tbuckley/cabot-search huggingface dataset:
Drug users must be treated as "patients first," says BMA
Authors: G. Iacobucci
Journal: BMJ (2013)

Drug policy in the United Kingdom should focus more on health to help reduce the negative effects of illegal drug use, says the BMA.

The new report from the BMA’s Board of Science says that the association was seeking to “open and refocus the debate on drug treatment and drug policy through the eyes of the medical profession,” amid concerns that health could be sidelined in the current debate on drug use.

The report, Drugs of Dependence: The Role of Medical Professionals ,1 acknowledges that the UK’s drug policies now show a greater sensitivity to social and economic factors than in the past but …
Familial Thyroxine-Excess Syndrome
Authors: J. R. STOCKIGT
Journal: Annals of Internal Medicine (1982)

Letters and Corrections1 July 1982Familial Thyroxine-Excess SyndromeJ. R. STOCKIGT, M.D., J. W. BARLOW, M.SC.J. R. STOCKIGT, M.D.Search for more papers by this author, J. W. BARLOW, M.SC.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-97-1-143_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The report by Silverberg and Premachandra (1) identifies a further euthyroid kindred with circulating thyroxine (T4) excess not due to an increase in levels of thyroxine-binding globulin. The authors point out similarities to other reported families (2-4) in whom a high total T4 level was associated with normal free T4 value. Their report differs in that both total and free T4 levels are increased in the two subjects studied. It is surprising to us that such a finding can be attributed to a binding abnormality. In view of the common authorship, it is puzzling that they do...References1. SILVERBERGPREMACHANDRA JB. Familial hyperthyroxinemia due to abnormal thyroid hormone binding. Ann Intern Med. 1982;96:183-6. LinkGoogle Scholar2. HENNEMANNDOCTERKRENNINGBosOTTENVISSER GREGMT. Raised total thyroxine and free thyroxine index but normal free thyroxine. Lancet. 1979;1:639-42. CrossrefMedlineGoogle Scholar3. LEEGOLDENVAN HERLELIPPEKAPLAN WMABS. Inherited abnormal thyroid hormone-binding protein causing selective increase of total serum thyroxine. J Clin Endocrinol Metab. 1979;49:292-9. CrossrefMedlineGoogle Scholar4. STOCKIGTTOPLISSBARLOWWHITEHURLEYTAFT JDJEDP. Familial euthyroid thyroxine excess: an appropriate response to abnormal thyroxine binding associated with albumin. J Clin Endocrinol Metab. 1981;53:353-9. CrossrefMedlineGoogle Scholar5. MAXONBURMANPREMACHANDRA HKB. Euthyroid, familial hyperthyroxinemia [Letter]. N Engl J Med. 1980;302:1263. CrossrefMedlineGoogle Scholar6. BARLOWWHITECSICSMANNFUNDERSTOCKIGT JEJWJ. Familial T4 excess: affinity, capacity, specificity and sulphydryl sensitivity of abnormal T4-binding to albumin [Abstract]. Proc Am Thyroid Assoc. 1981;T-4. Google Scholar1. SILVERBERGPREMACHANDRA JB. Familial hyperthyroxinemia due to abnormal thyroid hormone binding. Ann Intern Med. 1982;96:183-6. LinkGoogle Scholar2. MAXONBURMANPREMACHANDRA HKB. Euthyroid, familial hyperthyroxinemia [Utter]. N Engl J Med. 1980;302:1263. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Ewen Downie Metabolie Unit Alfred Hospital Melbourne 3181, Victoria Australia PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 July 1982Volume 97, Issue 1Page: 143-144KeywordsGlobulinsThyroxine Issue Published: 1 July 1982 PDF downloadLoading ...
Hypersensitivity to local anaesthetics: a direct challenge test with lignocaine for definitive diagnosis.
Authors: J A Wildsmith
Journal: BMJ (1982)

on nasal application of "asthmolysine" (containing adrenalin and posthypophyseal hor- mone) was measured on patients suffering from asthma.We found that both hormones were resorbed from the nasal mucosa and that about 530% of the effect of the same subcu- taneous dose could be achieved by this route.However, the effect was unstable and variable, and, therefore, we did not propose intranasal insulin treatment for the treatment of diabetes.In contrast to this, in certain cases of asthma the intranasal application of antiasthmatic preparations could enlarge our therapeutic possibilities.
CX3CR1 and vascular adhesion protein-1-dependent recruitment of CD16+ monocytes across human liver sinusoidal endothelium
Authors: Alexander I. Aspinall, Stuart M. Curbishley, Patricia F. Lalor, Chris J. Weston, None Miroslava Blahova, Evaggelia Liaskou, Rebecca M. Adams, Andrew P. Holt, David H. Adams
Journal: Hepatology (2010)

