tbuckley/cabot-search huggingface dataset:
Mortality among Diabetic Patients Using Continuous Subcutaneous Insulin-Infusion Pumps
Authors: Steven M. Teutsch, William H. Herman, Diane M. Dwyer, J. Michael Lane
Journal: New England Journal of Medicine (1984)

Because of concern about deaths among diabetic patients using continuous subcutaneous insulin-infusion pumps, we conducted an investigation to determine whether the number of such deaths was excessive. By October 1982 we had identified 35 deaths among the estimated 3500 diabetic patients using pumps in the United States. The observed number of deaths was not greater than the expected number calculated from age-specific death rates for conventionally treated patients with Type I diabetes. The causes of death were not unusual, with two exceptions. One death was associated with malfunction of the device, and the other was attributed to acute bacterial endocarditis that arose from an abscess at the catheter-insertion site. Patients who died had high rates of autonomic neuropathy (66 per cent) and renal disease (39 per cent with serum creatinine levels above 5 mg per deciliter). We conclude that the use of continuous subcutaneous insulin-infusion pumps is not associated with excess mortality. However, certain types of patients may be at greater risk for death, and physicians should take great care in selecting patients for pump therapy.
Quantitative assessment of allergic shiners in children with allergic rhinitis
Authors: Chien-Han Chen, Yu-Tsan Lin, Che-Yen Wen, Li-Chieh Wang, Kuo-Hung Lin, Shih-Hsuan Chiu, Yao-Hsu Yang, Jyh-Hong Lee, Bor-Luen Chiang
Journal: Journal of Allergy and Clinical Immunology (2009)
Predicting the Outcome From Hypoxic-Ischemic Coma: Medical and Ethical Implications
Authors: Peter McL. Black
Journal: JAMA (1985)

In a recent issue ofThe Journal, Levy et al<sup>1</sup>have presented a summary of their work on the outcome of coma in 210 patients with brain hypoxia or ischemia. This work is an extension of previous publications.<sup>2-4</sup>The statistics are somber: 57% of patients died without opening their eyes, 20% attained only the vegetative state, and only 13% recovered independent function. The authors believe that simple clinical data could have predicted the outcome in many of the 87% of patients who did not achieve independent function, data such as fixed pupils on the first day or absent or posturing motor responses after three days. The authors draw several conclusions about the care of comatose patients from these data. Two features of this article are of particular interest: the general applicability of its prognostic factors for predicting outcome from ischemic/hypoxic coma and the ethical implications of such predictions
Abnormal Sexual Development: A Genetic and Endocrine Approach to Differential Diagnosis
Authors: John W. Huffman
Journal: JAMA (1968)

Federman's<i>Abnormal Sexual Development</i>is a happy exception to the general rule that most books ought to be condensed to about one third of their size. In fact, this small volume could well be expanded into a larger work. Even if it was twice its size it would still hold the readers' interest. The author has taken subjects which are not easy to make either clear or interesting and has integrated descriptions of their clinical pictures with recent genetic and endocrinologic data. He has not only presented his material concisely but in doing so has written with a style that makes the text a pleasure to read. He guides the uninitiated reader through some rather dense cytogenetic jungles in a manner possible only for one who knows his subject thoroughly. The chapter on cellular division and the production of chromosomal errors is an example of clarity of scientific writing that
Quebec government wins settlement against tobacco giant
Authors: David Spurgeon
Journal: BMJ (2004)

The government of Quebec has obtained a court judgment ordering the tobacco giant JTI-Macdonald to pay nearly $C1.4bn (£0.6bn; $1.1bn; £0.9bn) in taxes immediately, the largest assessment for unpaid taxes in the province's history.

The order follows the federal government's claims last year of unpaid taxes ( BMJ 2003;326:570) on large numbers of Canadian cigarettes bound for the United States that were smuggled …
Theoretical Epidemiology: Principles of Occurrence Research in Medicine
Authors: Sander Greenland
Journal: JAMA (1986)

