tbuckley/cabot-search huggingface dataset:
Reinvestigation of lactose intolerant children: lack of correlation between continuing lactose intolerance and small intestinal morphology, disaccharidase activity, and lactose tolerance tests.
Authors: M Harrison, J A Walker-Smith
Journal: Gut (1977)

Thirty children on a lactose-free diet aged from 2-38 months who had previously been diagnosed as having secondary lactose intolerance were reinvestigated on 32 occasions by an oral lactose tolerance test, small intestinal biopsy, and measurement of disaccharidase activity in order to detect the presence of continuing lactose intolerance before reintroduction of milk. No correlation was found between continuing lactose intolerance, as diagnosed by the development of watery stools containing excess reducing substances after an oral load of lactose, and maximum blood glucose rise during a lactose tolerance test, lactase levels, and small intestinal morphology.
Effect of Aleglitazar on Cardiovascular Outcomes After Acute Coronary Syndrome in Patients With Type 2 Diabetes Mellitus
Authors: A. Michael Lincoff, Jean-Claude Tardif, Gregory G. Schwartz, Stephen J. Nicholls, Lars Rydén, Bruce Neal, Klas Malmberg, Hans Wedel, John B. Buse, Robert R. Henry, Arlette Weichert, Ruth Cannata, Anders Svensson, Dietmar Volz, Diederick E. Grobbee
Journal: JAMA (2014)

No therapy directed against diabetes has been shown to unequivocally reduce the excess risk of cardiovascular complications. Aleglitazar is a dual agonist of peroxisome proliferator-activated receptors with insulin-sensitizing and glucose-lowering actions and favorable effects on lipid profiles.To determine whether the addition of aleglitazar to standard medical therapy reduces cardiovascular morbidity and mortality among patients with type 2 diabetes mellitus and a recent acute coronary syndrome (ACS).AleCardio was a phase 3, multicenter, randomized, double-blind, placebo-controlled trial conducted in 720 hospitals in 26 countries throughout North America, Latin America, Europe, and Asia-Pacific regions. The enrollment of 7226 patients hospitalized for ACS (myocardial infarction or unstable angina) with type 2 diabetes occurred between February 2010 and May 2012; treatment was planned to continue until patients were followed-up for at least 2.5 years and 950 primary end point events were positively adjudicated.Randomized in a 1:1 ratio to receive aleglitazar 150 µg or placebo daily.The primary efficacy end point was time to cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Principal safety end points were hospitalization due to heart failure and changes in renal function.The trial was terminated on July 2, 2013, after a median follow-up of 104 weeks, upon recommendation of the data and safety monitoring board due to futility for efficacy at an unplanned interim analysis and increased rates of safety end points. A total of 3.1% of patients were lost to follow-up and 3.2% of patients withdrew consent. The primary end point occurred in 344 patients (9.5%) in the aleglitazar group and 360 patients (10.0%) in the placebo group (hazard ratio, 0.96 [95% CI, 0.83-1.11]; P = .57). Rates of serious adverse events, including heart failure (3.4% for aleglitazar vs 2.8% for placebo, P = .14), gastrointestinal hemorrhages (2.4% for aleglitazar vs 1.7% for placebo, P = .03), and renal dysfunction (7.4% for aleglitazar vs 2.7% for placebo, P < .001) were increased.Among patients with type 2 diabetes and recent ACS, use of aleglitazar did not reduce the risk of cardiovascular outcomes. These findings do not support the use of aleglitazar in this setting with a goal of reducing cardiovascular risk.clinicaltrials.gov Identifier: NCT01042769.
Abstract 1768: The oncogene Mdmx promotes genomic instability independent of p53.
Authors: Alexia N. Melo, Alyssa Bouska, Maria P. Arrate, Christine M. Eischen
Journal: Cancer Research (2013)

