tbuckley/cabot-search huggingface dataset:
MiR-145 functions as a tumor-suppressive RNA by targeting Sox9 and adducin 3 in human glioma cells
Authors: Sandhya B Rani, Sachin Shivaji Rathod, Shanmuganandam Karthik, Navjot Kaur, Dattatraya Muzumdar, Anjali S Shiras
Journal: Neuro-Oncology (2013)

MicroRNAs (miRNAs) are increasingly being recognized as being involved in cancer development and progression in gliomas.Using a model cell system developed in our lab to study glioma progression comprising human neuroglial culture (HNGC)-1 and HNGC-2 cells, we report here that miR-145 is one of the miRNAs significantly downregulated during malignant transformation in glioblastoma multiforme (GBM). In a study using tumor samples derived from various glioma grades, we show that expression of miR-145 is decreased in a graded manner, with GBM patients showing lowest expression relative to lower-grade gliomas (P < .05) and normal brain tissues (P < .0001). Functional studies involving ectopic expression of miR-145 in glioma cells had a negative impact on cell proliferation and tumor development, as well as invasion and induced apoptosis, providing further support to the concept that inactivation of miR-145 is important for glioma disease pathogenesis. More notably, these growth-suppressive effects of miR-145 are mediated through its target proteins Sox9 and the cell adhesion-associated molecule adducin 3 (ADD3).Inhibiting Sox9 and ADD3 rescued effects of miR-145 loss. Interestingly, miR-145 loss in glioma cells led to overexpression of molecules involved in cell proliferation, like cyclin D1, c-myc, and N-myc, as well as enhanced expression of cell adhesion- and invasion-related molecules N-cadherin and E-cadherin, an effect which was again restored upon miR-145 overexpression in glioma cells. The miR-145 promoter was methylated at its cytosine-phosphate-guanine (CpG) islands in the glioma cell lines studied.Our study demonstrates that miR-145 has a tumor-suppressive function in glioblastoma in that it reduces proliferation, adhesion, and invasion of glioblastoma cells, apparently by suppressing the activity of oncogenic proteins Sox9 and ADD3. Reduced levels of miR-145 may lead to neoplastic transformation and malignant progression in glioma due to unregulated activity of these proteins.
Treatment of alcohol-related liver disease with thioctic acid: a six month randomised double-blind trial.
Authors: A W Marshall, R S Graul, M Y Morgan, S Sherlock
Journal: Gut (1982)

A randomised double-blind trial of thioctic acid (alpha-lipoic acid), 300 mg/day versus placebo was carried out in 40 patients with pre-cirrhotic alcohol-related liver disease over a six month period. Twenty patients received the active drug and 20 placebo. Twenty-two of the 40 patients (55%) abstained from alcohol and showed significant improvements (p less than 0.01) in mean values for serum aspartate transaminase, serum glutamyl transpeptidase, and mean corpuscular volume. Seventeen of the 22 (77%) showed overall histological improvement on liver biopsy. The remaining 18 patients (45%) continued to drink but significantly reduced their mean daily alcohol intake (p less than 0.001). No significant changes occurred in their laboratory indices, but five of the 18 (28%) showed overall histological improvement. Changes occurred irrespective of treatment with thioctic acid, which suggested that, over six months, this drug did not influence the course of alcohol-related liver disease.
Gender-Related Differences in the Clinical Presentation and Outcome of Hypertrophic Cardiomyopathy
Authors: Iacopo Olivotto, Martin S. Maron, A. Selcuk Adabag, Susan A. Casey, Daniela Vargiu, Mark S. Link, James E. Udelson, Franco Cecchi, Barry J. Maron
Journal: Journal of the American College of Cardiology (2005)
Public health implications of establishing a national programme to screen young athletes in the UK
Authors: Julian Elston, Ken Stein
Journal: British Journal of Sports Medicine (2009)

