tbuckley/cabot-search huggingface dataset:
Living Modified Viruses as Immunizing Agents
Authors: H. R. Cox
Journal: BMJ (1954)

Every medical investigator of the twentieth century counts among his scientific forebears the two great Germans Paul Ehrlich and Emil von Behring.Born a day apart, friends and co-workers, both Nobel Prize winners, appropriately they have been called "twin sons of science and humanity."I leave to others the enumeration of their many accomplishments.One writer has said that Behring forged the sword of serotherapy, but Ehrlich ground its edge.On this occasion, no one can speak of the weapons against disease we are now creating without first acknowledg- ing the power of those fashioned by Ehrlich and von Behring.Jenner and Pasteur The purpose of this paper is to review a mighty weapon we now possess-namely, living modified viruses as immunizing vaccines.Unquestionably, Jenner's use of cowpox or vaccinia virus on a large scale to protect against smallpox was the first instance of immunization with a living, attenuated virus.It had been recognized for many years in England, France, and Germany that milkmaids who had contracted cowpox were spared during ravaging epidemics of smallpox.The observation of this fact was not original with Jenner.The merit of his work rests upon the fact that he started out with the hope of making his conception a permanent working principle in science, based upon experimental demonstration, and he succeeded.'In short, Jenner transformed a rural tradition into a living prophylactic principle.Popular aversion to vaccination was overcome, and the practice spread rapidly in Europe and America.The effect of Jenner's work is apparent in the rapid advances serotherapy and immunology have made, and in the results of compulsory vaccination in Germany and Holland, where the mortality curve of smallpox approaches zero.Striking, indeed, was the rela- tive immunity of the German army during the Franco- Prussian War in 1870-1, in which the unvaccinated French prisoners lost 1,963 out of 14,178 cases of small- pox, whereas the Germans, who had been revaccinated within two years' time, had 4,835 cases with only 278 deaths.2We are indebted to Pasteur, who, in his studies on fowl cholera, first recognized the importance of microbic variation for practical purposes of medical use.3His
WHO classification and WPSS predict posttransplantation outcome in patients with myelodysplastic syndrome: a study from the Gruppo Italiano Trapianto di Midollo Osseo (GITMO)
Authors: Emilio Paolo Alessandrino, Matteo Giovanni Della Porta, Andrea Bacigalupo, Maria Teresa Van Lint, Michele Falda, Francesco Onida, Massimo Bernardi, Anna Paola Iori, Alessandro Rambaldi, Raffaella Cerretti, Paola Marenco, Pietro Pioltelli, Luca Malcovati, Cristiana Pascutto, Rosi Oneto, Renato Fanin, Alberto Bosi
Journal: Blood (2008)
ABC of Diabetes. Insulin treatment.
Authors: P J Watkins
Journal: BMJ (1982)

The use of insulin has to be tailored to meet individual requirements.The aim is to achieve the best possible control in the circumstances, avoiding at : all costs the disabling hypoglycaemia that can occur if too fine a degree of control is attempted.In elderly patients or those who lack motivation it is therefore wise to aim only at alleviating symptoms and not to attempt very strict control.
GPs lack necessary tools and incentives to manage obesity, London conference hears
Authors: I. Torjesen
Journal: BMJ (2014)

GPs could do much more to manage obesity among their patients if they had the appropriate tools, training, and incentives, a London seminar on obesity heard last week.



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The seminar, “Tackling obesity—latest on commissioning services, engaging business and encouraging healthy choices,” was organised by the Westminster Food and Nutrition Forum.

