tbuckley/cabot-search huggingface dataset:
FDA: A Miracle in Rockville
Authors: Daniel S. Greenberg
Journal: New England Journal of Medicine (1978)

From agencies big and small throughout the government, the litany at the one-year mark of the Carter Administration is pretty much the same: the problems are worse than we realized, and correctives will take longer than we thought. The ebullience of last January has vanished, replaced by a kind of punch-drunk wariness and puzzlement over why it is so difficult to get things done in the government of the most powerful nation.Among the few exceptions, however, is a most improbable one. It is the Food and Drug Administration (FDA), traditionally the leakiest and least navigable scow in the sprawling . . .
Current Role of Platelet Glycoprotein IIb/IIIa Inhibitors in Acute Coronary Syndromes
Authors: Deepak L. Bhatt
Journal: JAMA (2000)

ContextThe central role of platelet-rich thrombus in the pathogenesis of acute coronary syndromes (ACSs) is well-known.Glycoprotein IIb/IIIa (Gp IIb/IIIa) receptor antagonists are potent inhibitors of platelet function that may be expected to affect favorably the natural history of ACSs.Objective To define the optimal role of Gp IIb/IIIa inhibitors in treatment strategies for ACSs.Data Sources A MEDLINE search was performed to identify all English-language articles regarding use of Gp IIb/IIIa inhibitors in ACSs published between 1966 and June 2000.In addition, relevant abstracts from the annual meetings of the American Heart Association, American College of Cardiology, and the European Society of Cardiology were reviewed. Study SelectionOnly studies of 500 or more patients were included.Of 15 studies identified, 10 randomized, placebo-controlled, double-blind trials of Gp IIb/IIIa inhibitors in ACSs were selected for review.Data Extraction Data quality was determined by publication in the peer-reviewed literature or presentation at an official cardiology society-sponsored meeting, as well as by verification with the primary author.Data Synthesis Three members of this class of drugs are available for intravenous use.Abciximab, eptifibatide, and tirofiban hydrochloride, each have data demonstrating their value in improving the outcomes of patients presenting with ACSs.Current evidence supports use of these drugs in both conservative and invasive treatment strategies.Glycoprotein IIb/IIIa-blocking therapy is safe, and with proper precautions, bleeding risks can be minimized.Biological differences exist among these agents, but as of yet, no head-to-head comparisons have been made of their clinical efficacy.Unlike intravenous Gp IIb/IIIa inhibitors, available data regarding any role of oral Gp IIb/IIIa inhibitors are not favorable. ConclusionCurrent data indicate that intravenous Gp IIb/IIIa inhibitor therapy merits a prominent role in the initial management of patients with ACSs.
Points: Time for action on hepatitis B immunisation
Authors: J K Anand
Journal: BMJ (1987)

Professor D C Carter (7 March, p 593) com- ments on the treatment of hepatic metastases by surgical debulking, but the value of hepatic arterial embolisation is not mentioned.'2In our experience, when vascular endocrine metastases are detected in the liver, providing that the intrahepatic portal veins are patent, hepatic arterial embolisation can provide
Association with the Auxiliary Subunit PEX5R/Trip8b Controls Responsiveness of HCN Channels to cAMP and Adrenergic Stimulation
Authors: Gerd Zolles, Daniela Wenzel, Wolfgang Bildl, Uwe Schulte, Andreas Hofmann, Catrin S. Müller, Jörg-Oliver Thumfart, Andreas Vlachos, Thomas Deller, Alexander Pfeifer, Bernd K. Fleischmann, Jochen Roeper, Bernd Fakler, Nikolaj Klöcker
Journal: Neuron (2009)
Tissue plasminogen activator (tPA) inhibits plasmin degradation of fibrin. A mechanism that slows tPA-mediated fibrinolysis but does not require alpha 2-antiplasmin or leakage of intrinsic plasminogen.
Authors: J H Wu, S L Diamond
Journal: Journal of Clinical Investigation (1995)

