tbuckley/cabot-search huggingface dataset:
Up-Front Tandem High-Dose Chemotherapy Compared With Standard Chemotherapy With Doxorubicin and Paclitaxel in Metastatic Breast Cancer: Results of a Randomized Trial
Authors: Peter Schmid, Walter Schippinger, Thorsten Nitsch, Gerdt Huebner, Volker Heilmann, Wolfgang Schultze, Hubert Hausmaninger, Manfred Wischnewsky, Kurt Possinger
Journal: Journal of Clinical Oncology (2005)

The role of high-dose chemotherapy (HDCT) in metastatic breast cancer remains controversial. Trials with late intensification HDCT have failed to show an advantage in overall survival. This study was initiated to compare up-front tandem HDCT and standard combination therapy in patients with metastatic breast cancer.Patients without prior chemotherapy for metastatic disease were randomly assigned to standard combination therapy with doxorubicin and paclitaxel (AT) or double HDCT with cyclophosphamide, mitoxantrone, and etoposide followed by peripheral-blood stem-cell transplantation. HDCT was repeated after 6 weeks. Patients were stratified by menopausal and hormone-receptor status. The primary objective was to compare complete response (CR) rates.A total of 93 patients were enrolled onto the trial. Intent-to-treat CR rates for patients randomized to HDCT and AT were 12.5% and 11.1%, respectively (P = .84). Objective response rates were 66.7% for patients in the high-dose group and 64.4% for patients in the AT arm (P = .82). In an intent-to-treat analysis, there were no significant differences between the two treatments in median time to progression (HDCT, 11.1 months; AT, 10.6 months; P = .67), duration of response (HDCT, 13.9 months; AT, 14.3 months; P = .98), and overall survival (HDCT, 26.9 months; AT, 23.4 months; P = .60). HDCT was associated with significantly more myelosuppression, infection, diarrhea, stomatitis, and nausea and vomiting, whereas patients treated with AT developed more neurotoxicity.This trial failed to show a benefit for up-front tandem HDCT compared with standard combination therapy. HDCT was associated with more acute adverse effects.
Left Circumflex Coronary Artery Hemodynamics in Conscious Dogs with Congenital Subaortic Stenosis
Authors: R. LEE PYLE, HOWARD S. LOWENSOHN, EDWARD M. KHOURI, DONALD E. GREGG, DONALD F. PATTERSON
Journal: Circulation Research (1973)

Coronary arterial hemodynamics were studied in three conscious dogs with congenital fibrous ring-type subaortic stenosis. Flow characteristics were recorded with electromagnetic flow transducers chronically implanted on the circumflex branch of the left coronary artery. Circumflex resting flow (ml/min 100 g -1 myocardium) was below that previously found in normal dogs studied by the same methods. Phasic coronary flow patterns at rest were abnormal, being characterized by reversed flow throughout most of ventricular systole. The mean reactive hyperemic response after 10 seconds of mechanical occlusion was comparable to that in normal dogs despite the essential absence of systolic forward flow. In one dog, moderate treadmill exercise substantially increased total circumflex flow despite a large increase in reversed circumflex flow.
Inflammatory Bowel Disease: Diagnosis and Therapeutics
Authors: S Ghosh
Journal: Gut (2003)

Cyclooxygenase 2 selective inhibitor induced bowel stricture: a case report Several reports have mentioned the role of non-steroidal anti-inflammatory drugs (NSAID) in inducing diaphragm disease and strictures in the small and large bowel. [1]2][3] To our knowledge, there is no such report in patients treated with cyclooxygenase 2 (COX-2) selective inhibitors.We report the case of a 55 year old man with a past history of axial spondylarthropathy, successfully treated with NSAID from 1975 to 2001; from February 2001, he was treated with celecoxib 400 mg per day for three weeks and then 200 mg/day for two years.He had previous abdominal surgery (appendicectomy) in 1965.He presented with a 24 hour history of central abdominal pain with persistent vomiting.Clinical and radiological examination confirmed small bowel obstruction.At laparoscopy, a distal ileal obstruction was identified.Coelioscopic laparotomy was then performed, showing evidence of bowel wall stricture; 10 cm of the distal ileum was spared.Macroscopic and microscopic examination of the resected specimen was consistent with a diagnosis of stricture on submucosal ulceration of the small bowel.This condition is known to be associated with long term use of NSAID.The COX-2 specific inhibitors have been developed in order to improve the gastrointestinal safety of therapy with NSAID.In various clinical trials, COX-2 selective inhibitors have been shown to have similar efficacy to NSAID, with a concomitant association with fewer endoscopic ulcers and serious lower gastrointestinal events. 3 This case suggests that COX-2 selective inhibitors can induce bowel wall ulcerations, followed by submucosa fibrosis, which may cause strictures or diaphragm-like disease.
The Central and Peripheral Influences of Opioids on Gastrointestinal Propulsion
Authors: L Manara, A Bianchetti
Journal: The Annual Review of Pharmacology and Toxicology (1985)

