tbuckley/cabot-search huggingface dataset:
OP0259 The Interleukin 33/MIR29 Axis Regulates Differential Collagen Production in Tendinopathy
Authors: N. L. Millar, D. S. Gilchrist, M. Kurowska-Stolarska, G. A. C. Murrell, I. B. McInnes
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Tendon disorders comprise the commonest musculoskeletal clinical presentation and accordingly represent a significant unmet clinical need. Recent animal and human studies have highlighted a central role for inflammation and subsequent matrix remodelling in tendon pathophysiology. Interleukin-33 (IL-33) acting via its receptor ST2 is increasingly recognised as a critical endogenous tissue danger signal that can initiate inflammation. <h3>Objectives</h3> We investigated the role of the IL-33/ST2 signallingpathway on tendon pathology in animal and human models of tendinopathy. <h3>Results</h3> We show here that human and mouse tendons over express IL-33 when damaged, and drives tenocytes to undergo an early switch in collagen matrix production toward a collagen III phenotype. Moreover, administration of rh IL-33 in an in vivo model of tendinopathy results in reduced biomechanical tendon strength at early time points while neutralising antibodies to IL-33 attenuates these changes. Furthermore we highlight a key regulatory role for the microRNA29 family in IL-33 induced collagen matrix changes through direct targeting of the soluble ST2 receptor and Collagen III. <h3>Image/graph</h3> <h3>Conclusions</h3> For the first time we provide evidence that IL-33/miR-29 pathway orchestrates inflammatory and matrix responses following tissue injury, and thus may offer future strategies to treat tendon diseases diseases. <h3>Disclosure of Interest</h3> None Declared
Alcoholics Anonymous: "The Big Book"
Authors: E. Loder
Journal: BMJ (2009)

Breathes there a doctor who has not heard of or referred a patient to Alcoholics Anonymous (AA)? Alcohol abuse is a medical problem in its own right and complicates many others, yet arguably its most successful treatment remains the lay-led self management system outlined in the multi-authored book Alcoholics Anonymous , often referred to simply as “the big book.”

It remains a bestseller that is periodically updated but retains substantial original content. Along with personal stories and testimonials from recovered alcoholics, the book laid out the now famous 12 steps to recovery, which began with the confession: “We admitted that we were powerless over alcohol—that our lives had become unmanageable.”

The structure of AA groups is the same the world over. They emphasise camaraderie, insist on the need for abstinence, and encourage reliance on a “higher …
Peering into the future: Hepcidin testing
Authors: Jatinder Goyal, Brandi McCleskey, Jill Adamski
Journal: American Journal of Hematology (2013)

Hepcidin, a small 25 amino acid peptide, has been well established as the iron regulatory hormone. Its expression is upregulated in response to iron and inflammatory cytokines, and downregulated in anemic or hypoxic states. Hepcidin decreases iron export into the plasma by binding to and inducing the degradation of ferroportin, an iron channel located on macrophages and the basolateral surface of enterocytes. This leads to decreased absorption of parental iron by the enterocytes, reduced recycling of erythrocyte iron by macrophages, and increased iron stores in the hepatocytes. Although hepcidin assays are not currently approved for clinical use in the United States, there is much interest in the potential use of this biomarker for management of iron related medical conditions. This review briefly summarizes the current hepcidin test platforms under investigation and the challenges associated with development of a clinical assay for this biomarker. In addition, selected potential future applications hepcidin testing in the clinical setting are addressed.
Furnace-generated acid aerosols: speciation and pulmonary effects.
Authors: M O Amdur, L C Chen
Journal: Environmental Health Perspectives (1989)

Guinea pigs were exposed to ultrafine aerosols (less than 0.1 micron) of zinc oxide with a surface layer of sulfuric acid. These acid-coated aerosols are typical of primary emissions from smelters and coal combustors. Repeated daily 3-hr exposures for 5 days produce decrements in lung volumes and pulmonary diffusing capacity and elevations of lung weight/body weight ratio, protein, and number of neutrophils in pulmonary lavage fluid at concentrations of 20 micrograms/m3. A single 1-hr exposure to 20 micrograms/m3 causes increased bronchial reactivity. Higher concentrations of conventionally generated sulfuric acid mist are required to produce responses of similar magnitude.
Stellate cells and the development of liver cancer: Therapeutic potential of targeting the stroma
Authors: Cédric Coulouarn, Bruno Clément
Journal: Journal of Hepatology (2014)

Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the most common types of primary tumors in the liver. Although major advances have been made in understanding the cellular and molecular mechanisms underlying liver carcinogenesis, HCC and ICC are still deadly cancers worldwide waiting for innovative therapeutic options. Growing evidence from the literature highlight the critical role of the tumor cell microenvironment in the pathogenesis of cancer diseases. Thus, targeting the microenvironment, particularly the crosstalk between tumor cells and stromal cells, has emerged as a promising therapeutic strategy. This strategy would be particularly relevant for liver cancers which frequently develop in a setting of chronic inflammation and microenvironment remodeling associated with hepatic fibrosis and cirrhosis, such processes in which hepatic stellate cells (HSC) greatly contribute. This review brings a genomic point of view on the alterations of the cellular microenvironment in liver cancers, particularly the stromal tissue within tumor nodules, emphasizing the importance of the crosstalk between tumor cells and stromal cells, notably activated HSC, in tumor onset and progression. Furthermore, potential therapeutic modalities of targeting the stroma and HSC are discussed.
Introductory Remarks Concerning the Urologic Aspects of Hypertension
Authors: R. M. NESBIT
Journal: Circulation (1958)

Urologic experience with uninephrectomy for renal hypertension is reviewed and a case with a prolonged postoperative period of normotension is presented. In certain instances aortograms are necessary to identify vascular lesions in the kidney causing hypertension, but renograms using radioactive I 131 may be of value as a screening procedure. An unusual case is described in which contrast material injected into the bladder could be seen to enter the renal pelves. The child went for prolonged periods without voiding and had demonstrable pyelonephritis. When antibiotics and a program of frequent voiding were commenced the blood pressure fell toward normal and has remained at only minimally elevated levels for the subsequent 2 years.
Suppressor and cytolytic cell function in multiple sclerosis. Effects of cyclosporine A and interleukin 2.
Authors: M B Bania, J P Antel, A T Reder, M K Nicholas, B G Arnason
Journal: Journal of Clinical Investigation (1986)

Patients with progressive multiple sclerosis (MS) demonstrated persistent reductions in levels of concanavalin A (Con A)-induced suppressor activity and heightened levels of in vitro pokeweed mitogen (PWM)-induced IgG secretion. The reduced Con A suppressor activity could not be reversed by addition of interleukin 2 (IL-2). Cyclosporine A (CsA) treatment did not alter the defect in Con A-induced suppressor activity, but did markedly inhibit T8+ cell-mediated alloantigen directed cytolytic activity; this latter defect was reversible by in vitro addition of IL-2. CsA-treated patients did not differ from placebo-treated patients with regard to levels of PWM-induced IgG secretion or proliferative responses of their mononuclear cells to Con A. The results indicate that CsA treatment of MS patients reduces cytolytic function from baseline normal values, but does not alter aberrant suppressor cell function.
Storm in a Test Tube — Prescription for Survival — An Edinburgh Meeting
Authors: John Lister
Journal: New England Journal of Medicine (1970)

THE publicity recently given to the fact that scientists at Cambridge have successfully fertilized a human ovum outside the body and now plan to collaborate with a gynecologist in helping a childless Lancashire couple to have a child by conception in a test tube, followed by implantation of the fertilized ovum in the woman's uterus, has sparked off another round of controversy on the ethics of modern medicine and medical research.In a leading article the Daily Telegraph1 conceded that public emotions are naturally stirred by any scientific discovery that affects matters so intimate and fundamental as the procreation of . . .
Book: Global Challenge of Healthcare Rationing
Authors: I. Durand-Zaleski
Journal: BMJ (2000)