Rachel Pryke, clinical champion for nutrition for health at the Royal College of General Practitioners, told the seminar that although there was some “fabulous” guidance from the National Institute for Health and Care Excellence on managing obesity, “we don’t have the implementation tools to translate that across …
A unique recombination event resulting in a C4A*Q0,C4B*Q0 double null haplotype.
Authors: M B Fasano, J A Winkelstein, T LaRosa, W B Bias, R H McLean
Journal: Journal of Clinical Investigation (1992)

The fourth component of complement (C4) is encoded by two closely linked genes (C4A and C4B) within the MHC. Null alleles at either locus (C4AQ0 or C4BQ0) are relatively common, occurring at the C4A locus in approximately 10% of normal individuals and at the C4B locus in approximately 16% of normal individuals. However, the presence of the double null haplotype (C4A*Q0,B*Q0) on the same chromosome is extremely rare. We recently studied a 7-yr-old patient with recurrent sinopulmonary infections in whom we documented the mechanism by which the C4A*Q0,B*Q0 double null haplotype arose. Evaluation revealed significantly reduced levels of both C4 antigen and C4 hemolytic activity. Analysis of extended haplotypes in the family was performed using MHC typing and genomic DNA analysis. The patient was found to have a C4A*3,B*Q0 haplotype and a C4A*Q0,B*Q0 haplotype. The C4A*3,B*Q0 haplotype was contributed by the father. The mother possessed a C4A*Q0,B*1 haplotype and a C4A*3,B*1 haplotype. The first maternal haplotype was involved in a recombination event within the C4B locus on her other chromosome and resulted in a new C4B*Q0 null allele and the patient's C4A*Q0,B*Q0 haplotype. Segregation analysis mapped the recombination to a region 3' to the unique 6.4-kb TaqI restriction fragment of the maternal C4B locus. This is the first demonstration of a recombination event producing a C4 double null haplotype.
High-dose therapy and autologous peripheral blood stem cell transplantation as salvage treatment for AIDS-related lymphoma: long-term results of the Italian Cooperative Group on AIDS and Tumors (GICAT) study with analysis of prognostic factors
Authors: Alessandro Re, Mariagrazia Michieli, Salvatore Casari, Bernardino Allione, Chiara Cattaneo, Maurizio Rupolo, Michele Spina, Rosa Manuele, Emanuela Vaccher, Mario Mazzucato, Luciano Abbruzzese, Pierino Ferremi, Giampiero Carosi, Umberto Tirelli, Giuseppe Rossi
Journal: Blood (2009)
Preventing and detecting early vascular effects of diabetes: Word of caution on peripheral arterial assessment
Authors: Saurabh Rai
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.
Longitudinal Study of Error Prevalence in Pennsylvania Physicians' Office Laboratories
Authors: Miriam J. Bloch
Journal: JAMA (1988)

We examined the results of the low-volume-laboratory proficiency testing program for new physician office participants in the Commonwealth of Pennsylvania. Serum glucose, hemoglobin, urinalysis, throat culture, urine culture, and Gram's stain were included in the study. Quarterly error rates for each analyte were determined; between one fourth and all of the laboratories that made at least one error during the first two quarters of proficiency testing made at least one more error in the same analyte during the subsequent two quarters. We show that participation in the quarterly proficiency testing program for a 12- to 15-month period did not lead to a measurable increase in performance. For proficiency testing to be effective, we suggest that it be supplemented by additional methods to lower error rates, such as regulation or intensive consultation and training services for personnel of physicians' office laboratories.
Elevated aldosterone levels in patients with androgenetic alopecia
Authors: S. Arias-Santiago, M.T. Gutiérrez-Salmerón, L. Castellote-Caballero, R. Naranjo-Sintes
Journal: British Journal of Dermatology (2009)

There is reported to be an elevated prevalence of hypertension among patients with androgenetic alopecia (AGA), and it has been proposed that both phenomena may be explained by the presence of hyperaldosteronism. However, no data on aldosterone levels in patients with AGA have been published to date.The objective of this pilot study was to evaluate aldosterone levels and the presence of hypertension in patients with AGA and in healthy controls.This case-control study included 40 patients with AGA and 40 healthy controls from the Dermatology Department of San Cecilio Hospital, Granada, Spain.Patients with AGA showed significantly higher systolic blood pressure values (136.23 vs. 124.10 mmHg, P = 0.01) and aldosterone levels (197.35 vs. 133.71 pg mL(-1), P = 0.007) vs. controls.The elevated aldosterone values in these patients may contribute, together with other mechanisms, to the development of AGA and may also explain the higher prevalence of hypertension. Blood pressure screening of patients with AGA will permit earlier diagnosis of an unknown hypertension and initiation of appropriate treatment.
Relationship Between Characteristics of Medications and Drug-Induced Liver Disease Phenotype and Outcome
Authors: Raj Vuppalanchi, Raghavender Gotur, K Rajender Reddy, Robert J Fontana, Marwan Ghabril, Andrzej S Kosinski, Jiezhun Gu, Jose Serrano, Naga Chalasani
Journal: Clinical Gastroenterology and Hepatology (2013)
Influence on Sexual Function of Abdominoperineal Resection for Ulcerative Colitis
Authors: LeRoy H. Stahlgren, L. Kraeer Ferguson
Journal: New England Journal of Medicine (1958)

