tbuckley/cabot-search huggingface dataset:
Professional Boxing, Bleeding, and HIV Testing
Authors: D. Peter Drotman
Journal: JAMA (1996)

To the Editor.  —As the epidemic of human immunodeficiency virus (HIV) infection continues, inevitably persons from all walks of life are directly affected, including world-class athletes. Public disclosures of HIV infection by Arthur Ashe, Greg Lougainis, Earvin Magic Johnson, and most recently boxer Tommy Morrison have attracted considerable press and public attention. The issue of HIV transmission in sports settings, particularly during athletic competition, has received much of the coverage. Fortunately, we have had years to consider this issue, and guidelines already exist to protect the health of all athletes and those who coach and care for them.1,2These guidelines, or approximate versions of them, have been adopted by virtually all major athletic organizations, including those at the scholastic, collegiate, professional, and international levels. The guidelines recommend that when a bleeding injury occurs, the game or match be stopped, all bleeding athletes receive care as soon as practical, and
Tinzaparin in acute ischaemic stroke (TAIST): a randomised aspirin-controlled trial
Authors: Philip MW Bath, Ewa Lindenstrom, Gudrun Boysen, Peter De Deyn, Pal Friis, Didier Leys, Reijo Marttila, Jan-Edwin Olsson, Desmond O'Neill, Jean-Marc Orgogozo, Bernd Ringelstein, Jan-Jacob van der Sande, Alexander GG Turpie
Journal: The Lancet (2001)
Genetic and functional identification of the likely causative variant for cholesterol gallstone disease at the ABCG5/8 lithogenic locus
Authors: Oliver von Kampen, Stephan Buch, Michael Nothnagel, Lorena Azocar, Hector Molina, Mario Brosch, Wiebke Erhart, Witigo von Schönfels, Jan Egberts, Marcus Seeger, Alexander Arlt, Tobias Balschun, Andre Franke, Markus M. Lerch, Julia Mayerle, Wolfgang Kratzer, Bernhard O. Boehm, Klaus Huse, Bodo Schniewind, Katharina Tiemann, Zhao-Yan Jiang, Tian-Quan Han, Balraj Mittal, Anshika Srivastava, Mogens Fenger, Torben Jφrgensen, Ramin Schirin-Sokhan, Anke Tönjes, Henning Wittenburg, Michael Stumvoll, Holger Kalthoff, Frank Lammert, Jürgen Tepel, Klaus Puschel, Thomas Becker, Stefan Schreiber, Matthias Platzer, Henry Völzke, Michael Krawczak, Juan Francisco Miquel, Clemens Schafmayer, Jochen Hampe
Journal: Hepatology (2012)

The sterolin locus (ABCG5/ABCG8) confers susceptibility for cholesterol gallstone disease in humans. Both the responsible variant and the molecular mechanism causing an increased incidence of gallstones in these patients have as yet not been identified. Genetic mapping utilized patient samples from Germany (2,808 cases, 2,089 controls), Chile (680 cases, 442 controls), Denmark (366 cases, 766 controls), India (247 cases, 224 controls), and China (280 cases, 244 controls). Analysis of allelic imbalance in complementary DNA (cDNA) samples from human liver (n = 22) was performed using pyrosequencing. Transiently transfected HEK293 cells were used for [(3) H]-cholesterol export assays, analysis of protein expression, and localization of allelic constructs. Through fine mapping in German and Chilean samples, an ∼250 kB disease-associated interval could be defined for this locus. Lack of allelic imbalance or allelic splicing of the ABCG5 and ABCG8 transcripts in human liver limited the search to coding single nucleotide polymorphisms. Subsequent mutation detection and genotyping yielded two disease-associated variants: ABCG5-R50C (P = 4.94 × 10(-9) ) and ABCG8-D19H (P = 1.74 × 10(-10) ) in high pairwise linkage disequilibrium (r(2) = 0.95). [(3) H]-cholesterol export assays of allelic constructs harboring these genetic candidate variants demonstrated increased transport activity (3.2-fold, P = 0.003) only for the ABCG8-19H variant, which was also superior in nested logistic regression models in German (P = 0.018), Chilean (P = 0.030), and Chinese (P = 0.040) patient samples.This variant thus provides a molecular basis for biliary cholesterol hypersecretion as the mechanism for cholesterol gallstone formation, thereby drawing a link between "postgenomic" and "pregenomic" pathophysiological knowledge about this common complex disorder. (HEPATOLOGY 2012).
Republished research: Effect of specific exercise strategy on need for surgery in patients with subacromial impingement syndrome: randomised controlled study
Authors: Theresa Holmgren, Hanna Björnsson Hallgren, Birgitta Öberg, Lars Adolfsson, Kajsa Johansson
Journal: British Journal of Sports Medicine (2013)

