tbuckley/cabot-search huggingface dataset:
Mutation of the fumarase gene in two siblings with progressive encephalopathy and fumarase deficiency.
Authors: T Bourgeron, D Chretien, J Poggi-Bach, S Doonan, D Rabier, P Letouzé, A Munnich, A Rötig, P Landrieu, P Rustin
Journal: Journal of Clinical Investigation (1994)

We report an inborn error of the tricarboxylic acid cycle, fumarase deficiency, in two siblings born to first cousin parents. They presented with progressive encephalopathy, dystonia, leucopenia, and neutropenia. Elevation of lactate in the cerebrospinal fluid and high fumarate excretion in the urine led us to investigate the activities of the respiratory chain and of the Krebs cycle, and to finally identify fumarase deficiency in these two children. The deficiency was profound and present in all tissues investigated, affecting the cytosolic and the mitochondrial fumarase isoenzymes to the same degree. Analysis of fumarase cDNA demonstrated that both patients were homozygous for a missense mutation, a G-955-->C transversion, predicting a Glu-319-->Gln substitution. This substitution occurred in a highly conserved region of the fumarase cDNA. Both parents exhibited half the expected fumarase activity in their lymphocytes and were found to be heterozygous for this substitution. The present study is to our knowledge the first molecular characterization of tricarboxylic acid deficiency, a rare inherited inborn error of metabolism in childhood.
SHO training: Teachers frustrated
Authors: J. Heyworth
Journal: BMJ (1993)

We hope that this extension ofour assessment of the senior house officers in our department proves to be both useful and acceptable to them.The main drawback to this form of assessment is that it is labour intensive, requiring the synchronous participation of both the junior and senior doctors of the department.This programme of assessment is being extended to include other hospitals in our region.Towards the end of this year we hope to report our experiences after assessing the training of further groups of senior house officers working in our department.
DHEA treatment of pulmonary hypertension: New insights into a complex mechanism
Authors: E DUBUIS
Journal: Cardiovascular Research (2007)

See article by Oka et al. [5] (pages 377–387) in this issue . 

Pulmonary arterial hypertension (PAHT) is an implacable killer. Patients developing PAHT present a survival rate of 40% after 36 months [1]. This deadly pathology remains actually an orphan in terms of long-term treatment and affects more than 100,000 patients in the United States and Europe, with an annual incidence estimated at 2 new cases for primary PAHT and 8 new cases for secondary PAHT per million individuals per year.

Pulmonary hypertension is classified into two main categories. The causes of primary PAHT remain largely unknown, but new studies have identified a gene located on chromosome 2 coding for bone morphogenetic protein receptor I (BMPR2), which belongs to the transforming growth factor β type-II receptor family, and inhibits cell growth. A mutation responsible for 6% of primary PAHT induces an abnormal response of the vascular endothelium to injury, leading to cancerous-like proliferation of endothelial cells [2].

Secondary PAHT has many causes that may vary from a prophylaxis reaction [3] to potassium current alterations like the decrease of Kv1.5 subunit expression in smooth muscle cells (SMC) induced by consumption of anorectic agents. … 

dubuis_e{at}yahoo.fr
Management of Gunshot Wounds
Authors: Judith E. Tintinalli
Journal: JAMA (1988)

Dr Ordog, an emergency physician at the Martin Luther King Hospital and assistant professor of emergency medicine at the Charles R. Drew/UCLA School of Medicine, certainly has the clinical and academic credentials to write a work of this nature. Dr Ordog has had published a number of reviews and clinical studies on ballistics and gunshot injuries. This text is a comprehensive review of missile injuries, including patterns of injuries in children, pregnant women, and the elderly; clinical management of injuries to major organ systems; wound ballistics and forensics; and socioeconomic effects of gunshot wounds. Although an attempt has been made to include "something for everyone," with chapters on prehospital care and nursing care, the book's primary audience will be made up of emergency physicians and surgeons (residents and practitioners). Only minor details have been left out. For example, the chapter on "Outpatient Management of Gunshot Wounds" does not mention the
Role of nitric oxide in restenosis after experimental balloon angioplasty in the hypercholesterolemic rabbit: effects on neointimal hyperplasia and vascular remodeling
Authors: Thierry Le Tourneau, Eric Van Belle, Delphine Corseaux, Benoı̂t Vallet, Gilles Lebuffe, Bernard Dupuis, Jean-Marc Lablanche, Eugène McFadden, Christophe Bauters, Michel E Bertrand
Journal: Journal of the American College of Cardiology (1999)
Knowledge of language and phrasal vocabulary acquisition
Authors: Koenraad Kuiper
Journal: Behavioral and Brain Sciences (2006)

