tbuckley/cabot-search huggingface dataset:
Cancer incidence and mortality in relation to body mass index in the Million Women Study: cohort study
Authors: Gillian K Reeves, Kirstin Pirie, Valerie Beral, Jane Green, Elizabeth Spencer, Diana Bull
Journal: BMJ (2007)

<b>Objective</b> To examine the relation between body mass index (kg/m<sup>2</sup>) and cancer incidence and mortality. <b>Design</b> Prospective cohort study. <b>Participants</b> 1.2 million UK women recruited into the Million Women Study, aged 50-64 during 1996-2001, and followed up, on average, for 5.4 years for cancer incidence and 7.0 years for cancer mortality. <b>Main outcome measures</b> Relative risks of incidence and mortality for all cancers, and for 17 specific types of cancer, according to body mass index, adjusted for age, geographical region, socioeconomic status, age at first birth, parity, smoking status, alcohol intake, physical activity, years since menopause, and use of hormone replacement therapy. <b>Results</b> 45 037 incident cancers and 17 203 deaths from cancer occurred over the follow-up period. Increasing body mass index was associated with an increased incidence of endometrial cancer (trend in relative risk per 10 units=2.89, 95% confidence interval 2.62 to 3.18), adenocarcinoma of the oesophagus (2.38, 1.59 to 3.56), kidney cancer (1.53, 1.27 to 1.84), leukaemia (1.50, 1.23 to 1.83), multiple myeloma (1.31, 1.04 to 1.65), pancreatic cancer (1.24, 1.03 to 1.48), non-Hodgkin9s lymphoma (1.17, 1.03 to 1.34), ovarian cancer (1.14, 1.03 to 1.27), all cancers combined (1.12, 1.09 to 1.14), breast cancer in postmenopausal women (1.40, 1.31 to 1.49) and colorectal cancer in premenopausal women (1.61, 1.05 to 2.48). In general, the relation between body mass index and mortality was similar to that for incidence. For colorectal cancer, malignant melanoma, breast cancer, and endometrial cancer, the effect of body mass index on risk differed significantly according to menopausal status. <b>Conclusions</b> Increasing body mass index is associated with a significant increase in the risk of cancer for 10 out of 17 specific types examined. Among postmenopausal women in the UK, 5% of all cancers (about 6000 annually) are attributable to being overweight or obese. For endometrial cancer and adenocarcinoma of the oesophagus, body mass index represents a major modifiable risk factor; about half of all cases in postmenopausal women are attributable to overweight or obesity.
Metabolism Alters the Selectivity of Angiotensin-(1-7) Receptor Ligands for Angiotensin Receptors
Authors: RAJASH K. HANDA
Journal: Journal of the American Society of Nephrology (2000)

Abstract. The present study examined whether metabolism of the putative angiotensin-(1-7) receptor agonist and antagonist [angiotensin-(1-7) and D-alanine 7 angiotensin-(1-7), respectively] altered their ability to interact with angiotensin AT 1 , AT 2 , and AT 4 receptor subtypes. Both angiotensin-(1-7) and D-alanine 7 angiotensin-(1-7) competed with low affinity for 125 I-sarcosine 1 , isoleucine 8 angiotensin II binding to AT 1 and AT 2 receptors in rat liver and adrenal medulla membranes, respectively, and competed with low affinity for 125 I-angiotensin IV binding to AT 4 receptors in bovine kidney epithelial cell membranes. In vitro renal metabolism of the angiotensin-(1-7) receptor ligands (incubating peptides with rat cortical tissue homogenates) had minimal influence on low-affinity binding to AT 1 and AT 2 receptors, yet caused a significant and dramatic shift toward high-affinity binding for AT 4 receptors. Low-affinity angiotensin II binding to the AT 4 receptor was also shifted toward high-affinity binding following renal metabolism of the peptide. Conversely, angiotensins with high affinity for the AT 4 receptor ( e.g. , angiotensin IV) were shifted toward low-affinity binding states following peptide metabolism. Incubation of 125 I-angiotensin-(1-7) with rat cortical tissue generated the high-affinity AT 4 receptor ligand 125 I-angiotensin-(3-7), whereas the renal metabolism of 125 I-angiotensin II generated both 125 I-angiotensin-(3-7) and 125 I-angiotensin IV. These results reveal that renal metabolism of angiotensin-(1-7) receptor ligands and angiotensin II yields products that have high affinity for the AT 4 receptor and could potentially contribute to the biologic actions of the parent peptide in the kidney.