▸ This article is an abridged version of a paper that was published on bmj.com. Cite this article as: BMJ 2012; 344 :e787

### Study question

Can a specific exercise strategy improve shoulder function and pain in patients with subacromial impingement syndrome, thereby decreasing the need for arthroscopic subacromial decompression?

### Summary answer

Compared with a control exercise group, patients in the specific exercise group had significantly greater improvements in shoulder function and pain and fewer patients needed surgery at the three month assessment.

### What is known and what this paper adds

Different exercise programmes are used as first line treatment in patients with subacromial impingement syndrome, but conclusive evidence to support the efficacy for these programmes is lacking. This …
Magnetic Resonance Imaging of the Peritoneal Cavity among Peritoneal Dialysis Patients, Using the Dialysate as “Contrast Medium”
Authors: Friedrich C. Prischl, Thomas Muhr, Eva M. Seiringer, Siegfried Funk, Gert Kronabethleitner, Manfred Wallner, Wolfgang Artmann, Reinhard Kramar
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. The objectives of this study were to evaluate whether adequate observation of abdominal pathologic features related to peritoneal dialysis (PD) was possible with magnetic resonance imaging (MRI) under routine conditions, i.e., against the background of the dialysate and without contrast medium. For 16 male and seven female patients (mean age, 51.8 ± 15.0 yr; mean duration of PD, 324 ± 542 d), 25 peritoneal MRI studies were performed with the intraperitoneal dialysate as usual. Indications were symptoms or combinations of symptoms, such as leakage or abdominal wall edema (n = 3), bloody dialysate (n = 4), suspected herniation (n = 1), suspected ultrafiltration failure (n = 2), and abdominal pain (n = 5), or routine assessment after initiation of PD (n = 12). The MRI protocol, which was performed with a 1.0-T scanner, consisted of breath-hold, coronal and transverse, T2-weighted, half-Fourier single-shot turbo spin-echo sequences, using a standard body-array coil. MRI studies were well tolerated and successfully completed for all except two patients. Results indicated a leak along the catheter (n = 1), a leak in an umbilical hernia (n = 1), suspected leakage (n = 1), hernias (n = 5, in three patients), intraperitoneal adhesions (n = 5, in four patients), a ruptured ovarian cyst (n = 1), and pleural effusions (n = 4). Pathologic findings unrelated to PD or located extra-abdominally were observed in 19 of the 25 studies. The catheter tip position was easily identified for all patients. In conclusion, this first report on peritoneal MRI using only dialysate as the "contrast medium" indicates that MRI permits detailed observation of all relevant, PD-related, abdominal pathologic features against the dialysate background, thus avoiding system contamination (and thus the risk of peritonitis).
Randomized Trial of Lifestyle Modification and Pharmacotherapy for Obesity
Authors: Thomas A. Wadden, Robert I. Berkowitz, Leslie G. Womble, David B. Sarwer, Suzanne Phelan, Robert K. Cato, Louise A. Hesson, Suzette Y. Osei, Rosalind Kaplan, Albert J. Stunkard
Journal: New England Journal of Medicine (2005)

