tbuckley/cabot-search huggingface dataset:
Enhancement of insulin action after oral glucose ingestion.
Authors: W J Kingston, J N Livingston, R T Moxley
Journal: Journal of Clinical Investigation (1986)

Previous investigations in normal humans and rats have shown an increase in insulin sensitivity and binding affinity of adipocytes isolated 1-3 h after glucose ingestion. To determine whether a rapid enhancement of the action of insulin follows glucose ingestion in vivo, the present studies have utilized 120-min 20 mU/m2 X min euglycemic insulin infusions before and after 7.5-, 15-, 25-, and 100-g oral glucose loads. Euglycemic insulin infusions after the carbohydrate challenge were begun after arterialized blood glucose and insulin values had returned to baseline. After 15- and 25-g oral glucose loads during the 20-120-min interval of insulin infusion, glucose infusion rates increased by 44 +/- 6% (P less than 0.0001) and 47 +/- 9% (P less than 0.0002), respectively. No significant differences in arterialized glucose or insulin values existed between basal and post-glucose insulin infusions. In addition, no significant differences in hepatic glucose production or counter-regulatory hormone levels were found between basal and post-glucose insulin infusions. Control infusion studies including subjects who ingested saline or mannitol failed to show an increase in insulin action. Studies were carried out to mimic the insulin curve seen after 15- and 25-g oral glucose loads. Euglycemic insulin infusions after these insulin simulation studies show a 34 +/- 7% enhancement compared to baseline euglycemic insulin infusions. These results demonstrate a rapid enhancement of insulin action after oral glucose challenge in normal humans. The insulin simulation studies suggest that insulin itself either directly or through release of another factor acts on muscle to increase insulin sensitivity. The increase in insulin action demonstrated in these investigations may represent an important regulatory mechanism to modulate tissue insulin sensitivity.
Who Is a Specialist?
Authors: Marvin L. Daves
Journal: JAMA (1969)

<h3>To the Editor:—</h3> Perhaps some official of the American Board of Radiology will write you regarding your editorial on "Who Is a Specialist?" (<b>207</b>:746, 1969). The subspecialty designations included parenthetically after radiology were apparently copied from a list of terms for which definitions are given in the<i>Booklet of Information of the Board</i>and has little to do with the specialties which it is empowered to certify, namely, radiology, diagnostic radiology, therapeutic radiology, and radiation physics. Subspecialties currently pressing hard for recognition are nuclear radiology, neuroradiology, and pediatric radiology. Further proliferation can be anticipated as follows: radiation biology and radiation chemistry, and diagnostic subspecialties in urologic, gastrointestinal, bone and joint, and cardiovascular radiology. My purpose is not to approve or disapprove but just to tell it as it is.
1.61 T-cells expressing TLR4 and CXCR4 are associated with an RA diagnostic in early inflammatory arthritis
Authors: R Parmar, Agata Burska, P Emery, Mario Mellado, Sandra Sacre, F Ponchel
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Biomarkers for the early diagnosis of RA are still needed despite the improvement brought about by ACR/EULAR-2010 criteria which include the ACPA biomarker. T-cell subset dys-regulation was shown to occur early in the RA disease continuum (Blood, 2002), to predict response to MTX (ARD, 2013) and safe discontinuation of biological when in clinical remission (ARD 2010). The aim of the current study is to determine whether T-cell subset phenotyping adding novel cell surface markers for TLR2, TLR4, IL-6R and 4 chemokine receptors (CCR3, CXCR4 CCR5 and CCR6) can discriminate between patients who are clearly RA from those with other (inflammatory) rheumatic diseases in an early arthritis clinic. <h3>Methods</h3> 46 patients with &lt;12 months IA were enrolled; age, CRP, joint counts, symptom duration, SE and ACPA were recorded. 6-8 colour flowcytometry was performed using standard protocols. 95 healthy controls (HC) were included to calculate age-corrected naïve cell frequency. <h3>Results</h3> 23 of the 46 patients were diagnosed with RA. 9 had undifferentiated arthritis and 14 other rheumatic diseases (AS, SPA, gout and self-limiting). Not surprisingly, as part of the EULAR-2010 criteria, ACPA positivity (P&lt;0.0001), CRP (P = 0.004) and swollen joint count (P = 0.003) were associated with RA. Naïve CD4+ T-cells tended to be reduced (p = 0.093) in RA and reached significance when RA and UA were compared to other diagnosis (p = 0.008). TLR4 expression was increased in RA (p = 0.100) and again significant in RA+ UA (P = 0.038). CXCR4 expression appeared increased in RA but a number of outliers reduced significance. CXCR4 expression was then analysed in relation with other chemokine receptors. The number of subset generated prevented classic statistical analysis so we used a clustering software which separated 2 groups of patients, one being associated with RA (p = 0.070) and ACPA-positivity (P = 0.072). Clustering was driven by increased CD4+ T-cell subsets positive for CXCR4 and expressing CCR5, CCR6 or IL-6R. This group was clearly associated with RA as well as ACPA-positivity. The second group was also characterised by increased CXCR4+ but on CD8+ T-cells with expression of CCR5, CCR6 or IL-6R and included mixed RA (mostly ACPA-negative) and non-RA patients. <h3>Conclusion</h3> There are clear T-cell related immunological differences in patients with RA: loss of naïve T-cell, increased TLR4 + and combination of chemokine expression on CD4+ T-cell. We will therefore need to evaluate these biomarkers in larger number of patients with a high risk of progression towards RA to establish their definite value.
Age-associated reductions in cardiac beta1- and beta2-adrenergic responses without changes in inhibitory G proteins or receptor kinases.
Authors: R P Xiao, E D Tomhave, D J Wang, X Ji, M O Boluyt, H Cheng, E G Lakatta, W J Koch
Journal: Journal of Clinical Investigation (1998)

