tbuckley/cabot-search huggingface dataset:
Resolution of cutaneous leishmaniasis: interleukin 12 initiates a protective T helper type 1 immune response.
Authors: J P Sypek, C L Chung, S E Mayor, J M Subramanyam, S J Goldman, D S Sieburth, S F Wolf, R G Schaub
Journal: The Journal of Experimental Medicine (1993)

Resistance to Leishmania major in mice is associated with the appearance of distinct T helper type 1 (Th1) and Th2 subsets. T cells from lymph nodes draining cutaneous lesions of resistant mice are primarily interferon gamma (IFN-gamma)-producing Th1 cells. In contrast, T cells from susceptible mice are principally Th2 cells that generate interleukin 4 (IL-4). Although existing evidence is supportive of a role for IFN-gamma in the generation of Th1 cells, additional factors may be required for a protective response to be maintained. A potential candidate is IL-12, a heterodimeric cytokine produced by monocytes and B cells that has multiple effects on T and natural killer cell function, including inducing IFN-gamma production. Using an experimental leishmanial model we have observed that daily intraperitoneal administration at the time of parasite challenge of either 0.33 micrograms IL-12 (a consecutive 5 d/wk for 5 wk) or 1.0 micrograms IL-12 per mouse (only a consecutive 5 d) caused a > 75% reduction in parasite burden at the site of infection, in highly susceptible BALB/c mice. Delay of treatment by 1 wk had less of a protective effect. Concomitant with these protective effects was an increase in IFN-gamma and a decrease in IL-4 production, as measured by enzyme-linked immunosorbent assay of supernatants generated from popliteal lymph node cells stimulated with leishmanial antigen in vitro. The reduction in parasite numbers induced by IL-12 therapy was still apparent at 10 wk postinfection. In addition, we observed that the administration of a rabbit anti-recombinant murine IL-12 polyclonal antibody (200 micrograms i.p. every other day for 25 d) at the time of infection to resistant C57Bl/6 mice exacerbated disease. These effects were accompanied by a shift in IFN-gamma production in vitro by antigen-stimulated lymph node cells indicative of a Th2-like response. These findings suggest that IL-12 has an important role in initiating a Th1 response and protective immunity.
Percutaneous endoscopic gastrostomy (PEG) feeding
Authors: M. Kurien, M. E. McAlindon, D. Westaby, D. S. Sanders
Journal: BMJ (2010)

#### Summary points

Percutaneous endoscopic gastrostomy (PEG) feeding, introduced into clinical practice in 1980,1 is now established as an effective way of providing enteral feeding to patients who have functionally normal gastrointestinal tracts but who cannot meet their nutritional needs because of inadequate oral intake.2 It is the preferred method of feeding when nutritional intake is likely to be inadequate for more than four to six weeks, and when enteral feeding is likely to prevent further weight loss, correct nutritional deficiencies, and stop the decline in quality of life in patients caused by insufficient nutritional intake.3 4 The beneficial effects of gastrostomy feeding on morbidity and mortality have been described only in certain subgroups of patients.5 6 Randomised studies in patients after stroke who received gastrostomy feeding have shown improved nutritional outcomes, higher likelihood of survival, and earlier discharge.6 7 However, gastrostomy tubes are increasingly being requested and inserted for indications where long term outcomes are uncertain.8 In this review we discuss the indications for, controversies surrounding, and complications of gastrostomy feeding and provide practical advice on the management of percutaneous endoscopic gastrostomies.