Since the spread of tobacco from the Americas hundreds of years ago, tobacco cigarettes and, more recently, alternative tobacco products have become global products of nicotine addiction. Within the evolving alternative tobacco product space, electronic ...Read More
Will moving into social and affordable housing in East Village, London, UK, increase family physical activity levels? Evaluation of a natural experiment
Authors: Christopher G Owen, Bina Ram, Venediktos Kapetanakis, Alicja R Rudnicka, Anne Ellaway, Ashley R Cooper, Angie Page, Daniel Lewis, Steve Cummins, Billie Giles-Corti, Derek G Cook, Peter H Whincup
Journal: The Lancet (2014)
Demonstration of a third structurally distinct human Ia beta chain by two-dimensional gel electrophoresis.
Authors: R W Karr, C C Kannapell, J A Stein, T C Fuller, R J Duquesnoy, G E Rodey, D L Mann, H M Gebel, B D Schwartz
Journal: The Journal of Experimental Medicine (1982)

Previous studies have indicated that HLA-DR homozygous cell lines express two Ia alpha and Ia beta chains that combine to form at least two Ia molecules. This report demonstrates by two-dimensional gel electrophoresis the existence of a third structurally distinct human Ia beta chain on DR2 and DR5 cell lines. This suggests that at least five separate genes control the expression of Ia molecules on HLA-DR homozygous cell lines.
A homozygous mutation in the endothelin-3 gene associated with a combined Waardenburg type 2 and Hirschsprung phenotype (Shah-Waardenburg syndrome)
Authors: Robert M.W. Hofstra, Jan Osinga, Gita Tan-Sindhunata, Ying Wu, Erik-J. Kamsteeg, Rein P. Stulp, Conny van Ravenswaaij-Arts, Daniëlle Majoor-Krakauer, Misha Angrist, Aravinda Chakravarti, Carel Meijers, Charles H.C.M. Buys
Journal: Nature Genetics (1996)
Low Sensitivity of the<i>ki-ras</i>Polymerase Chain Reaction for Diagnosing Pancreatic Cancer From Pancreatic Juice and Bile: A Multicenter Prospective Trial
Authors: Lorenz Trümper, Markus Menges, Heiner Daus, Daniel Köhler, Jan-Olaf Reinhard, Michael Sackmann, Cornelius Moser, Alexandra Sek, Georg Jacobs, Martin Zeitz, Michael Pfreundschuh
Journal: Journal of Clinical Oncology (2002)

Early detection of pancreatic cancer using molecular markers may improve outcome. Mutations of the ki-ras oncogene are detected in 70% to 90% of pancreatic adenocarcinomas. A prospective, partially blinded, multicenter diagnostic trial was performed to test the sensitivity and specificity of the ki-ras polymerase chain reaction (PCR) analysis of pancreatic juice and bile specimens.Specimens of pancreatic juice and bile were collected from 532 consecutive patients. Mutations in codon 12 of the ki-ras gene were identified by two independent enrichment PCRs and confirmed by direct sequencing.One hundred seventy-four of 532 patients were excluded from the final analysis (reasons: no amplifiable DNA, no specimen or only duodenal juice sent, lost to follow-up). Sixty-three of 358 patients had ductal pancreatic cancer. In 24 (38.1%) of 63 patients, a mutated ki-ras gene was identified in pancreatic juice and/or bile. Ki-ras mutations were found in four (8%) of 50 cases of chronic pancreatitis, in 10 (18.7%) of 53 cases of other malignancies of the pancreaticobiliary tree, and in 14 (7.3%) of 192 cases of benign diseases or normal findings. Sensitivity and specificity of the ki-ras PCR analysis for the detection of pancreatic cancer was 38.1% and 90.5%, respectively.In this prospective trial performed in nonselected patients, mutations of the ki-ras gene were detected in 38.1% of cases with pancreatic cancer. This test in its present form is not appropriate to confirm or screen for pancreatic cancer. More sensitive and/or quantitative PCR tests may improve the molecular diagnosis of pancreatic cancer.
A Randomized Trial of Epidural Glucocorticoid Injections for Spinal Stenosis
Authors: Janna L. Friedly, Bryan A. Comstock, Judith A. Turner, Patrick J. Heagerty, Richard A. Deyo, Sean D. Sullivan, Zoya Bauer, Brian W. Bresnahan, Andrew L. Avins, Srdjan S. Nedeljkovic, David R. Nerenz, Christopher Standaert, Larry Kessler, Venu Akuthota, Thiru Annaswamy, Allen Chen, Felix Diehn, William Firtch, Frederic J. Gerges, Christopher Gilligan, Harley Goldberg, David J. Kennedy, Shlomo Mandel, Mark Tyburski, William Sanders, David Sibell, Matthew Smuck, Ajay Wasan, Lawrence Won, Jeffrey G. Jarvik
Journal: New England Journal of Medicine (2014)

