tbuckley/cabot-search huggingface dataset:
Improving the Human Hazard Characterization of Chemicals: A Tox21 Update
Authors: Raymond R. Tice, Christopher P. Austin, Robert J. Kavlock, John R. Bucher
Journal: Environmental Health Perspectives (2013)

In 2008, the National Institute of Environmental Health Sciences/National Toxicology Program, the U.S. Environmental Protection Agency's National Center for Computational Toxicology, and the National Human Genome Research Institute/National Institutes of Health Chemical Genomics Center entered into an agreement on "high throughput screening, toxicity pathway profiling, and biological interpretation of findings." In 2010, the U.S. Food and Drug Administration (FDA) joined the collaboration, known informally as Tox21.
Hypergammaglobulinemic Renal Tubular Acidosis
Authors: Toshiro Fujita
Journal: JAMA (1975)

DURING the last ten years, several cases of concomitant hypergammaglobulinemia and renal tubular acidosis have been reported<sup>1-3</sup>; this combination appears to be more than coincidental. Several lines of evidence, however, suggest that renal tubular acidosis is not caused by hypergammaglobulinemia itself, but that it can be a functional expression of renal changes caused by a more general autoimmune disorder. <h3>Report of a Case</h3> A 40-year-old woman was hospitalized for severe muscle weakness. The left axillary and radial pulses were absent. The serum potassium level was 1.9 mEq/liter; chloride, 120 mEq/liter; carbon dioxide, 13 mEq/liter; and protein, 8.6 gm/100 ml (albumin, 4.6 gm/100 ml; gamma globulin, 2.2 gm/100 ml). Serum protein electrophoresis showed a generalized increase in immunoglobulin levels. The 24-hour endogenous creatinine clearance was 42 ml/min/1.48 sq m of body-surface area. Serologic tests showed that C-reactive protein, rheumatoid factor, antinuclear antibody, and antiaorta antibody<sup>4</sup>were present. Skin tests
GMC hears complaints about UK fertility specialist
Authors: Owen Dyer
Journal: BMJ (2006)

A well known UK fertility specialist charged patients for things they did not “want, need, or get,” the General Medical Council heard this week.

GMC counsel Joanna Glynn told the GMC's fitness to practise panel that Professor Ian Craft, director of the London Fertility Centre, had a “cavalier attitude” to warning patients about certain procedures.

“This case is about a financial sharp practice, charging patients for things they did not want, need, or get. It's about poor consenting procedures. It's about giving patients poor information,” she said.

The case against Professor Craft …
Five-Year Postoperative Results of First 500 Patients with Blalock-Taussig Anastomosis for Pulmonary Stenosis or Atresia
Authors: B. DANIEL WHITE, DAN G. MCNAMARA, S. RICHARD BAUERSFELD, HELEN B. TAUSSIG
Journal: Circulation (1956)

The evaluation of surgical corrective procedures depends to an important degree on the long-term benefits derived from the operation. Three hundred and eighty-nine of the first 500 patients with a Blalock-Taussig anastomosis for pulmonary stenosis or atresia survived 6 months or longer. Detailed information is now available on 244 of these patients, who were originally improved by operation and who have been followed for 5 years or longer. The results obtained on patients with tetralogy of Fallot are compared with those with other malformations. The alteration of the size of the heart over a period of years has been studied. A comparison between the preoperative and postoperative hemograms and arterial oxygen saturations is presented. The optimum age for operation, the causes of late deaths, and the incidence of bacterial endocarditis are discussed.
Playing politics with the poor: the cities
Authors: J. Roberts
Journal: BMJ (1995)

Not since the depression of the 1930s has the United States faced so great a social turnaround in political attitudes toward the poor as is happening now. Commentators in the media call the new move toward privatisation “the mean spiritedness of rich white men,” but, whatever the motivation, privatisation is going ahead in cities across the United States.

