tbuckley/cabot-search huggingface dataset:
Laron Dwarfism and Mutations of the Growth Hormone–Receptor Gene
Authors: Serge Amselem, Philippe Duquesnoy, Olivier Attree, Giuseppe Novelli, Souad Bousnina, Marie-Catherine Postel-Vinay, Michel Goossens
Journal: New England Journal of Medicine (1989)

Laron dwarfism is associated with resistance to growth hormone (GH). To investigate its genetic basis, we used genetic linkage to test whether the disorder results from a defect in the gene for the human GH receptor. Denaturing gradient gel electrophoresis and sequencing of specific GH-receptor-gene fragments allowed us to characterize specific intragenic DNA markers in 35 control subjects of Mediterranean descent, for use in linkage studies. In two Mediterranean families in which the parents were consanguineous and some of the children had Laron dwarfism, the disease trait and DNA polymorphisms were inherited together. Moreover, an analysis of the GH-receptor-gene RNA transcripts in lymphocytes from one of these families allowed us to identify a thymidine-to-cytosine substitution that generated a serine in place of a phenylalanine at position 96 in the extracellular coding domain of the mature protein. This defect probably affects the receptor adversely and is probably responsible for the lack of plasma GH-binding activity in the patients. This mutation was not found in the GH-receptor genomic sequences of seven unrelated subjects with Laron dwarfism who belonged to different population groups. An analysis of the GH-receptor markers in these patients indicated that different gene frameworks (polymorphic sites within the single gene) were associated with the mutant alleles. We conclude that Laron dwarfism is due to abnormalities in the gene for GH receptor, which may differ from family to family. (N Engl J Med 1989; 321:989–95.)
Determining the Benefits of the New York City Trans Fat Ban
Authors: Morton Satin
Journal: Annals of Internal Medicine (2010)

Letters2 February 2010Determining the Benefits of the New York City Trans Fat BanMorton Satin, MScMorton Satin, MScFrom Salt Institute, Alexandria, VA 22314.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-152-3-201002020-00017 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:What Angell and colleagues (1) could not say was how this initiative has actually helped the citizens of New York. The presumption is that ridding the food supply of TFAs will reduce the cholesterol levels of millions of people. Improving the cholesterol levels should result in reduced cardiovascular disease, but has it? Because most New Yorkers eat in restaurants, often several times a week, there should be a significant decrease in the number of heart attacks and heart attack deaths, right? And certainly, with all the modern statistical tools we have available and with a precise knowledge ...Reference1. Angell SY, Silver LD, Goldstein GP, Johnson CM, Deitcher DR, Frieden TR, et al. Cholesterol control beyond the clinic: New York City's trans fat restriction. Ann Intern Med. 2009;151:129-34. [PMID: 19620165] LinkGoogle Scholar Author, Article, and Disclosure InformationAuthors: Morton Satin, MScAffiliations: From Salt Institute, Alexandria, VA 22314.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoCholesterol Control Beyond the Clinic: New York City's Trans Fat Restriction Sonia Y. Angell , Lynn Dee Silver , Gail P. Goldstein , Christine M. Johnson , Deborah R. Deitcher , Thomas R. Frieden , and Mary T. Bassett Determining the Benefits of the New York City Trans Fat Ban Sonia Y. Angell , Lynn Dee Silver , and Gail P. Goldstein Determining the Benefits of the New York City Trans Fat Ban Gilbert L. Ross Metrics 2 February 2010Volume 152, Issue 3Page: 194KeywordsCardiovascular diseasesCholesterolConflicts of interestFatsFoodHealth statisticsMyocardial infarction ePublished: 2 February 2010 Issue Published: 2 February 2010 Copyright & PermissionsCopyright © 2010 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Antiarrhythmic Potential of Mesenchymal Stem Cell Is Modulated by Hypoxic Environment
Authors: Hye Jin Hwang, Woochul Chang, Byeong-Wook Song, Heesang Song, Min-Ji Cha, Il-Kwon Kim, Soyeon Lim, Eun Ju Choi, Onju Ham, Se-Yeon Lee, Jaemin Shim, Boyoung Joung, Hui-Nam Pak, Sung Soon Kim, Bum-Rak Choi, Yangsoo Jang, Moon-Hyoung Lee, Ki-Chul Hwang
Journal: Journal of the American College of Cardiology (2012)
AN IMPROVED METHOD FOR THE DETERMINATION OF BILIRUBIN IN BLOOD
Authors: A. A. H. van den Bergh, W. Grotepass
Journal: BMJ (1934)