To assess how much competitive sport contributes to sudden cardiac death (SCD) in young athletes and the impact on population health if this group were to be screened in the UK.Using reported and imputed incidence rates of SCD in athletes and non-athletes and false-negative and false-positive test rates reported in three key Italian screening studies, the authors calculated the population and attributable risk fractions of SCD in young athletes and the total population (athletes and non-athletes) aged 12-35 years before and after screening; the number of athletes needed to screen (NNS) to prevent one SCD and the sensitivity and the specificity of screening with electrocardiogram. Using these parameters, the authors developed a decision tree model based on the UK population aged 12-35 years to estimate the annual number of SCDs, the expected number of screening and diagnostic tests and the number of athletes disqualified from competitive sport per SCD prevented.Participation in competitive athletics contributes to 81.9% (62.4% to 91.6%) of SCD in athletes but only 26.6% (-20.3% to 55.8%) in the total population. After screening, the contribution in the total population falls to 7.2% (-10.7% to 22.4%). The NNS is 38 151 (20 534 to 267 380). A UK screening programme would result in 1 520 021 young athletes being screened, with 140 361 referred for diagnosis. Of an expected 196 SCDs per year, 40 (6 to 74) would be prevented. For every life saved, 791 athletes would be disqualified.The impact of screening on reducing SCD in young athletes is only modest and would be achieved with significant harms to population health.
Characteristics of coeliac disease (CD) in a cohort of elderly patients
Authors: S. Casella, B. Zanini, F. Lanzarotto, V. Villanacci, A. Magni, F. Caselani, A. Lanzini
Journal: Gut (2011)

<h3>Introduction</h3> CD is increasingly being diagnosed in elderly patients, but little information is available on clinical characteristics and on response to gluten free diet (GFD) in elderly CD. <h3>Methods</h3> To characterise CD in patients aged ≥65 years by comparison with patients aged 18–65 years and to assess the effects of GFD. Information on clinical, serological and histological characteristics collected before and during GFD were retrieved retrospectively from CD database of patients attending our Clinic from 1991 to 2010. We identified two cohorts of patients: Group A, age ≥65 years (n= 59 patients); Group B, age range 18–64 years (n= 1166). <h3>Results</h3> Elderly patients represented 5% of patients in our database. Mean ± SEM age was 70±0.6 years (range 65-83) in group A and 35.2±0.3 (range 18–64) in group B; male/female ratio was 1/2.7in both Groups. body mass index (BMI) was 22.5±0.7 in group A and 21.6±0.1 in group B respectively (p=0.1). Prevalence of diarrhoea (49% vs 41 %, p=0.3) and abdominal pain (27% vs 31 %, p=0.6) was similar, but weight loss (37% vs 21% p=0.005) and dyspepsia (22% vs 12%; p=0.04) were more frequent in group A than B. Incidence at diagnosis of non-Hodgkin lymphoma (NHL) was higher in group A (5%) than group B (0.3%, p=0.003). Differences before and during GFD on selected parameters are summarised in table 1. <h3>Conclusion</h3> CD is a common disease in the elderly and can be diagnosed in patients as old as 83 years of age. Clinical presentation is similar in the elderly as in younger patients, but elderly patients present more frequently with weight loss and bone disease. NHL is already present at time of CD diagnosis in a substantial proportion of elderly patients, emphasizing the importance of early diagnosis. Histological improvement during GFD is similar in elderly as in younger patients, but improvement of laboratory parameters is less marked in elderly CD.
Effectiveness of discontinuing antibiotic treatment after three days versus eight days in mild to moderate-severe community acquired pneumonia: randomised, double blind study
Authors: Rachida el Moussaoui, Corianne A J M de Borgie, Peterhans van den Broek, Willem N Hustinx, Paul Bresser, Guido E L van den Berk, Jan-Werner Poley, Bob van den Berg, Frans H Krouwels, Marc J M Bonten, Carla Weenink, Patrick M M Bossuyt, Peter Speelman, Brent C Opmeer, Jan M Prins
Journal: BMJ (2006)

To compare the effectiveness of discontinuing treatment with amoxicillin after three days or eight days in adults admitted to hospital with mild to moderate-severe community acquired pneumonia who substantially improved after an initial three days' treatment.Randomised, double blind, placebo controlled non-inferiority trial.Nine secondary and tertiary care hospitals in the Netherlands.Adults with mild to moderate-severe community acquired pneumonia (pneumonia severity index score < or = 110).Patients who had substantially improved after three days' treatment with intravenous amoxicillin were randomly assigned to oral amoxicillin (n = 63) or placebo (n = 56) three times daily for five days.The primary outcome measure was the clinical success rate at day 10. Secondary outcome measures were the clinical success rate at day 28, symptom resolution, radiological success rates at days 10 and 28, and adverse events.Baseline characteristics were comparable, with the exception of symptom severity, which was worse in the three day treatment group. In the three day and eight day treatment groups the clinical success rate at day 10 was 93% for both (difference 0.1%, 95% confidence interval--9% to 10%) and at day 28 was 90% compared with 88% (difference 2.0%,--9% to 15%). Both groups had similar resolution of symptoms. Radiological success rates were 86% compared with 83% at day 10 (difference 3%,--10% to 16%) and 86% compared with 79% at day 28 (difference 6%,--7% to 20%). Six patients (11%) in the placebo group and 13 patients (21%) in the active treatment group reported adverse events (P = 0.1).Discontinuing amoxicillin treatment after three days is not inferior to discontinuing it after eight days in adults admitted to hospital with mild to moderate-severe community acquired pneumonia who substantially improved after an initial three days' treatment.
Garcinia cambogia (Hydroxycitric Acid) as a Potential Antiobesity Agent
Authors: S B Heymsfield, D B Allison, J R Vasselli, A Pietrobelli, D Greenfield, C Nunez
Journal: JAMA (1998)