Eds Angela Coulter, Chris Ham Open University Press, £19.99, pp 288 ISBN 0 335 20463 5 Rating: ![Graphic][1]</img> ![Graphic][2]</img> ![Graphic][3]</img> In 1995, when Alain Juppé, the French prime minister, tried to reform the healthcare system and to introduce explicit rationing, the country went on strike for five weeks and was almost totally paralysed for that time. Healthcare rationing is indeed a challenge for policymakers, and few dare to do it explicitly. The Global Challenge of Healthcare Rationing presents a clear inventory of what healthcare rationing means and of why and how it should be done. The introductory chapter refers to the Oregon experiments, … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
Civil service chief has waived pay from drinks industry, but doctors still object to links
Authors: M. Limb
Journal: BMJ (2014)

UK medical experts have voiced fears for the integrity of public health policy after the appointment of John Manzoni as new chief executive of the civil service, despite his connections to the brewing group SABMiller, which has opposed public health measures such as a minimum price for a unit of alcohol.

The Cabinet Office, which has been criticised over Manzoni’s role as non-executive director of the brewers, announced on Thursday 30 October that he would be waiving his £100 000 (€130 000; $160 000) salary for the job and that his work for the company would end in the summer of 2015.

But Katherine Brown, director of the Institute of Alcohol Studies, said his work there should stop immediately and that his position remained “at odds with public health goals whether it is paid or …
Risk factors for premature death in middle aged men
Authors: B. Petersson, E. Trell, N.-C. Henningsen, B. Hood
Journal: BMJ (1984)

The causes of premature death and the associated risk factors were analysed in a cohort of 7935 middle aged men participating in a preventive population programme in Malmö. They were screened when aged 46-48 and then followed up for 3(1/2)-8 years. Two hundred and eighteen died, of whom 181 (83%) underwent necropsy. Three major causes of death were established: cancer in 61 (28%), deaths related to consumption of alcohol in 55 (25%), and coronary heart disease in 50 (23%).Distinctly different patterns of risk factors were found to be associated with each of the three main causes of premature death. In death due to coronary heart disease smoking (p=0.0062), serum cholesterol concentration (p=0.00014), serum triglyceride concentration (p=0.00013), systolic blood pressure (p=0.000012), and diastolic blood pressure (p=0.0021) were the strongest single determinants but diastolic blood pressure ceased to be a predictive factor in a multivariate analysis whereas all the other variables could be combined in a highly predictive logistic model. In death related to consumption of alcohol equal or even stronger associations were found for serum gamma glutamyltransferase activity (p<0.0001), points scored in a questionnaire screening for alcoholism (p<0.0001), and, inversely, serum cholesterol (p=0.0046) and serum creatinine (p<0.0001) concentrations both when applied independently and when combined in a logistic model. In death due to cancer significant associations were found for serum urate concentration (p=0.023) and, inversely, serum cholesterol concentration (p=0.056-0.031).Malignant diseases and diseases related to consumption of alcohol were at least as prominent as cardiovascular disorders in causing premature death in the cohort of men studied. All three types of conditions are potentially avoidable and seem to be associated with significant and distinctive patterns of risk factors. These patterns should be used, as blood pressure and serum lipid concentrations already are, to predict the risk of premature death and indicate preventive measures.
Suppression of T-Lymphocyte Rosettes by Rifampin
Authors: SUDHIR GUPTA
Journal: Annals of Internal Medicine (1975)

Studies of circulating T- and B-lymphocyte rosettes were done in 20 healthy controls and 29 patients with pulmonary tuberculosis, including 18 receiving rifampin chemotherapy. Eight of the 18 patients in the rifampin group (44%) had significant suppression of their T-cell rosettes as compared with patients with tuberculosis not receiving rifampin (P less than 0.005). Seven of the eight patients with suppressed T-cell rosettes had received the drug for longer than 6 weeks. No significant difference was observed in circulating T- and B-lymphocyte rosettes between healthy controls and patients not receiving rifampin. Administration of this drug to two healthy subjects in a dosage of 600 mg daily for 28 days was associated with suppression of T-lymphocyte rosettes. The maximum decreases of 40% and 37% were observed at 14 and 21 days respectively, with return to base-line values within 2 weeks of discontinuation of drug therapy; this indicates complete reversibility. Long-term sequential studies will be required to determine whether T-cell suppression after prolonged therapy with rifampin is also reversible or associated with any harmful sequels.
Hyperbaric Oxygen in Diabetic Gangrene Treatment
Authors: Giancarlo Baroni, Tommaso Porro, Ezio Faglia, Gianluigi Pizzi, Arturo Mastropasqua, Giorgio Oriani, Giorgio Pedesini, Favales Favales
Journal: Diabetes Care (1987)