57Eventually, when the child is more or less in extremis, it is sent to hospital in a state of health which makes any form of treatment a dangerous procedure.We would suggest that pyloric stenosis in infancy should be regarded far more than it is at present as an abdominal emergency, and it should be realized that the longer the delay in sending the child for treatment the less are its chances of survival.Admittedly, vomiting in infancy is a frequent occurrence, and is due, in the majority of cases, merely to some feeding defect or mismanagement; never- theless, we believe that until congenital pyloric stenosis is considered as a possibility in every case of forceful vomiting in infancy the mortality from every form of treatment must remain at a high level.It is probable that if the condition were diagnosed within one week of the commencement of symptoms and sent for operatton without delay, as in other cases of abdominal emergency, the operation mortality would be greatly reduced.Summary An analysis has been carried out of 145 cases of con- genital hypertrophic stenosis of the pylorus treated by operation.The proportion of males to females in this series was 6.25 to 1.More than half of the patients were first children, and it is revealed that the last child in a large family very rarely suffers from this condition.This analysis shows that the birth weights of the infants concerned were somewhat higher than the normal average for males.The average weight at birth for all the cases in this series was 8-lb.The first symptom noticed in the majority of cases was vomiting, and the average age at which it occurred was three weeks.Visible gastric peristalsis was an almost constant sign, whereas a palpable tumour in the pyloric region was noted in only 24 per cent.before operation.The operation mortality was 24.8 per cent., and there is no indication of any marked fall in mortality during the last ten years.The patients who failed to survive did not appear to differ significantly at the time of operation from the survivals, and in a high proportion of deaths no adequate cause could be discovered at necropsy.The time that elapses between the first manifestation of obstruction and the admission of the patient to hospital for treatment is between three and four weeks, and there is no ev;dence to show that pyloric stenosis in infancy is be'ng recognized any earlier to-day than it was ten years ago.We ws to record our thanks to the physicians and surgeons of the ITny*J Edinburgh Hospital for Sick Children, who have .dlypiced their case records at our disposal.We also .Oteffily
Treatment of hepatic hydatid disease with mebedazole: preliminary results in four cases.
Authors: A Bekhti, J P Schaaps, M Capron, J P Dessaint, F Santoro, A Capron
Journal: BMJ (1977)

Mebendazole was given to four patients with hepatic hydatid disease. In three patients hydatidosis had remained after surgery, and in the fourth it could not be treated surgically. Mebendazole was given orally in maximum doses of 400-600 mg three times a day during courses lasting 21 to 30 days. Ultrasonic echotomography showed a complete regression of the intrahepatic cysts after four to 13 months in all four cases. In three patients the course of treatment had to be repeated. Mebendazole also induced clinical improvement and a progressive lowering of the concentration of specific IgE of Echinococcus granulosus. During treatment circulating blood levels of specific immune complexes of antigen 5 were increased. These observations indicate that mebendazole has a lethal effect on E granulosus cysts in primary hydatid disease in man and that the efficacy of chemotherapy can be assessed with ultrasonography and by measuring changes in the concentration of specific IgE of E granulosus and circulating immune complexes.
Updating guidelines on stable angina
Authors: T. Lancaster, M. Moher
Journal: BMJ (2001)

Doctors vary greatly in the way they assess and manage angina.1 The problem is common and serious so valid, clinically useful guidelines are welcome. The North of England Guidelines Group has an impressive record of producing rigorous guidelines for primary care. Today, the updated version of the group's 1996 guideline for managing stable angina is published in full on bmj.com.2 The new guideline extends the literature search from 1994 to 1997. It fulfils the 1996 commitment to an update after three years. How do the two versions compare?

Recommendations for assessment and referral have changed little from 1996. They are closely aligned with those in the British government's national service framework for coronary heart disease.3 The continuing challenge is to implement them. In particular, many areas of the United Kingdom will still find it difficult to meet the recommendation for prognostic exercise testing for all patients with stable angina.

There are few changes to the recommendations for …
Firm involved in drug trial fiasco files for bankruptcy
Authors: Owen Dyer
Journal: BMJ (2006)

TeGenero, the German biotechnology firm whose experimental drug TGN1412 caused multiple organ failure in six men during a clinical trial in England, has filed for bankruptcy.