The liver contains macrophages and myeloid dendritic cells (mDCs) that are critical for the regulation of hepatic inflammation. Most hepatic macrophages and mDCs are derived from monocytes recruited from the blood through poorly understood interactions with hepatic sinusoidal endothelial cells (HSECs). Human CD16+ monocytes are thought to contain the precursor populations for tissue macrophages and mDCs. We report that CD16+ cells localize to areas of active inflammation and fibrosis in chronic inflammatory liver disease and that a unique combination of cell surface receptors promotes the transendothelial migration of CD16+ monocytes through human HSECs under physiological flow. CX3CR1 activation was the dominant pertussis-sensitive mechanism controlling transendothelial migration under flow, and expression of the CX3CR1 ligand CX3CL1 is increased on hepatic sinusoids in chronic inflammatory liver disease. Exposure of CD16+ monocytes to immobilized purified CX3CL1 triggered β1-integrin-mediated adhesion to vascular cell adhesion molecule-1 and induced the development of a migratory phenotype. Following transmigration or exposure to soluble CX3CL1, CD16+ monocytes rapidly but transiently lost expression of CX3CR1. Adhesion and transmigration across HSECs under flow was also dependent on vascular adhesion protein-1 (VAP-1) on the HSECs. Conclusion : Our data suggest that CD16+ monocytes are recruited by a combination of adhesive signals involving VAP-1 and CX3CR1 mediated integrin-activation. Thus a novel combination of surface molecules, including VAP-1 and CX3CL1 promotes the recruitment of CD16+ monocytes to the liver, allowing them to localize at sites of chronic inflammation and fibrosis. (Hepatology 2010)
Kinetics of in vitro bovine keratohyalin synthesis
Authors: PETER M. ELIAS, WALTER G. KLINGLER, PAUL M. MONTAGUE
Journal: British Journal of Dermatology (1976)

A system is described for the study of the in vitro synthesis of bovine keratohyalin for periods of up to 24 h. Keratohyalin granules appeared morphologically unaltered during culture, although histochemical stains for RNA indicate a markedly diminished RNA content by 6 h. Incorporation of tritiated histidine began slowly, then became linear between 4 and 24 h in serum-containing media. However, following pre-incubation in serum-free media, increased incorporation occurred from time zero. The internal variation of the system using a standard 6 h pulse was +/- 10, +/- 24, +/- 22, +/- 18% in four separate experiments. Measurements of modulations in bovine keratolhyalin synthesis in vitro may prove useful in the development of drugs of therapeutic potential in dermatology.
Cumulative organophosphate pesticide exposure and risk assessment among pregnant women living in an agricultural community: a case study from the CHAMACOS cohort.
Authors: Rosemary Castorina, Asa Bradman, Thomas E McKone, Dana B Barr, Martha E Harnly, Brenda Eskenazi
Journal: Environmental Health Perspectives (2003)

Approximately 230,000 kg of organophosphate (OP) pesticides are applied annually in California's Salinas Valley. These activities have raised concerns about exposures to area residents. We collected three spot urine samples from pregnant women (between 1999 and 2001) enrolled in CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas), a longitudinal birth cohort study, and analyzed them for six dialkyl phosphate metabolites. We used urine from 446 pregnant women to estimate OP pesticide doses with two deterministic steady-state modeling methods: method 1, which assumed the metabolites were attributable entirely to a single diethyl or dimethyl OP pesticide; and method 2, which adapted U.S. Environmental Protection Agency (U.S. EPA) draft guidelines for cumulative risk assessment to estimate dose from a mixture of OP pesticides that share a common mechanism of toxicity. We used pesticide use reporting data for the Salinas Valley to approximate the mixture to which the women were exposed. Based on average OP pesticide dose estimates that assumed exposure to a single OP pesticide (method 1), between 0% and 36.1% of study participants' doses failed to attain a margin of exposure (MOE) of 100 relative to the U.S. EPA oral benchmark dose(10) (BMD(10)), depending on the assumption made about the parent compound. These BMD(10) values are doses expected to produce a 10% reduction in brain cholinesterase activity compared with background response in rats. Given the participants' average cumulative OP pesticide dose estimates (method 2) and regardless of the index chemical selected, we found that 14.8% of the doses failed to attain an MOE of 100 relative to the BMD(10) of the selected index. An uncertainty analysis of the pesticide mixture parameter, which is extrapolated from pesticide application data for the study area and not directly quantified for each individual, suggests that this point estimate could range from 1 to 34%. In future analyses, we will use pesticide-specific urinary metabolites, when available, to evaluate cumulative OP pesticide exposures.
The emperor's pointer
Authors: J. A H R Claassen
Journal: BMJ (2002)

