tbuckley/cabot-search huggingface dataset:
New Light on Biotin Deficiency
Authors: Kay Tanaka
Journal: New England Journal of Medicine (1981)

Biotin deficiency is an entity that was once virtually ignored in clinical medicine. It has recently been attracting renewed interest, primarily from pediatricians, because of the progress made in the study of inborn metabolic disorders. This interest is indicated in the articles by Thoene and Mock and their colleagues in this issue of the Journal. A review of the history of biotin research will demonstrate the importance of contributions from different scientific disciplines in elucidating unknown facets of metabolism. It will also reveal a fascinating sequence of events.In 1927 M. A. Boas-Fixsen observed that the feeding of raw . . .
Sustained Complete Remission of Metastatic Sweat Gland Carcinoma
Authors: Kathleen E. Briscoe
Journal: JAMA (1978)

CARCINOMAS of the eccrine sweat glands are rare tumors that, once metastatic, generally have a poor prognosis.<sup>1-7</sup>When primary surgery has failed to control the disease, radiotherapy has been of little additional benefit.<sup>6</sup>Insufficient data are available to permit an assessment of the effectiveness of systemic chemotherapy. Hyperthermic perfusion with chemotherapy<sup>8</sup>has been successfully employed as an aggressive means of treating other cancers of the extremities, which avoids the need for amputation. Using this technique, a sustained complete remission was induced in a patient with an eccrine porocarcinoma of the right foot with multiple metastases to the entire leg. There was complete rehabilitation. <h3>Report of a Case</h3> A small sore between the right fourth and fifth toes developed in a 60-year-old man. It was treated with a variety of topical medications and allowed by the patient to grow, during a two-year period, into a large fungating mass.
EFFERENT FIBRES IN THE ILIO-INGUINAL NERVE AND THEIR RELATION TO INCISION FOR APPENDICECTOMY
Authors: H. J. Wade
Journal: BMJ (1933)

r THE BRITISR 561 would be 44,080.9This result encourages us to believe that the SbCl3 test is trustworthy for assaying the vitamin A value of halibut-liver oils of high potency.We are inclined to believe that solvent extracted oils, of which some are on the market, should be examined by applying the test to the unsaponifiable fractions.It is a curious fact that, although the liver of the
Evaluation du risque de pancréatite aiguë après entéroscopie double ballon: Résultats du suivi clinique et biologique de 30 patients consécutifs
Authors: M Frederic, M Delvaux, I Fassler, G Gay
Journal: Endoscopy (2008)

Introduction: L'entéroscopie double ballon (EDB) s'est développée récemment pour l'exploration endoscopique de l'intestin grêle. Quelques cas isolés de pancréatite aiguë (PA) ont été décrits au décours d'EDB par voie orale. Le but de cette étude était d'évaluer de manière prospective les signes cliniques et biologiques de PA chez des patients explorés par EDB voie orale et voie rectale, afin de préciser le risque de PA lié à cet examen.
Uridine supplementation antagonizes zalcitabine-induced microvesicular steatohepatitis in mice
Authors: Dirk Lebrecht, Yetlanezi A. Vargas-Infante, Bernhard Setzer, Janbernd Kirschner, Ulrich A. Walker
Journal: Hepatology (2006)

