tbuckley/cabot-search huggingface dataset:
Doctors are urged to set aside cynicism about government initiatives for the NHS
Authors: C. White
Journal: BMJ (2009)

Doctors are vital to the innovation and leadership needed to help the NHS cope with the looming squeeze on public spending, the NHS’s medical director, Bruce Keogh, said last week. Unfortunately, he added, their cynicism is getting in the way.

Speaking at the annual conference in Birmingham of NHS Employers, the body that helps negotiate pay and conditions for NHS staff, Professor Keogh made it clear that the Department of Health had no intention of giving up on quality improvement in NHS systems, whatever the prevailing financial climate.

He described a string of initiatives to drive up quality that the …
Combined Salmeterol 50 μ g and Fluticasone Propionate 250 μ g in the Diskus Device for the Treatment of Asthma
Authors: GAIL SHAPIRO, WILLIAM LUMRY, JAMES WOLFE, JOHN GIVEN, MARTHA V. WHITE, ANITA WOODRING, LESLIE BAITINGER, KAREN HOUSE, BARBARA PRILLAMAN, TUSHAR SHAH
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Three hundred forty-nine patients with asthma previously treated with medium doses of inhaled corticosteroids during a 2-wk, single-blind, run-in period were randomized to treatment with salmeterol 50 μ g combined with fluticasone propionate (FP) 250 μ g, salmeterol 50 μ g, FP 250 μ g, or placebo, each given twice daily through a Diskus device for 12 wk. Mean change in FEV1 at endpoint was significantly (p ⩽ 0.001) greater with the salmeterol/FP combination product (0.48 L) than with placebo ( − 0.11 L), salmeterol (0.05 L), or FP (0.25 L). The combination product significantly increased the area under the 12-h serial FEV1 curve relative to baseline over that with placebo, salmeterol, or FP at Day 1, Week 1, and Week 12 (p ⩽ 0.025). Patients in the combination-product group had a significantly greater probability of remaining in the study without being withdrawn because of worsening asthma than did patients in the placebo, salmeterol, or FP groups (p ⩽ 0.002). The combination product significantly increased (p < 0.001) morning PEF at endpoint (53.5 L/min) as compared with placebo ( − 14 L/min), salmeterol ( − 11.6 L/min), or FP (15.2 L/min). The combination product significantly (p ⩽ 0.011) reduced asthma symptom scores and supplemental albuterol use, and significantly increased the percentage of nights with no awakenings as compared with placebo, salmeterol, and FP (p ⩽ 0.016). Combination treatment with salmeterol 50 μ g and FP 250 μ g given twice daily from the Diskus device provided better asthma control and greater improvement in pulmonary function than did the individual agents, and may simplify the management of asthma in patients who need both classes of drugs for optimal control of their disease. Shapiro G, Lumry W, Wolfe J, Given J, White MV, Woodring A, Baitinger L, House K, Prillaman B, Shah T. Combined salmeterol 50 μ g and fluticasone propionate 250 μ g in the Diskus device for the treatment of asthma.
Streptozotocin for Insulinoma
Authors: EDIT PIROSKA
Journal: Annals of Internal Medicine (1971)

Letters, Comments, and Corrections1 September 1971Streptozotocin for InsulinomaEDIT PIROSKA, EVA KOLLINEDIT PIROSKASearch for more papers by this author, EVA KOLLINSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-75-3-477_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Schriebman, Goransky De Koliren, and Arky (Ann Intern Med 74:399-403, 1971) reported on a patient with metastatic insulinoma who had been treated with streptozotocin. The authors suggested that streptozotocin might be of value in benign functioning tumors where surgery has failed to control the disease.We have observed a 43-year-old female patient who had a history of hypoglycemia for 11 years. The first surgery was in 1960 for the removal of the suspected insulinoma. At surgery the tail and the body of the pancreas as well as the spleen were removed. Histology of the pancreas failed to... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: First Medical Clinic Semmelweis University Medical School Budapest, Hungary PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byEndokrine StörungenStreptozotocin for Islet-cell CarcinomaBoxing BrainsIslet Cell Tumors: Current Concepts and ManagementPHILIP S. SCHEIN, M.D., F.A.C.P., RONALD A. DeLELLIS, M.D., C. RONALD KAHN, M.D., PHILLIP GORDEN, M.D., F.A.C.P., AVRAM R. KRAFT, M.D. 1 September 1971Volume 75, Issue 3Page: 477-477KeywordsBenign tumorsHistologyHypoglycemiaInsulinomaPancreasSpleenSurgery Issue Published: 1 September 1971 PDF downloadLoading ...
Studies on the Relation of Diet, Cholesterol and Atheroma in Chickens
Authors: JOHN E. PETERSON, ALBERT E. HIRST
Journal: Circulation (1951)