Thrombolysis is dramatically slower when high concentrations of lytic agent are used. This paradoxical observation, first described as "plasminogen steal," was originally believed to be due to depletion of extrinsic plasminogen and consequent leaching of clot-bound plasminogen. We report that administration of increasing concentrations of recombinant human tissue plasminogen activator (tPA) to fibrin gels resulted in lysis rates that displayed a maximum, with significantly slower rates found at higher tPA, regardless of whether plasminogen was supplied extrinsically or intrinsically. A similar maximum in lysis rates was observed in a system lacking an extrinsic phase when plasminogen was added to fibrin suspensions preincubated with increasing tPA. Thus, intrinsic plasminogen leakage and alpha 2-antiplasmin were not required for the decreased lysis at high tPA. No maximum was observed for increasing concentrations of urokinase. Using fibrin suspensions or gels preincubated with tPA before addition of plasmin, we report that tPA, but not urokinase, caused a dose-dependent inhibition of the fibronolytic action of plasmin. With respect to optimal dosage schemes and the design of novel lytic agents, these findings indicate that (a) there exists a biochemical mechanism against minimizing reperfusion time with increasing tPA dosages and (b) the fibrin affinity of tPA may cause reduced fibrinolysis by plasmin.
Is Informed Consent Enough? Monetary Incentives for Research Participation and the Integrity of Biomedicine
Authors: Mark Kuczewski
Journal: The American Journal of Bioethics (2001)

(2001). Is Informed Consent Enough? Monetary Incentives for Research Participation and the Integrity of Biomedicine. The American Journal of Bioethics: Vol. 1, No. 2, pp. 49-51.
Electronic health records
Authors: J R Thornham
Journal: BMJ (1995)

EDITOR,—I fear that Dipak Kalra seems to have missed what is going on in computing in general practice in Britain while concentrating on other European countries.

Kalra says that “EDIFACT will soon be used in primary care to communicate fee claims.” In fact, links between general practices and family health services authorities for registration have functioned for at least two years, and last September my practice completed the first full year of …
A Range of CD4 T Cell Tolerance: Partial Inactivation to Organ-Specific Antigen Allows Nondestructive Thyroiditis or Insulitis
Authors: Srinivas Akkaraju, William Y Ho, Denise Leong, Karen Canaan, Mark M Davis, Christopher C Goodnow
Journal: Immunity (1997)

T cell receptor (TCR) transgenic mice specific for hen egg lysozyme (HEL) were crossed with mice expressing HEL on the thyroid epithelium, on pancreatic islet β cells, or systemically. Depending on the pattern of HEL expression, deletion of double-positive thymocytes ranged from minimal to complete, and peripheral CD4 cells exhibited graded reduction in TCR expression, in vitro responsiveness, and in vivo helper ability. CD4 cells were least tolerant in TCR/thyroid-HEL and TCR/islet-HEL mice, which developed an extensive lymphocytic thyroiditis or insulitis that nevertheless did not eliminate HEL-expressing endocrine cells. Autoreactive CD4 clones thus escape the thymus under a range of circumstances, retain sufficient function to initiate subclinical autoimmune inflammation when self-antigens are concentrated in the thyroid or pancreas, and may regulate progression of subclinical inflammation to destructive autoimmune disease.
Differential Role of K <sub>ATP</sub> Channels Activated by Conjugated Estrogens in the Regulation of Myocardial and Coronary Protective Effects
Authors: Tsung-Ming Lee, Tsai-Fwu Chou, Chang-Her Tsai
Journal: Circulation (2003)

Background— We have demonstrated that estrogen can reduce myocardial injury in ischemia-reperfusion via activation of ATP-sensitive potassium (K ATP ) channels. We sought to determine whether the protective effect of estrogen extends to epicardial coronary artery with attenuated vasoconstriction in patients after angioplasty by activation of such channels. Methods and Results— The study was designed to prospectively investigate 41 consecutive patients scheduled for elective coronary angioplasty. Pretreatment with estrogen limited myocardial ischemia during coronary occlusion and attenuated postangioplasty coronary vasoconstriction at the dilated and distal segments. An inhibitor of K ATP channels, glibenclamide, did not affect coronary vasomotor response, although it abolished the beneficial effect of estrogen on myocardial ischemia. Patients to whom estrogen was administered after the second balloon deflation experienced a similar magnitude of myocardial ischemia as controls but showed significantly attenuated vasoconstriction compared with controls ( P =0.0001). Endothelin-1 levels from the great cardiac vein rose significantly from 1.9±0.4 to 3.1±0.6 pg/mL ( P =0.001) 15 minutes after angioplasty in the control group; this was attenuated after estrogen was administered. Significant correlation was found between the changes in coronary vasomotion of the dilated segment and endothelin-1 levels ( r =0.65, P &lt;0.0001). Conclusions— These results demonstrate that estrogen is protective against both myocardial ischemia and coronary vasoconstriction through different mechanisms. The myocardial effect of estrogen was abolished by glibenclamide, which suggests that the cardioprotective effect of estrogen may result from activation of K ATP channels. In contrast, estrogen-induced attenuated vasoconstriction is associated with an attenuated release of endothelin-1, independent of K ATP activation.
A randomized controlled pilot study of strategies to increase adherence in teenagers with acne vulgaris
Authors: Brad A. Yentzer, Amy L. Gosnell, Adele R. Clark, Daniel J. Pearce, Rajesh Balkrishnan, Fabian T. Camacho, Trudye A. Young, Julie M. Fountain, Alan B. Fleischer, Luz E. Colón, Lori A. Johnson, Norman Preston, Steven R. Feldman
Journal: Journal of the American Academy of Dermatology (2011)
Mallory-Weiss Syndrome and Hypofibrinogenemia
Authors: Julien M. Goodman
Journal: JAMA (1964)

