tbuckley/cabot-search huggingface dataset:
A Randomized Trial of Rectal Indomethacin to Prevent Post-ERCP Pancreatitis
Authors: B. Joseph Elmunzer, James M. Scheiman, Glen A. Lehman, Amitabh Chak, Patrick Mosler, Peter D.R. Higgins, Rodney A. Hayward, Joseph Romagnuolo, Grace H. Elta, Stuart Sherman, Akbar K. Waljee, Aparna Repaka, Matthew R. Atkinson, Gregory A. Cote, Richard S. Kwon, Lee McHenry, Cyrus R. Piraka, Erik J. Wamsteker, James L. Watkins, Sheryl J. Korsnes, Suzette E. Schmidt, Sarah M. Turner, Sylvia Nicholson, Evan L. Fogel
Journal: New England Journal of Medicine (2012)

Preliminary research suggests that rectally administered nonsteroidal antiinflammatory drugs may reduce the incidence of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP).In this multicenter, randomized, placebo-controlled, double-blind clinical trial, we assigned patients at elevated risk for post-ERCP pancreatitis to receive a single dose of rectal indomethacin or placebo immediately after ERCP. Patients were determined to be at high risk on the basis of validated patient- and procedure-related risk factors. The primary outcome was post-ERCP pancreatitis, which was defined as new upper abdominal pain, an elevation in pancreatic enzymes to at least three times the upper limit of the normal range 24 hours after the procedure, and hospitalization for at least 2 nights.A total of 602 patients were enrolled and completed follow-up. The majority of patients (82%) had a clinical suspicion of sphincter of Oddi dysfunction. Post-ERCP pancreatitis developed in 27 of 295 patients (9.2%) in the indomethacin group and in 52 of 307 patients (16.9%) in the placebo group (P=0.005). Moderate-to-severe pancreatitis developed in 13 patients (4.4%) in the indomethacin group and in 27 patients (8.8%) in the placebo group (P=0.03).Among patients at high risk for post-ERCP pancreatitis, rectal indomethacin significantly reduced the incidence of the condition. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00820612.).
Protective effect of early and late treatment with nifedipine during myocardial infarction in the conscious dog.
Authors: J A Melin, L C Becker, G M Hutchins
Journal: Circulation (1984)

The effect of early and late nifedipine treatment on collateral blood flow and myocardial infarct size was investigated in 24 previously instrumented conscious dogs. Nifedipine was infused intravenously for 5 hr beginning 15 min (n = 9) and 3 hr (n = 6) after permanent occlusion of the midcircumflex coronary artery and compared with early and delayed vehicle treatment (controls; n = 9). Doses of nifedipine (90 to 168 micrograms/hr) were titrated to reduce mean arterial pressure by 5% to 10%. After animals died or were killed 2 to 7 days later, the anatomic risk region, or occluded coronary bed, was defined by postmortem coronary arteriography. The masses of infarct and risk region were measured by planimetry of weighed transverse sections of the left ventricle. Infarct size was smaller (p less than .05) with early and late nifedipine treatment compared with control, both as percent of left ventricle (15.6% and 14.6% vs 21.6%) and as percent of risk region (46.7% and 41.6% vs 65.7%). Collateral blood flow, measured with radioactive microspheres, increased 31% to 50% during 5 hr of nifedipine treatment, but the mean increase was not statistically greater than that seen in controls. Myocardial protection by nifedipine occurred consistently when epicardial collateral flow exceeded 0.40 ml/min/g and the increase after the drug was at least 0.1 ml/min/g. When flows were less than these amounts, however, only about half of the animals demonstrated reduced infarct size. The results suggest that an increase in collateral flow accounts for part of the beneficial effect of nifedipine but that direct mechanisms not mediated by flow may also contribute.
A phase I study of sequential irinotecan and5-fluorouracil/leucovorin
Authors: R.M. Goldberg, S.H. Kaufmann, P. Atherton, J.A. Sloan, A.A. Adjei, H.C. Pitot, S.R. Alberts, J. Rubin, L.L. Miller, C. Erlichman
Journal: Annals of Oncology (2002)
Evaluation of the interrupter technique in healthy, unsedated infants
Authors: G.L. Hall, J.H. Wildhaber, M. Cernelc, U. Frey
Journal: European Respiratory Journal (2001)

