tbuckley/cabot-search huggingface dataset:
Uric Acid, the Metabolic Syndrome, and Renal Disease
Authors: Pietro Cirillo, Waichi Sato, Sirirat Reungjui, Marcelo Heinig, Michael Gersch, Yuri Sautin, Takahiko Nakagawa, Richard J. Johnson
Journal: Journal of the American Society of Nephrology (2006)

Metabolic syndrome, characterized by truncal obesity, hypertriglyceridemia, elevated BP, and insulin resistance, is recognized increasingly as a major risk factor for kidney disease and also is a common feature of patients who are on dialysis. One feature that is common to patients with metabolic syndrome is an elevated uric acid. Although often considered to be secondary to hyperinsulinemia, recent evidence supports a primary role for uric acid in mediating this syndrome. Specifically, fructose, which rapidly can cause metabolic syndrome in rats, also raises uric acid, and lowering uric acid in fructose-fed rats prevents features of the metabolic syndrome. Uric acid also can accelerate renal disease in experimental animals and epidemiologically is associated with progressive renal disease in humans. It is proposed that fructose- and purine-rich foods that have in common the raising of uric acid may have a role in the epidemic of metabolic syndrome and renal disease that is occurring throughout the world.
Genomic loss of the putative tumor suppressor gene <i>E2A</i> in human lymphoma
Authors: Anne Steininger, Markus Möbs, Reinhard Ullmann, Karl Köchert, Stephan Kreher, Björn Lamprecht, Ioannis Anagnostopoulos, Michael Hummel, Julia Richter, Marc Beyer, Martin Janz, Claus-Detlev Klemke, Harald Stein, Bernd Dörken, Wolfram Sterry, Evelin Schrock, Stephan Mathas, Chalid Assaf
Journal: The Journal of Experimental Medicine (2011)

The transcription factor E2A is essential for lymphocyte development. In this study, we describe a recurrent E2A gene deletion in at least 70% of patients with Sézary syndrome (SS), a subtype of T cell lymphoma. Loss of E2A results in enhanced proliferation and cell cycle progression via derepression of the protooncogene MYC and the cell cycle regulator CDK6. Furthermore, by examining the gene expression profile of SS cells after restoration of E2A expression, we identify several E2A-regulated genes that interfere with oncogenic signaling pathways, including the Ras pathway. Several of these genes are down-regulated or lost in primary SS tumor cells. These data demonstrate a tumor suppressor function of E2A in human lymphoid cells and could help to develop new treatment strategies for human lymphomas with altered E2A activity.
Randomized, Double-Blind, Placebo-Controlled Study of Paliperidone Extended-Release and Quetiapine in Inpatients With Recently Exacerbated Schizophrenia
Authors: Carla M. Canuso, Bryan Dirks, Jennifer Carothers, Colette Kosik-Gonzalez, Cynthia A. Bossie, Young Zhu, C. V. Damaraju, Amir H. Kalali, Ramy Mahmoud
Journal: American Journal of Psychiatry (2009)

The authors compared paliperidone extended-release and quetiapine in patients with recently exacerbated schizophrenia requiring hospitalization.In a 6-week double-blind study, inpatients with a recent exacerbation of schizophrenia were randomly assigned to treatment with paliperidone extended-release, quetiapine, or placebo. A 2-week monotherapy phase was followed by a 4-week additive-therapy phase. Target doses were at the upper end of recommended ranges: paliperidone extended-release, 9 or 12 mg/day, and quetiapine, 600 or 800 mg/day. The primary endpoint was the difference in mean total change score on the Positive and Negative Syndrome Scale (PANSS) between paliperidone extended-release and quetiapine at the 2-week monotherapy phase endpoint.Six-week completion rates were 77.5% (124/160) with paliperidone extended-release, 66.7% (106/159) quetiapine, and 63.8% (51/80) placebo. Improvement in mean PANSS total change score was greater with paliperidone extended-release than with quetiapine from day 5 (-11.4 versus -8.2) through the monotherapy phase endpoint (-23.4 versus -17.1). Only paliperidone extended-release showed significantly greater PANSS improvement compared with placebo at 2 weeks. At the 6-week study endpoint, there was a significantly greater improvement with paliperidone extended-release compared with quetiapine despite similar use of additive therapy (predominantly other antipsychotics). Common adverse events with paliperidone extended-release, quetiapine, and placebo, respectively, were tremor (13.9%, 5.0%, 7.5%), somnolence (8.9%, 11.9%, 1.3%), insomnia (10.1%, 9.4%, 11.3%), and headache (12.0%, 7.5%, 13.8%). Six-week adverse event-related discontinuation rates were 6.3%, 10.1%, and 6.3%, respectively, in the paliperidone extended-release, quetiapine, and placebo groups.Compared with quetiapine, paliperidone extended-release improved symptoms earlier and to a greater degree in patients with recently exacerbated schizophrenia requiring hospitalization, with no unexpected tolerability findings.
Portal hypertensive gastropathy and gastric antral vascular ectasia (GAVE) syndrome
Authors: K W BURAK
Journal: Gut (2001)