For me and many of my colleagues, Miettinen's unpublished course text of the early 1970s was the first systematic introduction to theoretical epidemiology we saw; indeed, it was the only such text available (outside of some specialized infectious disease treatises) until the 1980s. This text embodied a landmark in epidemiologic thinking, if only because it synthesized so many previously disconnected theoretical developments (many of them Miettinen's) into a coherent, unitary theory. In 1981, Miettinen began writing an entirely new book, and the final finished product bears little resemblance to the 1970s text in either form or substance—although the inimitable (or inimical, depending on one's camp) Miettinen style remains intact. I suspect this new book will not be as much of a landmark as the first text, if only because the latter succeeded too well in its groundbreaking: the type of theory covered in both texts—highly abstract and often mathematical in
Too few primary care trusts have a strategy to tackle alcohol misuse, watchdog says
Authors: C. Dyer
Journal: BMJ (2008)

Local strategies to tackle the harm to health caused by alcohol are lacking or inadequate in many areas in England, the parliamentary watchdog on public spending concluded in a report released on Wednesday 29 October.

Service delivery is fragmented, and the allocation of resources is based on an incomplete picture of local need, the National Audit Office found.

Nearly a fifth (18%) of people in England drink at “hazardous” levels, and 1.1 million people have a degree of alcohol addiction or dependency, the report estimates. The annual number of alcohol related admissions to hospital has doubled in the past 11 years, and the number of deaths caused by alcohol has more …
'Type A' personalities in men 'mellowed' by beta blockers
Authors: Jack Martin
Journal: JAMA (1982)

The use of β-blockers to treat hypertensive men can actually change type A personality behavior—itself a risk factor for coronary heart disease—toward type B, according to a group of West German physicians.  The report was given at the recent American Psychosomatic Society meeting in Denver, where it attracted considerable interest. Investigators were Roland Schmieder, MD, Heinz Ruddel, MD, G. Friedrich, MD, and H. Neus, all of the Department of Medicine, University of Bonn. (Schmieder and Ruddel are currently at the Department of Preventive and Stress Medicine, University of Nebraska Medical Center, Omaha.)  Type A temperament, the hard-charging sort of personality linked some years ago with heart disease, is characterized by several stylistics, Ruddel told the meeting: loud and explosive speech, rapid and accelerated speaking, response latency, hostility, and verbal competition.  About 70% of male hypertensive patients are type A, he said. They also manifest higher cholesterol and triglyceride levels and
Derivation and Validation of a Simplified Predictive Index for Renal Replacement Therapy After Cardiac Surgery
Authors: Duminda N. Wijeysundera, Keyvan Karkouti, Jean-Yves Dupuis, Vivek Rao, Christopher T. Chan, John T. Granton, W. Scott Beattie
Journal: JAMA (2007)

A predictive index for renal replacement therapy (RRT; hemodialysis or continuous venovenous hemodiafiltration) after cardiac surgery may improve clinical decision making and research design.To develop a predictive index for RRT using preoperative information.Retrospective cohort of 20 131 cardiac surgery patients at 2 hospitals in Ontario, Canada. The derivation cohort consisted of 10,751 patients at Toronto General Hospital (1999-2004). The validation cohorts consisted of 2566 patients at Toronto General Hospital (2004-2005) and 6814 patients at Ottawa Heart Institute (1999-2003).Postoperative RRT.RRT rates in the derivation, Toronto validation, and Ottawa validation cohorts were 1.3%, 1.8%, and 2.2%, respectively. Multivariable predictors of RRT were preoperative estimated glomerular filtration rate, diabetes mellitus requiring medication, left ventricular ejection fraction, previous cardiac surgery, procedure, urgency of surgery, and preoperative intra-aortic balloon pump. The predictive index was scored from 0 to 8 points. An estimated glomerular filtration rate less than or equal to 30 mL/min was assigned 2 points; other components were assigned 1 point each: estimated glomerular filtration rate 31 to 60 mL/min, diabetes mellitus, ejection fraction less than or equal to 40%, previous cardiac surgery, procedure other than coronary artery bypass grafting, intra-aortic balloon pump, and nonelective case. Among the 53% of patients with low risk scores (< or =1), the risk of RRT was 0.4%; by comparison, this risk was 10% among the 6% of patients with high-risk scores (> or =4). The predictive index had areas under the receiver operating characteristic curve in the derivation, Toronto validation, and Ottawa validation cohorts of 0.81, 0.78, and 0.78, respectively. When these cohorts were stratified based on index scores, likelihood ratios for RRT were more concordant than observed RRT rates.RRT after cardiac surgery is predicted by readily available preoperative information. A simple predictive index based on this information discriminated well between low- and high-risk patients in derivation and validation cohorts. The index had improved generalizability when used to predict likelihood ratios for RRT.
Systemic Delivery of Modified mRNA Encoding Herpes Simplex Virus 1 Thymidine Kinase for Targeted Cancer Gene Therapy
Authors: Yuhua Wang, Hsing-hao Su, Yang Yang, Yunxia Hu, Lu Zhang, Pilar Blancafort, Leaf Huang
Journal: Molecular Therapy (2012)