Epidural glucocorticoid injections are widely used to treat symptoms of lumbar spinal stenosis, a common cause of pain and disability in older adults. However, rigorous data are lacking regarding the effectiveness and safety of these injections.In a double-blind, multisite trial, we randomly assigned 400 patients who had lumbar central spinal stenosis and moderate-to-severe leg pain and disability to receive epidural injections of glucocorticoids plus lidocaine or lidocaine alone. The patients received one or two injections before the primary outcome evaluation, performed 6 weeks after randomization and the first injection. The primary outcomes were the score on the Roland-Morris Disability Questionnaire (RMDQ, in which scores range from 0 to 24, with higher scores indicating greater physical disability) and the rating of the intensity of leg pain (on a scale from 0 to 10, with 0 indicating no pain and 10 indicating "pain as bad as you can imagine").At 6 weeks, there were no significant between-group differences in the RMDQ score (adjusted difference in the average treatment effect between the glucocorticoid-lidocaine group and the lidocaine-alone group, -1.0 points; 95% confidence interval [CI], -2.1 to 0.1; P=0.07) or the intensity of leg pain (adjusted difference in the average treatment effect, -0.2 points; 95% CI, -0.8 to 0.4; P=0.48). A prespecified secondary subgroup analysis with stratification according to type of injection (interlaminar vs. transforaminal) likewise showed no significant differences at 6 weeks.In the treatment of lumbar spinal stenosis, epidural injection of glucocorticoids plus lidocaine offered minimal or no short-term benefit as compared with epidural injection of lidocaine alone. (Funded by the Agency for Healthcare Research and Quality; ClinicalTrials.gov number, NCT01238536.).
Repeated Exposure to Methamphetamine Causes Long-Lasting Presynaptic Corticostriatal Depression that Is Renormalized with Drug Readministration
Authors: Nigel S. Bamford, Hui Zhang, John A. Joyce, Christine A. Scarlis, Whitney Hanan, Nan-Ping Wu, Véronique M. André, Rachel Cohen, Carlos Cepeda, Michael S. Levine, Erin Harleton, David Sulzer
Journal: Neuron (2008)
The atypical chemokine receptor D6 suppresses the development of chemically induced skin tumors
Authors: Robert J.B. Nibbs, Derek S. Gilchrist, Vicky King, Antonio Ferra, Steve Forrow, Keith D. Hunter, Gerard J. Graham
Journal: Journal of Clinical Investigation (2007)

A subset of CC chemokines, acting through CC chemokine receptors (CCRs) 1 to 5, is instrumental in shaping inflammatory responses. Recently, we and others have demonstrated that the atypical chemokine receptor D6 actively sequesters and destroys many of these proinflammatory CC chemokines. This is critical for effective resolution of inflammation in vivo. Inflammation can be protumorigenic, and proinflammatory CC chemokines have been linked with various aspects of cancer biology, yet there is scant evidence supporting a critical role for these molecules in de novo tumor formation. Here, we show that D6-deficient mice have increased susceptibility to cutaneous tumor development in response to chemical carcinogenesis protocols and, remarkably, that D6 deletion is sufficient to make resistant mouse strains susceptible to invasive squamous cell carcinoma. Conversely, transgenic D6 expression in keratinocytes dampens cutaneous inflammation and can confer considerable protection from tumor formation in susceptible backgrounds. Tumor susceptibility consistently correlated with the level of recruitment of T cells and mast cells, cell types known to support the development of skin tumors in mice. These data demonstrate the importance of proinflammatory CC chemokines in de novo tumorigenesis and reveal chemokine sequestration by D6 to be a novel and effective method of tumor suppression.
The Pathogenesis of Esophageal Dysfunction in Scleroderma and Raynaud's Disease
Authors: Sidney Cohen, Robert Fisher, William Lipshutz, Robert Turner, Allen Myers, Ralph Schumacher
Journal: Journal of Clinical Investigation (1972)