Zalcitabine is an antiretroviral nucleoside analogue that exhibits long-term toxicity to hepatocytes by interfering with the replication of mitochondrial DNA (mtDNA). Uridine antagonizes this effect in vitro. In the present study we investigate the mechanisms of zalcitabine-induced hepatotoxicity in mice and explore therapeutic outcomes with oral uridine supplementation. BalbC mice (7 weeks of age, 9 mice in each group) were fed 0.36 mg/kg/d of zalcitabine (corresponding to human dosing adapted for body surface), or 13 mg/kg/d of zalcitabine. Both zalcitabine groups were treated with or without Mitocnol (0.34 g/kg/d), a dietary supplement with high bioavailability of uridine. Liver histology and mitochondrial functions were assessed after 15 weeks. One mouse exposed to high dose zalcitabine died at 19 weeks of age. Zalcitabine induced a dose dependent microvesicular steatohepatitis with abundant mitochondria. The organelles were enlarged and contained disrupted cristae. Terminal transferase dUTP nick end labeling (TUNEL) assays showed frequent hepatocyte apoptosis. mtDNA was depleted in liver tissue, cytochrome c-oxidase but not succinate dehydrogenase activities were decreased, superoxide and malondialdehyde were elevated. The expression of COX I, an mtDNA-encoded respiratory chain subunit was reduced, whereas COX IV, a nucleus-encoded subunit was preserved. Uridine supplementation normalized or attenuated all toxic abnormalities in both zalcitabine groups, but had no effects when given without zalcitabine. Uridine supplementation was without apparent side effects. Conclusion: Zalcitabine induces mtDNA-depletion in murine liver with consequent respiratory chain dysfunction, up-regulated synthesis of reactive oxygen species and microvesicular steatohepatitis. Uridine supplementation attenuates this mitochondrial hepatotoxicity without apparent intrinsic effects. (HEPATOLOGY 2007;45:72–79.)
Foundation year doctors lack surgical experience
Authors: J. S. Bowness, B. Clift
Journal: BMJ (2011)

Junior doctors’ training is always changing: from large scale changes, such as training and applications for specialties, to smaller ones, such as approval for study leave and taster opportunities. Developments such as the European Working Time Directive, restructuring of junior doctors’ training, and the increasing strain on NHS budgets mean that pressures of time and money are increasingly taking their toll on all aspects of medical training. As these burdens filter down through the NHS it seems that the training element in foundation posts is also coming under increasing pressure, with service provision ever increasing as a proportion of foundation trainees’ work.

An example is the reduction in time spent in theatre in doctors’ first years of experience. Older doctors often say, “By your stage I could do . . .” For example, a decade ago …
Retinoic acid inhibits the regulated expression of vascular cell adhesion molecule-1 by cultured dermal microvascular endothelial cells.
Authors: J Gille, L L Paxton, T J Lawley, S W Caughman, R A Swerlick
Journal: Journal of Clinical Investigation (1997)

The regulated expression of cell adhesion molecules (CAM) on endothelial cells is central to the pathogenesis of various inflammatory processes. Retinoic acid and synthetic derivatives have been demonstrated to exert antiinflammatory effects in cutaneous diseases. To determine modes of retinoid action in the modulation of inflammatory responses, we explored effects of all-trans-retinoic acid (t-RA) on the TNFalpha-induced expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin in cultured human dermal microvascular endothelial cells. Pretreatment with t-RA specifically prevented TNFalpha-induced VCAM-1 expression, but not ICAM-1 and E-selectin induction. t-RA significantly reduced VCAM-1-dependent T cell binding to TNFalpha-treated human dermal microvascular endothelial cells as well. This differential modulation of TNFalpha-induced CAM expression by t-RA was reflected at steady state mRNA levels and in nuclear run-on studies. In transcriptional activation studies, the TNFalpha-mediated activation of the human VCAM-1 promoter was inhibited after t-RA treatment, while the ICAM-1 promoter activation was unaffected, indicating that the selective inhibition of CAM expression is regulated in part at the level of gene transcription. Furthermore, the transcriptional inhibition by t-RA appears to be mediated by its effects upon the activation of NF-kappaB-dependent complex formation. Analysis of protein-DNA binding assays revealed marked inhibition of specific NF-kappaB-dependent binding to the tandem NF-KB sites of the VCAM-1 promoter, but not to the functional NF-kappaB motif of the ICAM-1 promoter. The specific inhibition of cytokine-mediated VCAM-1 gene expression in vitro may provide a potential basis by which retinoids exert their biological effects at sites of inflammation in vivo.
Patient Symptomatology in Anal Dysplasia
Authors: Caitlin W. Hicks, Elizabeth C. Wick, Ira L. Leeds, Jonathan E. Efron, Susan L. Gearhart, Bashar Safar, Sandy H. Fang
Journal: JAMA Surgery (2015)