Effectiveness and safety of the interleukin 6-receptor antagonist tocilizumab after 4 and 24 weeks in patients with active rheumatoid arthritis: the first phase IIIb real-life study (TAMARA)
Authors: G. R. Burmester, E. Feist, H. Kellner, J. Braun, C. Iking-Konert, A. Rubbert-Roth
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Objectives</h3> To confirm the effectiveness and safety of the interleukin 6-receptor antagonist tocilizumab in patients with rheumatoid arthritis (RA) in a setting close to real-life medical care in Germany. <h3>Methods</h3> A multicentre open-label phase IIIb study was undertaken. Patients with active RA with a 28-joint Disease Activity Score (DAS28) &gt;3.2 despite previous disease-modifying antirheumatic drugs (DMARDs) were treated with tocilizumab 8 mg/kg every 4 weeks. The primary end point was the proportion of patients achieving LDAS ≤3.2 at week 24; secondary end points included American College of Rheumatology (ACR), European League Against Rheumatism (EULAR) or Clinical Disease Activity Index (CDAI) responses and decrease in acute phase. Analyses in subgroups such as rheumatoid factor (RF)-positive versus RF-negative patients and patients with an inadequate response to treatment with DMARDs (DMARD-IR) versus those with an inadequate response to tumour necrosis factor (TNF) antagonists (TNF antagonist-IR) were performed. Safety was assessed by adverse event documentation. <h3>Results</h3> 286 patients were treated and 83.6% completed the study. 41.6% had previously been treated with TNF antagonists. 57% of the intention-to-treat patients achieved the primary end point of LDAS, 47.6% achieved DAS remission &lt;2.6 and a EULAR 'good response' was achieved by 54.9%; ACR50/70 response rates at week 24 were 50.7% and 33.9%, respectively. The mean±SD decrease in CDAI from baseline to week 24 was 71±29%. C reactive protein levels normalised rapidly within 1 week. Major improvements in fatigue, pain and morning stiffness were observed in the first 4 weeks and further improved until week 24. DAS28, EULAR and ACR responses at week 24 did not differ between RF-positive and RF-negative patients. TNF antagonist-naive patients responded better than patients who had previously failed on TNF antagonists. The safety profile of tocilizumab was comparable to that previously observed in the phase III trial programme. Serious infections were observed in 3.1% of patients. <h3>Conclusions</h3> Tocilizumab is highly effective in a setting close to real-life medical care with a rapid and sustained improvement in signs and symptoms of RA. A manageable safety profile was seen over the 24-week study period.