“The unforeseeable adverse reactions caused by TGN1412 in the TGN1412-HV phase I trial have made it impossible to attract the investment necessary for the company to continue operations,” the company said in a statement. “In view of the fact that there appears [to be] no reasonable prospect that the company can continue its business, TeGenero's management had no alternative but to commence insolvency proceedings.”

The Bavarian company, founded in 2000 by scientists from Wurzburg University, will be administered by an official receiver as …
Medicare to implement new preventive services
Authors: Fred Charatan
Journal: BMJ (2004)

The Bush administration has given preventive care new emphasis in Medicare, the federal health programme for people aged over 65 years. Under a new Medicare law enacted in 2003, the number of preventive services covered by Medicare will expand, including a comprehensive physical examination for all people enrolling in the programme, to begin in 2005.

Tommy Thompson, secretary for health and human services, said, “Medicare had it backwards, spending 99% of its resources treating seniors after they got sick and only 1% on preventing illness and promoting wellness. With the new law, we are reversing this trend and focusing more on disease prevention and management.”

When Medicare was enacted in …
Mannose-binding lectin status is associated with risk of major infection following myeloablative sibling allogeneic hematopoietic stem cell transplantation
Authors: Charles G. Mullighan, Susan L. Heatley, Silke Danner, Melinda M. Dean, Kathleen Doherty, Uwe Hahn, Kenneth F. Bradstock, Robyn Minchinton, Anthony P. Schwarer, Jeff Szer, Peter G. Bardy
Journal: Blood (2008)
Abortion Rates and Universal Health Care
Authors: Patrick Whelan
Journal: New England Journal of Medicine (2010)

Among the most nettlesome obstacles in the yearlong debate over increasing the accessibility and affordability of health insurance has been the question of what effect health care reform legislation would have on the incidence of abortion. The recent experience in Massachusetts suggests that universal health care coverage has been associated with a decrease in the number of abortions performed, despite public and private funding of abortion that is substantially more liberal than the provisions of the federal legislation currently under consideration by Congress. Parties on both sides of the national debate on this issue, including the U.S. Conference of Catholic . . .
Validation of the Capsule Endoscopy Crohn’s Disease Activity Index (CECDAI or Niv score): a multicenter prospective study
Authors: Y. Niv, S. Ilani, Z. Levi, M. Hershkowitz, E. Niv, Z. Fireman, S. O’Donnel, C. O’Morain, R. Eliakim, E. Scapa, N. Kalantzis, C. Kalantzis, P. Apostolopoulos, E. Gal
Journal: Endoscopy (2011)

<b>Background and study aims:</b> The Capsule Endoscopy Crohn's Disease Activity Index (CECDAI or Niv score) was devised to measure mucosal disease activity using video capsule endoscopy (VCE). The aim of the current study was to prospectively validate the use of the scoring system in daily practice. <b>Methods:</b> This was a multicenter, double-blind, prospective, controlled study of VCE videos from 62 consecutive patients with isolated small-bowel Crohn's disease. The CECDAI was designed to evaluate three main parameters of Crohn's disease: inflammation (A), extent of disease (B), and stricture (C), in both the proximal and distal segments of the small bowel. The final score was calculated by adding the two segmental scores: CECDAI = ([A1 × B1] + C1) + ([A2 × B2] + C2). Each examiner in every site interpreted 6 – 10 videos and calculated the CECDAI. The de-identified CD-ROMs were then coded and sent to the principal investigator for CECDAI calculation. <b>Results:</b> The cecum was reached in 72 % and 86 % of examinations, and proximal small-bowel involvement was found in 56 % and 62 % of the patients, according to the site investigators and principal investigator, respectively. Significant correlation was demonstrated between the calculation of the CECDAI by the individual site investigators and that performed by the principal investigator. Overall correlation between endoscopists from the different study centers was good, with r = 0.767 (range 0.717 – 0.985; Kappa 0.66; <i>P</i> < 0.001). There was no correlation between the CECDAI and the Crohn's Disease Activity Index or the Inflammatory Bowel Disease Quality of Life Questionnaire or any of their components. <b>Conclusion:</b> A new scoring system of mucosal injury in Crohn's disease of the small intestine, the CECDAI, was validated. Its use in controlled trials and/or regular follow-up of these patients is advocated.
Urinary Metals and Heart Rate Variability: A Cross-Sectional Study of Urban Adults in Wuhan, China
Authors: Wei Feng, Xiaosheng He, Mu Chen, Siyun Deng, Gaokun Qiu, Xiaoliang Li, Chuanyao Liu, Jun Li, Qifei Deng, Suli Huang, Tian Wang, Xiayun Dai, Binyao Yang, Jing Yuan, Meian He, Xiaomin Zhang, Weihong Chen, Haidong Kan, Tangchun Wu
Journal: Environmental Health Perspectives (2014)