The interrupter technique may be used to monitor respiratory resistance and does not require active patient cooperation, but has yet to be applied in unsedated, spontaneously breathing infants. The aim of this study was to determine if the interrupter technique is feasible in spontaneously breathing infants and to investigate the influence of facemask types and analysis techniques on the interrupter resistance ( R int ). R int was measured in 14 healthy, unsedated, sleeping infants (aged 38.4 (31–56) days (mean (range)). Paired measurements were made using large volume, compliant (M comp ) and small volume, rigid (M rigid ) facemasks. Flow and pressure were measured at the airway opening prior to- and following a brief airway occlusion (500 ms). R int was calculated using four previously reported analysis techniques. R int could be measured in all infants. M comp , independent of the analysis method significantly underestimated R int (p&lt;0.001). The variability and magnitude of R int were significantly influenced by the choice of analysis method. The conclusion is that the interrupter technique is feasible in spontaneously breathing, unsedated infants. Equipment design and analysis method significantly influences interrupter resistance. Studies standardizing equipment and identifying the most appropriate analysis technique in this age group are needed.
Increasing Severity of Cardiovascular Risk Factors With Increasing Middle Cerebral Artery Stenotic Involvement in Type 2 Diabetic Chinese Patients With Asymptomatic Cerebrovascular Disease
Authors: G. Neil Thomas, Jian Wen Lin, Wynnie W.M. Lam, Brian Tomlinson, Vincent Yeung, Juliana C.N. Chan, Roxanna Liu, Ka Sing Wong
Journal: Diabetes Care (2004)

OBJECTIVE—To identify determinants associated with increasing severity of middle cerebral artery (MCA) stenosis in asymptomatic Chinese type 2 diabetic patients with and without MCA stenosis determined using transcranial Doppler. Conventional risk factors contribute to the pathogenesis of ischemic stroke, and differences in the pattern of these may explain the heterogeneity of disease presentation in different populations. In Chinese patients, MCA stenosis is the most commonly identified intracranial vascular lesion. RESEARCH DESIGN AND METHODS—Anthropometric and fasting biochemical parameters were compared between type 2 diabetic patients with MCA stenosis in one (n = 185) or both (n = 200) vessels and 1,492 type 2 diabetic patients without evidence of stenosis. RESULTS—Increasing MCA stenotic vascular involvement was associated with significantly increasing age, duration of diabetes, systolic blood pressure, and LDL cholesterol, but with lower glucose levels. There was also an increased prevalence of hypertension, dyslipidemia, and use of blood pressure–and glucose-lowering agents in the patients with MCA stenosis. Concomitant significant increases in the prevalence of peripheral vascular disease and retinopathy were also observed in the patients with MCA stenosis. CONCLUSIONS—Transcranial Doppler examination identified stenosis in one or both MCAs in over one-fifth of the Chinese type 2 diabetic subjects without symptoms of cerebrovascular disease. A number of conventional cardiovascular risk factors were closely associated with MCA stenosis. This technique may allow the identification of a particularly high-risk group, and further studies are required to determine whether asymptomatic MCA stenosis is predictive of primary cerebrovascular events and whether intensive treatment of risk factors would reduce the risk.
Helicobacter pylori and upper gastrointestinal disease: a survey of gastroenterologists in the United Kingdom.
Authors: R Milne, R P Logan, D Harwood, J J Misiewicz, D Forman
Journal: Gut (1995)

The objective of this study was to conduct a survey of the opinions and practices of gastroenterologists in the United Kingdom concerning the impact of Helicobacter pylori infection on the management of upper gastrointestinal diseases. A postal questionnaire was sent to all medically qualified members of the British Society of Gastroenterology working in the UK. Replies were received from 670 of 1037 eligible BSG members (65%). Of these, 73% thought that H pylori was a cause of duodenal ulcer and 84% thought that eradication of H pylori decreased ulcer recurrence in comparison with acid suppression. While 80% used anti-H pylori therapy for a chronic relapsing duodenal ulcer, only 25% used such therapy for an ulcer at first presentation and 17% never used anti-H pylori therapy for patients with duodenal ulcer. Although 75% of respondents did not agree that H pylori was a cause of non-ulcer dyspepsia, 69% used anti-H pylori therapy to treat a patient with this condition. At the time of the survey, 69% of those who used anti-H pylori therapy adopted some variant of standard triple therapy. Only 7% routinely tested for bacterial sensitivity to antibiotics and only 22% assessed their patients for eradication after treatment. There was a lack of consensus about whether H pylori was a cause of gastric ulcer or gastric cancer with only 47% and 17% respectively believing in these associations. In conclusion, at the time of the survey, the use of anti-H pylori therapy had been accepted by a majority of specialist UK gastroenterologists in the management of upper gastrointestinal disease. There was, however, a substantial degree of uncertainty and divergence about which patients should be treated.
DIAGNOSTIC AND PERSONALITY TESTING IN CLINICAL PSYCHOLOGY
Authors: R. W. PAYNE
Journal: American Journal of Psychiatry (1958)