End-systolic volume index at 90 to 180 minutes into reperfusion therapy for acute myocardial infarction is a strong predictor of early and late mortality. The Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO)-I Angiographic Investigators
Authors: RQ Migrino, JB Young, SG Ellis, HD White, CF Lundergan, DP Miller, CB Granger, AM Ross, RM Califf, EJ Topol
Journal: Circulation (1997)

BACKGROUND: Left ventricular remodeling is an important sequela of myocardial infarction (MI). Although remodeling occurs soon after MI, the effect of early left ventricular dilatation on outcome is not established and may be useful for early risk stratification. We assessed whether end-systolic volume index (ESVI) at 90 to 180 minutes into thrombolytic therapy for MI is associated with adverse outcomes. METHODS AND RESULTS: In the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO)-I study, 41021 patients with evolving MI received one of four thrombolytic regimens. At 90 or 180 minutes into reperfusion therapy, 1300 patients underwent left ventriculography. ESVI was measured and correlated with adverse outcomes: 30-day and 1-year mortality and in-hospital congestive heart failure, shock, and reinfarction. Clinical variables were also tested in a stepwise logistic regression analysis to determine predictors of left ventricular dilatation. ESVI was directly related to all adverse outcomes with univariate analysis. ESVI of &gt; or = 40 mL/m2 was independently associated with mortality (adjusted odds ratio [95% confidence interval]: 30-day, 3.4 [2.0 to 5.9]; 1-year, 4:1 [2.6 to 6.2], both P &lt; .001). Male sex, prior angina or MI, weight of &lt; 70 kg, heart rate of &gt; or = 80 bpm, systolic blood pressure of &lt; 110 mm.Hg, and anterior infarction were independent predictors of an ESVI of &gt; or = 40 mL/m2. CONCLUSIONS: Left ventricular ESVI early into reperfusion therapy for MI strongly predicts adverse outcomes, including early and late mortality. The study establishes the role of very early left ventricular dilatation on outcome in MI and may be useful in identifying high-risk patients who might benefit from aggressive treatment, including the early use of ACE inhibitors.
Factors Related to Methacholine Airway Responsiveness in Children
Authors: DENNIS R. OWNBY, EDWARD L. PETERSON, CHRISTINE C. JOHNSON
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Studies of airway responsiveness (AR) have typically used similar dose schedules of methacholine for adults and children despite large ranges in subject size. Reported declines in AR with increasing age in children could be due to maturational changes or to proportionately smaller doses of methacholine in taller (older) children. Other investigators have related both height and various measures of lung function to AR. We examined data related to AR in 471 children, aged 6 to 8 yr, from a birth cohort. Each child underwent spirometry followed by sequential challenge with five doses of methacholine, ranging from 0.025 to 25 mg/ml, given with a dosimeter. Continuous slope and end FEV1-change indexes of responsiveness were computed. Using stepwise regression modeling, we found no significant association between AR and either height or age after entering a variable reflecting asthma or wheezing. In contrast, we found that baseline measures of FVC, FEV1/FVC, and FEF25–75% were significantly related to AR after controlling for other variables (p = 0.001). However, when all three of the latter measures were added to models, FEF25–75% was most closely related to AR. We conclude that after control for other variables, FEF25–75% and FVC, but not height, are significantly related to methacholine responsiveness in children.
Treatment of duodenal ulcer with pirenzepine and cimetidine.
Authors: H Brunner, H Dittrich, P Kratochvil, G Brandstatter, E Hentschel, K Schutze, K H Tragl, H Kern, K Loffelmann, H Zeiler
Journal: Gut (1984)

The purpose of this single blind controlled multicentre trial was to compare the relative effectiveness of pirenzepine and cimetidine in healing endoscopically proven duodenal ulcers. One hundred and twenty six patients with duodenal ulcer were treated with a daily dose of 100 mg pirenzepine (50 mg each before breakfast and before the evening meal), and 128 patients were treated with 1000 mg cimetidine (200 mg with breakfast, lunch, and evening meal and 400 mg at bedtime). Endoscopy was repeated after four weeks by an endoscopist who had not been informed about the treatment. Pirenzepine showed a healing rate of 64.3%, cimetidine one of 73.4%. This difference is not statistically significant (one-sided test: chi 1(2) = 2.48). After four weeks a higher proportion of first ulcers than of recurrent lesions was healed. Pain relief was rapidly achieved with both drugs. A significant trend in favour of cimetidine may, however, not be clinically relevant considering the small difference in the absolute numbers of pain free days and nights. Adverse effects were rare and reversible. We conclude that the efficacy of pirenzepine is similar to that of cimetidine in healing duodenal ulcers.