#### Sources and selection criteria

We searched the Cochrane database of systematic reviews and did a PubMed search (from January 1980 until January 2010) using the keywords “percutaneous endoscopic …
Hyperglycaemia and mortality
Authors: Khairollah Asadollahi, Nicholas Beeching, Geoffrey Gill
Journal: Journal of the Royal Society of Medicine (2007)

Several studies over the last decade have linked hyperglycaemia on hospital admission with subsequent mortality risk. The evidence is strongest for patients with myocardial infarction or acute coronary syndromes, but evidence also links hyperglycaemia with mortality from stroke and other medical illnesses. The effect seems independent of a previous diagnosis of diabetes mellitus; indeed, some studies suggest that mortality may be higher in patients with hyperglycaemia and no previous diabetes diagnosis compared with known diabetic patients. The effect on outcome of therapeutically lowering blood glucose levels has been considered in a small number of studies, but so far the results are conflicting. Further work is needed, focusing on more standardized surveys—previous studies vary in their use of blood or plasma, as well as cut-off levels for hyperglycaemia—and larger intervention studies.
Follow-up of Glycemic Control and Cardiovascular Outcomes in Type 2 Diabetes
Authors: Rodney A. Hayward, Peter D. Reaven, Wyndy L. Wiitala, Gideon D. Bahn, Domenic J. Reda, Ling Ge, Madeline McCarren, William C. Duckworth, Nicholas V. Emanuele
Journal: New England Journal of Medicine (2015)

The Veterans Affairs Diabetes Trial previously showed that intensive glucose lowering, as compared with standard therapy, did not significantly reduce the rate of major cardiovascular events among 1791 military veterans (median follow-up, 5.6 years). We report the extended follow-up of the study participants.After the conclusion of the clinical trial, we followed participants, using central databases to identify procedures, hospitalizations, and deaths (complete cohort, with follow-up data for 92.4% of participants). Most participants agreed to additional data collection by means of annual surveys and periodic chart reviews (survey cohort, with 77.7% follow-up). The primary outcome was the time to the first major cardiovascular event (heart attack, stroke, new or worsening congestive heart failure, amputation for ischemic gangrene, or cardiovascular-related death). Secondary outcomes were cardiovascular mortality and all-cause mortality.The difference in glycated hemoglobin levels between the intensive-therapy group and the standard-therapy group averaged 1.5 percentage points during the trial (median level, 6.9% vs. 8.4%) and declined to 0.2 to 0.3 percentage points by 3 years after the trial ended. Over a median follow-up of 9.8 years, the intensive-therapy group had a significantly lower risk of the primary outcome than did the standard-therapy group (hazard ratio, 0.83; 95% confidence interval [CI], 0.70 to 0.99; P=0.04), with an absolute reduction in risk of 8.6 major cardiovascular events per 1000 person-years, but did not have reduced cardiovascular mortality (hazard ratio, 0.88; 95% CI, 0.64 to 1.20; P=0.42). No reduction in total mortality was evident (hazard ratio in the intensive-therapy group, 1.05; 95% CI, 0.89 to 1.25; P=0.54; median follow-up, 11.8 years).After nearly 10 years of follow-up, patients with type 2 diabetes who had been randomly assigned to intensive glucose control for 5.6 years had 8.6 fewer major cardiovascular events per 1000 person-years than those assigned to standard therapy, but no improvement was seen in the rate of overall survival. (Funded by the VA Cooperative Studies Program and others; VADT ClinicalTrials.gov number, NCT00032487.).
INTERNATIONAL HIKER WITH ACETAZOLAMIDE-INDUCED GLAUCOMA
Authors: M Tierney, G Pujalte
Journal: British Journal of Sports Medicine (2014)