At first I thought it was just me. I was attending my first scientific meeting, a young doctor eager to acquire new knowledge. It was clear that the first speaker had firmly embraced the concept of the PowerPoint presentation, and he was treating his audience to beautifully coloured slides. Like so many of us, he tended to put just a little too much information on each slide. One of his slides showed a comparison between groups, and we were promised that the third group would differ dramatically from the other two. I saw two lines cross the slide, one close to the other, but no third line. I looked at the key at the bottom of the graph and …
Insulin-Like Growth Factors and Their Binding Proteins: Biological Actions*
Authors: JOHN I. JONES, DAVID R. CLEMMONS
Journal: Endocrine Reviews (1995)

THE insulin-like growth factors were discovered on the basis of their ability to stimulate cartilage sulfation and to replace the "sulfation factor activity" of GH, as determined using an in vivo assay, in an in vitro test system (1). The biological significance of this finding was quickly expanded beyond the study of cartilage sulfation to include stimulation of DNA synthesis (2), proteoglycan synthesis (3), glycosaminoglycan synthesis (4), and protein synthesis (5). Most of these studies used tissue preparations such as isolated diaphragm, cartilage, or epididymal fat pads to study biologicalactivity. In recognition of its generalized pleiotypic actions, in the early 1970's sulfation factor was renamed somatomedin (mediator of the effects of somatotropin) and was included in the emerging classification of broad spectrum growth factors along with platelet derived growth factor, fibroblast growth factor, and epidermal growth factor (6). During the period in which the biological actions of sulfation factor were being characterized, parallel studies were initiated that attempted to define factors in serum that could stimulate insulin-like effects. Because these factors were known to be distinct from immunoreactive insulin, their bioassay was based on insulin-like actions that could not be abolished by the simultaneous addition of anti-insulin antibody, and the factors were termed nonsuppressible insulin-like activity (NSILA) (7). Initial biological studies of both NSILA and somatomedin were based on the use of crude serum extracts. Early attempts to extract these factors from tissues were generally not successful, and by 1970 it had been concluded that no concentrated organ source for them existed (8). However, highly purified preparations of both factors were prepared from serum extracts.
The Return of the White Plague: Global Poverty and the New Tuberculosis
Authors: David Mitchell
Journal: BMJ (2004)

Twenty five years ago the prevailing view was that infectious diseases were a problem of the past, thanks to vaccines and antibiotics, public health measures, and better socioeconomic conditions. HIV and AIDS changed everything—the devastating first example of many new infectious diseases, the latest being severe acute respiratory syndrome. At the same time old infectious diseases have returned, and tuberculosis leads the way, particularly in its new deadly partnership with HIV and its ability to develop multidrug resistance. Tuberculosis is now a leading cause of mortality in many parts of the world. Eds Matthew Gandy, Alimuddin Zumla Verso, £25, pp 330 ISBN 1859846696 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> The central conundrum with tuberculosis is why it continues to kill about two million people a year when it can easily be cured with cheap, effective antibiotics. Also, why, especially with the advent of multidrug resistant disease, have no new drugs been introduced for 40 years? Why is there still no effective vaccine? Why do antituberculous agents have to be taken for a minimum of six months to be fully effective? And why is there still no robust diagnostic test? Sputum … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
Danazol therapy for aplastic anemia refractory to immunosuppressive therapy
Authors: Tatsuya Chuhjo, Hirohito Yamazaki, Mitsuhiro Omine, Shinji Nakao
Journal: American Journal of Hematology (2007)