Evaluation of a randomised controlled trial of adult asthma education in a hospital setting
Authors: O Abdulwadud, M Abramson, A Forbes, A James, E H Walters
Journal: Thorax (1999)

<h3>BACKGROUND</h3> Although patient education is a key step in the Australian Asthma Management Plan, its impact has not been assessed in a hospital outpatient asthma clinic. <h3>METHODS</h3> A controlled trial was undertaken in 125 adults with asthma recruited from the Alfred Hospital Asthma and Allergy Clinic and randomly allocated to an intervention (n = 64) or control (n = 61) group. Subjects in the intervention group attended three education sessions, each of 90 minutes duration, spread over three successive weeks. Asthma knowledge, quality of life, self-management skills, and attitudes and beliefs about asthma were assessed by questionnaires at baseline and after six months. The intervention group was also assessed immediately after the three education sessions. The control group was evaluated after six months of usual care. <h3>RESULTS</h3> Asthma knowledge improved significantly in the intervention group after three education sessions (p = 0.0001) and this was retained six months later (p = 0.03). The impact of asthma on quality of life decreased significantly immediately after intervention (p = 0.03) but this was not maintained six months later (p = 0.35). On the other hand, the intervention had little impact on self-management skills or attitudes and beliefs about asthma. However, the control group had also improved their knowledge, quality of life and self-management skills after six months of usual care. The difference in mean change in knowledge score at six months between the intervention and control groups was not significant (p = 0.51). <h3>CONCLUSIONS</h3> In contrast to some other studies, a limited asthma education programme in a hospital outpatient setting had a positive impact on patients’ knowledge of asthma, but not on their quality of life, self-management skills, or attitudes and beliefs about asthma.
Aspirin, Warfarin, or Enoxaparin Thromboprophylaxis in Patients With Multiple Myeloma Treated With Thalidomide: A Phase III, Open-Label, Randomized Trial
Authors: Antonio Palumbo, Michele Cavo, Sara Bringhen, Elena Zamagni, Alessandra Romano, Francesca Patriarca, Davide Rossi, Fabiana Gentilini, Claudia Crippa, Monica Galli, Chiara Nozzoli, Roberto Ria, Roberto Marasca, Vittorio Montefusco, Luca Baldini, Francesca Elice, Vincenzo Callea, Stefano Pulini, Angelo M. Carella, Renato Zambello, Giulia Benevolo, Valeria Magarotto, Paola Tacchetti, Norbert Pescosta, Claudia Cellini, Claudia Polloni, Andrea Evangelista, Tommaso Caravita, Fortunato Morabito, Massimo Offidani, Patrizia Tosi, Mario Boccadoro
Journal: Journal of Clinical Oncology (2011)

Purpose In patients with myeloma, thalidomide significantly improves outcomes but increases the risk of thromboembolic events. In this randomized, open-label, multicenter trial, we compared aspirin (ASA) or fixed low-dose warfarin (WAR) versus low molecular weight heparin (LMWH) for preventing thromboembolism in patients with myeloma treated with thalidomide-based regimens. Patients and Methods A total of 667 patients with previously untreated myeloma who received thalidomide-containing regimens and had no clinical indication or contraindication for a specific antiplatelet or anticoagulant therapy were randomly assigned to receive ASA (100 mg/d), WAR (1.25 mg/d), or LMWH (enoxaparin 40 mg/d). A composite primary end point included serious thromboembolic events, acute cardiovascular events, or sudden deaths during the first 6 months of treatment. Results Of 659 analyzed patients, 43 (6.5%) had serious thromboembolic events, acute cardiovascular events, or sudden death during the first 6 months (6.4% in the ASA group, 8.2% in the WAR group, and 5.0% in the LMWH group). Compared with LMWH, the absolute differences were +1.3% (95% CI, −3.0% to 5.7%; P = .544) in the ASA group and +3.2% (95% CI, −1.5% to 7.8%; P = .183) in the WAR group. The risk of thromboembolism was 1.38 times higher in patients treated with thalidomide without bortezomib. Three major (0.5%) and 10 minor (1.5%) bleeding episodes were recorded. Conclusion In patients with myeloma treated with thalidomide-based regimens, ASA and WAR showed similar efficacy in reducing serious thromboembolic events, acute cardiovascular events, and sudden deaths compared with LMWH, except in elderly patients where WAR showed less efficacy than LMWH.