Failure of clinical trials of nonviral vector-mediated gene therapy arises primarily from either an insufficient transgene expression level or immunostimulation concerns caused by the genetic information carrier (e.g., bacteria-generated, double-stranded DNA (dsDNA)). Neither of these issues could be addressed through engineering-sophisticated gene delivery vehicles. Therefore, we propose a systemic delivery of chemically modified messenger RNA (mRNA) as an alternative to plasmid DNA (pDNA) in cancer gene therapy. Modified mRNA evaded recognition by the innate immune system and was less immunostimulating than dsDNA or regular mRNA. Moreover, the cytoplasmic delivery of mRNA circumvented the nuclear envelope, which resulted in a higher gene expression level. When formulated in the nanoparticle formulation liposome-protamine-RNA (LPR), modified mRNA showed increased nuclease tolerance and was more effectively taken up by tumor cells after systemic administration. The use of LPR resulted in a substantial increase of the gene expression level compared with the equivalent pDNA in the human lung cancer NCI-H460 carcinoma. In a therapeutic model, when modified mRNA encoding herpes simplex virus 1-thymidine kinase (HSV1-tk) was systemically delivered to H460 xenograft-bearing nude mice, it was significantly more effective in suppressing tumor growth than pDNA. Failure of clinical trials of nonviral vector-mediated gene therapy arises primarily from either an insufficient transgene expression level or immunostimulation concerns caused by the genetic information carrier (e.g., bacteria-generated, double-stranded DNA (dsDNA)). Neither of these issues could be addressed through engineering-sophisticated gene delivery vehicles. Therefore, we propose a systemic delivery of chemically modified messenger RNA (mRNA) as an alternative to plasmid DNA (pDNA) in cancer gene therapy. Modified mRNA evaded recognition by the innate immune system and was less immunostimulating than dsDNA or regular mRNA. Moreover, the cytoplasmic delivery of mRNA circumvented the nuclear envelope, which resulted in a higher gene expression level. When formulated in the nanoparticle formulation liposome-protamine-RNA (LPR), modified mRNA showed increased nuclease tolerance and was more effectively taken up by tumor cells after systemic administration. The use of LPR resulted in a substantial increase of the gene expression level compared with the equivalent pDNA in the human lung cancer NCI-H460 carcinoma. In a therapeutic model, when modified mRNA encoding herpes simplex virus 1-thymidine kinase (HSV1-tk) was systemically delivered to H460 xenograft-bearing nude mice, it was significantly more effective in suppressing tumor growth than pDNA.
Karaya Gum Hypersensitivity in An Enterostomal Therapist
Authors: William Wagner
Journal: JAMA (1980)

<h3>To the Editor.—</h3> Sixteen cases of karaya gum hypersensitivity were reported by Figley (114:747, 1940) in 1940. In this report respiratory symptoms were the most common manifestation of karaya gum hypersensitivity. One of the current uses of karaya gum is in the routine care of ileostomies and colostomies. The karaya gum serves as a skin barrier and is available in a variety of forms, including seal rings, paste, and a dry powder in a plastic squeeze bottle. The following is a case of karaya gum hypersensitivity in a nurse providing ostomy care. <h3>Report of a Case.—</h3> The patient is a 27-year-old female nurse who had been employed for three years as an enterostomal therapist before showing the development of respiratory symptoms. The patient smoked one pack of cigarettes per day. There had been no significant respiratory symptoms until the spring of 1979, when she had mild persistent rhinitis. In July
MEDICINE AS A UNIVERSITY GRADUATE STUDY
Authors: Maurice B. Visscher
Journal: JAMA (1960)