SUDDEN uncontrollable bleeding is an alarming and frustrating hazard of surgery. When control is possible, it is by immediate recognition and modification of the cause that proves life saving to the patient. <h3>Report of a Case</h3> A 46-year-old white male with recurrent unceration at the anastomotic site of a gastroduodenostomy done six years previously following a Billroth I gastrectomy for bleeding was admitted to the hospital for surgical treatment. He was re-explored through an upper midline incision, and a 5 mm unceration was found perforating through the posterior inferior portion of the anastomotic site and into the pancreas. A bilateral vagectomy with a resection of 50% of the remaining stomach and freeing of the ulcerated anastomosis from the pancreas was done, the duodenum transected beyond this ulcer and closed, and a retrocolic gastrojejunostomy accomplished. As packs were removed prior to closure, the patient began to hiccup violently and repeatedly until
Evaluation of a new enzyme immunoassay for hepatitis C virus (HCV) core antigen with clinical sensitivity approximating that of genomic amplification of HCV RNA
Authors: Eiji Tanaka, Chiharu Ohue, Katsumi Aoyagi, Kenjiro Yamaguchi, Shintaro Yagi, Kendo Kiyosawa, Harvey J. Alter
Journal: Hepatology (2000)

The aim of this study was to analyze the clinical performance of a new enzyme immunoassay (EIA) for hepatitis C virus (HCV) core antigen in comparison with the reverse transcription polymerase chain reaction (RT-PCR). A total of 310 patients with acute or chronic hepatitis C, and 132 HCV-negative controls were studied. Chemiluminescence EIA with monoclonal anti-HCV core antigen was used, and qualitative and quantitative commercial RT-PCRs and an in-house nested RT-PCR were performed. Compared with nested RT-PCR, the core antigen assay showed 97% sensitivity and 100% specificity in 75 patients with chronic hepatitis C and 132 controls. HCV core antigen was positive in 16 (94%) of 17 patients with acute hepatitis C at initial consultation. In 3 persons prospectively followed, core antigen was detected in the first available (1-3 weeks) post-transfusion sample. In 167 anti-HCV-positive individuals, 129 (77%) were viremic; core antigen was detected in 126 (98%) compared with 129 (100%) for nested RT-PCR and 121 (94%) for the commercial RT-PCR. In 48 patients with chronic hepatitis C treated with interferon alfa, the concentration of core antigen before treatment was significantly ( P &lt; .002) lower in patients with sustained response than in nonresponders. All responders had a sustained loss of core antigen, whereas all nonresponders remained core antigen positive. The concentrations of HCV core antigen and HCV RNA correlated significantly (n = 48, r = .627, P &lt; .001). In conclusion, the HCV core antigen assay is useful for the diagnosis of acute and chronic hepatitis C, and for predicting and monitoring the effect of interferon alfa treatment.
FDA approves first drug to prevent HIV infection
Authors: B. Roehr
Journal: BMJ (2012)

The US Food and Drug Administration this week approved for the first time a drug for use in the prevention of HIV infection. The drug, Truvada, is one of the most commonly used components of an anti-HIV “cocktail” regimen in the United States and Europe.

Truvada is two drugs combined in a single pill, tenofovir disoproxil fumarate and emtricitabine. Its preventive use is commonly referred to as PrEP (pre-exposure prophylaxis). Studies in different groups at high risk of infection have shown its efficacy.1

It was approved “to reduce the risk of HIV infection in uninfected individuals who are at high risk of HIV infection and who may engage in sexual activity with HIV-infected partners,” said Debra Birnkrant in a telephone press conference with reporters. She is director …
Two Generations of Broken Homes in the Genesis of Conduct and Behaviour Disorders in Childhood
Authors: C. J. Wardle
Journal: BMJ (1961)