Hydroxycitric acid, the active ingredient in the herbal compound Garcinia cambogia, competitively inhibits the extramitochondrial enzyme adenosine triphosphate-citrate (pro-3S)-lyase. As a citrate cleavage enzyme that may play an essential role in de novo lipogenesis inhibition, G cambogia is claimed to lower body weight and reduce fat mass in humans.To evaluate the efficacy of G cambogia for body weight and fat mass loss in overweight human subjects.Twelve-week randomized, double-blind, placebo-controlled trial.Outpatient weight control research unit.Overweight men and women subjects (mean body mass index [weight in kilograms divided by the square of height in meters], approximately 32 kg/m2).Subjects were randomized to receive either active herbal compound (1500 mg of hydroxycitric acid per day) or placebo, and both groups were prescribed a high-fiber, low-energy diet. The treatment period was 12 weeks. Body weight was evaluated every other week and fat mass was measured at weeks 0 and 12.Body weight change and fat mass change.A total of 135 subjects were randomized to either active hydroxycitric acid (n = 66) or placebo (n = 69); 42 (64%) in the active hydroxycitric acid group and 42 (61%) in the placebo group completed 12 weeks of treatment (P = .74). Patients in both groups lost a significant amount of weight during the 12-week treatment period (P<.001); however, between-group weight loss differences were not statistically significant (mean [SD], 3.2 [3.3] kg vs 4.1 [3.9] kg; P = .14). There were no significant differences in estimated percentage of body fat mass loss between treatment groups, and the fraction of subject weight loss as fat was not influenced by treatment group.Garcinia cambogia failed to produce significant weight loss and fat mass loss beyond that observed with placebo.
Summary Statement: Novel Agents in the Treatment of Lung Cancer: Advances in Epidermal Growth Factor Receptor-Targeted Agents
Authors: Thomas J. Lynch, Alex A. Adjei, Paul A. Bunn, Tim G. Eisen, Jeffrey Engelman, Glenwood D. Goss, Daniel A. Haber, John V. Heymach, Pasi A. Jänne, Bruce E. Johnson, David H. Johnson, Rogerio C. Lilenbaum, Matthew Meyerson, Alan B. Sandler, Lecia V. Sequist, Jeffrey Settleman, Kwok-Kin Wong, Carol S. Hart
Journal: Clinical Cancer Research (2006)

The Third Cambridge Conference on Novel Agents in the Treatment of Lung Cancer was convened in Cambridge, Massachusetts on September 23 to 24, 2005 to discuss ongoing research into the significance of the epidermal growth factor receptor (EGFR) pathway in the biology of non–small cell lung cancer
Short-Term Psychodynamic Psychotherapy and Cognitive-Behavioral Therapy in Generalized Anxiety Disorder: A Randomized, Controlled Trial
Authors: Falk Leichsenring, Simone Salzer, Ulrich Jaeger, Horst Kächele, Reinhard Kreische, Frank Leweke, Ulrich Rüger, Christel Winkelbach, Eric Leibing
Journal: American Journal of Psychiatry (2009)