THE accepted surgical treatment of far advanced ulcerative colitis involves the eradication of the diseased colon and rectum.1 Although this approach may seem radical, it is the only surgical method by which the disease can be successfully controlled in the advanced state. Recent reports have indicated that such operative management can be carried out with an acceptable mortality and morbidity.1 , 2 It has been stated that abdominoperineal resection of the rectum adversely affects sexual function. Since ulcerative colitis is primarily a disease of young adults, such a consideration is important. This concern seems justified when the literature on the reported effect . . .
Clinical Practice of Sports Injury Prevention and Care
Authors: M J Shalley
Journal: BMJ (1994)

Ed P A F H Renstrom, Blackwell Scientific, £49.50, pp 727 ISBN 0-632-03785-7

When I was reading through this book four major sports events were taking place and were being broadcast on most television channels. Other standard sports coverage was also being shown. One thing is certain: the media are essential to sport in reawakening interest and attracting new participants. This means that people, like myself, who run general sports injury clinics are seeing a much greater variety of sports and their resultant injuries. So publication of …
Metabolic clearance rate and blood production rate of testosterone and dihydrotestosterone in normal subjects, during pregnancy, and in hyperthyroidism
Authors: J. M. Saez, M. G. Forest, A. M. Morera, J. Bertrand
Journal: Journal of Clinical Investigation (1972)

The metabolic clearance rate (MCR) and blood production rate (BP) of testosterone (T) and dihydrotestosterone (DHT), the conversion of plasma testosterone to plasma dihydrotestosterone, and the renal clearance of androstenedione, testosterone, and dihydrotestosterone have been studied in man. In eight normal men, the MCR(T) (516+/-108 [SD] liters/m(2)/day) was significantly greater than the MCR(DHT) (391+/-71 [SD] liters/m(2)/day). In seven females, the MCR(T) (304+/-53 [SD] liters/m(2)/day) was also greater than the MCR(DHT) (209+/-45 [SD] liters/m(2)/day) and both values were less than their respective values in men (P < 0.001). In men the conversion of testosterone into dihydrotestosterone at 2.8+/-0.3% (SD) was greater than that found in females, 1.56+/-0.5% (SD) (P < 0.001). In five pregnant females the MCR(T) (192+/-36 [SD] liters/m(2)/day), the MCR(DHT) (89+/-30 [SD] liters/m(2)/day) and the conversion of testosterone into dihydrotestosterone (0.72+/-0.15%) (SD) were significantly less than the values found in nonpregnant women. In five females with hyperthyroidism, the MCR for testosterone and dihydrotestosterone were similar to those observed in pregnant females, but the conversion of testosterone into dihydrotestosterone (2.78+/-1.7%) (SD) was greater, and similar to that found in men. In men the production of dihydrotestosterone was 0.39+/-0.1 (SD) mg/day, 50% being derived from the transformation of plasma testosterone. In women the production of DHT was 0.05+/-0.028 (SD) mg/day, only 10% coming from testosterone. During pregnancy, the production of testosterone and dihydrotestosterone are similar to that in normal women. In three patients with testicular feminization syndrome (an adult with hyperthyroidism and two children) these two MCRs were greatly reduced compared to the normal females, but the conversion of testosterone into dihydrotestosterone was in the limits of normal male rangeIn the normal subjects the renal clearance of androstenedione was greater than that of testosterone and dihydrotestosterone. Less than 20% of the dihydrotestosterone and less than 10% of the androstenedione in the urine is derived from the plasma dihydrotestosterone and androstenedione.
Enhanced Activation of Human Dendritic Cells by Inducible CD40 and Toll-like Receptor-4 Ligation
Authors: Natalia Lapteva, Mamatha R. Seethammagari, Brent A. Hanks, Jianghong Jiang, Jonathan M. Levitt, Kevin M. Slawin, David M. Spencer
Journal: Cancer Research (2007)