When one proposes to speak about University Graduate Study one has the obligation to define one's terms. Probably no two experts in the field have precisely the same constellation of qualifications in mind when they use such terms. The least I can do is to give my own definition, and I can hope that it will not deviate too far from a generally acceptable one. To my way of thinking, graduate study has only one generally unique quality, namely, that it is aimed at preparation for creative scholarship rather than simply for vocational or professional application of knowledge. In this statement I distinguish sharply between postgraduate study, which is usually aimed at increased proficiency in applying knowledge, and graduate study, which aims at increasing knowledge. The aims rather than the methods represent the first difference, but the methods also become different when sound preparation for creative scholarship is projected and
Specialist ousted in research row
Authors: O. Dyer
Journal: BMJ (2003)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic autoimmune disease characterised by an inflammatory response in synovial joints. One family of tyrosine kinase receptors that mediates an anti-inflammatory feedback mechanism are Tyro3, Axl and Mer (gene <i>Mertk</i>; TAM). The role of TAM receptors in RA has not been elucidated and we studied the role of Axl and Mer in an experimental model of RA. <h3>Materials and methods</h3> The KRN serum transfer model of arthritis was induced by two intraperitoneal injections of arthritic K/BxN serum in <i>Axl<sup>-/-</sup></i>, <i>Mertk<sup>-/-</sup></i>, <i>Axl<sup>-/-</sup>Mertk<sup>-/-</sup></i>and wild-type (WT) mice. Ankle joints were macroscopically scored for 7 days. At day 0, 2 and 7, ankle and knee joints were isolated for histology and immunohistochemistry. <h3>Results</h3> <i>Mertk<sup>-/-</sup></i> mice had increased macroscopic ankle scores until day 4 whereas <i>Axl<sup>-/-</sup></i> mice had enhanced macroscopic scores from day 4 until day 7. Histology of ankle joints showed significantly more inflammation in <i>Mertk<sup>-/-</sup></i> mice at day 2 and increased arthritis pathology in <i>Axl<sup>-/-</sup></i>mice at day 7, reflecting macroscopic ankle scores. Histological analysis of ankle joints of <i>Axl<sup>-/-</sup>Mertk<sup>-/-</sup></i> mice at day 7 showed enhanced pathology compared to both <i>Axl<sup>-/-</sup></i> and WT mice, indicating an additive effect of Axl and Mer deficiency. In contrast to the ankle joints at day 7, enhanced macroscopic scores and arthritis pathology in knee joints of <i>Mertk<sup>-/-</sup></i>mice, compared to WT mice, was observed. To explain the discrepancy of Axl involvement between ankle and knee at day 7, we examined Axl expression in synovium before the onset of arthritis. The cells in the lining layer of ankle synovium were strikingly Axl positive whereas the synovium of the knee joints was Axl negative. <h3>Conclusions</h3> These findings identify the TAM receptors Axl and Mer as important players in arthritis. The Mer receptor plays a protective role at the onset of arthritis whereas the Axl receptor takes over this role in established disease in ankle joints. In the knee joints, however, Mer but not Axl, plays a prominent protective role, likely due to the lack of Axl in naïve knee joints. These findings highlight differences in topographically distinct synovial joints in inflammatory arthritis.
MyD88/TLR9 mediated immunopathology and gut microbiota dynamics in a novel murine model of intestinal graft-versus-host disease
Authors: M. M. Heimesaat, A. Nogai, S. Bereswill, R. Plickert, A. Fischer, C. Loddenkemper, U. Steinhoff, S. Tchaptchet, E. Thiel, M. A. Freudenberg, U. B. Gobel, L. Uharek
Journal: Gut (2010)