Locke &amp; Bogin's (L&amp;B's) main thesis can be extended to the acquisition of the phrasal vocabulary in that the acquisition of much phrasal vocabulary combines the acquisition of linguistic knowledge with pragmatics and performance and in that the apprenticeship system for such learning begins to flower in adolescence.
Effects of Racemic Epinephrine Inhalation on Cardiopulmonary Function in Normal Man and in Patients with Chronic Pulmonary Emphysema
Authors: JAMES K. ALEXANDER, JUNICHI MISE, EDWARD W. DENNIS, ROBERT L. HERSHBERGER
Journal: Circulation (1958)

Epinephrine inhalation is now widely used to provide bronchodilator therapy for patients with chronic obstructive pulmonary emphysema. In this study a variety of cardiorespiratory effects following epinephrine inhalation have been examined to compare responses in normal and emphysematous subjects, and to evaluate possible differences between inhalational and parenteral usage of the drug. Since previous studies on the effects of epinephrine in emphysematous patients have been largely concerned with the respiratory apparatus, particular attention here has been directed toward the pulmonary circulation.
Local Ablation for Hepatocellular Carcinoma in Taiwan
Authors: Shi-Ming Lin
Journal: Liver Cancer (2013)

Hepatocellular carcinoma (HCC) is the second commonest cancer in Taiwan. The national surveillance program can detect HCC in its early stages, and various curative modalities (including surgical resection, orthotopic liver transplantation, and local ablation) are employed for the treatment of small HCC. Local ablation therapies are currently advocated for early-stage HCC that is unresectable because of co-morbidities, the need to preserve liver function, or refusal of resection. Among the various local ablation therapies, the most commonly used modalities include percutaneous ethanol injection and radiofrequency ablation (RFA); percutaneous acetic acid injection and microwave ablation are used less often. RFA is more commonly employed than other local ablative modalities in Taiwan because the technique is highly effective, minimally invasive, and requires fewer sessions. RFA is therefore advocated in Taiwan as the first-line curative therapy for unresectable HCC or even for resectable HCC. However, current RFA procedures are less effective against tumors that are in high-risk or difficult-to-ablate locations, are poorly visualized on ultrasonography (US), or are large. Recent advancements in RFA in Taiwan can resolve these issues by the creation of artificial ascites or pleural effusion, application of real-time virtual US assistance, use of combination therapy before RFA, or use of switching RF controllers with multiple electrodes. This review article provides updates on the clinical outcomes and advances in local ablative modalities (mostly RFA) for HCC in Taiwan.
The second gasoline war and how we can prevent the third
Authors: I. Roberts
Journal: BMJ (2003)