Portal hypertensive gastropathy and gastric antral vascular ectasia (GAVE) syndromePortal hypertensive gastropathy (PHG) and gastric antral vascular ectasia (GAVE) syndrome are recently characterised entities that can be associated with gastrointestinal blood loss in patients with and without cirrhosis.Up to 65% of patients with portal hypertension from cirrhosis will develop PHG but it can also occur in the setting of non-cirrhotic portal hypertension.In patients with portal hypertension, PHG is often associated with the presence of oesophageal and/or gastric varices.The mechanisms involved in the pathogenesis of PHG have not been fully elucidated.However, regulation of gastric nitric oxide, prostaglandins, tumour necrosis factor (TNF-), and epidermal growth factor (EGF) production may be involved.The mechanisms involved in the development of GAVE syndrome are also unclear.The classic features of this syndrome include red, often haemorrhagic, lesions predominantly located in the gastric antrum which can result in significant blood loss.More than 70% of patients with GAVE syndrome do not have cirrhosis or portal hypertension.However, in the setting of cirrhosis, GAVE syndrome can be diYcult to diVerentiate from PHG.This distinction is paramount in that PHG generally responds to a reduction in portal pressures whereas those with GAVE syndrome and coexisting portal hypertension generally do not respond to such therapy.This review will focus on the incidence, clinical importance, aetiology, pathophysiology, and treatment of PHG and GAVE syndrome, including diVerentiation between GAVE syndrome and PHG in the setting of portal hypertension. Portal hypertensive gastropathy
Ethanol-induced activation of adenine nucleotide turnover. Evidence for a role of acetate.
Authors: J G Puig, I H Fox
Journal: Journal of Clinical Investigation (1984)

Consumption of alcohol causes hyperuricemia by decreasing urate excretion and increasing its production. Our previous studies indicate that ethanol administration increases uric acid production by increasing ATP degradation to uric acid precursors. To test the hypothesis that ethanol-induced increased urate production results from acetate metabolism and enhanced adenosine triphosphate turnover, we gave intravenous sodium acetate, sodium chloride and ethanol (0.1 mmol/kg per min for 1 h) to five normal subjects. Acetate plasma levels increased from 0.04 +/- 0.01 mM (mean +/- SE) to peak values of 0.35 +/- 0.07 mM and to 0.08 +/- 0.01 mM during acetate and ethanol infusions, respectively. Urinary oxypurines increased to 223 +/- 13% and 316 +/- 44% of the base-line values during acetate and ethanol infusions, respectively. Urinary radioactivity from the adenine nucleotide pool labeled with [8-14C] adenine increased to 171 +/- 27% and to 128 +/- 8% of the base-line values after acetate and ethanol infusions. These data indicate that both ethanol and acetate increase purine nucleotide degradation by enhancing the turnover of the adenine nucleotide pool. They support the hypothesis that acetate metabolism contributes to the increased production of urate associated with ethanol intake.
Gene Expression in the Urinary Bladder
Authors: Lars Dyrskjøt, Mogens Kruhøffer, Thomas Thykjaer, Niels Marcussen, Jens L. Jensen, Klaus Møller, Torben F. Ørntoft
Journal: Cancer Research (2004)

Abstract The presence of carcinoma in situ (CIS) lesions in the urinary bladder is associated with a high risk of disease progression to a muscle invasive stage. In this study, we used microarray expression profiling to examine the gene expression patterns in superficial transitional cell carcinoma (sTCC) with surrounding CIS (13 patients), without surrounding CIS lesions (15 patients), and in muscle invasive carcinomas (mTCC; 13 patients). Hierarchical cluster analysis separated the sTCC samples according to the presence or absence of CIS in the surrounding urothelium. We identified a few gene clusters that contained genes with similar expression levels in transitional cell carcinoma (TCC) with surrounding CIS and invasive TCC. However, no close relationship between TCC with adjacent CIS and invasive TCC was observed using hierarchical cluster analysis. Expression profiling of a series of biopsies from normal urothelium and urothelium with CIS lesions from the same urinary bladder revealed that the gene expression found in sTCC with surrounding CIS is found also in CIS biopsies as well as in histologically normal samples adjacent to the CIS lesions. Furthermore, we also identified similar gene expression changes in mTCC samples. We used a supervised learning approach to build a 16-gene molecular CIS classifier. The classifier was able to classify sTCC samples according to the presence or absence of surrounding CIS with a high accuracy. This study demonstrates that a CIS gene expression signature is present not only in CIS biopsies but also in sTCC, mTCC, and, remarkably, in histologically normal urothelium from bladders with CIS. Identification of this expression signature could provide guidance for the selection of therapy and follow-up regimen in patients with early stage bladder cancer.
Do the spatial characteristics of myocardial scar tissue determine the risk of ventricular arrhythmias?
Authors: A. Arenal, J. Hernandez, E. Perez-David, J. L. Rubio-Guivernau, M. J. Ledesma-Carbayo, F. Fernandez-Aviles
Journal: Cardiovascular Research (2012)