Weight-loss medications are recommended as an adjunct to a comprehensive program of diet, exercise, and behavior therapy but are typically prescribed with minimal or no lifestyle modification. This practice is likely to limit therapeutic benefits. In this one-year trial, we randomly assigned 224 obese adults to receive 15 mg of sibutramine per day alone, delivered by a primary care provider in eight visits of 10 to 15 minutes each; lifestyle-modification counseling alone, delivered in 30 group sessions; sibutramine plus 30 group sessions of lifestyle-modification counseling (i.e., combined therapy); or sibutramine plus brief lifestyle-modification counseling delivered by a primary care provider in eight visits of 10 to 15 minutes each. All subjects were prescribed a diet of 1200 to 1500 kcal per day and the same exercise regimen. At one year, subjects who received combined therapy lost a mean (+/-SD) of 12.1+/-9.8 kg, whereas those receiving sibutramine alone lost 5.0+/-7.4 kg, those treated by lifestyle modification alone lost 6.7+/-7.9 kg, and those receiving sibutramine plus brief therapy lost 7.5+/-8.0 kg (P<0.001). Those in the combined-therapy group who frequently recorded their food intake lost more weight than those who did so infrequently (18.1+/-9.8 kg vs. 7.7+/-7.5 kg, P=0.04). The combination of medication and group lifestyle modification resulted in more weight loss than either medication or lifestyle modification alone. The results underscore the importance of prescribing weight-loss medications in combination with, rather than in lieu of, lifestyle modification.
Media influence on Herceptin subsidization in Australia: application of the rule of rescue?
Authors: Ross MacKenzie, Simon Chapman, Glenn Salkeld, Simon Holding
Journal: Journal of the Royal Society of Medicine (2008)

Summary Background In August 2006, the Australian government announced that Herceptin (Trastuzumab) would be added to the national Pharmaceutical Benefits Scheme (PBS) of government-subsidized drugs, for treatment with adjuvant chemotherapy of HER2 breast cancer. Following initial reticence, the health minister responded to a campaign by patients and patient advocacy groups by announcing PBS subsidization which lowered the cost of a weekly dose from A$1000 to A$30. The cost to the government would be A$470 million over three years for treatment of an estimated 2100 women annually. Design We analysed the news frames used in all direct and attributed statements ( n=239) in television news coverage of the discourse preceding the Herceptin decision by the Australian government. Setting Five Sydney free-to-air channels between October 2005 and August 2006. Main outcome measures News frames or themes. Results Of five news frames identified, one (‘desperate, sick women in double jeopardy because of callous government/incompetent bureaucracy’) accounted for 54% of all reported statements. Government financial parsimony was framed as responsible for the women's plight, with drug industry pricing never mentioned. Claimed benefits of Herceptin often conflated cancer non-recurrence and survival and favoured quantification rhetoric which emphasized percentage increases in improvement rather than the more modest increases in absolute survival. Conclusions News frames invoking key tenets of the ‘rule of rescue’ dominated television discourse on Herceptin. Clinicians, patients, their families and patient advocacy groups invoking the rule of rescue can increase the likelihood of achieving their objective of gaining access to expensive healthcare such as pharmaceuticals. Rational, criteria-based public health policy will find it hard to resist the rule of rescue imperative.
Novel Therapies for Metastatic Castrate-Resistant Prostate Cancer
Authors: F. Dayyani, G. E. Gallick, C. J. Logothetis, P. G. Corn
Journal: JNCI Journal of the National Cancer Institute (2011)

Recent advances in tumor biology have made remarkable achievements in the development of therapy for metastatic castrate-resistant prostate cancer. These advances reflect a growing appreciation for the role of the tumor microenvironment in promoting prostate cancer progression. Prostate cancer is no longer viewed predominantly as a disease of abnormally proliferating epithelial cells but rather as a disease of complex interactions between prostate cancer epithelial cells (epithelial compartment) and the surrounding tissues (stromal compartment) in which they reside. For example, prostate cancers frequently metastasize to bone, an organ that contains a microenvironment rich in extracellular matrix proteins and stromal cells including hematopoietic cells, osteoblasts, osteoclasts fibroblasts, endothelial cells, adipocytes, immune cells, and mesenchymal stem cells. Multiple signaling pathways provide crosstalk between the epithelial and the stromal compartments to enhance tumor growth, including androgen receptor signaling, tyrosine kinase receptor signaling, and immune surveillance. The rationale to disrupt this "two-compartment" crosstalk has led to the development of drugs that target tumor stromal elements in addition to the cancer epithelial cell.
Predictive Value of Noninvasive Measures of Atherosclerosis for Incident Myocardial Infarction
Authors: Irene M. van der Meer, Michiel L. Bots, Albert Hofman, Antonio Iglesias del Sol, Deirdre A.M. van der Kuip, Jacqueline C.M. Witteman
Journal: Circulation (2004)