Synthetic materials displaying multi-modal ligands with exact chemiophysical properties for immune modulation are valuable research tools and a promising therapeutic platform. However, precise chemical conjugation of multiple proteins on biomaterial surfaces is challenging. Through DNA hybridization-mediated biomolecule loading, we achieved high density and precise ratiometric control of multiple ligands on nano-/micro-particles. We found increasing ratios of anti-CD3 to anti-CD28, 1:5, 1:3, 1:1, 3:1 to 5:1, on microparticles yielded a linear increase of <i>ex vivo</i> expansion of primary human CD4<sup>+</sup> and CD8<sup>+</sup> T cells until reaching a plateau at 3:1 ratio. For CD8<sup>+</sup> T cells, the ratio of 3:1 resulted in the highest percentage of central memory cells, 51.4 ± 7.2% vs. 14.4 ± 7.6% for 1:5 ratio (n = 5 donors). Particle surface presentation of IL-2 using an anti-IL-2 antibody (<i>in trans</i> to CD3/28 particles) yielded ~3 fold more <i>ex vivo</i> expansion of CD4<sup>+</sup> and CD8<sup>+</sup> T cells in 14 days when compared to the equivalent dose of soluble IL-2. Using intratumoral injection of microparticles presenting a ligand for a synthetic Notch receptor, we locally induced chimeric antigen receptor (CAR) expression on systemically infused engineered T cells and observed CAR T cell killing of the injected tumors, while sparing the uninjected identical tumors in the contralateral flank. These results highlight the potential of this platform in achieving better control of therapeutic cell manufacture and local tuning of immunotherapies. Ongoing work is using DNA origami-mediated patterning to dissect spatial requirements of various T cell activating ligands to better understand critical parameters of T cell activation with the goal to improve the design of immunotherapies.
Infiltration of intratumoral T cells and regulatory T cells are associated with p53 expression and ER status in early breast cancer: a Korean breast cancer study.
Authors: K Park, A Kim, O Woo, W Ryu, S Yoon, H Suh, I Choi, J Suh, Y Kim, J Kim, B Koo
Journal: Cancer Research (2009)

Abstract Abstract #5049 Background: Immune responses, such as rich lymphocyte infiltrate, have shown associated with improved clinical outcomes in patients with breast cancer. Recently, number of tumor-infiltrating regulatory T cell has been identified as a poor prognostic marker. There is, however, not enough data evaluating the associations between the clinicopathologic factors and quantity or quality of TILs in Asian breast cancer patients.&amp;#x2028; Material and methods: CD4-, CD8-, and Foxp3-positive tumor-infiltrating lymphocytes (TILs) were detected by immunohistochemistry using the paraffin-embedded samples from the 40 patients with early stage (I-III) breast cancer. Expression status of ER, PR, HER-2, p53, and Ki-67 were also evaluated by immunohistochemistry. Clinical data, such as pathologic stage, patient's age, were available for statistical analysis.&amp;#x2028; Results: Statistically significant correlation between ER expression and CD8/CD4 ratio of the TILs (Spearman r=0.447, p=0.024) was observed. Other clinicopathlogical factors, such as PR, tumor size, nodal metastasis, tumor grade, did not show significant correlation with ratio of the TILs. Additionally, tumors with more dense accumulation of p53 protein were associated with recruitment of higher number of Foxp3-positive regulatory T cells (Spearman r=0.52, p=0.0002). Ki-67, a proliferation index of the tumor cells, was also statistically significantly associated with infiltration of regulatory T cells (Spearman r=0.46, p=0.019).&amp;#x2028; Discussion: Our data showed that ER-positive tumors had higher ratio of CD8/CD4 TILs, which is opposite result from the previous studies. In addition, p53 overexpression and high proliferation index of the breast cancer were associated with high regulatory T cell infiltration, but not with total TIL. The role of the p53 overexpression of the tumor cells in determining immune balance and its prognostic implication will be evaluated in the future study. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5049.
Managing chronic disease
Authors: R. M Davis, E. H Wagner, T. Groves
Journal: BMJ (1999)

<b>Objective.</b> To validate the Jefferson Scale of Empathy-Health Profession Students version (JSE-HPS) in pharmacy students. <b>Methods.</b> The JSE-HPS (20 items), adapted from the original Jefferson Scale of Empathy for use among students in the healthcare professions, was completed by 187 first-year pharmacy students at Midwestern University Chicago College of Pharmacy. <b>Results.</b> Two factors, “perspective-taking” and “compassionate care,” emerged from factor analysis in this study, accounting for 31% and 8% of the variance, respectively. These factors are similar to the prominent ones reported in previous research involving physicians and medical students, supporting the construct validity of this instrument for pharmacy students. In the current study, mean JSE-HPS score was comparable to those reported for medical students, and consistent with previous findings with medical students and physicians. Women scored significantly higher than men. <b>Conclusions.</b> Findings support the construct validity and reliability of the JSE-HPS for measuring empathy in pharmacy students.
Guy Nicholson Constable
Authors: J. N Constable
Journal: BMJ (2002)

Former professor of anatomy and principal Christian Medical College, Ludhiana, India, and director of public health Bolton (b 1924; q Trinity College Dublin 1948; MA, MD, FFCMI), d 9 November 2001.