Initiation of antiretroviral therapy and viral suppression after home HIV testing and counselling in KwaZulu-Natal, South Africa, and Mbarara district, Uganda: a prospective, observational intervention study
Authors: Ruanne V Barnabas, Heidi van Rooyen, Elioda Tumwesigye, Pamela M Murnane, Jared M Baeten, Hilton Humphries, Bosco Turyamureeba, Philip Joseph, Meighan Krows, James P Hughes, Connie Celum
Journal: The Lancet HIV (2014)
Preoperative Diagnosis and Surgical Correction of Supravalvular Mitral Stenosis and Ventricular Septal Defect
Authors: M. F. LYNCH, N. J. RYAN, G. R. WILLIAMS, G. G. CAYLER, W. R. RICHARDSON, G. S. CAMPBELL, H. TAYBI
Journal: Circulation (1962)

A child with supravalvular mitral stenosis plus ventricular septal defect is reported in whom the correct diagnosis was suspected clinically, confirmed by cardiac catheterization, and successfully treated surgically. Only eight previous cases of supravalvular mitral stenosis have been reported; five of the eight have had associated ventricular septal defects. None was correctly diagnosed before autopsy or surgery. Our patient had a murmur and thrill characteristic of a ventricular septal defect. The pertinent clinical findings suggesting concomitant mitral stenosis consisted of a mitral mid-diastolic murmur that was unusually loud for the magnitude of the left-to-right shunt; a presystolic component to the diastolic murmur; marked left atrial enlargement by x-ray with only moderate pulmonary plethora; and electrocardiographic evidence of left atrial hypertrophy and marked pure right ventricular hypertrophy. Right heart catheterization showed labile passive pulmonary hypertension. Left atrial puncture revealed high proximal and low distal pressure. Surgical correction of both lesions by total cardiac bypass was accomplished through a midline sternal-splitting incision. The supravalvular mitral membrane was excised from the right atrium through an incision in the atrial septum.
Reported skin cancer screening of US adult workers
Authors: William G. LeBlanc, Liat Vidal, Robert S. Kirsner, David J. Lee, Alberto J. Caban-Martinez, Kathryn E. McCollister, Kristopher L. Arheart, Katherine Chung-Bridges, Sharon Christ, John Clark, John E. Lewis, Evelyn P. Davila, Panta Rouhani, Lora E. Fleming
Journal: Journal of the American Academy of Dermatology (2008)
Risks for Stroke, Bleeding, and Death in Patients With Atrial Fibrillation Receiving Dabigatran or Warfarin in Relation to the CHADS_2 Score: A Subgroup Analysis of the RE-LY Trial
Authors: Jonas Oldgren
Journal: Annals of Internal Medicine (2011)

Background: CHADS2 is a simple, validated risk score for predicting the risk for stroke in patients with atrial fibrillation not treated with anticoagulants. There are sparse data on the risk for thrombotic and bleeding complications according to the CHADS2 score in patients receiving anticoagulant therapy. Objective: To evaluate the prognostic importance of CHADS2 risk score in patients with atrial fibrillation receiving oral anticoagulants, including the vitamin K antagonist warfarin and the direct thrombin inhibitor dabigatran. Design: Subgroup analysis of a randomized, controlled trial. (ClinicalTrials.gov registration number: NCT00262600) Setting: Multinational study setting. Patients: 18 112 patients with atrial fibrillation who were receiving oral anticoagulants. Measurements: Baseline CHADS2 score, which assigns 1 point each for congestive heart failure, hypertension, age 75 years or older, and diabetes mellitus and 2 points for stroke. Results: Distribution of CHADS2 scores were as follows: 0 to 1—5775 patients; 2—6455 patients; and 3 to 6—5882 patients. Annual rates of the primary outcome of stroke or systemic embolism among all participants were 0.93% in patients with a CHADS2 score of 0 to 1, 1.22% in