tbuckley/cabot-search huggingface dataset:
A 2-year randomised placebo-controlled trial of doxycycline for lymphangioleiomyomatosis
Authors: W. Y. C. Chang, J. L. Cane, M. Kumaran, S. Lewis, A. E. Tattersfield, S. R. Johnson
Journal: European Respiratory Journal (2013)

Lymphangioleiomyomatosis (LAM) is characterised by lung cysts and airflow obstruction. Matrix metalloproteinases have been implicated in lung destruction in LAM. We performed a randomised, double-blind trial, comparing the matrix metalloproteinases inhibitor doxycycline with placebo on the progression of LAM. 23 females with LAM were randomised to doxycycline 100 mg daily for 3 months followed by 200 mg daily for 21 months, or matched placebo. Lung function, exercise capacity, quality of life and matrix metalloproteinases levels were measured. 21 patients completed 6 months of treatment, 17 completed 1 year of treatment and 15 completed 2 years of treatment. Eight withdrew from the trial due, four due to a pneumothorax and four because of other reasons. The mean±sd decline in FEV<sub>1</sub>, the primary endpoint, did not differ between the groups being -90±154 mL·year<sup>−1</sup> in the placebo group and -123±246 mL·year<sup>−1</sup> in the doxycycline group (difference -32.5, 95% CI -213–148; p=0.35). Doxycycline had no effect upon vital capacity, gas transfer, shuttle walk distance or quality of life. Urine matrix metalloproteinases-9 measurements were lower with doxycycline treatment (p=0.03). Although with limited numbers we cannot completely exclude an effect of doxycycline, the lack of effect on any outcome makes it unlikely that doxycycline has a useful effect in LAM.
A role of autoantibody-mediated platelet destruction in thrombocytopenia in patients with cirrhosis
Authors: Mikio Kajihara, Shinzo Kato, Yuka Okazaki, Yutaka Kawakami, Hiromasa Ishii, Yasuo Ikeda, Masataka Kuwana
Journal: Hepatology (2003)

Thrombocytopenia is a common manifestation in patients with liver cirrhosis (LC), but its underlying mechanism remains controversial. This study examined the role of anti–platelet autoimmunity in cirrhotic thrombocytopenia by determining the autoantibody response to GPIIb–IIIa, a major platelet surface autoantigen recognized by anti–platelet antibodies in patients with idiopathic thrombocytopenic purpura (ITP). Circulating B cells producing anti–GPIIb–IIIa antibodies as well as platelet–associated and plasma anti–GPIIb–IIIa antibodies were examined in 72 patients with LC, 62 patients with ITP, and 52 healthy controls. In vitro anti–GPIIb–IIIa antibody production was induced in cultures of peripheral blood mononuclear cells (PBMCs) by stimulation with GPIIb–IIIa. The frequency of anti–GPIIb–IIIa antibody–producing B cells in patients with LC was significantly greater than in healthy controls (10.9 ± 6.2 vs. 0.4 ± 0.3/10 5 PBMCs; P &lt; .0001) and was even higher than the frequency in patients with ITP (8.2 ± 5.2; P = .007). Anti–GPIIb–IIIa antibodies in the patients with LC and ITP were mainly present on the surfaces of circulating platelets rather than in the plasma in an unbound form. Furthermore, PBMCs from patients with LC and ITP produced anti–GPIIb–IIIa antibodies on antigenic stimulation with GPIIb–IIIa in vitro , and the specific antibodies produced had the capacity to bind normal platelet surfaces. In conclusion, the similar profile of the anti–GPIIb–IIIa autoantibody response in patients with LC and ITP suggests that autoantibody–mediated platelet destruction may contribute at least in part to cirrhotic thrombocytopenia.
Naturally occurring oncogenic GATA1 mutants with internal deletions in transient abnormal myelopoiesis in Down syndrome
Authors: Tsutomu Toki, Rika Kanezaki, Eri Kobayashi, Hiroshi Kaneko, Mikiko Suzuki, RuNan Wang, Kiminori Terui, Hirokazu Kanegane, Miho Maeda, Mikiya Endo, Tatsuki Mizuochi, Souichi Adachi, Yasuhide Hayashi, Masayuki Yamamoto, Ritsuko Shimizu, Etsuro Ito
Journal: Blood (2013)
889 CHRONIC HEPATITIS C (CHCV) IS ASSOCIATED WITH HYPEREXPRESSION OF PROGRAMMED DEATH (PD)-1 PATHWAY ON THE CELLULAR SUBSETS OF THE HOST ADAPTIVE/INNATE IMMUNE RESPONSE
Authors: A. Riva, A. Evans, S. Phillips, N.V. Naoumov, S. Chokshi
Journal: Journal of Hepatology (2009)
Guidelines on drug trials in children go out for consultation
Authors: Rory Watson
Journal: BMJ (2006)

Draft guidelines on the ethics of clinical trials involving children have been put out for public consultation by the European Commission and the European Medicines Agency.