High-resolution anoscopy (HRA) is becoming increasingly advocated as a method of screening for anal dysplasia in high-risk patients.To describe, through HRA findings, the association between patient symptomatology and anal dysplasia among patients at high risk for anal dysplasia.Univariable and multivariable analyses were conducted of data from a prospectively maintained HRA database on all patients undergoing HRA with biopsy from November 1, 2011, to March 13, 2014, at a tertiary care HRA clinic. Data included demographics, medical history and comorbidities, HIV status and related measures (CD4 cell counts, HIV viral load, and use of highly active antiretroviral therapy), sexual orientation (when available), patient symptoms at initial presentation, physical examination findings, anal Papanicolaou (Pap) smear findings.High-resolution anoscopy diagnosis of high- vs low-grade dysplasia or no dysplasia.One hundred sixty-one HRA biopsy specimens (mean [SEM], 1.77 [0.11] biopsy specimens per patient) were obtained from 91 patients (mean [SEM] age, 45.7 [1.2] years; 61 men [67%]; 47 black patients [52%]; and 70 human immunodeficiency virus-positive patients [77%]). Twenty-seven patients (30%) had high-grade dysplasia, 26 had low-grade dysplasia (29%), and 38 had no dysplasia (42%). The majority of patients (63 [69%]) were asymptomatic (anal pain, 11 [12%]; bleeding, 14 [15%]; and pruritus, 10 [11%]). Forty-one patients (45%) presented with anal pain (odds ratio, 5.25; 95% CI, 1.44-21.82; P = .02), and patients with either high- or low-grade dysplasia were more likely to present with anal lesions on physical examination compared with patients without dysplasia (odds ratio, 4.34; 95% CI, 1.78-11.20; P = .002). Multivariable analysis suggested that anal pain was independently associated with high-grade dysplasia (odds ratio, 6.42; 95% CI, 1.18-43.3; P = .03).Anal dysplasia is a silent disease that is frequently asymptomatic. However, patients with anal pain, anal lesions, and other high-risk factors are at increased risk of having high-grade anal dysplasia. These patients may benefit from routine screening with HRA.
Do Adult Squirrels Castrate Each Other?
Authors: Eugene S. Talbot
Journal: JAMA (1898)

Chicago, Jan. 25, 1897. <h3>To the Editor:</h3> —I have read with much interest Dr. Edmund Andrews' article on "The Oriental Eunuchs," in theJournal, Jan. 22, 1898, wherein speaking of the castration of animals and says anent squirrels: "Naturalists state that the black or gray male squirrels in fighting seek to castrate each other with their teeth, so that many of those taken by hunters are thus mutilated. As they do it only in adult life it does not materially change their general development." Commenting upon this, later, in a letter to the Journal dated Jan. 25, 1898, he quotes the observations of Dr. A. S. Allen. Being somewhat of squirrel-hunter myself I wish to confirm the report of Dr. Allen. I should say that fully one-half the male squirrels I have noticed were castrated. This is always done in early life, not merely in the nest as described by
Significant improvement of portopulmonary hypertension after 1-week terlipressin treatment
Authors: Georgios Kalambokis, Panagiotis Korantzopoulos, Spyros A. Nikas, Areti Theodorou, Epameinondas V. Tsianos
Journal: Journal of Hepatology (2008)

Cirrhosis associated with moderate and severe portopulmonary hypertension carries a poor prognosis. Optimal management has not yet been defined. Current treatment options, such as prostacyclin analogues, endothelin antagonists, and phosphodiesterase-5 inhibitors, are characterized by slow onset of action and various adverse effects, particularly in patients with advanced cirrhosis. Here, we report the significant reduction of pulmonary arterial pressure after 1-week terlipressin treatment in a patient with concomitant hepato-renal syndrome. Terlipressin could be a novel and safe treatment for portopulmonary hypertension.
Treatment of Recurrent Herpes Simplex
Authors: D. C. Hutfield
Journal: BMJ (1964)

those listed which give considerable force to the belief that this substance is a most useful therapeutic agent in the treatment of the iso- lated attack, both in the eye and on the skin.It would be a pity if your readers were led to the supposition that this substance should not at least be tried when dealing with such lesions.I would like to point out how important it is that the correct regimen is adhered to.In many cases my colleagues have approached me about the apparent ineffectiveness of the drug.On inquiry it has appeared that their notions of both the indications and administration have been somewhat astray.It should further be borne in mind that it is essential that treatment begin at the very earliest stage of the disease.It is hardly rational to expect much effect from any antiviral agent when the full tissue picture has developed.One might per- haps except the cornea and its own rather individual circumstances.-Iam, etc., Brighton.
DOES ALCOHOL CONSERVE TISSUE?An Essay Presented to the Committee on Dietetics at the Forty-first Annual Meeting of the American Medical Association, May, 1890.
Authors: ELISHA CHENERY
Journal: JAMA (1890)