BackgroundEpidemiological studies have suggested an association between external estimates of exposure to metals in air particles and altered heart rate variability (HRV). However, studies on the association between internal assessments of metals exposure and HRV are limited.ObjectivesThe purpose of this study was to examine the potential association between urinary metals and HRV among residents of an urban community in Wuhan, China.MethodsWe performed a cross-sectional analysis of 23 urinary metals and 5-min HRV indices (SDNN, standard deviation of normal-to-normal intervals; r-MSSD, root mean square of successive differences in adjacent normal-to-normal intervals; LF, low frequency; HF, high frequency; TP, total power) using baseline data on 2,004 adult residents of Wuhan.ResultsAfter adjusting for other metals, creatinine, and other covariates, natural log-transformed urine titanium concentration was positively associated with all HRV indices (all p < 0.05). Moreover, we estimated negative associations between cadmium and r-MSSD, LF, HF, and TP; between lead and r-MSSD, HF, and TP; and between iron, copper, and arsenic and HF, SDNN, and LF, respectively, based on models adjusted for other metals, creatinine, and covariates (all p < 0.10). Several associations differed according to cardiovascular disease risk factors. For example, negative associations between cadmium and r-MSSD were stronger among participants ≤ 52 years of age (vs. > 52), current smokers (vs. nonsmokers), body mass index < 25 kg/m2 (vs. ≥ 25), and among those who were not hypertensive.ConclusionsUrine concentrations of several metals were associated with HRV parameters in our cross-sectional study population. These findings need replication in other studies with adequate sample sizes.CitationFeng W, He X, Chen M, Deng S, Qiu G, Li X, Liu C, Li J, Deng Q, Huang S, Wang T, Dai X, Yang B, Yuan J, He M, Zhang X, Chen W, Kan H, Wu T. 2015. Urinary metals and heart rate variability: a cross-sectional study of urban adults in Wuhan, China. Environ Health Perspect 123:217–222; http://dx.doi.org/10.1289/ehp.1307563
Interpreting arterial blood gas results
Authors: N. J. Cowley, A. Owen, J. F. Bion
Journal: BMJ (2013)

#### Learning points

You have been called to see a 69 year old man on a surgical ward because he has become drowsy and short of breath. He had a large bowel resection the previous day, has a background of type 2 diabetes, and is a current smoker. On examination his arterial blood pressure is 104/65 mm Hg, his heart rate 132 beats/min and irregular, and his respiratory rate 22 breaths/min; his oxygen saturations with pulse oximetry are 94% on supplemental oxygen via a 40% Venturi-type mask. He is slightly confused and is complaining of abdominal pain despite using patient controlled analgesia with morphine. His chest is clear on auscultation.

You take a blood specimen for analysis of arterial blood gases for rapid biochemical evaluation to guide diagnosis and initial management. Table 1⇓ shows the results. It is important to adopt a systematic approach to interpreting results of arterial blood gases, as outlined in table 2⇓, preceded by a brief history and focused clinical examination. 

View this table:

Table 1 
 Report of arterial blood gases for the hypothetical patient described



View this table:

Table 2 
 Guide to systematic approach to analysis of a report of arterial blood gases 



### Step 1: Assess oxygenation

Arterial oxygen tension (PaO2) is the partial pressure of oxygen in arterial blood. The main determinants of PaO2 are the inspired …
PDZ Domain–Binding Motif Regulates Cardiomyocyte Compartment-Specific Na <sub>V</sub> 1.5 Channel Expression and Function
Authors: Diana Shy, Ludovic Gillet, Jakob Ogrodnik, Maxime Albesa, Arie O. Verkerk, Rianne Wolswinkel, Jean-Sébastien Rougier, Julien Barc, Maria C. Essers, Ninda Syam, Roos F. Marsman, Anneke M. van Mil, Samuel Rotman, Richard Redon, Connie R. Bezzina, Carol Ann Remme, Hugues Abriel
Journal: Circulation (2014)