The guidelines have been drawn up in line with EU legislation on the conduct of good clinical practice in trials of medicinal products for human use. This legislation specifically called for criteria to be agreed to protect children.

The guidelines are directed at sponsors of clinical trials, ethics committees, and investigators of clinical trials involving children of all ages (from birth to 18 years of age). They …
Accessory Atrioventricular Myocardial Connections in the Developing Human Heart
Authors: Nathan D. Hahurij, Adriana C. Gittenberger-De Groot, Denise P. Kolditz, Regina Bökenkamp, Martin J. Schalij, Robert E. Poelmann, Nico A. Blom
Journal: Circulation (2008)

Fetal and neonatal atrioventricular (AV) reentrant tachycardias can be life-threatening but resolve in most cases during the first year of life. The transient presence of accessory AV myocardial connections during annulus fibrosus development may explain this phenomenon.A total of 45 human embryonic, fetal, and neonatal sectioned hearts (4 to 36 weeks of development) were studied immunohistochemically. Accessory myocardial AV connections were quantified and categorized according to their specific location, and 3D reconstructions were made. Between 4 and 6 weeks of development, the atrial and ventricular myocardium was continuous at the primitive AV canal. At 6 to 10 weeks, numerous accessory myocardial AV connections were identified in the left (45%), right (35%), and septal (20%) regions of the AV junction. Most right-sided accessory connections comprised distinct myocardial strands, whereas left-sided connections consisted of larger myocardial continuities. At 10 to 20 weeks, all accessory AV connections comprised discrete myocardial strands and gradually decreased in number. The majority of accessory connections were located in the right AV junction (67%), predominantly in the lateral aspect (45%). Seventeen percent of the accessory connections were observed in the left AV junction, and 16% were observed in the septal region. 3D reconstructions of the developing AV nodal area at these stages demonstrated multiple AV node-related accessory connections. From 20 weeks until birth, and in neonatal hearts, no further accessory myocardial AV connections were observed.Isolation of the AV junction is a gradual and ongoing process, and right lateral accessory myocardial AV connections in particular are commonly found at later stages of normal human cardiac development. These transitory accessory connections may act as substrate for AV reentrant tachycardias in fetuses or neonates.
Corticotropin-induced reduction of plasma lipoprotein(a) concentrations in healthy individuals and hemodialysis patients: Relation to apolipoprotein(a) size polymorphism
Authors: Margret Arnadottir, Anna-Lena Berg, Florian Kronenberg, Arno Lingenhel, Therése Hugosson, Jörgen Hegbrant, Peter Nilsson-Ehle
Journal: Metabolism (1999)
The Relevance of History for the Community Mental Health Approach to Children
Authors: GEORGE MORA
Journal: American Journal of Psychiatry (1972)

The author reviews the content of two books—the Levines' A Social History of Helping Services and the report of the Joint Commission on Mental Health of Children—and points out that many elements of today's community mental health movement were in use in the past, a fact that is ignored in the Commission's report. He stresses the need for American psychiatry to examine and use its history.
Establishment of a binding assay for protein kinase C isozymes using synthetic C1 peptides and development of new medicinal leads with protein kinase C isozyme and C1 domain selectivity
Authors: Kazuhiro Irie, Akifumi Nakahara, Yu Nakagawa, Hajime Ohigashi, Mayumi Shindo, Hiroyuki Fukuda, Hiroaki Konishi, Ushio Kikkawa, Kaori Kashiwagi, Naoaki Saito
Journal: Pharmacology & Therapeutics (2002)
Alveolar inflammation and its relation to emphysema in smokers.
Authors: R Finkelstein, R S Fraser, H Ghezzo, M G Cosio
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