Abstract Despite the potency of dendritic cells (DC) as antigen-presenting cells for priming adaptive immunity, DC-based cancer vaccines have been largely insufficient to effectively reduce tumor burden or prevent tumor progression in most patients. To enhance DC-based vaccines, we used the combination of a synthetic ligand-inducible CD40 receptor (iCD40) along with Toll-like receptor-4 (TLR-4) ligation in human monocyte-derived DCs. The iCD40 receptor permits targeted, reversible activation of CD40 in vivo, potentially bypassing the essential role of CD4+ T cells for activation of DCs. As a rigorous preclinical study of this approach, we evaluated key parameters of DC activation and function. Whereas neither iCD40 nor TLR-4 signaling alone led to high levels of interleukin (IL)-12p70 and IL-6, using iCD40 in combination with lipopolysaccharide (LPS) or monophosphoryl lipid A led to strongly synergistic production of both. Furthermore, this approach led to high expression of DC maturation markers, epitope-specific CTL and T helper 1 responses, as well as DC migration in vitro and in vivo. Moreover, use of iCD40-modified and LPS-stimulated DCs led to targeted expansion of autologous T cells against tumor-associated antigens, including prostate-specific membrane antigen, and elimination of preestablished tumors, supporting this technology as a potent strategy for DC-based cancer immunotherapy. [Cancer Res 2007;67(21):10528–10]
Cocaine and Chest Pain: Clinical Features and Outcome of Patients Hospitalized to Rule Out Myocardial Infarction
Authors: Michael J. Gitter, Steven R. Goldsmith, David N. Dunbar, Scott W. Sharkey
Journal: Annals of Internal Medicine (1991)

To investigate the clinical features, electrocardiographic findings, and hospital course in patients admitted with acute chest pain temporally related to cocaine use.Retrospective data analysis.A 485-bed county hospital.One hundred and one consecutive patients with cocaine-related chest pain admitted to the hospital to rule out myocardial infarction.The quality of the chest pain frequently suggested myocardial ischemia. Dyspnea was common (56%). The onset of chest pain occurred during cocaine use in 21% of patients, within 1 hour of use in 37%, and after 1 hour of use in 42%. Admission electrocardiographic findings were interpreted as normal in 32% of patients; as acute myocardial injury in 8%; as early repolarization variant in 32%; as left ventricular hypertrophy in 16%; and as "other" in 12%. Forty-three percent of patients had ST-segment elevation meeting the electrocardiographic criteria for use of thrombolytic therapy, but such elevation was usually due to the early repolarization variant. The initial total creatine kinase was elevated more than 3.3 mu kat/L (200 U/L) in 43% of patients, and an elevated total creatine kinase was recorded at some time during the hospital course in 47% of patients. The creatine kinase MB fraction was less than 0.02 in all patients. Myocardial infarction was ruled out in all patients. No patient experienced in-hospital cardiovascular complications.The quality of acute chest pain related to cocaine use is indistinguishable from that experienced in acute myocardial ischemia. Abnormal or normal variant electrocardiographic findings are common in patients with chest pain related to cocaine use, but nevertheless the incidence of acute myocardial infarction is low. The ST-segment and T-wave changes can mimic acute myocardial injury and are most likely normal findings in young black men that can be readily recognized in the emergency department. Most of these patients do not require admission to an intensive care unit.
Specificity of monoclonal antibody anti-T-6 for Langerhans' cells in normal human skin
Authors: L. DUBERTRET, O. PICARD, M. BAGOT, M. TULLIEZ, M. FOSSE, C. AUBERT, R. TOURAINE
Journal: British Journal of Dermatology (1982)

The monoclonal antibody OKT 6 reacts specifically with Langerhans' cells, but not with macrophages, in human skin.
Food "responsibility deal" has cost 6000 lives, professor tells meeting
Authors: N. Hawkes
Journal: BMJ (2015)

A “responsibility deal,” under which food manufacturers and retailers agree to sell healthier products if the government refrains from legislation, has achieved gains “worth celebrating,” a meeting in London heard on 3 February.