Background This is a 63-year-old female hiker with normal corrected vision followed status post emergent surgery secondary to bilateral acute angle closure glaucoma (AACG). She was started on acetazolamide by a travel clinic for acute mountain sickness prophylaxis (AMS) prior to hiking Machu Picchu in Peru. Six days later, she rapidly developed blurry vision, headache and nausea. She had mild blurry vision at high altitude, but following descent, she rapidly developed near-irreversible blindness, with an intraocular pressure (IOP) of 60 mm Hg. She required bilateral iridotomies at the Hospital de Clinicas Pinchincha in Quito, Ecuador. Following the procedure, she was started on prednisone and high-dose acetazolamide. Her vision remained blurry with an elevated IOP of 15mm Hg, prior to flying back to the United States for further management. Objective Examining a rare case and understanding the mechanism behind acetazolamide-induced glaucoma. Design Case Report. Setting Machu Picchu, Peru; Hospital de Clinicas Pichincha in Quito, Ecuador; and Penn State Milton S. Hershey Medical Center, Hershey, PA, USA. Participant A 63-year-old American hiker. Interventions Peripheral iridotomies in Ecuador and discontinuation of acetazolamide in the United States. Main outcome measurements Slit-lamp, iridotomy, and intraocular pressure readings. Results Return to baseline visual acuity with normal intraocular pressures following the discontinuation of acetazolamide. Conclusions AACG is a rare side effect of acetazolamide reported in few patients following cataract surgery. This is the first case report of acetazolamide-induced glaucoma seen in a hiker secondary to the prophylactic dose for AMS. This case report highlights the potential harmful side effects of acetazolamide at low doses, pertinent for international hikers and any conditioned athletes who rapidly ascend or fly to high altitudes. Figure 1 Ciliochoroidal Edema. Figure 2 Ciliary Body edema (CB). .
Molecular Pathogenesis of Ewing Sarcoma: New Therapeutic and Transcriptional Targets
Authors: Stephen L. Lessnick, Marc Ladanyi
Journal: Annual Review of Pathology Mechanisms of Disease (2011)

Approximately one-third of sarcomas contain specific translocations. Ewing sarcoma is the prototypical member of this group of sarcomas; it was the first to be recognized pathologically as a singular entity and to have its signature translocation defined cytogenetically, which led to the identification of its key driver alteration, the EWS-FLI1 gene fusion that encodes this aberrant, chimeric transcription factor. We review recent progress in selected areas of Ewing sarcoma research, including the application of genome-wide chromatin immunoprecipitation analyses, to provide a comprehensive view of the EWS-FLI1 target gene repertoire, the identification of EWS-FLI1 target genes that may also point to therapeutically targetable pathways, and data from model systems as they relate to the elusive cell of origin of Ewing sarcoma and its possible similarities to mesenchymal stem cells.
Comparison of the damage-promoting effects of leukotrienes derived from eicosapentaenoic acid and arachidonic acid on the rat stomach.
Authors: J L Wallace, G W McKnight
Journal: The Journal of Experimental Medicine (1990)

The ability of leukotrienes derived from eicosapentaenoic acid were compared with counterpart leukotrienes derived from arachidonic acid in terms of their ability to affect susceptibility of the stomach to injury induced by a topical irritant and their ability to alter gastric blood flow. Intra-arterial infusion of leukotriene C4 (LTC4) and LTD4 (0.1-3 micrograms/kg/min for 5 min) produced dose-dependent increases in gastric mucosal damage induced by topically applied 20% ethanol, as assessed macroscopically, by changes in transmucosal potential difference and by measurement of efflux of protein into the gastric lumen. Similar doses of LTC5 or LTD5 did not produce significant changes in any of these three parameters, when compared with control rats receiving the vehicle. With a higher dose of LTC5 or LTD5 (5 micrograms/kg/min), significant damage was observed. LTC4 and LTD4 were also found to be more potent at reducing gastric blood flow than LTC5 and LTD5. These results demonstrate that the peptido-leukotrienes derived from eicosapentaenoic acid (LTC5 and LTD5) are on the order of five times less potent than the leukotrienes derived from arachidonic acid (LTC4 and LTD4), in terms of increasing the susceptibility of the gastric mucosa to damage and reducing gastric blood flow. These results may have important implications in terms of the hypothesis that fish oil diets may be protective or may accelerate healing in ulcerative diseases of the gastrointestinal tract.
Freezing of Infested Pork Muscle Kills Cysticerci
Authors: Julio Sotelo
Journal: JAMA (1986)