Sudden cardiac death is one of the main causes of mortality in patients with structural heart disease. Although an implantable cardioverter defibrillator significantly reduces the mortality rate, many patients never receive a shock. Identification of high-risk patients would reduce the costs associated with this therapy and prevent the deleterious effect of inappropriate discharges. As scar tissue is the substrate of ventricular arrhythmias in patients with structural heart disease, scar characterization could allow stratification of the risk. The objective of this article is to review the role of scar characteristics in the pathogenesis of ventricular arrhythmias in patients with structural heart disease.
Dance training intensity at 11–14 years is associated with femoral torsion in classical ballet dancers
Authors: D Hamilton, P Aronsen, J H Løken, I M Berg, R Skotheim, D Hopper, A Clarke, N K Briffa
Journal: British Journal of Sports Medicine (2006)

To examine in a cross sectional study the influence of femoral torsion (FT) and passive hip external rotation (PER) on turnout (TO). Starting age, years of classical ballet training, and current and past dance training intensity were assessed to determine their influence on FT, PER, and TO in pre-professional female dancers.Sixty four dancers (mean (SD) age 18.16 (1.80) years) were recruited from four different dance training programmes. They completed a dance history questionnaire. FT was measured using a clinical method. PER was measured with the subjects prone, and TO was measured with the subjects standing.Mean TO was 136 degrees, mean unilateral PER was 49.4 degrees, and mean FT was 18.4 degrees. A positive correlation was observed between PER combined (PERC) and TO (r = 0.443, p < 0.001). A negative association was found between FT combined (FTC) and PERC (r = -0.402, p = 0.001). No association was found between starting age or years of classical ballet training and FTC, PERC, or TO. Dancers who trained for six hours a week or more during the 11-14 year age range had less FT than those who trained less (mean difference 6 degrees, 95% confidence interval 1.4 to 10.3). Students currently training for longer had higher levels of TO (p < 0.001) but comparable PERC and FTC.FT is significantly associated with PERC. Dancers who trained for six hours a week or more at 11-14 years of age had significantly less FT. FTC had a significant influence on PERC, but no influence on the execution of TO.
Galectin-3 Expression Is Associated with Tumor Progression and Pattern of Sun Exposure in Melanoma
Authors: Victor G. Prieto, Alexandra A. Mourad-Zeidan, Vladislava Melnikova, Marcella M. Johnson, Adriana Lopez, A. Hafeez Diwan, Alexander J.F. Lazar, Steven S. Shen, Peter S. Zhang, Jon A. Reed, Jeffrey E. Gershenwald, Avraham Raz, Menashe Bar-Eli
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Most studies accept a multistep pathogenic process in melanoma that may include the phases of benign nevi and dysplastic nevi, melanoma, and metastatic melanoma. Dysregulation of cellular proliferation and apoptosis is probably involved in melanoma progression and response to therapy. We have studied the expression of galectin-3, a β-galactoside-binding protein involved in apoptosis, angiogenesis, and cell proliferation, in a large series of melanocytic lesions, and correlated the expression with clinical and histologic features. Experimental Design: Tissue microarray blocks of 94 melanocytic lesions were semiquantitatively evaluated by immunohistochemistry for the cytoplasmic or nuclear expression of galectin-3. Results: Primary and metastatic melanomas expressed galectin-3 at a significantly higher level than nevi in both cytoplasm and nuclei (P &amp;lt; 0.0073). There was a significant association between anatomic source (as indirect indication of level of sun-exposure) and cytoplasmic and nuclear expression. Lymph node and visceral metastases had a higher level of expression than s.c. lesions (P &amp;lt; 0.004). Interestingly, there was an almost significant finding of worse survival in those patients with lesions showing higher levels of cytoplasmic than nuclear galectin-3 expression (log-rank test, P = 0.06). Conclusions: Melanocytes accumulate galectin-3 with tumor progression, particularly in the nucleus. The strong association of cytoplasmic and nuclear expression in lesions of sun-exposed areas suggests an involvement of UV light in activation of galectin-3.
Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised double-blind placebo-controlled multicentre phase II efficacy trial
Authors: Luisa L Villa, Ronaldo LR Costa, Carlos A Petta, Rosires P Andrade, Kevin A Ault, Anna R Giuliano, Cosette M Wheeler, Laura A Koutsky, Christian Malm, Matti Lehtinen, Finn Egil Skjeldestad, Sven-Eric Olsson, Margareta Steinwall, Darron R Brown, Robert J Kurman, Brigitte M Ronnett, Mark H Stoler, Alex Ferenczy, Diane M Harper, Gretchen M Tamms, Jimmy Yu, Lisa Lupinacci, Radha Railkar, Frank J Taddeo, Kathrin U Jansen, Mark T Esser, Heather L Sings, Alfred J Saah, Eliav Barr
Journal: The Lancet Oncology (2005)
The impact of the ‘hub and spoke’ model of care for lung cancer and equitable access to surgery
Authors: Aamir Khakwani, Anna L Rich, Helen A Powell, Laila J Tata, Rosamund A Stanley, David R Baldwin, John P Duffy, Richard B Hubbard
Journal: Thorax (2014)