He and his wife Joan went to India as medical missionaries in 1954 to the Christian Medical College and Hospital in Ludhiana, where he became professor of anatomy in 1958 and principal in 1962. In 1971 he returned to England for family reasons and retrained in community medicine. He held consultant posts in Bury (1974-76), Ipswich (1976-81), and Bolton (1981-91) as director of public health.
Ethical problems with paying patients to improve adherence to treatment
Authors: G. Szmukler
Journal: BMJ (2013)

To offer patients financial incentives for taking antipsychotic drugs presents serious ethical problems,1 the most important of which can be termed “incommensurable values”2 or “commodification.”3

A stark example of commodification would be selling a baby. Such a transaction involves an exchange between “goods” lying in different spheres of valuation, one high and one low. Aligning …
Distinct sites of production and deposition of the putative cell death marker clusterin in the human thymus.
Authors: L E French, A P Sappino, J Tschopp, J A Schifferli
Journal: Journal of Clinical Investigation (1992)

Clusterin is a multifunctional protein endowed with cell-aggregating, complement-inhibitory, and lipid-binding properties. Since several studies have demonstrated highly increased clusterin gene expression in epithelial and nervous tissues regressing as a consequence of tissue involution and apoptotic cell death, clusterin is also considered as a specific marker of dying cells. To determine whether clusterin expression is also upregulated during thymocyte death occurring during the negative selection process we analyzed the cellular distribution of clusterin mRNA and protein by in situ hybridization and immunocytochemistry in the human thymus. We observed that the expression of clusterin mRNA was confined to cells present in the thymic medulla, concentrated mainly around Hassal's bodies. Immunostaining of adjacent sections with antikeratin Ab revealed that cells containing clusterin mRNA were predominantly epithelial. By contrast no clusterin mRNA was found in thymocytes by in situ hybridization and Northern blot analysis of total RNA from purified thymocyte populations. Clusterin protein colocalized with the membrane attack complex of complement and vitronectin in the center of the largest Hassal's bodies, but was not detectable by immunocytochemistry in or at the surface of epithelial cells. Our results demonstrate that clusterin gene expression does not take place in apoptotic thymocytes, and therefore that clusterin synthesis by the dying cell is probably not a prerequisite to its death. However, synthesis of clusterin by medullary epithelial cells may be related to their terminal differentiation, and, furthermore, its presence in Hassal's bodies raises the possibility that the secreted protein is involved in the disposal of cell debris resulting from thymocyte apoptosis.
43 Increases in RANTES mRNA and protein in the nasal mucosa and nasal secretions in hay fever patients after allergen challenge
Authors: K RAJAKULASINGAM, Q HAMIDMID, F OBRIEN, E SCHOTMAN, P JOSE, T WILLIAMS, M JACOBSON, J BARKANS, S DURHAM
Journal: Journal of Allergy and Clinical Immunology (1996)
Health Maintenance Organizations
Authors: Joseph L. Marcarelli
Journal: JAMA (1976)

A RETIRED regular Army colonel was asked how he liked civilian life. "I don't know," he said. "All these people running around, and nobody's in charge." Obviously, the colonel, used to doing things the Army way for 30 years, was finding it tough to understand and adapt to a different way of life. And so it is with health maintenance organizations (HMOs). Much is being written, laws have been passed, HMOs are springing up all over, and yet the public, and indeed many physicians and allied professionals, are in large measure uninformed and confused as to what HMOs are all about. This explains, at least in part, the difficulty some HMOs are experiencing in marketing and the resistance of segments of the medical profession in accepting and supporting them. <h3>A Definition</h3> Health maintenance organization, a brief and catchy phrase, proposes a profound change in our health care provision system. Note!
Ileo-ileal Intussusception Due to Meckel's Diverticulum and Complicated by Volvulus
Authors: R. E. B. Tagart
Journal: BMJ (1953)

are chosen by the current machinery of selection to meet the national need for leadership in industry; after obtaining a university degree they not unnaturally prefer a niche with academic freedom to the more strenuous daily demands of industrial life.Somatotype estimates of Oxford undergraduates were made while I was physician in charge of a pilot student health service at the Institute of Social Medicine, Oxford.Measurements on Birmingham students were made by kind permission of the senior university medical officer, Dr. R. H.
Validity of Lung Cancer Mortality Data
Authors: Milton B. Rosenblatt
Journal: JAMA (1967)