Objective: While several studies have shown that cognitive-behavioral therapy (CBT) is an efficacious treatment for generalized anxiety disorder, few studies have addressed the outcome of short-term psychodynamic psychotherapy, even though this treatment is widely used. The aim of this study was to compare short-term psychodynamic psychotherapy and CBT with regard to treatment outcome in generalized anxiety disorder. Method: Patients with generalized anxiety disorder according to DSM-IV were randomly assigned to receive either CBT (N=29) or short-term psychodynamic psychotherapy (N=28). Treatments were carried out according to treatment manuals and included up to 30 weekly sessions. The primary outcome measure was the Hamilton Anxiety Rating Scale, which was applied by trained raters blind to the treatment conditions. Assessments were carried out at the completion of treatment and 6 months afterward. Results: Both CBT and short-term psychodynamic psychotherapy yielded significant, large, and stable improvements with regard to symptoms of anxiety and depression. No significant differences in outcome were found between treatments in regard to the primary outcome measure. These results were corroborated by two self-report measures of anxiety. In measures of trait anxiety, worry, and depression, however, CBT was found to be superior. Conclusions: The results suggest that CBT and short-term psychodynamic psychotherapy are beneficial for patients with generalized anxiety disorder. In future research, large-scale multicenter studies should examine more subtle differences between treatments, including differences in the patients who benefit most from each form of therapy.
Explaining Interindividual Variability of Docetaxel Pharmacokinetics and Pharmacodynamics in Asians Through Phenotyping and Genotyping Strategies
Authors: Boon-Cher Goh, Soo-Chin Lee, Ling-Zhi Wang, Lu Fan, Jia-Yi Guo, Jatinder Lamba, Erin Schuetz, Robert Lim, Hong-Liang Lim, Ai-Bee Ong, How-Sung Lee
Journal: Journal of Clinical Oncology (2002)

To explain the variability of docetaxel pharmacokinetics through study of CYP3A phenotype and genotype, and MDR1 genotype.We studied the pharmacokinetics and pharmacodynamics of docetaxel in patients in whom it was indicated and who had not received known CYP3A4 substrates. Midazolam was administered intravenously to these patients at least 2 days before docetaxel treatment, and systemic clearances of both drugs were correlated. Patients were characterized for polymorphisms in the CYP3A4 promoter region, CYP3A5, and the C3435T polymorphism of MDR1.Thirty-two patients were enrolled, of whom 31 had full pharmacokinetic data sets. Docetaxel clearance correlated with midazolam clearance, body-surface area, serum albumin, and performance status. Docetaxel and midazolam clearances were normally distributed. In multiple linear regression analyses, midazolam clearance and performance status were the only significant covariates of docetaxel clearance, and the area under the curve of docetaxel, serum levels of alpha-1-acid glycoprotein, and ALT were significant predictors of nadir neutrophil count. No polymorphisms were detected in the 5' regulatory region of CYP3A4. Nine patients of 25 studied were homozygous for the CYP3A5*3 genotype, and had lower mean clearance of midazolam but not docetaxel. The T/T genotype at the C3435T of MDR1, which is associated with reduced P-glycoprotein function, was found in eight of 27 patients.Midazolam may be used as a probe drug for CYP3A activity to predict docetaxel clearances, hence reducing interindividual variability. Homozygotes for CYP3A5*3 and C3435T of MDR1 are common in our population, and their effects on pharmacokinetics of relevant substrates should be studied further.
Excess Risk of Primary Liver Cancer in Patients With Diabetes Mellitus
Authors: H.-O. Adami, W.-H. Chow, O. Nyren, C. Berne, M. S. Linet, A. Ekbom, A. Wolk, J. K. McLaughlin, J. F. Fraumeni
Journal: JNCI Journal of the National Cancer Institute (1996)

Chronic infection with hepatitis B virus, alcohol consumption, and cirrhosis of the liver are recognized risk factors for primary liver cancer. A few, but not all, studies have suggested that diabetes mellitus also increases risk for this cancer. We conducted a population-based cohort study to analyze the risk of developing primary liver cancer and biliary tract (gallbladder, extrahepatic bile ducts, and ampulla of Vater) cancers among patients with diabetes. A cohort of 153 852 patients with a hospital discharge diagnosis of diabetes in the period from 1965 through 1983 was identified by use of the Swedish In-patient Register. Follow-up for these patients extended from the date of cohort entry through December 31, 1989. Incident cases of cancer during follow-up were identified through the Swedish Cancer Registry. To minimize the impact of selection bias, we excluded from the analysis patients who were diagnosed with liver and biliary tract cancers during the first year of follow-up. Standardized incidence ratios (SIRs) and their 95% confidence intervals (CIs) were computed by use of nationwide rates of liver and biliary tract cancers, adjusted for age, sex, and calendar year, for comparison. During 1–24 years of follow-up, 819 incident cancers in the combined category of primary liver (n = 533) and biliary tract (n = 286) were identified in the cohort, yielding an overall SIR of 2.5 (95% CI = 2.3–2.6). The risk was higher in men (SIR = 3.2; 95% CI = 2.9–3.6) than in women (SIR = 2.0; 95% CI = 1.8–2.2). The incidence of primary liver cancer alone was increased fourfold (SIR = 4.1; 95% CI = 3.8–4.5); again, the risk was higher in men (SIR = 4.7; 95% CI = 4.2–5.2) than in women (SIR = 3.4; 95% CI = 2.9–3.9). Smaller increases in risk were seen for cancers of the gallbladder, the extrahepatic bile ducts, and the ampulla of Vater. After exclusion of diabetic patients with concomitant diseases that predispose to primary liver cancer, such as alcoholism, cirrhosis, and hepatitis, the persistence of an approximately threefold excess risk was observed. Our findings suggest that patients with diabetes are at increased risk of developing primary liver cancer and perhaps cancers of the biliary tract. The mechanisms involved in the association of diabetes and liver cancer remain to be clarified. Additional studies are needed to determine whether patients with insulin-dependent diabetes mellitus and those with non-insulin-dependent diabetes mellitus differ in their risk for primary liver cancer or whether the risk is affected by the type of diabetes treatment. [J Natl Cancer Inst 1996;88:1472-77]
Digoxin-quinidine interaction in patients with chronic renal failure.
Authors: P E Fenster, W D Hager, D Perrier, J R Powell, P E Graves, U F Michael
Journal: Circulation (1982)