The prevalent theory in the pathogenesis of emphysema proposes that increased numbers of activated neutrophils and/or alveolar macrophages produce large amounts of proteases, an activity that cannot be regulated by alpha 1-antiproteases, resulting in lung destruction. However, the cells in the lung parenchyma of smokers have not been properly identified. We characterized and quantitated the inflammatory cell load in the lungs of smokers and correlated these findings with the degree of lung destruction. Twenty-one patients, six nonsmokers and 15 smokers, undergoing lung resection were studied. Lungs or lobes were fixed and stained for light microscopy and neutrophil identification and immunohistochemically stained for identification of lymphocytes and macrophages. By point counting, we determined the extent of emphysema by the volume density of the lung parenchyma (Vvalv), and the different cell numbers per cubic millimeter in all lungs. In nonsmokers Vvalv was greater than in smokers. The number of neutrophils/mm3 of lung correlated directly with the Vvalv, (r = 0.71, p < 0.01), whereas the number of alveolar macrophages (r = -0.70) and T-lymphocytes (r = -0.78) correlated negatively with the Vvalv. The number of T-lymphocytes correlated negatively with the number of neutrophils (r = -0.58) and positively with the numbers of alveolar macrophages (r = 0.77). Our data suggest that as long as the inflammatory reaction is predominantly of neutrophils there is no destruction of the lung. However, the extent of lung destruction becomes evident, and its extent is directly related to the number of alveolar macrophages and T-lymphocytes/mm3. We conclude that the T-lymphocyte might be importantly implicated in the pathogenesis of emphysema in smokers.
Symptom Perception during Acute Bronchoconstriction
Authors: KIERAN J. KILLIAN, RICHARD WATSON, JOCELINE OTIS, TIMOTHY A. ST. AMAND, PAUL M. O'BYRNE
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

The hypothesis underlying the present study was that some of the variability in symptom intensity seen during acute bronchoconstriction may result from varying intensities of several stimuli yielding several sensations that can be identified by specific descriptive expressions (symptoms). A total of 232 subjects inhaled methacholine in doubling concentrations to a 20% decrease in FEV(1), or 64 mg/ml. The study identified the prevalence of dyspnea, nonspecific discomfort associated with the act of breathing, and 10 specific symptom expressions. Each symptom intensity was rated in Borg scale units. The contribution of the specific symptoms to the intensity of dyspnea is illustrated in the following equation (r = 0. 84): Dyspnea = 0.44 + 0.19 Difficult breathing + 0.41 Chest tightness + 0.20 Breathlessness + 0.14 Labored breathing + 0.11 Chest pain. Dyspnea was more intense with broncho-constriction, baseline pulmonary impairment, weight, and sex (being female). Dyspnea was less intense with age (being older) and as airway responsiveness to methacholine increased (p < 0.05 for all factors). Chest tightness and chest pain were at polar extremes on the discrimination scale, i.e., easily discriminated; chest tightness, difficult and labored breathing were not easily discriminated.
PATHOLOGICAL REPORT ON A CASE OF DERMATITIS VESICULO-BULLOSA ET GANGRÆNOSA MUTILANS MANUUM (DUHRING), WITH A CONSIDERATION OF THE RELATIONS OF VASCULAR AND NERVOUS CHANGES TO SPONTANEOUS GANGRENE AND RAY NAUD'S DISEASE
Authors: William G. Spiller
Journal: The Journal of Experimental Medicine (1900)

PLATES IV AND V
Th17/Treg ratio in human graft-versus-host disease
Authors: Philippe Ratajczak, Anne Janin, Regis Peffault de Latour, Christophe Leboeuf, Allison Desveaux, Keyvan Keyvanfar, Marie Robin, Emmanuel Clave, Corine Douay, Anne Quinquenel, Claire Pichereau, Philippe Bertheau, Jean Yves Mary, Gérard Socié
Journal: Blood (2010)
Is your enema really necessary?
Authors: M L Romney, H Gordon
Journal: BMJ (1981)

Two hundred and seventy-four women admitted for delivery of singleton infants were studied for the effects of a preparatory enema on faecal contamination, duration of labour, and the incidence of infection in the newborn. Altogether 149 of the women were given an enema (controls) and 125 were not. The two groups showed no significant difference in the degree of faecal contamination during the first and second stages of labour, and the incidences of gross contamination were similar. Contamination after an enema was especially difficult to control, since it was more likely to be fluid. Seven neonates in each group showed evidence of infection, bowel organisms being isolated from four in the no-enema group and two in the control group. Durations of labour, though not strictly comparable, were similar in the two groups. The findings suggest that when preparing for normal labour the enema should be reserved for women who have not had their bowels open in the past 24 hours and have an obviously loaded rectum on initial pelvic examination.
Generation of oxygen radicals by minerals and its correlation to cytotoxicity.
Authors: V Vallyathan
Journal: Environmental Health Perspectives (1994)