A method for culturing cysticerci that allows successful evagination and growth of scolexes from metacestodes of<i>Taenia solium</i>was used to study the survival of cysticerci subjected to low temperatures. Refrigeration of pork muscle infested with cysticerci at temperatures above 0°C did not affect the parasites' survival in culture. Conversely, freezing of meat prevented survival of cysts. A practical procedure to kill cysticerci is the storage of pork muscle for four days at —5°C, three days at —15°C, or one day at —24°C. These simple measures would help prevent the most frequent parasitosis of man's central nervous system. (<i>JAMA</i>1986;256:893-894)
The transrepressive activity of peroxisome proliferator-activated receptor alpha is necessary and sufficient to prevent liver fibrosis in mice
Authors: Michal Pawlak, Eric Baugé, William Bourguet, Karolien De Bosscher, Fanny Lalloyer, Anne Tailleux, Corinna Lebherz, Philippe Lefebvre, Bart Staels
Journal: Hepatology (2014)

Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent and strongly associated with central obesity, dyslipidemia, and insulin resistance. According to the multiple-hit model of NAFLD pathogenesis, lipid accumulation drives nonalcoholic steatohepatitis (NASH) initiation by triggering oxidative stress, lipotoxicity, and subsequent activation of hepatic inflammatory responses that may progress, in predisposed individuals, to fibrosis and cirrhosis. While there is an unmet therapeutical need for NASH and fibrosis, recent preclinical studies showed that peroxisome proliferator-activated receptor (PPAR)-α agonism can efficiently oppose these symptoms. To dissect the relative contribution of antisteatotic versus anti-inflammatory PPAR-α activities in counteracting dietary-induced liver fibrosis, we used a PPAR-α mutant lacking its DNA-binding-dependent activity on fatty acid metabolism. Liver-specific expression of wild-type or a DNA-binding-deficient PPAR-α in acute and chronic models of inflammation were used to study PPAR-α's anti-inflammatory versus metabolic activities in NASH and fibrosis. Pharmacologically activated PPAR-α inhibited hepatic inflammatory responses and the transition from steatosis toward NASH and fibrosis through a direct, anti-inflammatory mechanism independent of its lipid handling properties. The transrepression activity of PPAR-α on chronic liver inflammation is sufficient to prevent progression of NASH to liver fibrosis. Dissociated PPAR-α agonists, selectively modulating PPAR-α transrepression activity, could thus be an option to prevent NASH and fibrosis progression.
Cost-effectiveness of adjuvant docetaxel for node-positive breast cancer patients: results of the PACS 01 economic study
Authors: P. Marino, C. Siani, H. Roché, C. Protière, P. Fumoleau, M. Spielmann, A.-L. Martin, P. Viens, A.-G. Le Corroller Soriano
Journal: Annals of Oncology (2009)
Effect of Cholesterol Atherosclerosis, Hypertension and Cortisone on Aortic Oxygen Consumption in Rabbit
Authors: EDWIN R. FISHER, J. H. GELLER
Journal: Circulation Research (1960)

In vitro estimation of aortic QO 2 in normal rabbits revealed the thoracic portion to be lower than that of the arch and abdominal segments. These latter were not significantly different. Renal hypertension, cortisone administration and their combination with or without cholesterol feeding resulted in significant elevations of the oxygen consumption of all segments. The thoracic portion under these conditions was lowest and that of the arch was greater than that observed in the abdominal aorta. A depression of QO 2 was observed in the aortas from normotensive rabbits subjected to cholesterol feeding with or without cortisone treatment. Although these findings indicate that hypertension and cortisone may profoundly alter the metabolic activity of the aorta, they could not be correlated with the degrees of cholesterol atherosclerosis observed in the various experimental situations explored.
Prognostic Value of Ambulatory Blood-Pressure Recordings in Patients with Treated Hypertension
Authors: Denis L. Clement, Marc L. De Buyzere, Dirk A. De Bacquer, Peter W. de Leeuw, Daniel A. Duprez, Robert H. Fagard, Peter J. Gheeraert, Luc H. Missault, Jacob J. Braun, Roland O. Six, Patricia Van Der Niepen, Eoin O'Brien
Journal: New England Journal of Medicine (2003)