Abstract Mdmx is upregulated in many human cancers. As a member of the Mdm2 protein family, Mdmx functions similar to Mdm2 as a negative regulator of the tumor suppressor p53. With the ability to form heterodimers with Mdm2, p53 regulation by Mdmx predictably relies on Mdm2. However, while the p53- and Mdm2-dependent functions of Mdmx understandably contribute to cancer, Mdmx has also displayed p53- and Mdm2-independent functions in tumor development that are less well characterized. Therefore, we investigated novel avenues in which Mdmx contributes to tumorigenesis. We demonstrate increased expression of Mdmx results in an inhibition in double-strand DNA break repair and a delay in DNA damage signaling that was independent of p53 and surprisingly, independent of Mdm2. We identified a novel association between Mdmx and a key mediator of DNA repair, the Mre11-Rad50-Nbs1 complex. We also detected increased genomic instability and promotion of in vitro transformation as a result of Mdmx overexpression that was also independent of p53 and Mdm2. Our data show that Mdmx interacts with the Mre11-Rad50-Nbs1 complex and delays DNA break repair, which leads to genome instability and cellular transformation. This novel function of Mdmx provides insight into an alternative mechanism by which Mdmx contributes to tumor formation and possibly tumor progression independent of its interaction with Mdm2 or its negative regulation of p53. These data also highlight the potential for novel therapeutic intervention strategies that capitalize on this newly identified function of Mdmx. Citation Format: Alexia N. Melo, Alyssa Bouska, Maria P. Arrate, Christine M. Eischen. The oncogene Mdmx promotes genomic instability independent of p53. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1768. doi:10.1158/1538-7445.AM2013-1768
Applying environmental product design to biomedical products research.
Authors: J Messelbeck, L Sutherland
Journal: Environmental Health Perspectives (2000)

The principal themes for the Biomedical Research and the Environment Conference Committee on Environmental Economics in Biomedical Research include the following: healthcare delivery companies and biomedical research organizations, both nonprofit and for-profit, need to improve their environmental performance; suppliers of healthcare products will be called upon to support this need; and improving the environmental profile of healthcare products begins in research and development (R&D). The committee report begins with requirements from regulatory authorities (e.g., U.S. Environmental Protection Agency [EPA], the U.S. Food and Drug Administration), and the healthcare delivery sector). The 1998 American Hospital Association and EPA Memorandum of Understanding to reduce solid waste and mercury from healthcare facilities is emblematic of these requirements. The dominant message from the requirements discussion is to ensure that R&D organizations do not ignore customer, environmental, and regulatory requirements in the early stages of product development. Several representatives from healthcare products manufacturers presented their companies' approaches to meeting these requirements. They reported on efforts to ensure that their R&D processes are sensitive to the environmental consequences from manufacturing, distributing, using, and disposing of healthcare products. These reports describe representatives' awareness of requirements and the unique approaches their R&D organizations have taken to meet these requirements. All representatives reported that their R&D organizations have embraced environmental product design because it avoids the potential of returning products to R&D to improve the environmental profile. Additionally, several reports detailed cost savings, sustainability benefits, and improvements in environmental manufacturing or redesign, and increased customer satisfaction. Many companies in healthcare delivery are working to improve environmental performance. Fundamental to these efforts is the necessity of motivating suppliers to improve the environmental profile of new products used in the healthcare delivery sector.
Heatstroke in a "run for fun".
Authors: T D Noakes, L H Opie
Journal: BMJ (1979)

cases of travellers' diarrhoea belonged to sero- groups previously associated with infantile gastroenteritis.Indeed, one of our toxigenic strains could not be typed at all.Therefore in screening for ETEC in travellers with diarrhoea not associated with Salmonella and Shigella we feel that it is important to underline the need to test several colonies of E coli isolated from the primary culture, regardless of serotype.
Dopamine Depresses Minute Ventilation in Patients With Heart Failure
Authors: Philippe van de Borne, Ron Oren, Virend K. Somers
Journal: Circulation (1998)