Occupational exposure to mineral dust causes pneumoconiosis and other diseases. A cytotoxicity assay to predict the potential of minerals to cause disease would be of great value as a prevention strategy. This study compares the ability of several minerals to generate the more potent oxidizing agent, hydroxyl radical (.OH), and their cytotoxicity and lipid peroxidation potentials. Crystalline silica, the most potent cytotoxic and pathogenic mineral studied, showed the least ability to generate .OH radicals while inducing the maximal lipid peroxidation. Coal mine dust, showing the maximal ability to generate .OH radicals, was the least cytotoxic in bioassays of toxicity and induction of lipid peroxidation. Based on these results, it would appear that the ability of minerals to induce lipid peroxidation provides a better correlation with known cytotoxicity and pathogenicity of minerals than does their ability to generate oxygen radicals.
Aspirin and suspected myocardial infarction
Authors: B K K Shetty
Journal: BMJ (1994)

EDITOR, - Michael Moher and Neil Johnson, and also Hazel R Wyllie and Francis G Dunn, cite the second international study of infarct survival (ISIS-2) to recommend that general practitioners should carry aspirin and give aspirin to patients with suspected acute myocardial infarction before transfer to hospital.1,2 They imply that giving aspirin three or four hours before the patient receives thrombolysis, rather than giving …
1003-87 Reperfusion time-dependent myocardial salvage in patients with acute myocardial infarction who undergo emergent percutaneous coronary intervention with distal protection device percuSurge
Authors: Hiroaki Mukawa, Takahito Sone, Hideyuki Tsuboi, Itsuro Morishima, Masahiko Satoda, Michitaka Uesugi
Journal: Journal of the American College of Cardiology (2004)
Leukocyte migration inhibition test in children with cow milk allergy
Authors: T. Vanto, E. M. Smogorzewska, M. Viander, K. Kalimo, A. Koivikko
Journal: Allergy (1987)

The usefulness of the leukocyte migration inhibition factor (LIF) test to detect cow milk (CM) hypersensitivity was studied in 40 children with suspected allergy to CM. Hyper‐sensitivity was carefully investigated by oral milk challenges, which gave a final confirmation of cow milk hypersensitivity in 12 subjects, and excluded it in the remaining 28 subjects. Leukcocyte migration inhibition was measured using β‐lactoglobulin (BLG), α‐lactalbumin (ALA), α‐casein (ACA) and bovine serum albumin (BSA) as antigens. IgA and IgG antibodies to these antigens were measured by an enzyme‐linked immunosorbent assay, and IgE antibodies to these antigens and to CM by radioallergosorbent test (RAST). Skin prick test with CM was performed in 38 subjects, and with BLG, ALA, ACA and BSA in 29 subjects. Leukocyte migration was more often inhibited by cow milk antigens in the CM challenge positive (CM +) subjects than in the challenge negative (CM‐) subjects. Of the specific milk antigens, ALA was the most potent inhibitor, and gave a positive LIF test result in all CM + subjects, and significantly ( P &lt; 0.02) less often (15/24) in CM‐ subjects. Also in the skin prick test and RAST, ALA gave positive results more often than the other milk antigens. BLG, ACA and BSA had an inhibiting effect on leukocyte migration, but the difference between the CM + and CM‐ subjects was not statistically significant. Two of the 12 CM + subjects had no demonstrable IgE antibodies to CM proteins; both of them, however, had a positive LIF test with at least one of the CM antigens. No significant correlation was observed between leukocyte migration inhibition and the serum levels of IgA, IgG or IgE antibodies to milk antigens. The results of this study suggest that cell‐mediated immunity may play a role in cow milk allergy, also in subjects with demonstrable IgE antibodies to CM. Even though the LIF test is sensitive in the diagnosis of cow milk allergy, it is not useful as a diagnostic test, since many challenge‐negative subjects had a positive LIF test.
Diagnosis and treatment of lung cancer: summary of updated NICE guidance
Authors: D. R. Baldwin, B. White, M. Schmidt-Hansen, A. R. Champion, A. M. Melder
Journal: BMJ (2011)

Each year in the United Kingdom over 35 000 people die from lung cancer, 4000 more than from breast and bowel cancer combined,1 and survival remains lower than in other developed countries.2 Inequality exists in the UK in the delivery of treatment with curative intent3 as well as in delivery of active treatments generally. All healthcare professionals involved at any stage of the care pathway have important roles to play in tackling these inequalities. Thus the 2005 guidance from the National Institute for Health and Clinical Excellence (NICE) on the diagnosis and treatment of lung cancer was updated to advise healthcare professionals of important advances in management and to ensure patients have a supported, informed choice of the treatment that will help them most. This article summarises the recommendations from the updated NICE guideline on the diagnosis and treatment of lung cancer.4 NICE recommendations are based on systematic reviews of best available evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on the Guideline Development Group's experience and opinion of what constitutes good practice. Evidence levels for the recommendations are given in italic in square brackets. ### Early diagnosis and referral #### Referral (recommendations retained from 2005)
The Migration of a Needle.
Authors: Sara A. Kime
Journal: JAMA (1889)