It is uncertain whether ambulatory blood-pressure measurements recorded for 24 hours in patients with treated hypertension predict cardiovascular events independently of blood-pressure measurements obtained in the physician's office and other cardiovascular risk factors.We assessed the association between base-line ambulatory blood pressures in treated patients and subsequent cardiovascular events among 1963 patients with a median follow-up of 5 years (range, 1 to 66 months).We documented new cardiovascular events in 157 patients. In a Cox proportional-hazards model with adjustment for age, sex, smoking status, presence or absence of diabetes mellitus, serum cholesterol concentration, body-mass index, use or nonuse of lipid-lowering drugs, and presence or absence of a history of cardiovascular events, as well as blood pressure measured at the physician's office, higher mean values for 24-hour ambulatory systolic and diastolic blood pressure were independent risk factors for new cardiovascular events. The adjusted relative risk of cardiovascular events associated with a 1-SD increment in blood pressure was 1.34 (95 percent confidence interval, 1.11 to 1.62) for 24-hour ambulatory systolic blood pressure, 1.30 (95 percent confidence interval, 1.08 to 1.58) for ambulatory systolic blood pressure during the daytime, and 1.27 (95 percent confidence interval, 1.07 to 1.57) for ambulatory systolic blood pressure during the nighttime. For ambulatory diastolic blood pressure, the corresponding relative risks of cardiovascular events associated with a 1-SD increment were 1.21 (95 percent confidence interval, 1.01 to 1.46), 1.24 (95 percent confidence interval, 1.03 to 1.49), and 1.18 (95 percent confidence interval, 0.98 to 1.40).In patients with treated hypertension, a higher ambulatory systolic or diastolic blood pressure predicts cardiovascular events even after adjustment for classic risk factors including office measurements of blood pressure.
Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge
Authors: Richa Saxena, Marie-France Hivert, Claudia Langenberg, Toshiko Tanaka, James S Pankow, Peter Vollenweider, Valeriya Lyssenko, Nabila Bouatia-Naji, Josée Dupuis, Anne U Jackson, W H Linda Kao, Man Li, Nicole L Glazer, Alisa K Manning, Jian'an Luan, Heather M Stringham, Inga Prokopenko, Toby Johnson, Niels Grarup, Trine W Boesgaard, Cécile Lecoeur, Peter Shrader, Jeffrey O'Connell, Erik Ingelsson, David J Couper, Kenneth Rice, Kijoung Song, Camilla H Andreasen, Christian Dina, Anna Köttgen, Olivier Le Bacquer, François Pattou, Jalal Taneera, Valgerdur Steinthorsdottir, Denis Rybin, Kristin Ardlie, Michael Sampson, Lu Qi, Mandy van Hoek, Michael N Weedon, Yurii S Aulchenko, Benjamin F Voight, Harald Grallert, Beverley Balkau, Richard N Bergman, Suzette J Bielinski, Amelie Bonnefond, Lori L Bonnycastle, Knut Borch-Johnsen, Yvonne Böttcher, Eric Brunner, Thomas A Buchanan, Suzannah J Bumpstead, Christine Cavalcanti-Proença, Guillaume Charpentier, Yii-Der Ida Chen, Peter S Chines, Francis S Collins, Marilyn Cornelis, Gabriel J Crawford, Jerome Delplanque, Alex Doney, Josephine M Egan, Michael R Erdos, Mathieu Firmann, Nita G Forouhi, Caroline S Fox, Mark O Goodarzi, Jürgen Graessler, Aroon Hingorani, Bo Isomaa, Torben Jørgensen, Mika Kivimaki, Peter Kovacs, Knut Krohn, Meena Kumari, Torsten Lauritzen, Claire Lévy-Marchal, Vladimir Mayor, Jarred B McAteer, David Meyre, Braxton D Mitchell, Karen L Mohlke, Mario A Morken, Narisu Narisu, Colin N A Palmer, Ruth Pakyz, Laura Pascoe, Felicity Payne, Daniel Pearson, Wolfgang Rathmann, Annelli Sandbaek, Avan Aihie Sayer, Laura J Scott, Stephen J Sharp, Eric Sijbrands, Andrew Singleton, David S Siscovick, Nicholas L Smith, Thomas Sparsø, Amy J Swift, Holly Syddall, Gudmar Thorleifsson, Anke Tönjes, Tiinamaija Tuomi, Jaakko Tuomilehto, Timo T Valle, Gérard Waeber, Andrew Walley, Dawn M Waterworth, Eleftheria Zeggini, Jing Hua Zhao
Journal: Nature Genetics (2010)
Association of <i>MDM2</i> SNP309, Age of Onset, and Gender in Cutaneous Melanoma
Authors: Elnaz F. Firoz, Melanie Warycha, Jan Zakrzewski, Danuta Pollens, Guimin Wang, Richard Shapiro, Russell Berman, Anna Pavlick, Prashiela Manga, Harry Ostrer, Julide Tok Celebi, Hideko Kamino, Farbod Darvishian, Linda Rolnitzky, Judith D. Goldberg, Iman Osman, David Polsky
Journal: Clinical Cancer Research (2009)