This paper argues that the practice of validating diagnostic tests solely against psychiatric diagnosis is pointless. The reason is, that if this method of validation is used, none of the consequences of the diagnostic label necessarily follow from the test score. Tests should be directly validated for the purpose to which they are being put. In clinical psychology, tests are usually used to provide a description of the patient, to provide a prognosis, to suggest a treatment, or to suggest some aetiology. Unless tests have been directly shown to have validity for these purposes, they should not be used.
EVALUATION OF THIENOPYRIDINE COMPLIANCE AND STENT THROMBOSIS RATES AFTER EVEROLIMUS-ELUTING AND PACLITAXEL-ELUTING STENT IMPLANTATION: 3-YEAR RESULTS FROM THE SPIRIT III ANALYSIS
Authors: David Alan Cox, Krishnankutty Sudhir, James B. Hermiller, Robert J. Applegate, Paul C. Gordon, Julie Doostzadeh, Lalitha K. Jonnavithula, Kai Koo, Thomas H. Maloney, Alexandra J. Lansky, Charles A. Simonton, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2010)
Female Mice Lacking Estrogen Receptor β Display Prolonged Ventricular Repolarization and Reduced Ventricular Automaticity After Myocardial Infarction
Authors: Thomas Korte, Martin Fuchs, Andreas Arkudas, Sebastian Geertz, Rainer Meyer, Ajmal Gardiwal, Gunnar Klein, Michael Niehaus, Andrée Krust, Pierre Chambon, Helmut Drexler, Klaus Fink, Christian Grohé
Journal: Circulation (2005)

Major gender-based differences in the incidence of ventricular tachyarrhythmia after myocardial infarction have been shown in humans. Although the underlying mechanisms are unclear, earlier studies suggest that estrogen receptor-mediated effects play a major role in this process.We examined the effect of estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta) on the electrophysiological phenotype in female mice with and without chronic anterior myocardial infarction. There was no significant difference in overall mortality, infarct size, and parameters of left ventricular remodeling when we compared infarcted ERalpha-deficient and ERbeta-deficient mice with infarcted wild-type animals. In the 12-hour telemetric ECG recording 6 weeks after myocardial infarction, surface ECG parameters did not show significant differences in comparisons of ERalpha-deficient mice versus wild-type controls, infarcted versus noninfarcted ERalpha-deficient mice, and infarcted ERalpha-deficient versus infarcted wild-type mice. However, infarcted ERbeta-deficient versus noninfarcted ERbeta-deficient mice showed a significant prolongation of the QT (61+/-6 versus 48+/-8 ms; P<0.05) and QTc intervals (61+/-7 versus 51+/-9 ms; P<0.05) and the JT (42+/-6 versus 31+/-4 ms; P<0.05) and JTc intervals (42+/-7 versus 33+/-4 ms; P<0.05). Furthermore, infarcted ERbeta-deficient versus infarcted wild-type mice showed a significant prolongation of the QT (61+/-6 versus 53+/-8 ms; P<0.05) and QTc intervals (61+/-7 versus 53+/-7 ms; P<0.05) and the JT (42+/-6 versus 31+/-5 ms; P<0.05) and JTc intervals (42+/-7 versus 31+/-5 ms; P<0.05), accompanied by a significant decrease of ventricular premature beats (7+/-21/h versus 71+/-110/h; P<0.05). Finally, real-time polymerase chain reaction-based quantitative analysis of mRNA levels showed a significantly lower expression of Kv4.3 (coding for I(to)) in ERbeta-deficient mice (P<0.05).Estrogen receptor beta deficiency results in prolonged ventricular repolarization and decreased ventricular automaticity in female mice with chronic myocardial infarction.
Is the small non-cleaved-cell lymphoma histologic subtype a poor prognostic factor in adult patients? A case-controlled analysis. The Groupe d'Etude des Lymphomes de l'Adulte.
Authors: M Diviné, E Lepage, J Brière, P Pautier, B Dupriez, P Lederlin, P Mineur, H Tilly, M Blanc, B Audhuy, R Herbrecht, B Coiffier, F Reyes
Journal: Journal of Clinical Oncology (1996)