To determine the pathogenesis of esophageal dysfunction in scleroderma and Raynaud's disease, the lower esophageal sphincter (LES) was tested with: (a) methacholine acting directly at the cholinergic receptor on the muscle; (b) edrophonium, a cholinesterase inhibitor, enhancing the effect of released acetylcholine; and (c) gastrin I, acting through the release of acetylcholine. 10 patients with Raynaud's disease and 22 patients with scleroderma were compared with 20 normals and 20 patients with isolated LES incompetence. The mean basal LES pressure in normals was significantly greater than that recorded in both patients with scleroderma and Raynaud's disease. Six patients having scleroderma with normal peristalsis had an LES pressure significantly greater than that noted in 16 patients having scleroderma with abnormal peristalsis. In all groups, the per cent increase in LES pressure was similar when tested by direct muscle stimulation by methacholine. The response to agents that acted indirectly through intact cholinergic nerves differed in these groups. The LES response to gastrin I distinguished patients with normal peristalsis from those with abnormal peristalsis. The patients with normal peristalsis, either with scleroderma or with Raynaud's disease showed only a partial reduction in their response to gastrin I. The response to gastrin I was markedly reduced only in patients with abnormal peristalsis. These data indicate that in patients with scleroderma and Raynaud's disease, the LES response to direct muscle stimulation by methacholine was intact while the response to gastrin I and edrophonium was diminished.
Circulating microRNAs as potential markers of human drug-induced liver injury
Authors: Philip J. Starkey Lewis, James Dear, Vivien Platt, Kenneth J. Simpson, Darren G.N. Craig, Daniel J. Antoine, Neil S. French, Neeraj Dhaun, David J. Webb, Eithne M. Costello, John P. Neoptolemos, Jonathan Moggs, Chris E. Goldring, Kevin B. Park
Journal: Hepatology (2011)

New biomarkers of liver injury are required in the clinic and in preclinical pharmaceutical evaluation. Previous studies demonstrate that two liver-enriched microRNAs (miR-122 and miR-192) are promising biomarkers of acetaminophen-induced acute liver injury (APAP-ALI) in mice. We have examined these molecules, for the first time, in humans with APAP poisoning. Serum miR-122 and miR-192 were substantially higher in APAP-ALI patients, compared to healthy controls (median ΔΔCt [25th, 75th percentile]) (miR-122: 1,265 [491, 4,270] versus 12.1 [7.0, 26.9], P < 0.0001; miR-192: 6.9 [2.0, 29.2] versus 0.44 [0.30, 0.69], P < 0.0001). A heart-enriched miR-1 showed no difference between APAP-ALI patients and controls, whereas miR-218 (brain-enriched) was slightly higher in the APAP-ALI cohort (0.17 [0.07, 0.50] versus 0.07 [0.04, 0.12]; P = 0.01). In chronic kidney disease (CKD) patients, miR-122 and -192 were modestly higher, compared to controls (miR-122: 32.0 [21.1, 40.9] versus 12.1 [7.0, 26.9], P = 0.006; miR-192: 1.2 [0.74, 1.9] versus 0.44 [0.30, 0.69], P = 0.005), but miR-122 and -192 were substantially higher in APAP-ALI patients than CKD patients (miR-122: P < 0.0001; miR-192: P < 0.0004). miR-122 correlated with peak ALT levels in the APAP-ALI cohort (Pearson R = 0.46, P = 0.0005), but not with prothrombin time. miR-122 was also raised alongside peak ALT levels in a group of patients with non-APAP ALI. Day 1 serum miR-122 levels were almost 2-fold higher in APAP-ALI patients who satisfied King's College Criteria (KCC), compared to those who did not satisfy KCC, although this did not reach statistical significance (P = 0.15).This work provides the first evidence for the potential use of miRNAs as biomarkers of human drug-induced liver injury.
Distal splenorenal vs. portal-systemic shunts after hemorrhage from varices: A randomized controlled trial
Authors: Norman D. Grace, Harold O. Conn, Robert H. Resnick, Roberto J. Groszmann, Colin E. Atterbury, Stephen C. Wright, Richard J. Gusberg, Rudolph Vollman, Guadalupe Garcia-Tsao, Rosemarie L. Fisher, Edward T. O’Hara, William V. McDermott, Peter J. Maselli, Warren Widrich, Daniel S. Matloff, Douglas Horst, Naomi Banks, Jeanne Alberts
Journal: Hepatology (1988)

