tbuckley/cabot-search huggingface dataset:
Predicting likelihood of gastroenteritis from sea bathing: results from randomised exposure
Authors: D Kay, F Jones, M.D Wyer, J.M Fleisher, R.L Salmon, A.F Godfree, A Zelenauch-Jacquotte, R Shore
Journal: The Lancet (1994)

The health effects of bathing in coastal waters is an area of scientific controversy. We conducted the first ever randomised "trial" of an environmental exposure to measure the health effects of this activity. The trial was spread over four summers in four UK resorts and 1216 adults took part. Detailed interviews were used to collect data on potential confounding factors and intensive water quality monitoring was used to provide more precise indices of exposure. 548 people were randomised to bathing, and the exposure included total immersion of the head. Crude rates of gastroenteritis were significantly higher in the exposed group (14.8 per 100) than the unexposed group (9.7 per 100; p = 0.01). Linear trend and multiple logistic regression techniques were used to establish relations between gastroenteritis and microbiological water quality. Of a range of microbiological indicators assayed only faecal streptococci concentration, measured at chest depth, showed a significant dose-response relation with gastroenteritis. Adverse health effects were identified when faecal streptococci concentrations exceeded 32 per 100 mL. This relation was independent of non-water-related predictors of gastroenteritis. We do not suggest that faecal streptococci caused the excess of gastrointestinal symptoms in sea bathers but these microorganisms do seem to be a better indicator of water quality than the traditional coliform counts. Bathing water standards should be revised with these findings in mind.
New insights into the prognostic impact of the karyotype in MDS and correlation with subtypes: evidence from a core dataset of 2124 patients
Authors: Detlef Haase, Ulrich Germing, Julie Schanz, Michael Pfeilstöcker, Thomas Nösslinger, Barbara Hildebrandt, Andrea Kundgen, Michael Lübbert, Regina Kunzmann, Aristoteles A. N. Giagounidis, Carlo Aul, Lorenz Trümper, Otto Krieger, Reinhard Stauder, Thomas H. Müller, Friedrich Wimazal, Peter Valent, Christa Fonatsch, Christian Steidl
Journal: Blood (2007)
Unstable Carotid Plaques Exhibit Raised Matrix Metalloproteinase-8 Activity
Authors: K.J. Molloy, M.M. Thompson, J.L. Jones, E.C. Schwalbe, P.R.F. Bell, A.R. Naylor, I.M. Loftus
Journal: Circulation (2004)

Background— The fibrous cap of atherosclerotic plaques is composed predominantly of type I and III collagen. Unstable carotid plaques are characterized by rupture of their cap, leading to thromboembolism and stroke. The proteolytic mechanisms causing plaque disruption are undefined, but the collagenolytic matrix metalloproteinase (MMP) -1, -8, and -13 may be implicated. The aim of this study was to quantify the concentrations of these collagenases in carotid plaques and to determine their relationship to markers of plaque instability. Methods and Results— Atherosclerotic plaques were collected from 159 patients undergoing carotid endarterectomy. The presence and timing of carotid territory symptoms were ascertained. Preoperative embolization was recorded by transcranial Doppler. Each plaque was assessed for histological features of instability. Plaque MMP concentrations were quantified with ELISA. Significantly higher concentrations of active MMP-8 were observed in the plaques of symptomatic patients (20.5 versus 11.4 ng/g; P =0.0002), in plaques of emboli-positive patients (22.7 versus 13.5 ng/g; P =0.0037), and in those plaques showing histological evidence of rupture (20.8 versus 14.7 ng/g; P =0.0036). No differences were seen in the levels of MMP-1 and MMP-13. Immunohistochemistry, in situ hybridization, and colocalization studies confirmed the presence of MMP-8 protein and mRNA within the plaque, which colocalized with macrophages. Conclusions— These data suggest that the active form of MMP-8 may be partly responsible for degradation of the collagen cap of atherosclerotic plaques. This enzyme represents an attractive target for drug therapy aimed at stabilizing vulnerable plaques.
Anti-Endotoxin Monoclonal Antibodies
Authors: H S Warren, R L Danner, R S Munford
Journal: New England Journal of Medicine (1992)