In certain cancers, MDM2 SNP309 has been associated with early tumor onset in women. In melanoma, incidence rates are higher in women than in men among individuals less than 40 years of age, but among those older than 50 years of age, melanoma is more frequent in men than in women. To investigate this difference, we examined the association among MDM2 SNP309, age at diagnosis, and gender among melanoma patients.
Greater Survival After Breast Cancer in Physically Active Women With High Vegetable-Fruit Intake Regardless of Obesity
Authors: John P. Pierce, Marcia L. Stefanick, Shirley W. Flatt, Loki Natarajan, Barbara Sternfeld, Lisa Madlensky, Wael K. Al-Delaimy, Cynthia A. Thomson, Sheila Kealey, Richard Hajek, Barbara A. Parker, Vicky A. Newman, Bette Caan, Cheryl L. Rock
Journal: Journal of Clinical Oncology (2007)

Purpose Single-variable analyses have associated physical activity, diet, and obesity with survival after breast cancer. This report investigates interactions among these variables. Patients and Methods A prospective study was performed of 1,490 women diagnosed and treated for early-stage breast cancer between 1991 and 2000. Enrollment was an average of 2 years postdiagnosis. Only seven women were lost to follow-up through December 2005. Results In univariate analysis, reduced mortality was weakly associated with higher vegetable-fruit consumption, increased physical activity, and a body mass index that was neither low weight nor obese. In a multivariate Cox model, only the combination of consuming five or more daily servings of vegetables-fruits, and accumulating 540+ metabolic equivalent tasks-min/wk (equivalent to walking 30 minutes 6 d/wk), was associated with a significant survival advantage (hazard ratio, 0.56; 95% CI, 0.31 to 0.98). The approximate 50% reduction in risk associated with these healthy lifestyle behaviors was observed in both obese and nonobese women, although fewer obese women were physically active with a healthy dietary pattern (16% v 30%). Among those who adhered to this healthy lifestyle, there was no apparent effect of obesity on survival. The effect was stronger in women who had hormone receptor–positive cancers. Conclusion A minority of breast cancer survivors follow a healthy lifestyle that includes both recommended intakes of vegetables-fruits and moderate levels of physical activity. The strong protective effect observed suggests a need for additional investigation of the effect of the combined influence of diet and physical activity on breast cancer survival.
Neoadjuvant bevacizumab and anthracycline–taxane-based chemotherapy in 678 triple-negative primary breast cancers; results from the geparquinto study (GBG 44)
Authors: B. Gerber, S. Loibl, H. Eidtmann, M. Rezai, P.A. Fasching, H. Tesch, H. Eggemann, I. Schrader, K. Kittel, C. Hanusch, R. Kreienberg, C. Solbach, C. Jackisch, G. Kunz, J.U. Blohmer, J. Huober, M. Hauschild, V. Nekljudova, M. Untch, G. von Minckwitz
Journal: Annals of Oncology (2013)