Throughout this century Americans with no health insurance and no money have been able to turn to the 450 public hospitals run by cities, counties, and states. New York's Bellevue Hospital, Boston City Hospital, and Chicago's Cook County Hospital, for example, have grand histories as places whose doors have never closed to the poor. No one claims that these centres have been efficient: staffing is poor, day to day they are …
ABC of Emergency Radiology: THE WRIST
Authors: D W Hodgkinson, N Kurdy, D A Nicholson, P A Driscoll
Journal: BMJ (1994)

Most injuries to the wrist result from a fall on an outstretched hand The wrist is composed of eight bones arranged in a proximal row (scaphoid, lunate, triquetrum, and pisiform) and distal row (trapezium, trapezoid, capitate, and hamate).Each row fimctions as a separate unit.Three articulations make up the carpus (figs 1 and 2)..i'FIG 1-Normal posteroanterior radiograph of the wrist with line drawing showing anatomy.ie wrist with line drawing showing FIG 2-Norn anatomy.Radiocarpal joint-The distal radius articulates with the bones of the proximal carpal row (except the pisiform and triquetrum).This joint complex is supported by strong radiocarpal and intercarpal ligaments.Carpocarpal joints-The proximal carpal row articulates with the distal row.These articulations are also supported by strong intercarpal ligaments that can be damaged in isolation after wrist sprains or in combination with scaphoid fractures and carpal dislocations.Carpometacarpal joints-The distal carpal row articulates with the proximal end of the metacarpal bones.The finger carpometacarpal joints allow little movement compared with that of the thumb.The carpal bones are bound to each other by short intercarpal ligaments, such as the scapholunate and the triquetrolunate.The articulation of the distal radioulnar joint including the triangular fibrocartilage allows pronation and supination at the wrist joint.
RECONSTRUCTIVE SURGERY AND OLD FACIAL BURNS
Authors: HOWARD L. UPDEGRAFF
Journal: JAMA (1933)

One of the first demands for reconstructive surgery came through the necessity of repair of old facial burns. The custom in early warfare of pouring boiling pitch over the walls onto the invading host doubtless furnished many cases. The last war evolved certain surgical procedures now in general use: the Stent graft (Esser outlay), the perfection of the tube flap and the popularization of larger skin grafts. The present-day machine age has so greatly multiplied the number of burned faces that they are more numerous today than they were in war time. There is now more opportunity to study these cases, as they are usually carried through to reconstruction in one hospital. Constant observation of these cases over several years has brought new emphasis on methods of determining scar causation and treatment. The cause of the burn is not particularly important, as reconstructive surgery is not advisable until the tissue
Infections with Reoviruses
Authors: A. Martin Lerner, James D. Cherry, Jerome O. Klein, Maxwell Finland, Priscilla Bills, Ann Ewalt, Roberta Kay, Mette Lian
Journal: New England Journal of Medicine (1962)

REOVIRUSES, formerly designated as ECHO virus Type 10,1 have been isolated from cattle,2 chimpanzees,1 monkeys,3 , 4 mice5 and men,1 , 6 7 8 and "antibodies" to one or more types of reovirus have been found in serum specimens from rabbits,9 , 10 rhesus monkeys (Macaca mulatta),9 , 10 grivet monkeys (Cercopithecus aethiops),10 chimpanzees,10 cattle,10 horses,10 swine,10 cats,10 dogs,10 mice5 and man.6 , 9 , 10 Similarly, reoviruses, in contrast to enteroviruses, multiply in primate and nonprimate cell cultures.11 , 12 The importance of these viruses and the probable mode of spread between animal and human hosts remains to be determined.Infections with Types 1 and 3 reoviruses have been associated with undifferentiated febrile . . .
Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy: A Consensus Statement of the American Diabetes Association and the European Association for the Study of Diabetes
Authors: Alexander R. Cobitz, Phil Ambery
Journal: Diabetes Care (2009)

GlaxoSmithKline regrets the recommendation (1) of the recent American Diabetes Association/European Association for the Study of Diabetes consensus statement against the use of rosiglitazone for treatment of type 2 diabetes because it is contrary to scientific evidence.

The evidence regarding a possible association of rosiglitazone with increased risk of cardiovascular ischemic morbidity remains inconclusive. Data from clinical trials assessing cardiovascular outcomes are inconsistent with the hypotheses of increases in myocardial ischemia or death that have arisen from meta-analyses. No long-term clinical trials have confirmed an increased cardiovascular ischemic risk with rosiglitazone. Moreover, data from …
TCT-67 Impact of Hemodynamic Support With Impella vs Intraaortic Balloon Counterpulsation on Prognostically Important Ischemic Endpoints: Results from the PROTECT-II Trial
Authors: George Dangas, Samin Sharma, Annapoorna Kini, Kleanthis Theodoropoulos, Jose Henriques, Gregg Stone, William O. Neill
Journal: Journal of the American College of Cardiology (2012)
An epidemic of pseudomembranous colitis: importance of person to person spread.
Authors: N P Nolan, C P Kelly, J F Humphreys, C Cooney, R O'Connor, T N Walsh, D G Weir, D S O'Briain
Journal: Gut (1987)