Background —Low-dose dopamine is frequently used in patients in the intensive care setting. Dopamine may inhibit chemoreceptor afferents and hence decrease chemoreflex sensitivity to hypoxia. Methods and Results —In a double-blind, randomized, crossover study, we determined the effects of dopamine (5 μg · kg −1 · min −1 ) and placebo infusion on oxygen saturation, minute ventilation, and sympathetic nerve activity during normoxia and 5 minutes of hypoxia in 10 normal young subjects. We further investigated the effects of dopamine and placebo on minute ventilation during normoxic breathing in 8 patients with severe heart failure and in 8 age-matched control subjects. Dopamine did not decrease minute ventilation during normoxia in normal subjects. During hypoxia, minute ventilation was 12.9±1.3 L/min on dopamine and 15.8±1.5 L/min on placebo ( P &lt;0.0001). Oxygen saturation during hypoxia was lower with dopamine (78±3%) than placebo (84±2%; P &lt;0.0001). Sympathetic nerve activity during hypoxia was not enhanced with dopamine despite the lower O 2 saturation. Subjects were able to maintain a voluntary apnea to a lower oxygen saturation on dopamine than on placebo ( P &lt;0.05). In heart failure patients breathing room air, but not in age-matched control subjects, dopamine decreased minute ventilation despite decreased oxygen saturation and increased P etco 2 during dopamine (all P ≤0.02). Conclusions —Dopamine inhibits chemoreflex responses during hypoxic breathing in normal humans, preferentially affecting the ventilatory response more than the sympathetic response. Dopamine also depresses ventilation in normoxic heart failure patients breathing room air. Ventilatory inhibition by low-dose dopamine may adversely influence outcome in hypoxic patients, especially in patients with heart failure.
Advances in Diagnosis and Management of Gastric Cancer: II. Trends in the Management of Gastric Cancer
Authors: S. W. Arhelger
Journal: CA A Cancer Journal for Clinicians (1957)

preceding year and the year following in dicated a stomach that was definitely achlorhydric.Of the75 per centof pa tients who were normal as far as gastric secretion is concerned, there has been no indication of a gastric cancer developing during this follow-up period of eight years and three months.The completeness of our annual survey with all examinees at the Detection Center makes this fact cer tain.
Abstract 4244: Dysadherin can enhance tumorigenesis through conferring properties of stem-like cells to hepatocellular carcinoma cells
Authors: Jeong-Ran Park, Ran-Ju Kim, Yoo-Kyung Lee, Soo-Rim Kim, Kyung-Jin Roh, Jeong-Seok Nam
Journal: Cancer Research (2010)

Abstract Hepatocellular carcinoma (HCC) is associated with a high potential for metastasis and disease recurrence, even after surgical resection. The cancer stem cell (CSC) hypothesis proposes that CSCs are responsible for chemo-resistance, recurrence and metastasis. Dysadherin is a prognostic indicator of metastasis and poor survival in many different cancer types. In this study, we investigated the possible link between dysadherin and CSC in HCC. The transfection of dysadherin cDNA into the liver cancer cell line PLC/PRF/5 enhanced the properties of CSC, including anti-apoptosis, sphere-forming ability, side population (SP) phenotype and tumor initiation ability in vivo. Furthermore, knockdown of dysadherin in the liver cancer cell line SK-Hep1 suppressed its stem cell-like properties. In particular, SP phenotype is mediated by the ATP-binding cassette (ABC) transporter proteins which are responsible for multidrug resistance (MDR) that is a major obstacle in cancer chemotherapy. Dysadherin was also shown to regulate ABCB1 expression. Taken together, these results show that new roles for the dysadherin in cancer progression that was in part dependent on CSC dynamics. Therefore, these findings suggest that dysadherin may be a potential molecular prognostic marker of HCC and may aid in the development of more effective therapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4244.
Passport to clean competition
Authors: Kirsten Patrick
Journal: BMJ (2012)

OBJECTIVE: To assess the actual impact on coronary mortality of equipping ambulances with defibrillators. DESIGN: Retrospective analysis of routine medical and legal records of all those who had a cardiac arrest attributed to coronary heart disease occurring outside hospital in a defined population before and after the introduction of Heartstart. SETTING: City of Glasgow, North of the River Clyde, 1984 and 1990. PATIENTS: 296 and 267 men and women aged 25-64 inclusive in 1984 and 1990 respectively who had a cardiac arrest outside hospital which was attributed to coronary heart disease (International Classification of Diseases codes 410-414, ninth revision). RESULTS: The impact on coronary mortality in 1990 of equipping ambulances with defibrillators concurred with the earlier prediction of less than 1% of all coronary deaths. The circumstances of cardiac arrest were largely unchanged; most occurred outside hospital in the victim9s home and the principal witnesses were members of the victim9s family. A call for help before cardiac arrest was made in very few cases and cardiopulmonary resuscitation was attempted by laypersons in less than a third of the deaths they witnessed. There was a significant increase in the number of cardiopulmonary resuscitation attempts made by ambulance crews (16% v 32%, P &lt; 0.01). Ambulance crews, however, still attended less than half of all cases (44% and 47%). CONCLUSION: The impact of equipping ambulances with defibrillators will remain small unless strategies are introduced that focus on improving the public9s response to coronary emergencies by calling for help promptly and initiating cardiopulmonary resuscitation before the arrival of the emergency services.
Are drugs targeted at Alzheimer's disease useful? 2. Insufficient evidence of worthwhile benefit.
Authors: E J Byrne, T Arie
Journal: BMJ (1990)