Between 1975 and 1983, 303 cirrhotic patients with endoscopically proven major variceal hemorrhage were admitted to the participating hospitals of the Boston-New Haven Collaborative Liver Group. Of these, 274 were evaluated for admission to a prospective, randomized controlled trial comparing portal-systemic shunts with distal splenorenal shunts. The criteria for inclusion were as follows: (i) a portohepatic pressure gradient ≥ 12 mmHg; (ii) angiographic evidence of antegrade portal venous flow; (iii) angiographic demonstration that the inferior vena cava and portal, splenic and left renal veins were anatomically suitable for either a portal-systemic or distal splenorenal shunt, and (iv) the patient was a reasonable operative risk. Eighty-one patients from the six participating hospitals fulfilled the criteria and consented to participate. Thirty-eight patients were randomly assigned to have portal-systemic shunt and 43 to have distal splenorenal shunt. After a follow-up period of 11 years (mean = 3.5 years for all patients), survival was found to be similar in the two groups of patients. The 30-day operative mortality was 13% for the portal-systemic shunt group and 9% for the distal splenorenal shunt patients. Late mortality was 55% for the portal-systemic shunt and 37% for the distal splenorenal shunt group. Total mortality was 68% for the portal-systemic shunt and 46% for the distal splenorenal shunt group. None of these differences is statistically significant. In those patients who survived &gt;30 days after surgery, recurrent variceal hemorrhage occurred in four (12%) in the portal-systemic shunt group compared to seven in the distal splenorenal shunt group (18%) (NS). Portal-systemic encephalopathy occurred in 15 (45%) of the operative survivors in the portal-systemic shunt group compared to 20 (51%) in the distal splenorenal shunt group. Severe portal-systemic encephalopathy was observed with equal frequency in the two groups. There was no difference in the time of onset nor the severity of encephalopathy in the two groups. We conclude that the operative mortality and cumulative survival are similar for the two operations and that the frequency and severity of hepatic encephalopathy following distal splenorenal shunt are similar to that after portal-systemic shunt. Based on our observations and previously published data, recurrent hemorrhage from varices appears to be more frequently prevented by portacaval anastomosis than by distal splenorenal shunt.
Respiratory function tests prior to cardiac surgery: Prediction of post-operative outcomes
Authors: James McKeon, Nicholas McKeon, Sjane Stevens, Heather Stewart
Journal: European Respiratory Journal (2014)

Chronic obstructive pulmonary disease (COPD) and low DLCO are associated with increased mortality after cardiac surgery in men (Adabag et al. Am Heart J 2010;159:691-7). COPD can be defined by FEV1/FVC% less than 70% (GOLD) or by FEV1/FVC% below the lower 5th percentile of normal (LLN).  We aimed to determine whether pre-op respiratory function tests (RFTs) in men and women correlate with post-op outcomes and to determine which definition of COPD correlates more closely with post-op outcomes.  We studied 283 patients at one hospital in Brisbane between January 2010 and December 2013. The patients performed spirometry and gas transfer tests according to ERS/ATS guidelines.  There were 283 patients (184 men and 99 women); mean(sd) age 70(12) years; FEV1%pred 86(21)%; FEV1/FVC% 70.8(9.6)%; DLCO%pred 76.3(21)%. Eight patients (6 women, 2 men) (2.8%) died within 30 days of surgery; mean(sd) age was 73.1(7.5) years; FEV1%pred 65.5(24); FEV1/FVC% 61.5(14)% and DLCO%pred 51(21)%. Of 133 patients with FEV1 greater than 80%pred and FEV1/FVC% greater than 70% and DLCO greater than 50% pred, one (0.8%) died post-op (OR=1). Six of 30 patients (20%) with DLCO less than 50% pred died post-op (OR=25). Five of 24 patients (21%) with FEV1 less than 80%predicted and DLCO less than 50% pred died post-op (OR=26).  115 (41%) of the 283 patients were defined as having COPD by GOLD criteria compared to 58 (21%) patients defined as having COPD by LLN criteria.  The preliminary data support the hypothesis that pre-operative RFTs and particularly DLCO are useful in predicting post-operative outcomes. Further analysis will determine which definition of COPD is more closely associated with post-operative outcomes.
von Willebrand factor cleaving protease and ADAMTS13mutations in childhood TTP
Authors: Reinhard Schneppenheim, Ulrich Budde, Florian Oyen, Dorothea Angerhaus, Volker Aumann, Elke Drewke, Wolf Hassenpflug, Johannes Häberle, Karim Kentouche, Elisabeth Kohne, Karin Kurnik, Dirk Mueller-Wiefel, Tobias Obser, René Santer, Karl-Walter Sykora
Journal: Blood (2003)