Several monoclonal antibodies directed against bacterial lipopolysaccharide (endotoxin) are being developed for the adjunctive treatment of gram-negative sepsis. Two of these, E5 (XOMA, Berkeley, Calif.)1 and HA-1A (Centocor, Malvern, Pa.),2 have been studied in clinical trials and evaluated by the Food and Drug Administration for use in the United States. An open advisory-committee meeting was held by the FDA on September 4, 1991, at which new information was presented about the preclinical and clinical studies of these two products.3 This article discusses some of the issues relating to the development and evaluation of these agents in the context of this . . .
Improving access to treatment for HIV in sub-Saharan Africa
Authors: S. Bautista-Arredondo, V. J. Wirtz, S. M. Bertozzi
Journal: BMJ (2010)

Additional funding is important, but using it more efficiently is key 

Between 2000 and 2007, funding for HIV and AIDS programmes increased from $2.4bn (£1.5bn; €1.8bn) to $10bn. Antiretroviral drugs are the costliest component of delivering antiretroviral treatment, making up at least half of total treatment costs (excluding programme level costs) in low, lower middle, and upper middle income countries, respectively.1

Previous analyses have noted that in developing countries as coverage of antiretroviral treatment increases the cost falls. Others have focused on factors that influence the cost of antiretrovirals: third party negotiations, volume commitment, the country’s income, costs of active drug ingredients, and product type—generic or innovative.2 3

In the linked study (doi:10.1136/bmj.c6218), Bendavid and colleagues looked at the dramatic fall in the cost of first line antiretroviral drugs that accompanied the equally dramatic rise in foreign assistance between 2003 and 2008 in 13 countries in sub-Saharan Africa.4 Unsurprisingly, they found that both factors were significantly associated with increasing coverage. They also found that the country’s own public health expenditure and a composite World Bank measure of government effectiveness were also positively …
Medical Education Toward the 21st Century-Reply
Authors: James V. Warren
Journal: JAMA (1985)

In Reply.—  We are pleased that our article has stimulated correspondence. A major purpose of the conference, and the article, was to arouse interest in the problems of adapting medical education for the future. The readers should remember that the subtitle of the article is Thoughts on Listening to a Conference on Medical Education for the 21st Century. It is, in effect, a report on what took place at that conference. Certainly, as all reporting must, the document does reflect to some degree the views of the receptors. A different reporter might have interpreted the conference discussions differently. We should also point out that the conference dealt more with problems facing medical education rather than with prescribing solutions. Many of the problems have been recognized for a long time, but we have come to the point where action rather than further listing of problems is necessary.  The letter by Drs
Survival in Schistosomiasis-Associated Pulmonary Arterial Hypertension
Authors: Caio Julio Cesar dos Santos Fernandes, Carlos Vianna Poyares Jardim, Andre Hovnanian, Susana Hoette, Bruno Arantes Dias, Silvia Souza, Marc Humbert, Rogerio Souza
Journal: Journal of the American College of Cardiology (2010)
Effects of renin gene transfer on blood pressure and renin gene expression in a congenic strain of Dahl salt-resistant rats.
Authors: E M St Lezin, M Pravenec, A L Wong, W Liu, N Wang, S Lu, H J Jacob, R J Roman, D E Stec, J M Wang, I A Reid, T W Kurtz
Journal: Journal of Clinical Investigation (1996)