We treated a group of 18 hospitalized adult diabetic patients (all with retinopathy, 17 with symptomatic neuropathy, and 6 with macroangiopathy) presenting with gangrenous lesions of the foot by a combined regime consisting of strict metabolic control, daily debridement of necrotic tissues, and daily hyperbaric oxygen (HBO) treatments given in a multiplace oxygen chamber. Another group of 10 adult subjects with comparable foot lesions (all with retinopathy, 9 with symptomatic neuropathy, and 4 with macroangiopathy) was treated in exactly the same way except for HBO. In the test treatment group, 16 patients were healed, and the remaining 2 showed no improvement and later underwent amputation. The number of HBO treatments required for healing was significantly related to the size of gangrenous lesions. In the non-HBO-treated group, only 1 patient improved, 5 of 10 showed no change, and 4 of 10 worsened until leg amputation was unavoidable. Comparison of the two groups by X2-test revealed a highly significant difference (P = .001). In practical terms, HBO treatment drastically reduced leg amputations in patients so treated in the last 3 yr compared with earlier and current figures for patients not receiving HBO treatment.
Hematologic Effects of Cimetidine
Authors: FORTUNATO V. ELIZAGA
Journal: Annals of Internal Medicine (1981)

Letters and Corrections1 February 1981Hematologic Effects of CimetidineFORTUNATO V. ELIZAGA, M.D., ROBERT T.S. JIM, M.D., CARLOS B.C. LAM, M.D., STEVEN J. BERMAN, M.D.FORTUNATO V. ELIZAGA, M.D.Search for more papers by this author, ROBERT T.S. JIM, M.D.Search for more papers by this author, CARLOS B.C. LAM, M.D.Search for more papers by this author, STEVEN J. BERMAN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-94-2-280_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The confirmatory case report by Carloss and colleagues (1) prompted us to describe two patients who similarly developed severe granulocytopenia while on cimetidine.A 28-year-old Japanese female student with a history of ulcerative colitis and vasculitis was admitted to the hospital on 30 July 1980 because of pain and numbness of her right leg. Arteriogram showed occlusion of the right popliteal artery. She underwent thrombectomy, which was unsuccessful. Streptokinase therapy was given. She also received cimetidine (1200 mg/d, orally), cyclophosphamide (100 mg/d, orally), prednisone (100 mg/d), and cephalothin sodium. Her initial leukocyte count was 4100/mm3with 80%...References1. CARLOSSTAVASSOLIMCMILLAN HMR. Cimetidine-induced granulocytopenia. Ann Intern Med. 1980;93(Part 1):57-8. LinkGoogle Scholar2. FRESTON J. Cimetidine and granulocytopenia. Ann Intern Med. 1979;90:264-5. Editorial. LinkGoogle Scholar3. RATEBONNELLCHERVENAKPAVINICH RMCG. Cimetidine and hematologic effects. Ann Intern Med. 1979;91:795. Letter. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: 2228 Liliha Street, Suite 104; Honolulu, HI 96817 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byIs cimetidine associated with neutropenia?Haematological Adverse Effects of Histamine H2-Receptor AntagonistsCimetidine suppression of CFU-C in malesAntihistamines 1 February 1981Volume 94, Issue 2Page: 280-280KeywordsArteriesCyclophosphamideSodiumUlcerative colitisVasculitis Issue Published: 1 February 1981 PDF downloadLoading ...
Problems of Terminology
Authors: Don Lehmkuhl
Journal: JAMA (1971)