Abstract Although there are anecdotal reports of the efficacy of danazol in the treatment of aplastic anemia (AA), there has been no systematic study to clarify its efficacy and toxicity. Therefore, we assessed the efficacy of danazol for treatment of patients with AA refractory to immunosuppressive therapy (IST) and those who relapsed after IST, in a prospective clinical trial. Sixteen patients (12 males and four females; six severe cases and 10 moderate cases) were treated with 300 mg of danazol daily for 12 weeks. All patients completed the treatment period without occurrence of severe toxicity. Three female patients achieved partial remission, whereas only two of the 12 male patients did so. None of the responders had shown a response to previous IST or an increase in the percentage of paroxysmal nocturnal hemoglobinuria (PNH)‐type cells which are known to be a marker for a good response to IST. These findings indicate that danazol is effective for a subset of AA patients, and particularly for female patients with AA refractory to IST. Am. J. Hematol., 2008. © 2007 Wiley‐Liss, Inc.
The Threat of Infectious Disease in Americans Returning from Operation Desert Storm
Authors: Robert A. Gasser, Alan J. Magill, Charles N. Oster, Edmund C. Tramont
Journal: New England Journal of Medicine (1991)

Whenever Americans spend time in foreign lands, they may become infected with pathogens alien to the United States and bring these pathogens back with them. Mass deployments of the U.S. Armed Forces abroad amplify this risk since military personnel are more intimately exposed than ordinary travelers to each other, to local people, and to the natural environment. The breakdown of public health measures, hygiene, sanitation, and nutrition that inevitably accompanies warfare further magnifies this peril. Since August 1990, more than 500,000 Americans have been sent to the Middle East, where they have encountered a variety of infectious diseases endemic to . . .
Bacteremia Associated With Toothbrushing and Dental Extraction
Authors: Peter B. Lockhart, Michael T. Brennan, Howell C. Sasser, Philip C. Fox, Bruce J. Paster, Farah K. Bahrani-Mougeot
Journal: Circulation (2008)

Antibiotic prophylaxis recommendations for the prevention of infective endocarditis are based in part on studies of bacteremia from dental procedures, but toothbrushing may pose a greater threat. The purpose of this study was to compare the incidence, duration, nature, and magnitude of endocarditis-related bacteremia from single-tooth extraction and toothbrushing and to determine the impact of amoxicillin prophylaxis on single-tooth extraction.In this double-blind, placebo-controlled study, 290 subjects were randomized to (1) toothbrushing, (2) single-tooth extraction with amoxicillin prophylaxis, or (3) single-tooth extraction with identical placebo. Blood was drawn for bacterial culturing and identification at 6 time points before, during, and after these interventions. The focus of our analysis was on bacterial species reported to cause infective endocarditis. We identified 98 bacterial species, 32 of which are reported to cause endocarditis. Cumulative incidence of endocarditis-related bacteria from all 6 blood draws was 23%, 33%, and 60% for the toothbrushing, extraction-amoxicillin, and extraction-placebo groups, respectively (P<0.0001). Significant differences were identified among the 3 groups at draws 2, 3, 4, and 5 (all P<0.05). Amoxicillin resulted in a significant decrease in positive cultures (P<0.0001).Although amoxicillin has a significant impact on bacteremia resulting from a single-tooth extraction, given the greater frequency for oral hygiene, toothbrushing may be a greater threat for individuals at risk for infective endocarditis.
Points from Letters: Errors in Operations
Authors: A. Sengupta
Journal: BMJ (1964)

BRTSw=Hcomings of others-presumably they hope their own virtues will show up better by contrast; but, really, 800 purple hearts a day are too much for any of us to swallow, literally or figuratively.No details have been given, so far as I know, of how many were in the family or how long the tablets were supposed to last, or whether the circum- stances justified the prescribing of purple hearts in any quantity.This statement has been so damaging to the profession in lay eyes and so surprising and shocking to the vast majority of doctors in general practice who never prescribe more than two Drinamyl a day-and these with some diffidence-that the Ministry should justify the statement of the official by supply- ing details to the profession by way of Prescribers' Notes or in the B.M.7.
Adjuvant Therapy with Tolazamide and Insulin Improves Metabolic Control in Type I Diabetes Mellitus
Authors: Uaya M Kabadi
Journal: Diabetes Care (1985)