<h3>To the Editor:—</h3> The concern about the accuracy of lung cancer mortality statistics evinced by Dr. Skinner (<b>198</b>:1374, 1966) is shared by other observers. Autopsy follow-up of cases clinically diagnosed as bronchogenic carcinoma has often revealed the pulmonary lesion to be secondary to carcinoma of the pancreas, breast, stomach, colon, prostate, kidney, or adrenal gland. With approximately 300,000 deaths from cancer annually, the potentiality for mistaken diagnoses is considerable. When an erroneous diagnosis of bronchogenic carcinoma is corrected at autopsy, there are no procedures readily available for the amending of death certificates, nor is modification encouraged by local or national authorities. By the time the pathologic examination has been completed, the case has long been classified as primary lung cancer in official vital statistic bureaus and tumor registries. There is an even greater reservoir for inaccuracy in lung cancer data in the vast majority of cases certified without autopsy
Effects of free fatty acid availability, glucagon excess, and insulin deficiency on ketone body production in postabsorptive man.
Authors: J M Miles, M W Haymond, S L Nissen, J E Gerich
Journal: Journal of Clinical Investigation (1983)

The present studies were undertaken to assess the relative effects of free fatty acid (FFA) availability, glucagon excess, and insulin deficiency on ketone body (KB) production in man. To determine whether an increase in FFA availability would augment KB production in the absence of insulin deficiency and glucagon excess, plasma insulin and glucagon were maintained at basal concentrations by infusion of somatostatin and exogenous insulin and glucagon, and plasma FFA were increased from 0.32 +/- 0.06 to 1.4 +/- 0.1 mM by a 2.5-h-infusion of a triglyceride emulsion plus heparin. KB production increased fivefold from 2.2 +/- 0.4 to 11.4 +/- 1.2 mumol . kg-1 . min-1, P less than 0.001. To determine whether insulin deficiency would further augment KB production, analogous experiments were performed but the replacement infusion of insulin was stopped. Despite a greater increase in plasma FFA (from 0.26 +/- 0.04 to 1.95 +/- 0.3 mM), KB production increased (from 1.5 +/- 0.3 to 11.1 +/- 1.8 mumol . kg-1 . min-1) to the same extent as in the absence of insulin deficiency. To determine whether hyperglucagonemia would augment KB production beyond that accompanying an increase in plasma FFA and, if so, whether this required insulin deficiency, similar experiments were performed in which the glucagon infusion rate was increased to produce plasma glucagon concentrations of 450-550 pg/ml with and without maintenance of the basal insulin infusion. When basal plasma insulin concentrations were maintained, hyperglucagonemia did not further increase KB production; however, when the basal insulin infusion was discontinued, hyperglucagonemia increased KB production significantly, whereas no change was observed in saline control experiments. These studies indicate that, in man, FFA availability is a major determinant of rates of KB production; insulin does not appear to influence ketogenesis rates by a direct hepatic effect, and glucagon can further augment KB production when FFA concentrations are increased but only in the setting of insulin deficiency.
Rushing the Net and Retinal Detachment
Authors: Morton H. Seelenfreund
Journal: JAMA (1976)

With the growth in popularity of tennis has come an increase in ocular injuries due to tennis balls. This report describes ten patients who sustained ocular contusion from high-speed tennis balls. Seven of the patients required either retinal surgery, laser photocoagulation, or both. Early detection of retinal damage is essential, but of greater importance is prevention. For that reason, we advise use of some sort of ocular protection device for high-risk individuals. (<i>JAMA</i>235:2723-2726, 1976)