Background— Several noninvasive methods are available to investigate the severity of extracoronary atherosclerotic disease. No population-based study has yet examined whether differences exist between these measures with regard to their predictive value for myocardial infarction (MI) or whether a given measure of atherosclerosis has predictive value independently of the other measures. Methods and Results— At the baseline (1990–1993) examination of the Rotterdam Study, a population-based cohort study among subjects age ≥55 years, carotid plaques and intima-media thickness (IMT) were measured by ultrasound, abdominal aortic atherosclerosis by x-ray, and lower-extremity atherosclerosis by computation of the ankle-arm index. In the present study, 6389 subjects were included; 258 cases of incident MI occurred before January 1, 2000. All 4 measures of atherosclerosis were good predictors of MI independently of traditional cardiovascular risk factors. Hazard ratios were equally high for carotid plaques (1.83 [1.27 to 2.62], severe versus no atherosclerosis), carotid IMT (1.95 [1.19 to 3.19]), and aortic atherosclerosis (1.94 [1.30 to 2.90]) and slightly lower for lower-extremity atherosclerosis (1.59 [1.05 to 2.39]), although differences were small. The hazard ratio for MI for subjects with severe atherosclerosis according to a composite atherosclerosis score was 2.77 (1.70 to 4.52) compared with subjects with no atherosclerosis. The predictive value of MI for a given measure of atherosclerosis was independent of the other atherosclerosis measures. Conclusions— Noninvasive measures of extracoronary atherosclerosis are strong predictors of MI. The relatively crude measures directly assessing plaques in the carotid artery and abdominal aorta predict MI equally well as the more precisely measured carotid IMT.
Retroviral gp70 immune complexes in NZB x NZW F2 mice with murine lupus nephritis.
Authors: S Izui, P J McConahey, J P Clark, L M Hang, I Hara, F J Dixon
Journal: The Journal of Experimental Medicine (1981)

NZB x NZW (NZB x W) F1 hybrid mice spontaneously develop a disease most prominently characterized by immune complex glomerulonephritis (GN), which seems to be associated with both antibodies to DNA and to the serum retroviral envelope glycoprotein, gp70. To evaluate the contribution of each of these autoimmune responses to the pathogenesis of the GN, we studied NZB x W F2 mice in which the two responses appeared to segregate relatively independently. Use of this model permitted analysis of possible correlations between each response and the G.N. The presence of circulating anti-gp 70-complexed gp70 correlated significantly with the development of fatal GN and one could predict the course of renal disease by computing the rising serum levels of gp70 complexed with antibodies. In contrast, the presence of free antibodies to either double-stranded or single-stranded DNA was not significantly associated with the development of fatal GN. This association of anti-gp70 antibody production with these animals' early death from GN strongly suggests that the gene(s) governing production of antibodies to serum retroviral gp70 may be one of the major genes responsible for spontaneous renal disease segregated in NZB x W F2 generations.
Acidosis during ischemia promotes adenosine triphosphate resynthesis in postischemic rat heart. In vivo regulation of 5'-nucleotidase.
Authors: M I Bak, J S Ingwall
Journal: Journal of Clinical Investigation (1994)

Capacity for ATP resynthesis during recovery from ischemia or hypoxia is limited to the size of the adenine nucleotide pool, which is determined in part by the activity of cytosolic 5'-nucleotidase (5'-NT): AMP-->adenosine plus inorganic phosphate (Pi). To define in vivo regulation of 5'-NT, we used the tools of 31P nuclear magnetic resonance (NMR), spectroscopy and chemical assay to measure the substrates (AMP), products (Pi, adenosine, and its catabolites), and inhibitors (Pi and H+) of 5'-NT in isolated perfused rat hearts exposed to hypoxia (where pH remains near 7) and no flow, global ischemia (where pH falls to 6.1). We estimated 5'-NT reaction velocity, assessed the relative contributions of Pi and H+ to enzyme inhibition, and defined the consequences of changes in 5'-NT activity on ATP resynthesis after hypoxia and ischemia. We conclude that (a) 5'-NT is activated during hypoxia and early ischemia but is inhibited during prolonged ischemia, (b) H+ (pH < 6.2) is a potent inhibitor of 5'-NT, and (c) differences in AMP accumulation are sufficient to explain the differences in the capacity for net ATP resynthesis in ischemic and hypoxic tissue. These observations have implications for our understanding of heterogeneity of ischemic injury and myocardial protection during ischemia.
Hydrolyzed Infant Formula and Early β-Cell Autoimmunity
Authors: Mikael Knip, Hans K. Åkerblom, Dorothy Becker, Hans-Michael Dosch, John Dupre, William Fraser, Neville Howard, Jorma Ilonen, Jeffrey P. Krischer, Olga Kordonouri, Margaret L. Lawson, Jerry P. Palmer, Erkki Savilahti, Outi Vaarala, Suvi M. Virtanen
Journal: JAMA (2014)