Sulfonylurea agents have been well documented to be effective in type II diabetes mellitus by increasing insulin secretion as well as by enhancing cellular binding of endogenous insulin. We have examined in 20 type I diabetic subjects the efficacy of tolazamide, a common sulfonylurea agent, as adjuvant therapy in combination with an appropriate diet and insulin. This regimen decreased the insulin dose while continuing to maintain adequate metabolic control, as reflected by fasting plasma glucose (FPG) &amp;lt;150 mg/dl and HbA1 levels &amp;lt;9%, and reduced number of hypoglycemic episodes to almost nil in a group of subjects with adequate metabolic control before institution of combination therapy. In subjects in whom metabolic control was inadequate (FPG &amp;gt; 150 mg/dl and HbA1 &amp;gt; 9%) with insulin alone, the adjuvant therapy with tolazamide improved or normalized hyperglycemia and HbA1. In 13 subjects in whom adequate metabolic control was achieved with combination therapy, metabolic control worsened on withdrawal of tolazamide while continuing insulin in the same dosage and adequate metabolic control promptly returned on reinstitution of combination therapy with insulin and tolazamide. In the remaining seven subjects, metabolic control remained adequate with combination therapy during the 4–10-mo follow-up period. This study therefore demonstrates that combination therapy with sulfonylurea agent and insulin may be beneficial in management of type I diabetes. Furthermore, this regimen may be helpful in prevention of extreme plasma glucose excursions observed in brittle diabetic individuals. A larger, long-term clinical trial with this regimen in type I diabetic subjects must be undertaken to establish this preliminary finding.
Michael Landon Treated at NCI Clinical Trial Facility
Authors: L. Fintor
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Michael Landon Treated at NCI Clinical Trial Facility Get access Lou Fintor Lou Fintor Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 12, 19 June 1991, Pages 818–819, https://doi.org/10.1093/jnci/83.12.818 Published: 19 June 1991
Case fatality rates after hospital admission for stroke: Covariates were not measured
Authors: M. D Hill
Journal: BMJ (2003)

EDITOR—The article by Roberts et al on stroke mortality in hospital and at one year after stroke raises several issues.1 The case-mix ratio, presence or absence of on-site neurosurgical services, and stroke unit care should be emphasised as important and easily measured explanatory covariates.

Unfortunately, the most important predictor of 30 day mortality is stroke severity at baseline, and this variable …
Effect of selective angiotensin II receptor antagonism and angiotensin converting enzyme inhibition on the coronary vasculature in vivo. Intravascular two-dimensional and Doppler ultrasound studies.
Authors: K Sudhir, J S MacGregor, M Gupta, S D Barbant, R Redberg, P G Yock, K Chatterjee
Journal: Circulation (1993)

Although angiotensin converting enzyme (ACE) inhibitors have been reported to increase coronary blood flow, the effect of selective angiotensin II (AT1)-receptor antagonism on the coronary circulation has not been defined.We examined the effects of the AT1-receptor antagonist Losartan (DuP 753, 0.2-3.2 mg/kg) on coronary arteries in vivo in 11 dogs, using a combination of intravascular two-dimensional and Doppler ultrasound. In six dogs, a 30-MHz, 4.3F ultrasound imaging catheter was placed in the midsegment of the circumflex coronary artery to measure cross-sectional area (CSA), and a 0.018-in. Doppler wire was placed alongside to measure coronary flow velocity. At peak effect (1.6 mg/kg), Losartan increased mean coronary CSA from 7.9 +/- 0.5 to 9.5 +/- 0.8 mm2 and average peak velocity (APV) from 32 +/- 10 to 56 +/- 18 cm/sec, resulting in an increase in coronary blood flow from 74 +/- 19 to 151 +/- 36 mL/min. The maximal effect of the ACE inhibitor enalaprilat (5 mg) was an increase in CSA from 7.7 +/- 0.7 to 8.4 +/- 0.8 mm2 and an increase in APV from 36 +/- 10 to 53 +/- 20 cm/sec, with an increase in coronary blood flow from 82 +/- 25 to 122 +/- 41 mL/min. Relative to maximal hyperemia with adenosine (6 mg i.c.), the magnitude of flow increase from baseline was 0.37 with the AT1-receptor antagonist and 0.19 with the ACE inhibitor (p < 0.05). These effects were seen without changes in heart rate or systemic arterial pressure. In an additional five dogs, the ultrasound imaging catheter was introduced directly over a 0.014-in. Doppler wire, and the effects of indomethacin, propranolol, and N omega-nitro-L-arginine methylester (L-NAME) on the vasodilator effect of Losartan (1.6 mg/kg) were examined. Indomethacin and propranolol had no effect on Losartan-induced vasodilation, suggesting that it was not mediated via prostaglandins or beta-adrenoceptors. However, Losartan-induced epicardial vasodilation was partially inhibited by L-NAME, suggesting an action partly dependent on endothelial release of nitric oxide.Thus, these acute studies in anesthetized dogs suggest that inhibition of AT1-receptors in the coronary circulation results in vasodilator responses greater in magnitude than ACE inhibition and partly endothelium dependent. The exact role for AT1-receptors in human coronary physiology and pathology remains to be defined.