To investigate whether a BP-regulatory locus exists in the vicinity of the renin locus on rat chromosome 13, we transferred this chromosome segment from the Dahl salt-sensitive (S) rat onto the genetic background of the Dahl salt-resistant (R) rat. In congenic Dahl R rats carrying the S renin gene and fed an 8% salt diet, systolic BP was significantly lower than in progenitor Dahl R rats: 127 +/- 1 mmHg versus 138 +/- 4 mmHg, respectively (P < 0.05). Moreover, the decreased BP in the congenic Dahl R strain was associated with decreased kidney renin mRNA and decreased plasma renin concentration. These findings demonstrate that the Dahl S strain carries alleles in or near the renin locus that confer lower plasma renin concentration and lower BP than the corresponding alleles in the Dahl R strain, at least when studied on the genetic background of the Dahl R rat and in the environment of a high salt diet. The occurrence of coincident reductions in kidney renin mRNA, plasma renin concentration, and BP after interstrain transfer of naturally occurring renin gene variants strongly suggests that genetically determined variation in renin gene expression can affect BP.
“Atrial systolic notch” and “early diastolic notch” on the interventricular septal echogram in constrictive pericarditis
Authors: J. Candell-Riera, L. Gutierrez-Palau, H. Garcia-Del-Castillo, G. Perm An Yer-Miralda, J. Soler-Soler
Journal: Journal of the American College of Cardiology (1985)
The therapeutic potential of modulating the ceramide/sphingomyelin pathway
Authors: Richard Kolesnick
Journal: Journal of Clinical Investigation (2002)

Membrane lipids of the sphingolipid class contain a long-chain sphingoid base backbone (such as sphingosine), an amide-linked, long-chain fatty acid, and one of various polar head groups. The structure of these head groups defines the various sphingolipid subtypes, with a hydroxyl group found in ceramide, phosphorylcholine in sphingomyelin (SM), and carbohydrates in glycosphingolipids (Figure ​(Figure11 and not shown). Because SM is concentrated in the outer leaflet of the plasma membrane and provides a barrier to the extracellular environment (1), it was long assumed to serve only structural roles. However, in 1987 our laboratory reported for the first time rapid sphingomyelinase (SMase) activation in response to 1,2-diacylglycerols but not phorbol esters (2), and proposed the existence of an SM-based signaling pathway (3, 4). Subsequently, Hannun and coworkers showed that this pathway can be activated by receptor-mediated mechanisms (5) and provided evidence that ceramide is a second messenger (6). Indeed, sphingolipid metabolism has proved to be a dynamic process, and sphingolipid metabolites — including ceramide, sphingosine, and sphingosine 1-phosphate (S1P) — are now recognized as messengers playing essential roles in cell growth, survival, and death (7, 8).



Figure 1

Schematic representation of sphingolipid intermediary metabolism.
Mechanisms of the genotoxicity of crocidolite asbestos in mammalian cells: implication from mutation patterns induced by reactive oxygen species.
Authors: An Xu, Hongning Zhou, Dennis Zengliang Yu, Tom K Hei
Journal: Environmental Health Perspectives (2002)

Asbestos is an important environmental carcinogen in the United States and remains the primary occupational concern in many developing countries; however, the underlying mechanisms of its genotoxicity are not known. We showed previously that asbestos is a potent gene and chromosomal mutagen in mammalian cells and that it induces mostly multilocus deletions. Furthermore, reactive oxygen species (ROS) are associated with the mutagenic process. To evaluate the contribution of ROS to the mutagenicity of asbestos, we examined their generation, particularly hydrogen peroxide, and compared the types of mutants induced by crocidolite fibers with those generated by H(2)O(2 )in human-hamster hybrid (A(L)) cells. Using confocal scanning microscopy together with the radical probe 5,6 -chloromethy-2,7 -dichlorodihydrofluorescein diacetate (CM-H(2)DCFDA), we found that asbestos induces a dose-dependent increase in the level of ROS among fiber-treated A(L) cells, which is suppressed by concurrent treatment with dimethyl sulfoxide. Using N-acetyl-3,7-dihydroxyphenoxazine (Amplex Red reagent) together with horseradish peroxidase, we further demonstrated that there was a dose-dependent induction of H(2)O(2) in crocidolite-treated A(L) cells. The amount of H(2)O(2 )induced by asbestos reached a plateau at a dose of 6 microg/cm(2). Concurrent treatment with catalase (1,000 U/mL) inhibited this induction by 7- to 8-fold. Mutation spectrum analysis showed that the types of CD59(-) mutants induced by crocidolite fibers were similar to those induced by equitoxic doses of H(2)O(2). These results provide direct evidence that the mutagenicity of asbestos is mediated by ROS in mammalian cells.
Preventing and detecting early vascular effects of diabetes: Improvement must continue or costs will escalate
Authors: D J Kinshuck
Journal: BMJ (2006)