While an age-associated diminution in myocardial contractile response to beta-adrenergic receptor (beta-AR) stimulation has been widely demonstrated to occur in the context of increased levels of plasma catecholamines, some critical mechanisms that govern beta-AR signaling must still be examined in aged hearts. Specifically, the contribution of beta-AR subtypes (beta1 versus beta2) to the overall reduction in contractile response with aging is unknown. Additionally, whether G protein-coupled receptor kinases (GRKs), which mediate receptor desensitization, or adenylyl cyclase inhibitory G proteins (Gi) are increased with aging has not been examined. Both these inhibitory mechanisms are upregulated in chronic heart failure, a condition also associated with diminished beta-AR responsiveness and increased circulatory catecholamines. In this study, the contractile responses to both beta1-AR and beta2-AR stimulation were examined in rat ventricular myocytes of a broad age range (2, 8, and 24 mo). A marked age-associated depression in contractile response to both beta-AR subtype stimulation was observed. This was associated with a nonselective reduction in the density of both beta-AR subtypes and a reduction in membrane adenylyl cyclase response to both beta-AR subtype agonists, NaF or forskolin. However, the age-associated diminutions in contractile responses to either beta1-AR or beta2-AR stimulation were not rescued by inhibiting Gi with pertussis toxin treatment. Further, the abundance or activity of beta-adrenergic receptor kinase, GRK5, or Gi did not significantly change with aging. Thus, we conclude that the positive inotropic effects of both beta1- and beta2-AR stimulation are markedly decreased with aging in rat ventricular myocytes and this is accompanied by decreases in both beta-AR subtype densities and a reduction in membrane adenylate cyclase activity. Neither GRKs nor Gi proteins appear to contribute to the age-associated reduction in cardiac beta-AR responsiveness.
Candidate for NHS England top job says GP federations are the future
Authors: G. Iacobucci
Journal: BMJ (2013)

General practices in the United Kingdom must be willing to adapt and move away from working in isolation to meet the healthcare challenges of the future, one of the leading candidates to be the next head of the NHS in England has said.