<h3>To the Editor:</h3> —On Dec. 9, 1888, Miss Nellie S., æt. 17, called at my office and stated that she believed she had a needle in her arm. Upon careful inquiry I could find no reason for such a supposition, except that she could feel something like a needle, one end of which was beneath the skin, while the other was deep in the muscles near the bone. She had never run a needle into her arm or in any other part of her body, and it was with much doubt as to the correctness of her belief that I began my examination. Miss Nellie pinched up a roll of integument and muscle on her arm, and thrust one end of the supposed needle against the skin. It had all the appearance of some such foreign material, and I cut down upon the projecting point with forceps; I then removed
Cancer and Thyroid Function
Authors: Richard D. Liechty, Robert E. Hodges, Janice Burket
Journal: JAMA (1963)

MALIGNANT DISEASE, according to a remote clinical impression, occurs less commonly in thyrotoxic persons than it does in others. Some references support this association, but not all agree. 1-4   The unknown factors regulating cellular growth challenge medical science. Clinicians recognize that in some patients a neoplasm may grow wildly and cause death within a short time, whereas a similar neoplasm in another patient may grow slowly and allow prolonged survival. In a few well-documented instances, the growth of malignant metastatic lesions has stopped abruptly for prolonged periods without apparent cause. 5 Presumably the rate of growth of malignant cells is dependent upon unidentified factors which regulate metabolic activity of these cells.  Thyroid activity usually reflects the underlying state of cellular metabolic activity. Does occurrence of cancer vary with altered thyroid metabolic states? This question provides the central theme of the following study which compares the incidence and type of
Need-Based Requirements for Primary Care Physicians
Authors: Pamela C. Roddy
Journal: JAMA (1980)

THE SHORTAGE of primary care physicians resulting from a maldistribution of physicians among the specialties is considered one of the major problems in today's health care system. What constitutes "an adequate supply" of primary care providers has not been defined. The proportion in 1975 was 38% of the total physician supply.<sup>1</sup>The stated goal of the American Medical Association and the recommendations of the Institute of Medicine is 50% of the total physician supply. The rationale for this goal is difficult to determine and appears to be conjectural, based on opinion and on physician specialty distributions in other countries and in health maintenance organizations (HMOs). The literature abounds with primary care requirements studies, with estimates ranging far below and far above this stated goal.<sup>2</sup> I examined primary care physician requirements from a "need" perspective. The concept of need is defined by Lee and Jones in their 1933 study
Identification of the low density lipoprotein receptor-binding site in apolipoprotein B100 and the modulation of its binding activity by the carboxyl terminus in familial defective apo-B100.
Authors: J Boren, I Lee, W Zhu, K Arnold, S Taylor, T L Innerarity
Journal: Journal of Clinical Investigation (1998)

Familial defective apolipoprotein B100 (FDB) is caused by a mutation of apo-B100 (R3500Q) that disrupts the receptor binding of low density lipoproteins (LDL), which leads to hypercholesterolemia and premature atherosclerosis. In this study, mutant forms of human apo-B were expressed in transgenic mice, and the resulting human recombinant LDL were purified and tested for their receptor-binding activity. Site-directed mutagenesis and other evidence indicated that Site B (amino acids 3,359-3,369) binds to the LDL receptor and that arginine-3,500 is not directly involved in receptor binding. The carboxyl-terminal 20% of apo-B100 is necessary for the R3500Q mutation to disrupt receptor binding, since removal of the carboxyl terminus in FDB LDL results in normal receptor-binding activity. Similarly, removal of the carboxyl terminus of apo-B100 on receptor-inactive VLDL dramatically increases apo-B-mediated receptor-binding activity. We propose that the carboxyl terminus normally functions to inhibit the interaction of apo-B100 VLDL with the LDL receptor, but after the conversion of triglyceride-rich VLDL to smaller cholesterol-rich LDL, arginine-3,500 interacts with the carboxyl terminus, permitting normal interaction between LDL and its receptor. Moreover, the loss of arginine at this site destabilizes this interaction, resulting in receptor-binding defective LDL.