Correction of neurotransmitter deficits Cholinergic systemPrecursor-choline, lecithin Anticholinesterase-tacrine (tetrahydroaminoacridine), physostigmine Enhancement ofrelease-4-aminopyridine Serotoninergic system: Inhibition ofreuptake-alaproclate, zimeldine hydrochloride Agonist-trazodone (m-chlorophenylpiperazine) Dopaminergic system Inhibition of monoamine oxidase fi-selegiline * Neuropeptides-somatostatin, vasopressin, corticotrophin, and
Inhaled Foreign Bodies in a Series of Sudanese Cases
Authors: W. A. L. MacGowan
Journal: Thorax (1959)

In England and Wales during 1954, 11 deaths were recorded from the inhalation of foreign bodies.The importance of such accidents in the Sudan has been demonstrated by the Thoracic Surgical Unit of Khartoum Civil Hospital since its establishment in February, 1957.The removal of inhaled foreign bodies has been the commonest emergency procedure undertaken by the Unit, and 14 patients with this condition were admitted for treatment in the Unit's first 12 months of operation.The condition is common in the Sudan owing to the large numbers of nuts and seeds eaten in the average daily diet, and peanuts and melon seeds accounted for eight of these cases (Table I).Children are especially prone to inhalation accidents and in this series were more commonly affected than adults (Table II).TABLE I FOREIGN BODIES INHALED Type of Foreign Body Number of Cases Peanuts . . 4 Melon seeds .4Mud, pebble, and stones ..
Altered NK Cell Development and Enhanced NK Cell-Mediated Resistance to Mouse Cytomegalovirus in NKG2D-Deficient Mice
Authors: Biljana Zafirova, Sanja Mandarić, Ronald Antulov, Astrid Krmpotić, Helena Jonsson, Wayne M. Yokoyama, Stipan Jonjić, Bojan Polić
Journal: Immunity (2009)
Treatment of Ulcerative Colitis with Antimetabolites
Authors: R. H. D. Bean
Journal: BMJ (1966)

Ulcerative colitis is a disease of widely varying severity. The course in any patient is difficult to predict. In this community repeated episodes commonly lead to a chronic active stage, in which the sufferer becomes an invalid unless the process is relieved by colectomy. In this phase exacerbations and com plications are common, and not infrequently lead to death. It is with patients in this group that the present trial has been concerned. While ulcerative colitis as representative of an autoimmune disorder fails to fill all the criteria enumerated by McKay and Burnet (1963) for autoimmune disease, there remains strong evidence for immunological disturbance. This evidence has been reviewed by Kirsner (1961). I do not propose to discuss at length whether this disturbance represents a normal response to modified tissue or a defect of the immune mechanism. I consider the action of antimetabolites, together with observa tions made during this therapy, supports the view of primary tissue damage or modification. With the exception of steroid hormones, the most powerful suppressants of the immune response, as measured by failure of graft rejection, are all agents developed for the treatment of cancer. These agents may be considered in their main groupings?nitrogen mustard and its derivatives, the sulphur mustards, the antimetabolites, and antibiotics. There is prob ably some selectivity of action of these agents, antagonism occurring between the antimetabolites, mercaptopurine, and the folic-acid antagonists. In our early trials we used the anti metabolites mercaptopurine and 6-thioguanine. More recently the sulphur mustard busulphan has been employed.
Cruel Compassion: Psychiatric Control of Society's Unwanted
Authors: J. S Callender
Journal: BMJ (1994)

Thomas Szasz Wiley, pounds sterling 16.50, pp 264 ISBN 0-471-01012-X

In Cruel Compassion Thomas Szasz develops a thesis that psychiatry is an exercise in social control, which allows society to remove from its midst and incarcerate people who are unwanted and dependent. Underpinning this are the assumptions that mental illness does not exist and that psychiatric practice largely consists of coercion and control.