Mark Britnell, chairman and partner of global health practice at consultancy firm KPMG, who is tipped as a potential successor to David Nicholson as chief executive of NHS England, also called for the NHS to adopt innovative ways of working from abroad, echoing the recent recommendations of healthcare regulator Monitor.1

In a speech at the Best Practice 2013 conference in Birmingham on 16 October, Britnell, who worked in the NHS for 20 years before taking up his current role—most recently as the director of commissioning at the Department of Health—said that UK primary care was envied across the world, …
High Hopes—and Many Morals
Authors: Lloyd W. Kitchen
Journal: JAMA (1990)

<h3>To the Editor.—</h3> Dr Zuger's<sup>1</sup>sensitive, insightful essay entitled "High Hopes" highlights the maddeningly difficult problem of cardiopulmonary resuscitation in the occasional hopelessly ill patient who insists on it. Patients' autonomy and control over their own treatment are important principles that must be considered in every instance. However, Jerry Silver's physician was correct to work patiently to dissuade him from a futile effort at resuscitation. Despite our best intentions, patients (other than health care workers) cannot be fully informed about cardiopulmonary resuscitation—its frequently gruesome trappings (blood, electrical shocks, vomitus, tubes, and chaos), the relatively low percentage of successful efforts in certain groups of patients, and the remote chance that a successfully resuscitated patient with underlying end-stage disease will ever leave the hospital. The era of the paternalistic, omniscient physician is past. However, there are situations, particularly those concerning the end of life, where the concerned, compassionate physician often does
Mizolastine therapy also has an effect on nasal blockade in perennial allergic rhinoconjunctivitis
Authors: C. Bachert, J. Brostoff, G. K. Scadding, J. Tasman, A. Stalla‐Bourdillon, M. Murrieta, RIPERAN Study Group
Journal: Allergy (1998)

Background Mizolastine is a new, nonsedating antihistamine with additional anti‐inflammatory properties, providing relief in allergic rhinitis and urticaria. The aim of this study was to determine the efficacy and safety of 10 mg o.d. mizolastine given to patients with perennial allergic rhinoconjunctivitis. Methods This double‐blind, placebo‐controlled study involved 257 patients suffering from the disease for more than 10 years. They were allocated, after a 1‐week placebo run‐in, to receive mizolastine (n = 133) or placebo (n = 124) for 4 weeks. Results Mizolastine‐treated patients showed significantly greater alleviation of nasal symptoms, with a mean decrease of 36% compared with pretreatment score, compared to a mean decrease of 10% in placebo patients (P&lt;0.001). Nasal blockade responded favorably to mizolastine compared to placebo and was associated with a significant reduction in rhinoscopy findings (P=0.030). Likewise, the mean ocular symptom score decreased 40% in mizolastine‐treated patients compared to 7% in the placebo group (P&lt;0.003). The safety profile of mizolastine was satisfactory and similar to that of placebo. Conclusions In patients suffering from perennial allergic rhinoconjunctivitis, mizolastine is a safe and potent treatment. Mizolastine's pronounced effect on nasal blockade could possibly be linked to its anti‐inflammatory properties.
Effects of high arterial oxygen tension on function, blood flow distribution, and metabolism in ischemic myocardium.
Authors: B A Cason, J A Wisneski, R A Neese, W C Stanley, R F Hickey, C B Shnier, E W Gertz
Journal: Circulation (1992)