Elsewhere in this issue (pp 1362 and 1368) two communications seeks to offer solutions for some of the problems associated with finding appropriate words to be used in communicating about health careers. Misunderstandings, confusion, and ill will sometimes develop among students, educators, and clinicians in various health occupations, as well as among spokesmen for different professional organizations. The source of these undesirable reactions can often be identified as lack of uniformity in terminology applied to the various occupational groups, and terminology applied to the functions performed by members of the groups. When a given term has different meanings for different people, communication disintegrates and problems multiply. Partial solution lies in attempting to reach consensus about what particular terms are going to mean. Though some groups have developed definitions and, possibly, a glossary of terms to suit their own needs, specific terms often have a different connotation when applied to similar
Place of ultrasound and radiography in obstetrics.
Authors: H B Meire, P Farrant, R A Wilkins
Journal: BMJ (1978)

In the two years after an ultrasound service was introduced at this hospital obstetric referrals for abdominal radiography decreased by over 55%. Most of these were for estimation of fetal maturity. Out of 349 such patients subjected to radiography in 1976, 176 had already been examined by ultrasound; in only four did radiography appear to influence management. We believe that if a satisfactory ultrasound scan is obtained before 30 weeks of gestation subsequent radiological estimation of fetal maturity is unjustified. Radiography may still be necessary, however, for diagnosing fetal abnormalities.
Genes, environments, development and asthma: a reappraisal
Authors: F. D. Martinez
Journal: European Respiratory Journal (2006)

Significant advances have been made in our understanding of the role of genetic variation in determining complex human phenotypes such as asthma. It is now well established that there is no single “gene for asthma”, in the way that the cystic fibrosis transmembrane receptor is the “gene for cystic fibrosis”. It is also clear that among all genetic variants eventually found to be associated with asthma, only a few will be replicated, and in the same direction, in the majority of well-performed studies. Current evidence suggests that most asthma-related polymorphisms determine risk for the disease in a context-dependent manner, i . e . they interact with environmental factors, with polymorphisms in other genes and with the specific developmental phase of the disease in which the association is tested. Elucidating these complex interactions will allow us to understand better the heterogeneity of the disease and thus to develop therapeutic tools tailored to the specific form of the disease in each patient.
Academic freedom is at risk in dispute over Gardasil, lecturers say
Authors: Melissa Sweet
Journal: BMJ (2008)

A new report is calling for changes in the conduct of clinical trials in the United States to reduce disparities of age, sex, race, and comorbidity.The goal is to give a more representative picture of the benefits and risks of a treatment across the entire population but particularly among those who bear the greatest burden of the morbidity.The eliminating disparities in clinical trials (EDICT) initiative was conducted over two years by the Baylor College of Medicine in Houston and the Intercultural Cancer Council.It is part of an ongoing four year project to reduce barriers to participation in trials.The report of the initiative was released on 1 April in Washington, DC.The report describes itself as a "nationwide call to action . . .that removes the barriers to clinical trial participation and advances education and information sharing [as] a critical step to improving the health status of all Americans."Recommendations include harmonising the Food and Drug Administration's regulations on trial design and conduct with those of the National Institutes of Health requiring diversity; increasing collaboration between government and industry in trials; and fostering community involvement in all phases of trial design and implementation.It calls on journals to require researchers to include an analysis of how their trial participants match the population that bears the greatest burden of that condition.It also seeks better education of institutional review boards on their ethical responsibilities and of the general public about the trials process.Calls for better education of review boards and the public are likely to draw little opposition.But other recommendations are likely to require an increase in the size of a trial to provide sufficient numbers for subgroup analysis according to sex, race, age, and comorbidity.This will increase the cost of trials and could delay the introduction of new drugs to the marketplace.Information on EDICT is available at www.bcm.edu/edict. Trial participants need to represent patients betterUK NEWS Wakefield tells GMC he was motivated by concern for autistic children, p 738 World NEWS Australian drug firms give details of sums spent courting doctors, p 742 bmj.com reducing inequalities in health will need a long timeframe, MPs are told