Does alcohol conserve the bodily tissues in the sense of saving them alive, thus staying physiological decay? Or does it simply check the elimination of what dies and ought to go off? If the former, it is one of the marvelous boons to humanity; if the latter only, it is the worst substance which enters the alimentary canal; for, while other substances, in common with it, affect the nervous system, none other, like it, retards elimination and heaps up effete matters within. But before studying this question, let us glance at the recent advances concerning the food value of this agent. For what purpose do we eat and drink? First, for the development and repair of the bodily organism; and second, for the production of force—just the same as we put water and fuel into an engine. The idea of spirituality must here be excluded, whatever our religious notions may
Comparison of BMI and Physical Activity Between Old Order Amish Children and Non-Amish Children
Authors: Kristen G. Hairston, Julie L. Ducharme, Margarita S. Treuth, Wen-Chi Hsueh, Ania M. Jastreboff, Kathy A. Ryan, Xiaolian Shi, Braxton D. Mitchell, Alan R. Shuldiner, Soren Snitker
Journal: Diabetes Care (2012)

OBJECTIVE The Old Order Amish (OOA) is a conservative Christian sect of European origin living in Pennsylvania. Diabetes is rare in adult OOA despite a mean BMI rivaling that in the general U.S. non-Hispanic white population. The current study examines childhood factors that may contribute to the low prevalence of diabetes in the OOA by comparing OOA children aged 8–19 years with National Health and Nutrition Examination Survey (NHANES) data and children from Maryland’s Eastern Shore (ES), a nearby, non-Amish, rural community. We hypothesized that pediatric overweight is less common in OOA children, that physical activity (PA) and BMI are inversely correlated, and that OOA children are more physically active than ES children. RESEARCH DESIGN AND METHODS We obtained anthropometric data in 270 OOA children and 229 ES children (166 non-Hispanic white, 60 non-Hispanic black, 3 Hispanic). PA was measured by hip-worn accelerometers in all ES children and in 198 OOA children. Instrumentation in 43 OOA children was identical to ES children. RESULTS OOA children were approximately 3.3 times less likely than non-Hispanic white ES children and NHANES estimates to be overweight (BMI ≥85th percentile, Centers for Disease Control and Prevention). Time spent in moderate/vigorous PA (MVPA) was inversely correlated to BMI z-score (r = −0.24, P = 0.0006). PA levels did not differ by ethnicity within the ES group, but OOA children spent an additional 34 min/day in light activity (442 ± 56 vs. 408 ± 75, P = 0.005) and, impressively, an additional 53 min/day in MVPA (106 ± 54 vs. 53 ± 32, P &amp;lt; 0.0001) compared with ES children. In both groups, boys were more active than girls but OOA girls were easily more active than ES boys. CONCLUSIONS We confirmed all three hypotheses. Together with our previous data, the study implies that the OOA tend to gain their excess weight relatively late in life and that OOA children are very physically active, both of which may provide some long-term protection against diabetes.
ELEVEN YEARS' WORK IN A PUBLIC SCHOOL DENTAL CLINIC
Authors: T. C. Stretton, G. E. Friend
Journal: BMJ (1934)

An account of a public school dental clinic carried on under uniform conditions during the eleven years from 1923 to 1933 inclusive may be of practical interest.The school in question, Christ's Hospital, Horsham, has an average boy population of over 800, the yearly turnover being about 150.The boys are under regular dental supervision, the dental surgeon attending one day a week during term time, and where after-care is necessary it is
Abstract 2608: An intronic polymorphism determines TGF-alpha expression and is associated with cellular resistance to erlotinib
Authors: Liu Wanqing, Mark J. Ratain
Journal: Cancer Research (2010)