Although oxygen inhalation therapy has long been used in the treatment of acute myocardial ischemia, experimental evidence that increased arterial PO2 has any beneficial effect in the absence of hypoxemia is equivocal. In this study, we used a swine model of subendocardial myocardial ischemia to determine the effects of arterial hyperoxia on regional myocardial contractile function (sonomicrometry), myocardial blood flow distribution (microspheres), and regional myocardial glycolytic metabolism (carbon isotope-labeled substrates).In 10 domestic swine, the left anterior descending coronary artery was cannulated and flow to this artery was strictly controlled via a roller pump in the perfusion circuit. Arterial PO2 was controlled by manipulating inspired oxygen concentration (FIO2). Low-flow myocardial ischemia was induced by reducing pump flow to 50% of the control value, which diminished regional endocardial systolic shortening to 30-50% of normal. After a 15-minute period of flow stability, each animal was exposed in randomized order to two additional 15-minute experimental periods: coronary normoxia (PO2 = 90-110 mm Hg) and coronary hyperoxia (PO2 greater than 400 mm Hg). At each level of oxygenation, we measured regional myocardial function, regional myocardial blood flow and metabolism, and hemodynamic indexes of myocardial oxygen demand. Myocardial ischemia during normoxia reduced systolic shortening to 10.9 +/- 5.3% in the ischemic zone. Hyperoxia increased ischemic zone systolic shortening substantially to 15.2 +/- 4.6%. During myocardial ischemia, endocardial blood flow was decreased to 0.26 +/- 0.06 ml.g-1.min-1 in the ischemic zone. During hyperoxia, endocardial blood flow rose to 0.34 +/- 0.10 ml.g-1.m-1. The endocardial: epicardial flow ratio was 0.45 +/- 0.18 in the initial ischemia period and rose to 0.61 +/- 0.23 in the hyperoxic period. Myocardial ischemia increased regional uptake of glucose, conversion of glucose to released lactate, and net myocardial lactate release. In the ischemic myocardium, coronary hyperoxia decreased both chemically measured lactate production and isotopically measured lactate release and decreased glucose extraction and the conversion of glucose to lactate.These data demonstrate for the first time that increasing arterial PO2 to high levels during acute low-flow myocardial ischemia improves both function and flow distribution in the ischemic myocardium and decreases glycolytic metabolism in the ischemic zone. The degree of improvement in contractile function (5% absolute increase in systolic shortening or 25% change normalized to preischemic values) is consistent with the observed increase in subendocardial blood flow.
Metabolic Control of Vesicular Glutamate Transport and Release
Authors: Narinobu Juge, John A. Gray, Hiroshi Omote, Takaaki Miyaji, Tsuyoshi Inoue, Chiaki Hara, Hisayuki Uneyama, Robert H. Edwards, Roger A. Nicoll, Yoshinori Moriyama
Journal: Neuron (2010)
Training requirements for cosmetic surgery
Authors: D C Herbert, N G Buchan
Journal: BMJ (1980)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Training requirements for cosmetic surgery Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
CAESAREAN SECTION IN A CASE OF CONTRACTED PELVIS WITH TWIN PREGNANCY
Authors: G. H. Cowen
Journal: BMJ (1907)

CAESAREAN SECTION.[MI JOuV& I89Minor measures, such as curetting and electrical treat- ment, are, I believe, absolutely useless.As regards the latter, I confess frankly I have had no personal expe- rience, but that conditions I am constantly meeting on the operating table can be cured by electrolysis I absolutely refuse to believe.We come now to the much-vexed question of ,ophorectomy.We used to get fairly good results from it.Even now, given a small fibroid with appendages so inflamed, so diseased as to demand removal, I would remove the appendages and leave the uterus.As a routine treatment of fibroids it is not to be compared with hysterectomy.1.The operation of oophorectomy is attended by quite as large, if not a larger, mortality than hysterectomy.
Britain's breast cancer services need overhaul
Authors: L. Dillner
Journal: BMJ (1995)

Britain's mortality from breast cancer--one of the highest in the world--could be due to poor treatment, says a report from the government's health committee. The committee makes 42 recommendations for improving services for breast cancer, one of which is that the Department of Health should commission research into why Britain is near the bottom of the league for survival rates. The report also recommends that screening should be extended from 65 years of age to 69. It says that screening should be offered more often than every three years if research currently being carried out shows this is effective.

Britain does not have a particularly high incidence of breast cancer, but in 1992 there were nearly …
Fatal Polymyositis in D-Penicillamine-Treated Rheumatoid Arthritis
Authors: DEBORAH R. DOYLE
Journal: Annals of Internal Medicine (1983)

Thirteen reports of patients who developed polymyositis or dermatomyositis during treatment with D-penicillamine are reviewed and a fourteenth case is described. Twelve of the fourteen patients recovered after D-penicillamine was withdrawn; two patients died from cardiac involvement. Proximal muscle weakness was present in 13 patients and dermatomyositis in 4 patients. Dysphagia was the presenting symptom in 6 patients. Although D-penicillamine is useful in the management of rheumatoid arthritis, this drug should be used with caution and patients monitored closely for evidence of polymyositis or dermatomyositis.
Long‐term ANP evaluation in rats: No induction of myocardial apoptosis via the ANP‐cGMP axis
Authors: T. Neumann, H. Heinrich, H. Schumann, D.H. Heublein, H.C. Burnett, S.P. Müller, R. Schulz, G. Heusch, J. Holtz
Journal: European Journal of Heart Failure (2000)
Predictive Performance of Microarray Gene Signatures: Impact of Tumor Heterogeneity and Multiple Mechanisms of Drug Resistance
Authors: Charlotte K.Y. Ng, Britta Weigelt, Roger A'Hern, Francois-Clement Bidard, Christophe Lemetre, Charles Swanton, Ronglai Shen, Jorge S. Reis-Filho
Journal: Cancer Research (2014)