A prescription for better prescribing Medical education is a continuumEditor-The editorial by Aronson et al raises important concerns about the preparedness of newly qualified doctors to prescribe safely and effectively, but fails to provide evidence to support the claims that are made. 1 Importantly, the authors assume that the number of curricular hours equates to learning.The General Medical Council issues and regularly updates requirements for the content and outcomes of undergraduate medical education and the first foundation year.We deliberately do not tell medical schools how many hours must be spent on a particular subject: it is the acquisition of our learning objectives that is important.Medical education is a continuum.With respect to prescribing, as with so many other areas of medical education, we expect principles to be learnt and understood at medical school and then put into practice, under supervision, during the F1 year.Our requirements are laid out clearly in Tomorrow's Doctors and The New Doctor and include very clear expectations about the quality and extent of knowledge about the safe and effective use of drugs.Despite the strength of views expressed in the editorial, the authors have not presented robust and generally applicable evidence to show serious inadequacies in the learning of clinical pharmacology in the undergraduate medical curriculum.We look forward, however, to engaging with all interested parties to clarify the issues surrounding this very important subject.
Reporting Enrollment in Clinical Trials
Authors: Scott D. Halpern
Journal: Annals of Internal Medicine (2002)

Letters17 December 2002Reporting Enrollment in Clinical TrialsScott D. Halpern, MSCEScott D. Halpern, MSCEUniversity of Pennsylvania; Philadelphia, PA 19104-6021Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-137-12-200212170-00019 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Gross and colleagues (1) point out that failure to report the quantitative details of the recruitment process and to provide qualitative descriptions of the population being recruited limit the generalizability of randomized, controlled trials (RCTs). Although more thorough reporting would certainly help identify trials with potentially limited generalizability, it would not help clinicians apply trial results to individual patients.To enhance the applicability of RCTs, investigators must obtain patient-level data on those who choose not to participate. Methods to do this have been proposed (2, 3). Only by understanding the precise types of patients lost during the ...Reference1. Gross CP, Mallory R, Heiat A, Krumholz HM. Reporting the recruitment process in clinical trials: who are these patients and how did they get there? Ann Intern Med. 2002;137:10-6. [PMID: 12093240] LinkGoogle Scholar2. . Coronary artery surgery study (CASS): a randomized trial of coronary artery bypass surgery. Comparability of entry characteristics and survival in randomized patients and nonrandomized patients meeting randomization criteria. J Am Coll Cardiol. 1984;3:114-28. [PMID: 6361099] CrossrefMedlineGoogle Scholar3. Halpern SD. Prospective preference assessment: a method to enhance the ethics and efficiency of randomized, controlled trials. Control Clin Trials. 2002;23:274-88. [PMID: 12057879] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: University of Pennsylvania; Philadelphia, PA 19104-6021 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoReporting the Recruitment Process in Clinical Trials: Who Are These Patients and How Did They Get There? Cary P. Gross , Raburn Mallory , Asefeh Heiat , and Harlan M. Krumholz Reporting Enrollment in Clinical Trials Joseph H. Friedman Reporting Enrollment in Clinical Trials Gregory A. Abel Reporting Enrollment in Clinical Trials Cary P. Gross and Harlan Krumholz Metrics Cited ByRecruitment and Retention in Clinical ResearchRecruitment and Retention 17 December 2002Volume 137, Issue 12Page: 1007KeywordsClinical trial reportingForecasting ePublished: 17 December 2002 Issue Published: 17 December 2002 CopyrightCopyright © 2002 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Topical nasal anaesthesia for fibreoptic bronchoscopy.
Authors: B R O'Driscoll, J R Webb
Journal: Thorax (1990)