Abstract An intronic polymorphism determines TGF-alpha expression and is associated with cellular resistance to erlotinib Wanqing Liu, Mark J Ratain Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA. Background Responsiveness to EGFR-targeting agents has been demonstrated in lung cancer patients bearing EGFR mutations. However, the detailed mechanism underlying both sensitivity and resistance to these agents has not been completely revealed. Expression of transforming growth factor alpha (TGFA), one of the major EGFR ligands, appears to affect the inhibition potency of EGFR inhibitors. The aim of this study is to identify the genetic variants that may affect TGFA expression and confer susceptibility to response to EGFR-targeting agents. Methods Genome-wide genotyping of 100K single nucleotide polymorphisms (SNPs) had been previously performed in the NCI-60 cancer cell panel. SNPs in the TGFA gene region were selected to perform correlations with TGFA mRNA expression measured by real-time PCR. Confirmation of the SNP genotypes was performed by both sequencing and restriction enzyme digestion. The SNP genotype was correlated with cytotoxicity data of erlotinib and other EGFR inhibitors. Results A total of 10 SNPs in the TGFA gene were genotyped on the 100K SNP Chip. The genotypes were confirmed. A SNP (rs3821262 C/T) in the second intron of TGFA was significantly associated with decreased TGFA gene expression and cellular resistance to both erlotinib (p=0.01) and other 11 EGFR inhibitors (p=0.05) tested in the NCI-60. Conclusion The SNP rs3821262 C/T may contribute to cellular resistance to EGFR inhibitors by modulating the gene expression. However, since this is a hypothesis-generating study and the association was not adjusted for multiple testing, the finding must be validated further in both preclinical and clinical settings, in particular combined with mechanistic studies. 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 2608.
View from the research and development office
Authors: Tony Soteriou
Journal: BMJ (2004)

English NHS trusts are obliged to implement research governance for all NHS health and social care research.1 The NHS trust that I work for, which funded the research highlighted by Jones and Bamford,2 sees research as integral to providing high quality health and social care services, and research governance is paramount to our research strategy.

Research involving NHS patients or service users should be reviewed by the NHS research ethics committee and be of appropriate scientific quality. If a research protocol changes, then it needs to be reassessed for the new methods and research ethics. Research not meeting these ethical and quality standards can represent a potential risk to patients, researchers, and wider NHS research, as shown by the Alder Hey and other inquiries.3–5 Trusts therefore need to implement training for researchers, together with governance …
Basic Fibroblast Growth Factor Restores Endothelium-Dependent Responses After Balloon Injury of Rabbit Arteries
Authors: Thibaud Meurice, Christophe Bauters, Jean-Luc Auffray, Benoı̂t Vallet, Martial Hamon, Franck Valero, Eric Van Belle, Jean-Marc Lablanche, Michel E. Bertrand
Journal: Circulation (1996)

Background After experimental angioplasty, partial or complete reendothelialization of the denuded surface occurs; the function of the regenerated endothelium has, however, been shown to be abnormal. Basic fibroblast growth factor (bFGF) is mitogenic for endothelial cells in vitro and in vivo. We investigated whether chronic administration of bFGF in a rabbit model of balloon denudation might not only improve endothelial regrowth but also restore normal physiological responses to endothelium-dependent agonists. Methods and Results Thirty-nine New Zealand White rabbits underwent balloon denudation of the right iliac artery. Twenty rabbits received intravenous administration of bFGF (2.5 μg twice a week for 2 weeks). Nineteen rabbits receiving saline injections served as controls. Animals were killed on day 28 for assessment of reendothelialization and neointimal thickening and for analysis of in vitro vasoreactivity. Animals in the bFGF group had a significantly ( P &lt;.005) greater degree of reendothelialization than controls (115±13 versus 55±6 mm 2 ). Neointimal thickening was similar in the two groups. Four weeks after denudation, endothelium-independent responses did not differ significantly between the two groups. In contrast, the maximal endothelium-dependent acetylcholine-induced relaxation of the bFGF-treated animals (E max , 40±7%) was significantly greater than that of the control group (E max , 11±9%; P &lt;.05). Conclusions Systemic administration of bFGF restores, in large part, the responses of previously denuded arterial segments to endothelium-dependent vasodilators. Angiogenic growth factors may help to reestablish normal endothelial cell function in patients who have undergone angioplasty.