Gene signatures have failed to predict responses to breast cancer therapy in patients to date. In this study, we used bioinformatic methods to explore the hypothesis that the existence of multiple drug resistance mechanisms in different patients may limit the power of gene signatures to predict responses to therapy. In addition, we explored whether substratification of resistant cases could improve performance. Gene expression profiles from 1,550 breast cancers analyzed with the same microarray platform were retrieved from publicly available sources. Gene expression changes were introduced in cases defined as sensitive or resistant to a hypothetical therapy. In the resistant group, up to five different mechanisms of drug resistance causing distinct or overlapping gene expression changes were generated bioinformatically, and their impact on sensitivity, specificity, and predictive values of the signatures was investigated. We found that increasing the number of resistance mechanisms corresponding to different gene expression changes weakened the performance of the predictive signatures generated, even if the resistance-induced changes in gene expression were sufficiently strong and informative. Performance was also affected by cohort composition and the proportion of sensitive versus resistant cases or resistant cases that were mechanistically distinct. It was possible to improve response prediction by substratifying chemotherapy-resistant cases from actual datasets (non-bioinformatically perturbed datasets) and by using outliers to model multiple resistance mechanisms. Our work supports the hypothesis that the presence of multiple resistance mechanisms in a given therapy in patients limits the ability of gene signatures to make clinically useful predictions.
Calyceal Pertechnetate as a False-positive Focus of Ectopic Gastric Mucosa
Authors: SURESH MUKHERJI, JOHN HARBERT, THOMAS LEE
Journal: Clinical Nuclear Medicine (1985)

This case report describes a patient in whom concentration of Tc-99m pertechnetate in a renal calyx created a false diagnostic impression of ectopic gastric mucosa. The administration of furosemide demonstrated the benign cause of the focus.
DISTRIBUTION AND CLEARANCE OF CIRCULATING ENDOTOXIN*
Authors: William B. Herring, John C. Herion, Richard I. Walker, Jeffress G. Palmer
Journal: Journal of Clinical Investigation (1963)

MATERIALS AND METHODSNew Zealand white rabbits weighing 1.9 to 3.5 kg were studied.To produce febrile tolerance, unlabeled endotoxin, 3 to 4 ttg per kg, was given intravenously to one group of animals for five consecutive days before ad- ministration of labeled endotoxin (2).Temperature meas- urements on four rabbits demonstrated definite febrile tolerance after the third injection; therefore it was con- sidered unnecessary to test each animal for tolerance.The endotoxin (E. coli lipopolysaccharide, lot 026: B6, Difco Laboratories, Detroit) was labeled in vitro by an adaptation of the method of Braude, Carey, Sutherland, and Zalesky (8).Endotoxin, 69 to 207 IAg per ml of sterile phosphate buffer (pH 7.0), was incubated with Cr5"Cl, (Chromitope, Squibb) at 370 C for 48 hours.The concentration of chromium ranged from 0.24 to 1.25
Reduced blood CD123+ (lymphoid) and CD11c+ (myeloid) dendritic cell numbers in primary HIV-1 infection
Authors: Jérôme Pacanowski, Sandrine Kahi, Marjorie Baillet, Pierre Lebon, Christiane Deveau, Cécile Goujard, Laurence Meyer, Eric Oksenhendler, Martine Sinet, Anne Hosmalin
Journal: Blood (2001)
European Commission wants drug companies to test products for use in children
Authors: Rory Watson
Journal: BMJ (2004)

Pharmaceutical companies will have to secure special authorisation to market new drugs for children, under draft legislation tabled by the European Commission at the end of September. The proposal, which is the result of four years of widespread consultation, follows from a specific request from European Union governments to find ways to increase the number of drugs intended for use in children. Just under a quarter of the union's 480 million citizens are below 19 years of age. But …
Safer Therapies for Newborns Probed
Authors: Bridget M. Kuehn
Journal: JAMA (2009)

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