those with a score of 2, and 2.24% in those with a score of 3 to 6. Annual rates of other outcomes among all participants with CHADS2 scores of 0 to 1, 2, and 3 to 6, respectively, were the following: major bleeding, 2.26%, 3.11%, and 4.42%; intracranial bleeding, 0.31%, 0.40%, and 0.61%; and vascular mortality, 1.35%, 2.39%, and 3.68% (P < 0.001 for all comparisons). Rates of stroke or systemic embolism, major and intracranial bleeding, and vascular and total mortality each increased in the warfarin and dabigatran groups as CHADS2 score increased. The rates of stroke or systemic embolism with dabigatran, 150 mg twice daily, and of intracranial bleeding with dabigatran, 150 mg or 110 mg twice daily, were lower than those with warfarin; there was no significant heterogeneity in subgroups defined by CHADS2 scores. Limitation: These analyses were not prespecified and should be deemed exploratory. Conclusion: Higher CHADS2 scores were associated with increased risks for stroke or systemic embolism, bleeding, and death in patients with atrial fibrillation receiving oral anticoagulants. Primary Funding Source: Boehringer Ingelheim.
Reliability of transient elastography for the detection of fibrosis in Non-Alcoholic Fatty Liver Disease and chronic viral hepatitis
Authors: Silvia Gaia, Silvia Carenzi, Angela L. Barilli, Elisabetta Bugianesi, Antonina Smedile, Franco Brunello, Alfredo Marzano, Mario Rizzetto
Journal: Journal of Hepatology (2010)
3,5-diiodo-l-thyronine, by modulating mitochondrial functions, reverses hepatic fat accumulation in rats fed a high-fat diet
Authors: Maria Pina Mollica, Lillà Lionetti, Maria Moreno, Assunta Lombardi, Pieter De Lange, Alessandro Antonelli, Antonia Lanni, Gina Cavaliere, Antonio Barletta, Fernando Goglia
Journal: Journal of Hepatology (2009)
Is Cytomegalovirus a Therapeutic Target in Glioblastoma?
Authors: John H. Sampson, Duane A. Mitchell
Journal: Clinical Cancer Research (2011)

Several investigators have now demonstrated the expression of genes unique to cytomegalovirus (CMV) in malignant gliomas. Many of these genes promote oncogenesis, alter tumor microenvironment, and serve as immunologic targets. Is the level of CMV infection within tumor cells sufficient to drive important oncogenic or immunosuppressive processes? Can CMV serve as a target for therapeutic intervention?
Eicosanoids and Their Drugs in Cardiovascular Diseases: Focus on Atherosclerosis and Stroke
Authors: Valérie Capra, Magnus Bäck, Silvia S. Barbieri, Marina Camera, Elena Tremoli, G. Enrico Rovati
Journal: Medicinal Research Reviews (2012)

Abstract Eicosanoids are biologically active lipids in both physiologic and pathophysiologic situations. These mediators rapidly generate at sites of inflammation and act through specific receptors that following the generation of a signal transduction cascade, lead to coordinated cellular responses to specific stimuli. Prostanoids, that is, prostaglandins and thromboxane A 2 , are active products of the cyclooxygenase pathway, while leukotrienes and lipoxins derive from the lipoxygenase pathway. In addition, a complex family of prostaglandin isomers called isoprostanes is derived as free‐radical products of oxidative metabolism. While there is a wide consensus on the importance of the balance between proaggregating (thromboxane A 2 ) and antiaggregating (prostacyclin) cyclooxygenase products in cardiovascular homeostasis, an increasing body of evidence suggests a key role also for other eicosanoids generated by lipoxygenases, epoxygenases, and nonenzymatic pathways in cardiovascular diseases. This intricate network of lipid mediators is unique considering that from a single precursor, arachidonic acid, may derive an array of bioproducts that interact within each other synergizing or, more often, behaving as functional antagonists.