The deal has been criticised as being soft on the food industry and easily manipulated, but Susan Jebb, of the University of Oxford, who chairs the deal’s food network, put up a stout defence of its record at a Westminster Food and Nutrition Forum held at the Royal Aeronautical Society. “It’s a judgement call, but I personally don’t buy the case that it would have been better done by legislation,” she said. “That’s very difficult when you’re talking about product composition.”

Parliament …
Vitamin E dietary supplementation protects against carbon tetrachloride—induced chronic liver damage and cirrhosis
Authors: Maurizio Parola, Gabriella Leonarduzzi, Fiorella Biasi, Emanuele Albano, Maria E. Biocca, Giuseppe Poli, Mario U. Dianzani
Journal: Hepatology (1992)

ABSTRACT Previous studies have shown that α–tocopherol (vitamin E) pretreatment of experimental animals can protect against acute liver necrosis induced by carbon tetrachloride. In this study we investigated whether the increase of vitamin E liver content by dietary supplementation influences chronic liver damage and cirrhosis induced by carbon tetrachloride in the rat. Our data indicate that vitamin E supplementation did not interfere with the growth rate of the animals and increased about threefold the liver's content of the vitamin. Vitamin E supplementation significantly reduced oxidative liver damage, but it was not effective in protecting against development of fatty liver and did not interfere with metabolic activation of carbon tetrachloride. Moreover, vitamin E—fed animals showed incomplete but significant prevention of liver necrosis and cirrhosis induced by carbon tetrachloride. This has been shown by means of histological examination, analysis of serum parameters and biochemical evaluation of collagen content. These results show that an increased liver content of vitamin E can afford a significant degree of protection against carbon tetrachloride-induced chronic liver damage and cirrhosis. (HEPATOLOGY 1992;16:1014-1021)
Differential regulation of TGF-β–induced, ALK-5–mediated VEGF release by SMAD2/3 versus SMAD1/5/8 signaling in glioblastoma
Authors: Katharina Seystahl, Isabel Tritschler, Emese Szabo, Ghazaleh Tabatabai, Michael Weller
Journal: Neuro-Oncology (2014)

The transforming growth factor (TGF)-β and vascular endothelial growth factor (VEGF) pathways have a major role in the pathogenesis of glioblastoma, notably immunosuppression, migration, and angiogenesis, but their interactions have remained poorly understood. We characterized TGF-β pathway activity in 9 long-term glioma cell lines (LTCs) and 4 glioma-initiating cell lines (GICs) in relation to constitutive and exogenous TGF-β-induced VEGF release. Results were validated using The Cancer Genome Atlas transcriptomics data. Glioma cells exhibit heterogeneous patterns of constitutive TGF-β pathway activation reflected by phosphorylation not only of SMAD2 and SMAD3 but also of SMAD1/5/8. Constitutive TGF-β pathway activity depends on the type I TGF-β receptor, ALK-5, and accounts for up to 69% of constitutive VEGF release, which is positively regulated by SMAD2/3 and negatively regulated by SMAD1/5/8 signaling in a cell line-specific manner. Exogenous TGF-β induces VEGF release in most cell lines in a SMAD- and ALK-5–dependent manner. There is no correlation between the fold induction of VEGF secretion induced by TGF-β compared with hypoxia. The role of SMAD5 signaling is highly context and cell-line dependent with a VEGF inhibitory effect at low TGF-β and pSMAD2 levels and a stimulatory effect when TGF-β is abundant. TGF-β regulates VEGF release by glioma cells in an ALK-5–dependent manner involving SMAD2, SMAD3, and SMAD1/5/8 signaling. This crosstalk between the TGF-β and VEGF pathways may open up new avenues of biomarker-driven exploratory clinical trials focusing on the microenvironment in glioblastoma.