We evaluated the effect of quinidine on digoxin pharmacokinetic in six patients with severe renal failure. Quinidine reduced the total body clearance of digoxin from 1.87 to 1.06 l/hour (p less than 0.001), and prolonged the digoxin half-life of elimination from 5.20 to 9.61 days (p less than 0.01). The digoxin volume of distribution was unchanged. Renal clearance of digoxin was negligible; thus, the decrease in total body clearance was due to a decrease in the nonrenal clearance of digoxin. The mean trough serum concentrations of quinidine ranged from 1.0 to 3.0 micrograms/ml. We conclude that in patients with chronic renal failure, the dose of digoxin should be decreased by 50% if quinidine therapy is initiated.
Combination Antibiotic Therapy Lowers Mortality among Severely Ill Patients with Pneumococcal Bacteremia
Authors: Larry M. Baddour, Victor L. Yu, Keith P. Klugman, Charles Feldman, Ake Ortqvist, Jordi Rello, Arthur J. Morris, Carlos M. Luna, David R. Snydman, Wen Chien Ko, M. Bernadete F. Chedid, David S. Hui, Antoine Andremont, Christine C. C. Chiou
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Retrospective studies have suggested that combination antibiotic therapy for severe bacteremic pneumococcal pneumonia may reduce mortality. We assessed this issue in a prospective, multicenter, international observational study of 844 adult patients with bacteremia due to Streptococcus pneumoniae. The effect of combination antibiotic therapy versus monotherapy on mortality was examined by univariate analyses and by logistic regression models. The 14-day mortality was not significantly different for the two groups. However, among critically ill patients, combination antibiotic therapy was associated with lower 14-day mortality (23.4 versus 55.3%, p = 0.0015). This improvement in survival was independent of country of origin, intensive care unit support, class of antibiotics, or in vitro activity of the antibiotics prescribed. Combination antibiotic therapy improved survival among critically ill patients with bacteremic pneumococcal illness.
Acetylcholinesterase in the human erythron. III. Regulation of differentiation
Authors: Ronald D. Barr, Marijke Koekebakker
Journal: American Journal of Hematology (1990)

Acetylcholinesterase (AChE) is present in both primitive and mature erythroid cells, but a role for the enzyme in human hematopoiesis has not been defined. This prospect represented the primary objective of the following study. In clonal culture of normal human bone marrow cells, a "wave" of AChE activity was demonstrated, rising from undetectable levels to a peak (of 1.48 femto-moles per min per cell) at 10 days in the course of progressive erythroid clonogenesis. At concentrations of enzyme inhibitor that clearly reduced AChE activity in a dose-dependent fashion, there was no overall effect on erythropoiesis in vitro, but the clones were generally smaller and significantly more often multi-focal than in control cultures. Furthermore, in the presence of AChE inhibitors, a concentration-dependent increase in the myeloid-erythroid ratios of the culture harvests was observed. Likewise, a clear reduction in hemoglobination was revealed, in cells of 10 day cultures, from a mean hemoglobin concentration of 35.0 pg per cell in controls to 20.1 pg per cell in the presence of the maximal concentration of the inhibitor (10(-6) M eserine). These data point to a role for AChE in the regulation of differentiation in the human erythron.