To study the prognostic significance of the small non-cleaved-cell lymphoma (SNCCL) histologic subtype, we compared the outcome of adult patients with SNCCL with that of patients with aggressive lymphoma other than SNCCL by means of two case-controlled studies.We analyzed the results of the doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) regimen used as a reference scheme in our cooperative study group (Groupe d'Etude des Lymphomes de l'Adult [GELA]) in 52 adult SNCCL patients with no bone marrow (BM) or CNS involvement. Forty-five SNCCL patients younger than 60 years could be compared with two separate case-matched groups of patients with aggressive lymphoma other than SNCCL undergoing the same therapeutic regimen. In the first case-controlled study, matching ensured identity of each risk factor of the age-adjusted International Index (ie, Ann Arbor stage, performance status, and lactate dehydrogenase [LDH] level); in the second study, matching was performed according to the number of presenting risk factors (zero, one, two, or three), regardless of their nature.The 5-year overall survival rates were not significantly different between SNCCL and control patients in both case-controlled studies: 48% versus 51% in the first study, and 48% versus 55% in the second study.These results support the thesis that in patients with no bone marrow or CNS involvement, the SNCCL histologic subtype does not confer a prognosis worse than that of other aggressive lymphoma.
Imaging of Podocyte Foot Processes by Fluorescence Microscopy
Authors: Ivica Grgic, Craig R. Brooks, Andreas F. Hofmeister, Vanesa Bijol, Joseph V. Bonventre, Benjamin D. Humphreys
Journal: Journal of the American Society of Nephrology (2012)

Visualizing podocyte foot processes requires electron microscopy, a technique that depends on special equipment, requires immunogold for colabeling, and does not take advantage of the growing number of in vivo fluorophores available. To address these limitations, we developed a genetic strategy to allow detailed visualization of single podocytes and their foot processes by conventional fluorescence microscopy. We generated a transgenic mouse line expressing a GFP-Cre-ERT2 fusion protein under the control of the collagen α1(I) promoter with strong podocyte expression. Administration of submaximal tamoxifen allowed genetic labeling of single podocytes when crossed with a Cre-reporter line. Of three different reporter systems that we evaluated for the ability to reveal fine structural details of podocytes, bigenic Coll1α1GCE;Gt(ROSA)26Sortm9(CAG-tdTomato) mice allowed podocyte labeling with a strong and homogeneous reporter signal that was easily observed by epifluorescence. We could easily detect anatomic features of podocytes down to tertiary foot processes, and we were able to visualize and quantitate ultrastructural changes to foot processes after podocyte injury. In summary, using this method of genetic labeling and conventional fluorescence microscopy to visualize podocyte foot processes will complement electron microscopy and facilitate the analysis of podocytes and their precursors in vivo.
Highly Specific Auto-Antibodies against Claudin-18 Isoform 2 Induced by a Chimeric HBcAg Virus-Like Particle Vaccine Kill Tumor Cells and Inhibit the Growth of Lung Metastases
Authors: Thorsten Klamp, Jens Schumacher, Georg Huber, Christoph Kühne, Ulrich Meissner, Abderraouf Selmi, Thomas Hiller, Sebastian Kreiter, Jürgen Markl, Özlem Türeci, Ugur Sahin
Journal: Cancer Research (2011)

Strategies for antibody-mediated cancer immunotherapy, such as active immunization with virus-like particle (VLP)-based vaccines, are gaining increasing attention. We developed chimeric hepatitis B virus core antigen (HBcAg)-VLPs that display a surface epitope of the highly selective tumor-associated cell lineage marker claudin-18 isoform 2 (CLDN18.2) flanked by a mobility-increasing linker. Auto-antibodies elicited by immunization with these chimeric HBcAg-VLPs in 2 relevant species (mouse and rabbit) bind with high precision to native CLDN18.2 at physiologic densities on the surface of living cells but not to the corresponding epitope of the CLDN18.1 splice variant that differs by merely one amino acid. The induced auto-antibodies are capable of efficiently killing CLDN18.2 expressing cells in vitro by complement-dependent and antibody-dependent cell-mediated cytotoxicity. Moreover, they provide partial protective immunity against the challenge of mice with syngeneic tumor cells stably expressing CLDN18.2. Our study provides a first proof-of-concept that immunization combining VLPs as antigen carriers with specific conformational epitopes of a highly selective differentiation antigen may elicit auto-antibodies with high cytocidal and tumoricidal potential.
Are superficial lesions of the distal part of the ileum early indicators of Crohn's disease in adult patients with abdominal pain? A clinical and radiologic long term investigation.
Authors: O Ekberg, L Baath, B Sjostrom, T Lindhagen
Journal: Gut (1984)