<h3>Objectives</h3> To determine the influence of where a patient is first seen (either surgical or non-surgical centre) and patient features on having surgery for non-small cell lung cancer (NSCLC). <h3>Design</h3> Cross-sectional study from individual patients, between 1January 2008 and 31March 2012. <h3>Setting</h3> Linked National Lung Cancer Audit and Hospital Episode Statistics datasets. <h3>Participants</h3> 95 818 English patients with a diagnosis of NSCLC, of whom 12 759 (13%) underwent surgical resection. <h3>Main outcome measure</h3> Odds of having surgery based on the empirical catchment population of the 30 thoracic surgical centres in England and whether the patient is first seen in a surgical centre or a non-surgical centre. <h3>Results</h3> Patients were more likely to be operated on if they were first seen at a surgical centre (OR 1.37; 95% CI 1.29 to 1.45). This was most marked for surgical centres with the largest catchment populations. In these surgical centres with large catchment populations, the resection rate for local patients was 18% and for patients first seen in a non-surgical centre within catchment was 12%. <h3>Conclusions</h3> Surgical centres that serve the largest catchment populations have high resection rates for patients first seen in their own centre but, in contrast, low resection rates for patients first seen at the surrounding centres they serve. Our findings demonstrate the importance of going further than relating resection rates to hospital volume or surgeon number, and show that there is a pressing need to design lung cancer services which enable all patients, including those first seen at non-surgical centres, to have equal access to lung cancer surgery.
Induction of Therapeutic Hypothermia by Paramedics After Resuscitation From Out-of-Hospital Ventricular Fibrillation Cardiac Arrest
Authors: Stephen A. Bernard, Karen Smith, Peter Cameron, Kevin Masci, David M. Taylor, D. James Cooper, Anne-Maree Kelly, William Silvester
Journal: Circulation (2010)

Background— Therapeutic hypothermia is recommended for the treatment of neurological injury after resuscitation from out-of-hospital cardiac arrest. Laboratory studies have suggested that earlier cooling may be associated with improved neurological outcomes. We hypothesized that induction of therapeutic hypothermia by paramedics before hospital arrival would improve outcome. Methods and Results— In a prospective, randomized controlled trial, we assigned adults who had been resuscitated from out-of-hospital cardiac arrest with an initial cardiac rhythm of ventricular fibrillation to either prehospital cooling with a rapid infusion of 2 L of ice-cold lactated Ringer’s solution or cooling after hospital admission. The primary outcome measure was functional status at hospital discharge, with a favorable outcome defined as discharge either to home or to a rehabilitation facility. A total of 234 patients were randomly assigned to either paramedic cooling (118 patients) or hospital cooling (116 patients). Patients allocated to paramedic cooling received a median of 1900 mL (first quartile 1000 mL, third quartile 2000 mL) of ice-cold fluid. This resulted in a mean decrease in core temperature of 0.8°C ( P =0.01). In the paramedic-cooled group, 47.5% patients had a favorable outcome at hospital discharge compared with 52.6% in the hospital-cooled group (risk ratio 0.90, 95% confidence interval 0.70 to 1.17, P =0.43). Conclusions— In adults who have been resuscitated from out-of-hospital cardiac arrest with an initial cardiac rhythm of ventricular fibrillation, paramedic cooling with a rapid infusion of large-volume, ice-cold intravenous fluid decreased core temperature at hospital arrival but was not shown to improve outcome at hospital discharge compared with cooling commenced in the hospital. Clinical Trial Registration— URL: http://www.anzctr.org.au. Unique identifier: ACTRN12605000179639.
Contemporary Diagnostic Imaging Modalities for the Staging and Surveillance of Melanoma Patients: a Meta-analysis
Authors: Y. Xing, Y. Bronstein, M. I. Ross, R. L. Askew, J. E. Lee, J. E. Gershenwald, R. Royal, J. N. Cormier
Journal: JNCI Journal of the National Cancer Institute (2010)