Twenty three cases of pseudomembranous colitis (PMC) occurred in three hospitals in 10 months. Retrospective analysis shows that they represented a single epidemic with a readily traceable chain of person-to-person contact within and between hospitals. Most patients had severe pre-existing illness and all had broad spectrum antibiotics, including either ampicillin/amoxycillin, a broad spectrum cephalosporin (particularly cefotaxime), or both. All patients had severe diarrhoea and all responded to vancomycin, but relapse occurred in five. Ten patients eventually died, principally because of underlying disease rather than from PMC. Failure to find fibrin thrombi in blood vessels in biopsies and the scanty distribution of non-invasive bacteria supports the concept of mucosal damage by bacterial toxin, rather than by direct infection, or ischaemia. Although environmental colonisation cannot be excluded, the observed pattern of spread suggests a major role for direct person-to-person crossinfection in the spread of disease in this outbreak.
Intracardiac flow dynamics regulate atrioventricular valve morphogenesis
Authors: Stamatia Kalogirou, Nikos Malissovas, Enrico Moro, Francesco Argenton, Didier Y.R. Stainier, Dimitris Beis
Journal: Cardiovascular Research (2014)

Valvular heart disease is responsible for considerable morbidity and mortality. Cardiac valves develop as the heart contracts, and they function throughout the lifetime of the organism to prevent retrograde blood flow. Their precise morphogenesis is crucial for cardiac function. Zebrafish is an ideal model to investigate cardiac valve development as it allows these studies to be carried out in vivo through non-invasive imaging. Accumulating evidence suggests a role for contractility and intracardiac flow dynamics in cardiac valve development. However, these two factors have proved difficult to uncouple, especially since altering myocardial function affects the intracardiac flow pattern. Here, we describe novel zebrafish models of developmental valve defects. We identified two mutant alleles of myosin heavy chain 6 that can be raised to adulthood despite having only one functional chamber—the ventricle. The adult mutant ventricle undergoes remodelling, and the atrioventricular (AV) valves fail to form four cuspids. In parallel, we characterized a novel mutant allele of southpaw, a nodal-related gene involved in the establishment of left–right asymmetry, which exhibits randomized heart and endoderm positioning. We first observed that in southpaw mutants the relative position of the two cardiac chambers is altered, affecting the geometry of the heart, while myocardial function appears unaffected. Mutant hearts that loop properly or exhibit situs inversus develop normally, whereas midline, unlooped hearts exhibit defects in their transvalvular flow pattern during AV valve development as well as defects in valve morphogenesis. Our data indicate that intracardiac flow dynamics regulate valve morphogenesis independently of myocardial contractility.
John Cecil Nicholson Wakeley
Authors: C. Wakeley, L. d. Cossart
Journal: BMJ (2012)

Not all people who become housebound suffer from agoraphobia. Other emotional illnesses can underlie this behaviour. Early diagnosis is important. Some conditions can be treated by family physicians without special training, and some are appropriately treated only in special settings. This paper describes psychiatric disorders that may present as a "housebound syndrome" and outlines the principles of treatment for each.
Hepatic Gaucheroma mimicking focal nodular hyperplasia
Authors: Ludger Wilhelm Poll, Stephan vom Dahl
Journal: Hepatology (2009)