Letters to the Editor patibility.The temporal relation in the fall in PEF and arterial oxygen tension during haemodialysis, confirmed by Dr Wu and his colleagues, supports our initial contention that changes in PEF may be due to the activation of inflammatory mediators con- sequent on the activation of complement, neutrophils, monocytes, and platelets after the blood-dialyser interaction, resulting in an increase in pulmonary arteriolar tone and ventilation-perfusion mismatch and a reduc- tion in tissue oxygen delivery.'This is sup- ported by data obtained during the reuse of cuprophan dialysers, when the expected fall in PEF' and arterial oxygen tension and increase in platelet activation were much less than when the dialyser was used the first time.3
Effects of Chenodeoxycholic and Ursodeoxycholic Acids on Lipid Metabolism and Gallstone Formation in the Prairie Dog
Authors: Bertram I. Cohen, Anil K. Singhal, Richard J. Stenger, Patricia May-Donath, Judith Finver-Sadowsky, Charles K. Mcsherry, Erwin H. Mosbach
Journal: Hepatology (1984)

The prevention of cholesterol cholelithiasis by dietary chenodeoxycholic and ursodeoxycholic acids was studied in the male prairie dog (Cynotttys ludovicianus). Gallstones were induced by administration of a semisynthetic diet containing 0.4% cholesterol for a period of 8 weeks. Groups of 5 or 6 animals received the lithogenic diet with added chenodeoxycholic or ursodeoxycholic acid (0.03% “low dose” or 0.06% “high dose”). Under the conditions used, the incidence of gallstones was reduced with the high dose of chenodeoxycholic acid and the low dose of ursodeoxycholic acid, but cholesterol crystals were detected in the biles of 20 of the 22 animals fed these bile acids. A control group maintained on a low (0.08%) cholesterol semisynthetic diet exhibited neither crystals nor stones and was the only group with a lithogenic index below 1.0. The administered bile acids tended to reduce the accumulation of cholesterol in liver and plasma. The activity of hepatic HMG-CoA reductase was significantly inhibited with all cholesterol-supplemented diets. Cholesterol 7α-hydroxylase activity was elevated 83% in prairie dogs fed 0.4% cholesterol, but tended to return to normal levels when bile acids were added to this diet. Histologically, the livers of all animals on the semisynthetic (cholesterol-supplemented) diet exhibited bile duct proliferation, as well as portal fibrosis and inflammatory infiltration. These morphologic alterations were ameliorated by low dose supplementation with either chenodeoxycholic or ursodeoxycholic acid, but high dose bile acid supplementation failed to reduce these pathologic changes.
A STUDY OF THE BONY PELVIS IN ONE HUNDEED AND FIFTY CASES.
Authors: EFFA V. DAVIS
Journal: JAMA (1905)

trogressive metamorphoses that are attributed to the eels of this tumor.DISCUSSION.Dr. W. O. Henry, Omaha, said that hemorrhages follow- ing abortion or labor, and the rapid growth of the tumor and its early metastasis, should lead the physician to sus- pect that it is of malignant character.This is a particularly
Clonal Mast Cell Disorderas in Patients with Severe Hymenoptera Allergy and Normal Serum Tryptase
Authors: Patrizia Bonadonna, Carla Lombardo, Giovanni Passalacqua, Roberta Zanotti, Cristian Caimmi, Masimiliano Bonifacio, Livio Simioni, Beatrice Bilo, Giovanni Marchi, Moira Busa
Journal: Journal of Allergy and Clinical Immunology (2015)
Platelet and coagulation factor variations induced in vitro by polyethylene terephthalate (Dacron®) coated with pyrolytic carbon
Authors: Elisabetta Cenni, Carla Renata Arciola, Gabriela Ciapetti, Donatella Granchi, Lucia Savarino, Susanna Stea, Daniela Cavedagna, Tiziano Curti, Giuseppina Falsone, Arturo Pizzoferrato
Journal: Biomaterials (1995)
Colin Henry Woodham
Authors: Basil Shepstone
Journal: BMJ (2006)

Founder epidemiologist of the Framingham heart studyIn 1945 the Western world emerged from the second world war, only to be confronted by an epidemic of heart disease.The US government responded by setting up a study to identify the causes and to diagnose and treat early disease, though the latter aim was dropped as there was no treatment available.The town of Framingham in Massachusetts was chosen as the site for this study because it had a stable population of 28 000 and was close to Harvard University.The Framingham study, as it was known, became world famous."Along with Ancel Keys's seven country study, this was the work on which all other epidemiology of heart disease stands.There isn't a study that doesn't owe its origin to Framingham,"