There is no place in this view for consideration of the anguish and disability suffered by the mentally ill or the distress and despair which this creates in their families. Instead, Szasz gives an account of how a …
The PlA2 polymorphism of integrin β3 enhances outside-in signaling and adhesive functions
Authors: K. Vinod Vijayan, Pascal J. Goldschmidt-Clermont, Christine Roos, Paul F. Bray
Journal: Journal of Clinical Investigation (2000)

Genetic factors are believed to influence the development of arterial thromboses. Because integrin αIIbβ3 plays a crucial role in thrombus formation, we analyzed receptor adhesive properties using Chinese hamster ovary and human kidney embryonal 293 cells overexpressing the PlA1 or PlA2 polymorphic forms of αIIbβ3. Soluble fibrinogen binding was no different between PlA1 and PlA2 cells, either in a resting state or when αIIbβ3 was activated with anti-LIBS6. PlA1 and PlA2 cells bound equivalently to immobilized fibronectin. In contrast, significantly more PlA2 cells bound to immobilized fibrinogen in an αIIbβ3-dependent manner than did PlA1 cells. Disruption of the actin cytoskeleton by cytochalasin D abolished the increased binding of PlA2 cells. Compared with PlA1 cells, PlA2 cells exhibited a greater extent of polymerized actin and cell spreading, enhanced tyrosine phosphorylation of pp125FAK, and greater fibrin clot retraction. These adhesion differences appear to depend on a signaling mechanism sensitive to receptor occupancy. Thus, the PlA2 polymorphism altered integrin-mediated functions of adhesion, spreading, actin cytoskeleton rearrangement, and clot retraction.
Basal Ganglia High-Energy Phosphate Metabolism in Neuroleptic-Naive Patients With Schizophrenia: A 31-Phosphorus Magnetic Resonance Spectroscopic Study
Authors: B.N. Gangadhar, P.N. Jayakumar, D.K. Subbakrishna, N. Janakiramaiah, M.S. Keshavan
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: This study used 31-phosphorus magnetic resonance spectroscopy (31P MRS) to investigate basal ganglia abnormalities in neuroleptic-naive patients with schizophrenia. METHOD: Nineteen schizophrenia patients and 31 age- and sex-matched healthy comparison subjects underwent 31P MRS. RESULTS: The phosphocreatine/total phosphorus and phosphocreatine/total ATP ratios in both basal ganglia were significantly lower in patients. CONCLUSIONS: Schizophrenia patients showed features of increased metabolism in the basal ganglia consistent with impaired activity of the frontostriatal pathways.
Menstrual Cyclic Variation of Myocardial Ischemia in Premenopausal Women with Variant Angina
Authors: Hiroaki Kawano, Takeshi Motoyama, Masamichi Ohgushi, Kiyotaka Kugiyama, Hisao Ogawa, Hirofumi Yasue
Journal: Annals of Internal Medicine (2001)

Background: An abundance of ovarian hormones is assumed to be a major contributor to the low incidence of ischemic heart disease in premenopausal women. However, the effects of ovarian hormones remain undetermined. Objective: To examine whether the variation in ovarian hormone levels throughout a menstrual cycle affects myocardial ischemia in women with variant angina. Design: Prospective, observational study. Setting: University medical center in Japan. Participants: 10 premenopausal women with variant angina. Measurements: Frequency of spontaneous ischemic episodes, flow-mediated dilation of brachial artery, and serum levels of estradiol and progesterone. Results: Frequency of ischemic episodes was highest from the end of the luteal phase to the beginning of the menstrual phase and was lowest in the follicular phase. Flow-mediated vasodilation and estradiol levels were lowest from the end of the luteal phase to the beginning of the menstrual phase and were highest in the follicular phase. Conclusions: In premenopausal women with variant angina, we documented a cyclic variation in endothelial function and the frequency of myocardial ischemia that was associated with the variation in estrogen levels.
EBV-Induced Human CD8+ NKT Cells Synergise CD4+ NKT Cells Suppressing EBV-Associated Tumours Upon Induction of Th1-Bias
Authors: Wei Xiao, Li Li, Rui Zhou, Ruijing Xiao, Yujuan Wang, Xiang Ji, Mengjun Wu, Lan Wang, Wei Huang, Xiaoling Zheng, Xinti Tan, Lang Chen, Tao Xiong, Jie Xiong, Youxin Jin, Jinquan Tan, Yuling He
Journal: Cellular and Molecular Immunology (2009)