A 23-year-old man was referred to the hospital because of weakness, bone pain, and fatigue. Physical examination showed a marked hepatomegaly. His hemoglobin level was 133 g/L (normal < 140 g/L) and liver aminotransferases were moderately elevated (aspartate aminotransferase was 63 U/L [normal < 35] and alanine aminotransferase was 60 U/L [normal < 45]). Ultrasound of the abdomen showed hepatomegaly with a hyperechoic mass (7.4 cm × 7.3 cm × 9.0 cm) adjacent to the left liver lobe, requiring further work-up. Liver magnetic resonance imaging (MRI) demonstrated a well-delineated mass, which appeared hyperintense in comparison to the adjacent liver parenchyma on T2-weighted images (Fig. 1). A central hypointense scar was detected, suggestive of focal nodular hyperplasia (FNH). At the age of 5 years, splenomegaly had been diagnosed and subsequent splenectomy had shown Gaucher cells. Here, the diagnosis of Gaucher disease was confirmed by diminished blood β-glucocerebrosidase activity and increased plasma chitotriosidase. Magnetic resonance imaging: Axial T2-weighted MRI of the upper abdomen showing a hyperintense mass (white arrows) adjacent to the left liver lobe in a patient with Gaucher disease who underwent splenectomy. A central hypointense scar (white arrowhead) within the mass suggests FNH. FNH, focal nodular hyperplasia; HCC, hepatocellular carcinoma; MRI, magnetic resonance imaging. An ultrasound-guided fine-needle biopsy showed an extensive accumulation of Gaucher cells within liver sinusoids (Fig. 2). There was no histological evidence of FNH or malignancy, and hepatic Gaucheroma (Gaucher-cell pseudotumor) was diagnosed. Histology: Histopathological specimen (hematoxylin & eosin stain, ×1100) from the mass shown in Fig. 1 revealed lipid-laden macrophages with brittle cytoplasm, which are classical Gaucher cells. FNH is a circumscribed, usually solitary lesion composed of nodules of benign hyperplastic hepatocytes surrounding a central stellate fibrous scar. It is usually asymptomatic and often presents as an incidental finding at imaging. The hepatic lesion in this patient exhibited some MR characteristics typical of FNH.1 Although hepatic "pseudotumors" within or adjacent to parenchymal tissues are a common finding in Gaucher disease,2 hepatocellular carcinoma (HCC) should be excluded in this disease by biopsy. HCC without preexisting cirrhosis is increased in Gaucher disease,3, 4 and HCC may mimic the morphological pattern of FNH.5
Immunologic Reactions to Drugs
Authors: N. Raphael Shulman
Journal: New England Journal of Medicine (1972)

The clinical finding by Eisner and Shahidi (page 376) that a metabolite of a drug but not the drug itself can be responsible for an immunologic reaction was anticipated by the basic studies of Landsteiner 50 years ago. Landsteiner found that antigenic organic compounds (especially those containing benzene rings) could be modified by attachment of simple inorganic radicals (e.g., sulfate) to produce new antigens that elicited non-cross-reacting antibodies.1 Two of the chemical analogues that he used, p-aminobenzoic acid and p-aminobenzene sulfonic acid, are remarkably similar in structure to the drug (acetylated p-amino-hydroxybenzene) and metabolite (the sulfate ester) involved in the . . .
EMPYEMA TREATED BY PERTHES' METHOD.
Authors: WILLIAM S. CHEESMAN
Journal: JAMA (1905)

After evacuation of the pus in cases of empyema, the huge suppurating cavity that remains must be obliterated. In cases in which the lung, though compressed against the spine or mediastinum, is not yet held in its false position by strong adhesions or by thick deposits of organized new material, aseptic opening and plentiful gauze dressings are sufficient. These dressings act as a valve as well as a protection from infection, and they absorb discharge. Air or gas present in the pleural cavity with every cough, indeed with every expiration, is expelled little by little into the gauze covering the orifice of the wound, while this mass of gauze applies itself too firmly to the chest to permit entrance of air from without, and there is produced within the thorax a tendency to a vacuum, a negative pressure, which sucks the collapsed lung out toward the chest wall.
Chemoattractant-induced activation of c-fos gene expression in human monocytes.
Authors: Y S Ho, W M Lee, R Snyderman
Journal: The Journal of Experimental Medicine (1987)

Human monocytes use the products of phosphoinositide hydrolysis (1,2-diacylglycerol and inositol 1,4,5-triphosphate) as second messengers to trigger rapid cellular activation during the occupancy of chemoattractant receptors. The effect of chemoattractants on modulation of gene expression in monocytes was examined in this study. The chemoattractants FMLP and platelet-activating factor induced the progressive increase of c-fos RNA to 6-15-fold over those of control within 30 min after treatment. Similar kinetics of c-fos gene activation was also observed when cells were treated with PMA or sn-1,2-dioctanoylglycerol, but not with the calcium mobilizer ionomycin, suggesting a role for protein kinase C in gene regulation by chemoattractant receptors. Activation of c-fos gene expression by FMLP is mediated through a pertussis toxin-sensitive G protein, since pertussis toxin treatment of the cells blocked the induction of the c-fos gene by FMLP but not PMA. The level of c-myc RNA was slightly decreased after 1 h of treatment with chemoattractants, but not with PMA or diacylglycerol. This implies that chemoattractant receptor occupancy generates signals beyond protein kinase C activation that are capable of selectively downregulating monocyte gene expression. The effect of FMLP and PMA on the accumulation of c-fos RNA appears to result from altering both the rate of transcription and message stability. These observations indicate that signals generated through chemoattractant receptor occupancy may regulate monocyte function at the genetic level.
Clinical Phenotype and Mutant TRα1
Authors: Alies van Mullem, Ramona van Heerebeek, Dionisios Chrysis, Edward Visser, Marco Medici, Maria Andrikoula, Agathocles Tsatsoulis, Robin Peeters, Theo J. Visser
Journal: New England Journal of Medicine (2012)