FUNCTIONAL " DISORDERSB do what he can to correct anxiety and the more obvious environmental factors which may be contributing to the symptoms.The impression from the follow-up reports of the functional cases is that both physical and mental health have been quite good during the years that followed consultation and that the reassurance provided at the clinic was in many instances justified by the course of events.We have no means of determining accurately the benefit to mental health which accrued from the advice given at consultation, and have relied-as others have-on the repor,s of the patient's personal medical attendant.In this sEries the generally good prognosis in neurosis is in accordance with the findings of others.Eysenck (1952), while surveying the effects of psychotherapy, came to the conclusion that there was little to support the hypothesis that psychotherapy facilitated recovery in neurotic patients.Nevertheless, the role of the doctor as a therapeutic agent is well recognized, and this aspect has been studied and emphasized by Wolf (1959) and by Hankoff et al. (1960).Our impression, therefore, is that the psychological effect of a properly conducted out-patient examination Wan be very valuable and is worthy of special study.Summary About 5% of out-patients attending a neurological clinic were thought by the consultants concerned to have no significant organic disease'to account for their symptoms.A series of 100 of these " functional " cases, which had been treated chiefly by reassurance and explanation, were followed up over five years later.Eight had left the district and could not be traced.Of the remaining 92, 78 were in good health and had no apparent organic disease, but in 26 of these some minor symptoms persisted although these were not disabling.Two patients died two and a half years after being seen-one of carcinoma of the stomach and one with disseminated sclerosis.Two patients developed epilepsy, one had a facial pain later relieved by tooth extraction, one developed hypertension, one developed myxoedema, and one developed a prolapsed disk.Six patients developed organic illness which had no obvious connexion with the original presenting symptoms.It is suggested that consultants should in most instances endeavour themselves to treat the functional cases attending their clinics and that by conducting follow-up studies they can check on the standard of work.It seems desirable that the most experienced personnel available should work in the out-patient departments of hospitals.ADDENDUM.-Sincepreparation of the paper two further patients have been traced.Both have remained in very good health at the end of a five-year follow-up.
The dangers of desire
Authors: Susie Orbach
Journal: The Lancet (2007)

Amélie Nothomb's The Life of Hunger has many purpose and many pleasures. Using the form of the fictional memoir, a highly imaginative expatriate child moved from country to country tells us about hunger. With elegance, she introduces us to hunger's historical and cultural consequences. Her exuberant, sensual desire and hunger for life captivate us until we watch her enter into the abject state of finding her desire for life and her desire for food turned against herself as she succumbs to the grip of anorectic behaviour.
Langerhans cell histiocytosis following childhood acute lymphoblastic leukemia
Authors: Ashok Raj, Robert Bendon, Thomas Moriarty, Carlos Suarez, Salvatore Bertolone
Journal: American Journal of Hematology (2001)

Abstract Langerhans cell histiocytosis (LCH) is a clonal proliferation of Langerhans cells of unknown etiology that results in a range of clinical manifestations. LCH has been known to be associated with a variety of malignant diseases. A 7‐year‐old boy was treated for standard‐risk acute lymphoblastic leukemia (ALL) at age 2 years, on a Children's Cancer Group chemotherapy protocol for 3 years and developed LCH 2 years after completion of chemotherapy. The case and a review of literature on the association of LCH and ALL are presented. Am. J. Hematol. 68:284–286, 2001. © 2001 Wiley‐Liss, Inc.
Characterization of direct antiglobulin test‐negative autoimmune hemolytic anemia: A study of 154 cases
Authors: Toyomi Kamesaki, Tomonori Toyotsuji,, Eiji Kajii
Journal: American Journal of Hematology (2012)

Direct antiglobulin test (DAT)-negative (DAT-)autoimmune hemolytic anemia (AIHA) is empirically thought to show the same clinical conditions as DAT-positive (DAT+)AIHA, with the exception of an adequate amount of red blood cell (RBC)-bound immunoglobulin (Ig)G. We investigated the clinical characteristics of DAT-AIHA in comparison with DAT+AIHA. Of the 582 patients referred to our laboratory with undiagnosed hemolytic anemia, AIHA was clinically diagnosed in 216 patients (DAT-AIHA, n = 154; DAT+AIHA, n = 62). The percentage of reticulocytes, mean corpuscular volume, RBC-IgG levels, white blood cell count, and total protein (TP) levels were significantly higher in patients with DAT+AIHA than patients with DAT-AIHA. The hemoglobin level was significantly lower in patients with DAT+AIHA. No significant differences between patients with DAT-AIHA and DAT+AIHA existed with respect to age, gender, idiopathic/secondary nature, complications such as Evans syndrome, effectiveness of steroid treatment, or survival rate at 1 year following diagnosis. Patients with DAT-AIHA required significantly lower doses of steroids for maintenance therapy. Based on multivariate analysis of idiopathic DAT-AIHA (n = 110), TP and Evans syndrome were associated with the effectiveness of steroids (adjusted odds ratio [aOR], 1.36/[0.1 g/dl]; 95% confidence interval [CI], 1.01-1.84) and survival at the 1-year follow-up (aOR, 0.1; 95% CI, 0.01-0.88). Our results indicate that patients with DAT-AIHA generally suffer milder anemia and hemolysis than patients with DAT+AIHA, respond equally well to steroids, and have comparable survival at 1-year.
Rosette-forming T Lymphocytes and Cell-mediated Immunity in Malnutrition
Authors: R. K. Chandra
Journal: BMJ (1974)

