women had an intact uterus at the time of study entry. Results During a median follow-up of 12.5 years, 1,123 women were diagnosed with incident invasive endometrial cancer. Ever use of bisphosphonates was associated with reduced endometrial cancer risk (adjusted hazard ratio, 0.80; 95% CI, 0.64 to 1.00; P = .05), with no interactions observed with age, body mass index, or indication for use. Conclusion In this large prospective cohort of postmenopausal women, bisphosphonate use was associated with a statistically significant reduction in endometrial cancer risk.
Performance and safety of the second-generation female condom (FC2) versus the Woman's, the VA worn-of-women, and the Cupid female condoms: a randomised controlled non-inferiority crossover trial
Authors: Mags E Beksinska, Gilda Piaggio, Jennifer A Smit, Junqing Wu, Yufeng Zhang, Jacqueline Pienaar, Ross Greener, Ying Zhou, Carol Joanis
Journal: The Lancet Global Health (2013)
Dabigatran versus Warfarin in the Treatment of Acute Venous Thromboembolism
Authors: Sam Schulman, Clive Kearon, Ajay K. Kakkar, Patrick Mismetti, Sebastian Schellong, Henry Eriksson, David Baanstra, Janet Schnee, Samuel Z. Goldhaber
Journal: New England Journal of Medicine (2009)

The direct oral thrombin inhibitor dabigatran has a predictable anticoagulant effect and may be an alternative therapy to warfarin for patients who have acute venous thromboembolism.In a randomized, double-blind, noninferiority trial involving patients with acute venous thromboembolism who were initially given parenteral anticoagulation therapy for a median of 9 days (interquartile range, 8 to 11), we compared oral dabigatran, administered at a dose of 150 mg twice daily, with warfarin that was dose-adjusted to achieve an international normalized ratio of 2.0 to 3.0. The primary outcome was the 6-month incidence of recurrent symptomatic, objectively confirmed venous thromboembolism and related deaths. Safety end points included bleeding events, acute coronary syndromes, other adverse events, and results of liver-function tests.A total of 30 of the 1274 patients randomly assigned to receive dabigatran (2.4%), as compared with 27 of the 1265 patients randomly assigned to warfarin (2.1%), had recurrent venous thromboembolism; the difference in risk was 0.4 percentage points (95% confidence interval [CI], -0.8 to 1.5; P<0.001 for the prespecified noninferiority margin). The hazard ratio with dabigatran was 1.10 (95% CI, 0.65 to 1.84). Major bleeding episodes occurred in 20 patients assigned to dabigatran (1.6%) and in 24 patients assigned to warfarin (1.9%) (hazard ratio with dabigatran, 0.82; 95% CI, 0.45 to 1.48), and episodes of any bleeding were observed in 205 patients assigned to dabigatran (16.1%) and 277 patients assigned to warfarin (21.9%; hazard ratio with dabigatran, 0.71; 95% CI, 0.59 to 0.85). The numbers of deaths, acute coronary syndromes, and abnormal liver-function tests were similar in the two groups. Adverse events leading to discontinuation of the study drug occurred in 9.0% of patients assigned to dabigatran and in 6.8% of patients assigned to warfarin (P=0.05).For the treatment of acute venous thromboembolism, a fixed dose of dabigatran is as effective as warfarin, has a safety profile that is similar to that of warfarin, and does not require laboratory monitoring. (ClinicalTrials.gov number, NCT00291330.)
Alopecia areata occurring during anti-TNF therapy: A national multicenter prospective study
Authors: Marie Tauber, Sébastien Buche, Pascal Reygagne, Jean-Marie Berthelot, François Aubin, Pierre-Dominique Ghislain, Jean-David Cohen, Pascal Coquerelle, Elisa Goujon, Denis Jullien, Hedia Brixi, Géraldine Jeudy, Xavier Guennoc, Antoine Martin, Emilie Brénaut, Emmanuel Hoppé, Antoine Bertolotti, Thomas Bardin, Emmanuel Delaporte, Matthieu Allez, Hervé Bachelez, Julien Seneschal, Manuelle Viguier
Journal: Journal of the American Academy of Dermatology (2014)
Impact of diabetes against the future risk of developing gout
Authors: García Rodríguez, Lucia Cea Soriano, Hyon K Choi
Journal: Annals of the Rheumatic Diseases (2010)

Objective Although hyperuricaemia and gout are associated with an increased future risk of diabetes, diabetes may reduce the future risk of gout through the uricosuric effect of glycosuria or the impaired inflammatory response. The present work evaluates the impact of diabetes on the future risk of developing gout. Methods A case-control study nested in a UK general practice database (the health improvement network) was conducted by identifying all incident cases of gout (N=24 768) and randomly sampling 50 000 controls who were 20–89 years between 2000 and 2007. The independent effect of type 1 and type 2 diabetes on the development of incident gout was examined. Results After adjusting for age, sex, body mass index, general practitioner visits, smoking, alcohol intake, ischaemic heart disease and presence of cardiovascular risk factors, the RR for incident gout among patients with diabetes, as compared with individuals with no diabetes was 0.67 (95% CI 0.63 to 0.71). The multivariate RRs with the duration of diabetes of 0–3, 4–9 and ≥10 years were 0.81 (95% CI 0.74 to 0.90), 0.67 (95% CI 0.61 to 0.73) and 0.52 (95% CI 0.46 to 0.58), respectively. The inverse association was stronger with type 1 diabetes than with type 2 diabetes (multivariate RR, 0.33 vs 0.69) and stronger among men than women (p value for interaction &lt;0.001). Conclusions Individuals with diabetes are at a lower future risk of gout independent of other risk factors. These data provide support for a substantial role of the pathophysiology associated with diabetes against the risk of developing gout.
Myocardial Contrast Echocardiography Versus Thrombolysis in Myocardial Infarction Score in Patients Presenting to the Emergency Department With Chest Pain and a Nondiagnostic Electrocardiogram
Authors: Khim Leng Tong, Sanjiv Kaul, Xin-Qun Wang, Diana Rinkevich, Saul Kalvaitis, Todd Belcik, Wolfgang Lepper, William A. Foster, Kevin Wei
Journal: Journal of the American College of Cardiology (2005)