Generic Atorvastatin and Health Care CostsTo the Editor: In their Perspective article on generic atorvastatin and health care costs, Jackevicius et al. (Jan.19 issue) 1 refer to agreements that we at Pfizer have reached with health plans and pharmacy benefit managers to ensure that patients can continue to have access to Lipitor in the 180-day period after the loss of market exclusivity.They ask "whether these agreements will discourage generics manufacturers from competing in the atorvastatin market."We believe our programs (the Lipitor for You program and Lipitor contracting strategies with payers and retail pharmacies) enhance competition by affording both patients and payers access to branded Lipitor at a cost that is at or lower than the cost of a generic during the 180-day period following the loss of market exclusivity.In addition to Lipitor, generic alternatives from Ranbaxy and Watson are also available.After the 180day period, we expect that multiple additional generics will enter the market and that the cost of generic products will decline appreciably.We appreciate the focus on ways to safely and effectively cut costs in the U.S. health care system.We believe we are doing just that by introducing greater competition to the marketplace earlier than would occur without our programs.
Negative Regulation of FcεRI-mediated Degranulation by CD81
Authors: Tony J. Fleming, Emmanuel Donnadieu, Chang Ho Song, Francois Van Laethem, Stephen J. Galli, Jean-Pierre Kinet
Journal: The Journal of Experimental Medicine (1997)

Signaling through the high affinity receptor for immunoglobulin E (FcεRI) results in the coordinate activation of tyrosine kinases before calcium mobilization. Receptors capable of interfering with the signaling of antigen receptors, such as FcεRI, recruit tyrosine and inositol phosphatases that results in diminished calcium mobilization. Here, we show that antibodies recognizing CD81 inhibit FcεRI-mediated mast cell degranulation but, surprisingly, without affecting aggregation-dependent tyrosine phosphorylation, calcium mobilization, or leukotriene synthesis. Furthermore, CD81 antibodies also inhibit mast cell degranulation in vivo as measured by reduced passive cutaneous anaphylaxis responses. These results reveal an unsuspected calcium-independent pathway of antigen receptor regulation, which is accessible to engagement by membrane proteins and on which novel therapeutic approaches to allergic diseases could be based.
Health committee questions benefit of foundation hospitals to patients
Authors: Z. Kmietowicz
Journal: BMJ (2003)

The government announced a new scheme to help all hospitals achieve foundation status within the next five years this week, just days ahead of the second reading of the controversial Health and Social Care Bill in the House of Commons on 7 May.

The NHS improvement programme will have a £200m ($321m; €285m) “help fund” with which to ensure that all NHS hospitals and primary care trusts that are rated with two, one, or zero stars achieve the three star rating needed to gain foundation status by 2008.

However, in a report on foundation trusts, the House of Commons health committee casts doubt on whether all trusts will be eligible for foundation status in the time scale outlined by the government. It also raises several concerns about how the policy will work in practice and whether it will truly benefit patients.

In the report, which was published on the day of the Commons …
RNA Metabolism in Embryonic Development and Differentiation
Authors: Paul R. Gross
Journal: New England Journal of Medicine (1967)

The Changing Pattern of SynthesisThe conversion of an oocyte to an ovum is more than a process of growth. Recent attempts to identify some of the macromolecular working parts of an egg, and to specify some of the locations provided for them during oogenesis, represent no discontinuity with the embryologic past, since it has been understood for a long time that the purposeful operations of early development are in large measure the working out of a program built into the cytoplasm of the egg.55 It is a more recent idea that the program can at least in part be . . .
1096. Physical Determinants for Efficient Hydrodynamic Gene Delivery to Liver
Authors: Takeshi Suda, Regis Vollmer, Dexi Liu
Journal: Molecular Therapy (2005)

Backgrounds & Aims: Hydrodynamic delivery has opened a new avenue for in vivo gene transfer. However, prerequisites of a large volume and high injection speed are not feasible in clinic. In this study we tried to determine parameters affecting gene delivery efficiency of hydrodynamic delivery. The study aimed to establish clinically acceptable procedure for an efficient gene delivery to hepatocytes.