<h3>Importance</h3> The disease process leading to clinical type 1 diabetes often starts during the first years of life. Early exposure to complex dietary proteins may increase the risk of β-cell autoimmunity in children at genetic risk for type 1 diabetes. Extensively hydrolyzed formulas do not contain intact proteins. <h3>Objective</h3> To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of diabetes-associated autoantibodies in young children. <h3>Design, Setting, and Participants</h3> A double-blind randomized clinical trial of 2159 infants with HLA-conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries; 1078 were randomized to be weaned to the extensively hydrolyzed casein formula and 1081 were randomized to be weaned to a conventional cows' milk–based formula. The participants were observed to April 16, 2013. <h3>Interventions</h3> The participants received either a casein hydrolysate or a conventional cows' milk formula supplemented with 20% of the casein hydrolysate. <h3>Main Outcomes and Measures</h3> Primary outcome was positivity for at least 2 diabetes-associated autoantibodies out of 4 analyzed. Autoantibodies to insulin, glutamic acid decarboxylase, and the insulinoma-associated–2 (IA-2) molecule were analyzed using radiobinding assays and islet cell antibodies with immunofluorescence during a median observation period of 7.0 years (mean, 6.3 years). <h3>Results</h3> The absolute risk of positivity for 2 or more islet autoantibodies was 13.4% among those randomized to the casein hydrolysate formula (n = 139) vs 11.4% among those randomized to the conventional formula (n = 117). The unadjusted hazard ratio for positivity for 2 or more autoantibodies among those randomized to be weaned to the casein hydrolysate was 1.21 (95% CI, 0.94-1.54), compared with those randomized to the conventional formula, while the hazard ratio adjusted for HLA risk, duration of breastfeeding, vitamin D use, study formula duration and consumption, and region was 1.23 (95% CI, 0.96-1.58). There were no clinically significant differences in the rate of reported adverse events between the 2 groups. <h3>Conclusions and Relevance</h3> Among infants at risk for type 1 diabetes, the use of a hydrolyzed formula, when compared with a conventional formula, did not reduce the incidence of diabetes-associated autoantibodies after 7 years. These findings do not support a benefit from hydrolyzed formula. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT00179777
An isoform-specific mutation in the protein 4.1 gene results in hereditary elliptocytosis and complete deficiency of protein 4.1 in erythrocytes but not in nonerythroid cells.
Authors: J G Conboy, J A Chasis, R Winardi, G Tchernia, Y W Kan, N Mohandas
Journal: Journal of Clinical Investigation (1993)

Multiple protein 4.1 isoforms are expressed in a variety of tissues through complex alternative pre-mRNA splicing events, one function of which is to regulate use of two alternative translation initiation signals. Late erythroid cells express mainly the downstream initiation site for synthesis of prototypical 80-kD isoforms; nonerythroid cells in addition use an upstream site to encode higher molecular mass isoform(s). In this study, we examined the effects of a 5' gene rearrangement in a family with hereditary elliptocytosis and complete deficiency of erythrocyte 4.1 protein on 4.1 isoform expression in erythroid vs. nonerythroid cells. Patient 4.1 mRNAs from reticulocytes, fibroblasts, and B lymphocytes were amplified by reverse transcriptase/polymerase chain reaction techniques and shown to exhibit a 318-nucleotide deletion that encompasses the downstream AUG, but leaves intact the upstream AUG. Immunoblot analysis revealed a total deficiency of 4.1 in patient red cells and a selective deficiency of 80-kD isoform(s) but not high molecular weight 4.1 in patient nonerythroid cells. Thus, the 4.1 gene mutation in this family produces an isoform-specific deficiency that is manifested clinically in tissue-specific fashion, such that red cells are affected but other cell types are unaffected because of tissue-specific differences in RNA splicing and translation initiation.