The frequency of rosette-forming thymus-dependent lymphocytes was reduced in the peripheral blood of malnourished infants and children. The reduced frequency parallelled the impairment of delayed hypersensitivity response to 2, 4-dinitrochlorobenzene and decreased DNA synthesis by lymphocytes challenged with phytohaemagglutinin. The abnormalities were reversed on nutritional improvement.
A missense mutation at codon 188 of the human lipoprotein lipase gene is a frequent cause of lipoprotein lipase deficiency in persons of different ancestries.
Authors: M V Monsalve, H Henderson, G Roederer, P Julien, S Deeb, J J Kastelein, L Peritz, R Devlin, T Bruin, M R Murthy
Journal: Journal of Clinical Investigation (1990)

Lipoprotein lipase (LPL) plays a crucial role in the regulation of lipoprotein metabolism by hydrolysing the core triglycerides of circulating chylomicrons and VLDL. Human, bovine, mouse, and guinea pig complementary DNA clones have recently been isolated and the organization of the human LPL gene is now known to comprise 10 exons spanning approximately 30 kb. Here we report a similar mutation on 21 alleles from 13 unrelated affected probands with LPL deficiency of French Canadian, English, Polish, German, Dutch, and East Indian ancestry. We show that an identical missense mutation within exon 5, resulting in an amino acid substitution of glutamic acid for glycine at position 188, is responsible for LPL deficiency in 21 of 88 LPL alleles assessed. This mutation alters an Ava II restriction site in exon 5 and will allow a rapid screening test for this mutation in patients with LPL deficiency. This mutation has occurred on the same haplotype in all the unrelated affected persons suggesting a common origin. The amino acid substitution lies within the longest segment of homology for LPL in different species and results in a protein that is catalytically defective.
Tuberculin Booster Reactions and Conversions
Authors: Richard Menzies
Journal: Annals of Internal Medicine (1994)

Letters1 September 1994Tuberculin Booster Reactions and ConversionsRichard Menzies, MDRichard Menzies, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-121-5-199409010-00043 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:In response to the letters of Drs. Harrington and Dr. Sobel, our data suggest that, compared with those with positive initial tuberculin reactions, the participants with positive booster reactions (defined as a PPd-T2 reaction of ≥ 10mm and a PPd-T2 minus PPd-T1 reaction of ≥ 6 mm) were more likely to have had bacille Calmette–Guérin vaccination or sensitization to atypical mycobacterial antigens, both considered causes of false-positive tuberculin reactions. Dr. Sobel's data from Israeli school children support our conclusion that positive booster reactions are much less likely to represent previous tuberculous infection (that is, true-positive) than initial tuberculin ...References1. Ferebee SH. Controlled chemoprophylaxis trials in tuberculosis. Adv Tuberculosis Res. 1969; 17:28-106. Google Scholar2. Stead WW, Lofgren JP, Warren E, Thomas C. Tuberculosis as an endemic and nosocomial infection among the elderly in nursing homes. N Engl J Med. 1985; 312:1483-7. Google Scholar3. Stead WW, To T. The significance of the tuberculin skin test in elderly persons. Ann Intern Med. 1987; 107:837-42. Google Scholar4. Menzies R, Vissandje B, Rocher E, St. Germain Y. The booster effect in two-step tuberculin testing among young adults in Montreal. Ann Intern Med. 1994; 120:190-8. Google Scholar Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byHigh Risk for Tuberculosis in Hospital Physicians, Peru 1 September 1994Volume 121, Issue 5Page: 387-388KeywordsAntigensChildrenPediatric infectionsPreventive medicineSpecificityTuberculinTuberculin testsYoung adults ePublished: 15 August 2000 Issue Published: 1 September 1994 Copyright & PermissionsCopyright © 1994 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...