<h3>Background</h3> The bacterial microflora aggravates graft-versus-host-disease (GvHD) after allogeneic stem cell transplantation, but the underlying mechanisms of manifestations of intestinal GvHD (iGvHD) in the gut remain poorly understood. <h3>Aim</h3> To analyse the gut flora composition and the impact of bacterial sensing via Toll-like receptors (TLRs) in iGvHD. <h3>Methods</h3> By mimicking clinical low-intensity conditioning regimens used in humans, a novel irradiation independent, treosulfan and cyclophosphamide-based murine allogeneic transplantation model was established. A global survey of the intestinal microflora by cultural and molecular methods was performed, the intestinal immunopathology in TLR-deficient recipient mice with iGvHD investigated and finally, the impact of anti-TLR9 treatment on iGvHD development assessed. <h3>Results</h3> The inflammatory responses in iGvHD were accompanied by gut flora shifts towards enterobacteria, enterococci and <i>Bacteroides/Prevotella</i> spp. Analysis of iGvHD in MyD88<sup>-/-</sup>, TRIF<sup>-/-</sup>, TLR2/4<sup>-/-</sup>, and TLR9<sup>-/-</sup> recipient mice showed that bacterial sensing via TLRs was essential for iGvHD development. Acute iGvHD was characterised by increasing numbers of apoptotic cells, proliferating cells, T cells and neutrophils within the colon. These responses were significantly reduced in MyD88<sup>-/-</sup>, TLR2/4<sup>-/-</sup>, TRIF<sup>-/-</sup> and TLR9<sup>-/-</sup> mice, as compared with wild-type controls. However, TRIF<sup>-/-</sup> and TLR2/4<sup>-/-</sup> mice were not protected from mortality, whereas TLR9<sup>-/-</sup> mice displayed increased survival rates. The important role of TLR9-mediated immunopathology was independently confirmed by significantly reduced macroscopic disease symptoms and colonic apoptosis as well as by reduced T-cell and neutrophil numbers within the colon after treatment with a synthetic inhibitory oligonucleotide. <h3>Conclusions</h3> These results emphasise the critical role of gut microbiota, innate immunity and TLR9 in iGvHD and highlight anti-TLR9 strategies as novel therapeutic options.
Improving COPD and asthma outcomes to EU average would save 2000 lives a year in the UK
Authors: S. Mayor
Journal: BMJ (2011)

Reducing inequalities and improving prevention and ongoing care are key outcomes in a new strategy for chronic obstructive pulmonary disease (COPD) and asthma published by the Department of Health on 18 July.

The UK currently has the second highest mortality rates for COPD and asthma in Europe, the strategy warns. Premature mortality for COPD is almost twice as high in the UK as in the rest of Europe, and that for asthma it is 1.5 times higher.

A working group of specialists, organisations working in respiratory disease, patients, and carers have identified the outcomes they consider essential to reducing deaths and improving patients’ quality of life. If the UK met the EU average outcomes for respiratory disease this would save more than 2000 lives each year.

“This is an important document that attaches priority to COPD and asthma, and sets out a framework for the management of these common …
Sirt1 inhibition promotes in vivo arterial thrombosis and tissue factor expression in stimulated cells
Authors: Alexander Breitenstein, Sokrates Stein, Erik W. Holy, Giovanni G. Camici, Christine Lohmann, Alexander Akhmedov, Remo Spescha, Peter J. Elliott, Christoph H. Westphal, Christian M. Matter, Thomas F. Lüscher, Felix C. Tanner
Journal: Cardiovascular Research (2010)

The mammalian silent information regulator-two 1 (Sirt1) blunts the noxious effects of cardiovascular risk factors such as type 2 diabetes mellitus and obesity. Nevertheless, the role of Sirt1 in regulating the expression of tissue factor (TF), the key trigger of coagulation, and arterial thrombus formation remains unknown.Human as well as mouse cell lines were used for in vitro experiments, and C57Bl/6 mice for in vivo procedures. Sirt1 inhibition by splitomicin or sirtinol enhanced cytokine-induced endothelial TF protein expression as well as surface activity, while TF pathway inhibitor protein expression did not change. Sirt1 inhibition further enhanced TF mRNA expression, TF promoter activity, and nuclear translocation as well as DNA binding of the p65 subunit of nuclear factor-kappa B (NFκB/p65). Sirt1 siRNA enhanced TF protein and mRNA expression, and this effect was reduced in NFκB/p65(-/-) mouse embryonic fibroblasts reconstituted with non-acetylatable Lys(310)-mutant NFκB/p65. Activation of the mitogen-activated protein kinases p38, c-Jun NH(2)-terminal kinase, and p44/42 (ERK) remained unaffected. In vivo, mice treated with the Sirt1 inhibitor splitomicin exhibited enhanced TF activity in the arterial vessel wall and accelerated carotid artery thrombus formation in a photochemical injury model.We provide pharmacological and genetic evidence that Sirt1 inhibition enhances TF expression and activity by increasing NFκB/p65 activation in human endothelial cells. Furthermore, Sirt1 inhibition induces arterial thrombus formation in vivo. Hence, modulation of Sirt1 may offer novel therapeutic options for targeting thrombosis.