The possibility of early superficial Crohn9s disease should be considered when mucosal irregularities without transmural abnormalities are seen in the distal 15 cm of the ileum in young patients with protracted symptoms of abdominal pain and diarrhoea. Radiologic assessment of the small bowel is improved using the barium/air double contrast technique and in this study mucosal abnormalities were categorised as a 9mucosal nodularity pattern9, an 9abnormal mucosal fold pattern9, and a 9specks of barium pattern9. None of the 21 patients followed prospectively for four to seven years developed established criteria for Crohn9s disease, or any other chronic progressive disease of the small bowel. Colon examinations were normal. In comparison 26 patients with histologically proven Crohn9s disease of the ileum were studied retrospectively and no similar clinical or radiologic characteristics were present. It is concluded, therefore, that such isolated superficial lesions are not pathognomonic and are not early indicators of Crohn9s disease or any other chronic progressive disease of the small bowel.
Alterations in myofibrillar function and protein profiles after complete global ischemia in rat hearts.
Authors: M V Westfall, R J Solaro
Journal: Circulation Research (1992)

We studied changes in myofibrillar function and protein profiles after complete global ischemia with anoxia in rat hearts. Hearts were exposed to global ischemia and anoxia (CGI) for 30 or 60 minutes at 37 degrees C, and myofibrils were prepared for measurement of Ca(2+)-dependent Mg(2+)-ATPase activity at pH 7.0 and 6.5. Hearts incubated in cold saline (1 +/- 1 degrees C) and nonincubated hearts served as controls. Maximum ATPase activity was unchanged at pH 7.0 and pH 6.5 in myofibrils from hearts treated with 30 or 60 minutes of CGI. At pH 7.0, the Hill coefficient, which is an index of cooperative interactions among thin-filament proteins, was unchanged after 30 minutes of CGI but was significantly increased after 60 minutes of CGI. A similar trend for increased cooperativity was observed when myofibrillar ATPase activity was measured at pH 6.5 in myofibrils from rat hearts made ischemic for 30 or 60 minutes. Both 30 and 60 minutes of CGI resulted in increased pCa50 values (half-maximally activating free [Ca2+]) at pH 7.0 and pH 6.5. Densitometric analysis of myofibrillar proteins separated with sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that troponin I and troponin T were degraded during 60 minutes of CGI. Two new protein bands appearing in ischemia-treated myofibrils were identified as partially degraded troponin I and troponin T with Western blots. The troponin I fragment could be phosphorylated by cAMP-dependent protein kinase. In addition, we observed phosphorylation of a protein band that corresponded to myosin light chain-2 in myofibrils from CGI-treated hearts. These results suggest that degradation of thin-filament proteins may contribute to the changes in cooperativity of Ca2+ regulation of ATPase activity observed in the myofibrils from rat hearts exposed to CGI.
Obstructive Coronary Atherosclerosis and Ischemic Heart Disease: An Elusive Link!
Authors: Mario Marzilli, C. Noel Bairey Merz, William E. Boden, Robert O. Bonow, Paola G. Capozza, William M. Chilian, Anthony N. DeMaria, Giacinta Guarini, Alda Huqi, Doralisa Morrone, Manesh R. Patel, William S. Weintraub
Journal: Journal of the American College of Cardiology (2012)
Blockade of the Effects of TGF-β1 on Mesangial Cells by Overexpression of Smad7
Authors: Ruihua Chen, Cancan Huang, Thomas A. Morinelli, Maria Trojanowska, Richard V. Paul
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Smad7, a protein induced by transforming growth factor–β1 (TGF-β1) in many target cells, inhibits TGF-β1 signal transduction and is thought to mediate an intracellular negative feedback response that limits TGF-β1 effects. It is possible that overexpression of Smad7 could block specified effects of TGF-β1 on mesangial cells, a TGF-β target in glomerular disease. Smad7 mRNA was induced by TGF-β1 within 1 h in a concentration-dependent manner in a transformed mouse mesangial cell (MMC) line. Uptake of 14C-spermidine from the medium by MMC and the transcriptional activity of a segment of the human collagen pro-α2 type 1 chain (COL1A2) promoter fused to a luciferase reporter gene were used as indices of TGF-β1. Treatment with TGF-β1 increased 14C-spermidine uptake rate in a time-, concentration-, and temperature-dependent manner. For example, exposure to 1 ng/ml TGF-β1 for 15 h increased uptake approximately twofold, a response that was attenuated by cycloheximide. Transfection of Smad7 expression vector into MMC abrogated both TGF-β1-dependent stimulation of spermidine uptake and COL1A2 promoter activity. It is concluded that: (1) TGF-β1 induces Smad7 in MMC; (2) 14C-spermidine uptake is a convenient quantitative index of TGF-β1 effect in these cells; and (3) overexpression of Smad7 is a highly effective method of blocking at least some mesangial cell effects of TGF-β1 that may warrant evaluation in vivo in experimental glomerular disease.