Meta-analyses were performed to examine the utility of ultrasonography, computed tomography (CT), positron emission tomography (PET), and a combination of both (PET-CT) for the staging and surveillance of melanoma patients. Patient-level data from 74 studies containing 10 528 patients (between January 1, 1990, and June, 30, 2009) were used to derive characteristics of the diagnostic tests used. Meta-analyses were conducted by use of Bayesian bivariate binomial models to estimate sensitivity and specificity. Diagnostic odds ratios [ie, true-positive results/false-negative results)/(false-positive results/true-negative results)] and their 95% credible intervals (CrIs) and positive predictive values were used as indicators of test performance. Among the four imaging methods examined for the staging of regional lymph nodes, ultrasonography had the highest sensitivity (60%, 95% CrI = 33% to 83%), specificity (97%, 95% CrI = 88% to 99%), and diagnostic odds ratio (42, 95% CrI = 8.08 to 249.8). For staging of distant metastases, PET-CT had the highest sensitivity (80%, 95% CrI = 53% to 93%), specificity (87%, 95% CrI = 54% to 97%), and diagnostic odds ratio (25, 95% CrI = 3.58 to 198.7). Similar trends were observed for melanoma surveillance of lymph node involvement, with ultrasonography having the highest sensitivity (96%, 95% CrI = 85% to 99%), specificity (99%, 95% CrI = 95% to 100%), and diagnostic odds ratio (1675, 95% CrI = 226.6 to 15,920). For distant metastases, PET-CT had the highest sensitivity (86%, 95% CrI = 76% to 93%), specificity (91%, 95% CrI = 79% to 97%), and diagnostic odds ratio (67, 95% CrI = 20.42 to 229.7). Positive predictive values were likewise highest for ultrasonography in lymph node staging and for PET-CT in detecting distant metastases. Among the compared modalities, ultrasonography was superior for detecting lymph node metastases, and PET-CT was superior for the detection of distant metastases in both the staging and surveillance of melanoma patients.
Fasting Versus Postload Plasma Glucose Concentration and the Risk for Future Type 2 Diabetes
Authors: Muhammad A. Abdul-Ghani, Valeriya Lyssenko, Tiinamaija Tuomi, Ralph A. DeFronzo, Leif Groop
Journal: Diabetes Care (2008)

OBJECTIVE—The purpose of this study was to assess the efficacy of the postload plasma glucose concentration in predicting future risk of type 2 diabetes, compared with prediction models based on measurement of the fasting plasma glucose (FPG) concentration. RESEARCH DESIGN AND METHODS—A total of 2,442 subjects from the Botnia Study, who were free of type 2 diabetes at baseline, received an oral glucose tolerance test (OGTT) at baseline and after 7–8 years of follow-up. Future risk for type 2 diabetes was assessed with area under the receiver-operating characteristic curve for prediction models based up measurement of the FPG concentration 1) with or without a 1-h plasma glucose concentration during the OGTT and 2) with or without the metabolic syndrome. RESULTS—Prediction models based on measurement of the FPG concentration were weak predictors for the risk of future type 2 diabetes. Addition of a 1-h plasma glucose concentration markedly enhanced prediction of the risk of future type 2 diabetes. A cut point of 155 mg/dl for the 1-h plasma glucose concentration during the OGTT and presence of the metabolic syndrome were used to stratify subjects in each glucose tolerance group into low, intermediate, and high risk for future type 2 diabetes. CONCLUSIONS—The plasma glucose concentration at 1 h during the OGTT is a strong predictor of future risk for type 2 diabetes and adds to the prediction power of models based on measurements made during the fasting state. A plasma glucose cut point of 155 mg/dl plus the Adult Treatment Panel III criteria for the metabolic syndrome can be used to stratify nondiabetic subjects into low-, intermediate-, and high-risk groups.