Background— Sodium channel Na V 1.5 underlies cardiac excitability and conduction. The last 3 residues of Na V 1.5 (Ser-Ile-Val) constitute a PDZ domain–binding motif that interacts with PDZ proteins such as syntrophins and SAP97 at different locations within the cardiomyocyte, thus defining distinct pools of Na V 1.5 multiprotein complexes. Here, we explored the in vivo and clinical impact of this motif through characterization of mutant mice and genetic screening of patients. Methods and Results— To investigate in vivo the regulatory role of this motif, we generated knock-in mice lacking the SIV domain (ΔSIV). ΔSIV mice displayed reduced Na V 1.5 expression and sodium current ( I Na ), specifically at the lateral myocyte membrane, whereas Na V 1.5 expression and I Na at the intercalated disks were unaffected. Optical mapping of ΔSIV hearts revealed that ventricular conduction velocity was preferentially decreased in the transversal direction to myocardial fiber orientation, leading to increased anisotropy of ventricular conduction. Internalization of wild-type and ΔSIV channels was unchanged in HEK293 cells. However, the proteasome inhibitor MG132 rescued ΔSIV I Na , suggesting that the SIV motif is important for regulation of Na V 1.5 degradation. A missense mutation within the SIV motif (p.V2016M) was identified in a patient with Brugada syndrome. The mutation decreased Na V 1.5 cell surface expression and I Na when expressed in HEK293 cells. Conclusions— Our results demonstrate the in vivo significance of the PDZ domain–binding motif in the correct expression of Na V 1.5 at the lateral cardiomyocyte membrane and underline the functional role of lateral Na V 1.5 in ventricular conduction. Furthermore, we reveal a clinical relevance of the SIV motif in cardiac disease.
Protein Degradation in Normal and Beige (Chediak-Higashi) Mice
Authors: Robert T. Lyons, Henry C. Pitot
Journal: Journal of Clinical Investigation (1978)

The beige mouse, C57BL/6 (bg/bg), is an animal model for the Chediak-Higashi syndrome in man, a disease characterized morphologically by giant lysosomes in most cell types. Half-lives for the turnover of [14C]bicarbonate-labeled total soluble liver protein were determined in normal and beige mice. No significant differences were observed between the normal and mutant strain for both rapidly and slowly turning-over classes of proteins. Glucagon treatment during the time-course of protein degradation had similar effects on both normal and mutant strains and led to the conclusion that the rate of turnover of endogenous intracellular protein in the beige mouse liver does not differ from normal.
Cumulative Changes in the Use of Long-Term Medications: A Measure of Prescribing Complexity
Authors: Khoa D. Lam, Yinghui Miao, Michael A. Steinman
Journal: JAMA Internal Medicine (2013)

Polypharmacy is a major concern in older adults, yet a simple cross-sectional count of medications does not capture the potential complications (and benefits) that occur when medications are started, stopped, and changed over time. The increased complexity that arises from multiple medication changes may lead to problems with adherence and confusion about proper medication use.[Van Wijk, Choudhry] In addition, because adverse drug reactions often occur relatively soon after a medication is started, patients with recent medication changes may be at increased risk of adverse drug events.[Forster] In this study, we sought to longitudinally measure medication changes in a national sample of older veterans as a measure of prescribing complexity in older adults.
Danger of Hypertonic-Saline-Induced Abortion
Authors: Yukio Manabe
Journal: JAMA (1969)

<h3>To the Editor:—</h3> In recent years attention has been focused on hypertonic-saline-induced abortion at midpregnancy. This method was originally reported by the Rumanian obstetrician, Aburel, in 1939. Since its advocation by Scandinavian physicians, this method has gradually gained popularity in several countries, including the United States and Great Britain. The crux of the idea is the intrauterine application of hypertonic saline. Delivery can be terminated in one or two days. This method unfortunately has many drawbacks and may be dangerous for the mother. It is recognized that the use of this method results in the death of the fetus during treatment, thus its use for term cases cannot be considered. Its ill effects to the mother are crucial, and various severe complications<sup>1-4</sup>and maternal deaths<sup>5-8</sup>have been reported in recent years. Inadvertent direct injection or rapid absorption of the solution through the highly developed vascularity of the uterus