In this study cockerels were fed varying diets supplemented with lard, vegetable oil, and cholesterol. The degree of atherosclerosis was compared in serial autopsies and only the cholesterol-fed group showed a significant difference. During a period of two years there was no apparent change in the degree of atheroma when the diet was supplemented with cottonseed oil or lard. Reversibility of the cholesterol-induced atheroma was also studied in a few chickens, and it appears that the early lesions may undergo considerable regression after cholesterol feeding is stopped. Older lesions, on the other hand, appear to be quite fixed.
What is sports medicine? Medical students don't know
Authors: Benjamin Baby
Journal: British Journal of Sports Medicine (2000)

Use of imaging data for predicting clinical outcomeEDITOR,-We would like to air three points that arise from the paper Sonographic incidence of tendon microtears in athletes with chronic Achilles tendinosis. 1 Firstly, unfortunately the word "partial" has been omitted from the conclusion (abstract).The conclusion currently reads "There appears to be an association between microtear formation and Achilles tendon rupture".The distinction needs to be made, as the paper's Take home message concludes with the words "There may be a role for ultrasound in identifying athletes at high risk of tendon rupture", and in this case it appears that the authors mean complete tendon rupture.It is important that this ambiguity is clarified.Secondly, although it is well accepted that in many cases tendinosis precedes "spontaneous" tendon rupture, 2 it does not necessarily follow that sonographic abnormality will lead to (complete) tendon rupture.The tissue based pathologies found by Kannus and Jozsa may be more subtle than can be detected by sonography.We feel that, without longitudinal data in a large cohort with an appropriate control group, Gibbon and colleagues are not in a position to draw a conclusion on sonographic screenings of athletes.Thirdly, given the cross sectional study design, the authors should provide caveats emphasising that their theory of tendon remodelling paralleling that of bone is purely speculative.Cross sectional athlete-control comparisons (such as those provided to sustain the argument on tendon remodelling) do not provide evidence of causality-such diVerences can result merely from selection bias.If athlete-control diVerence were causally related, then one could take up basketball in order to grow tall.We emphasise the need for prospectively collected data to predict future outcome.Researchers and clinicians should desist from speculating as to the longitudinal clinical significance of imaging data collected at one point in time only.To our knowledge, there is only one published prospective ultrasonography and clinical correlation study in the tendon literature at present, 3 and it shows rather poor predictive value of ultrasonography in terms of development of symptoms and clinical findings of patellar tendinopathy in female basketball players.Until researchers and reviewers acknowledge the importance of longitudinally collected data for predicting clinical outcome, our imaging field will continue to be mired in a debate based on speculation rather than science.
Antiestrogen Fulvestrant Enhances the Antiproliferative Effects of Epidermal Growth Factor Receptor Inhibitors in Human Non–Small-Cell Lung Cancer
Authors: Edward B. Garon, Richard J. Pietras, Richard S. Finn, Naeimeh Kamranpour, Sharon Pitts, Diana C. Márquez-Garbán, Amrita J. Desai, Judy Dering, Wylie Hosmer, Erika M. von Euw, Steven M. Dubinett, Dennis J. Slamon
Journal: Journal of Thoracic Oncology (2013)
STUDIES ON THE VIRULENCE OF TUBERCLE BACILLI
Authors: Hubert Bloch, Hans Noll
Journal: The Journal of Experimental Medicine (1953)

Tubercle bacilli were grown in the presence of different concentrations of tween 80, ranging from 0.05 to 2.1 per cent. Equal numbers of viable bacteria from these cultures were compared in infection experiments in the mouse. The average survival time of the mice was used as a criterion for the virulence of the bacilli. High tween concentrations in the culture medium caused a reduction of the bacterial virulence. The reduction was slight in bacterial suspensions from cultures with tween 80 ranging from 0.05 to 1.0 per cent, but considerable in cultures with 2.1 per cent tween. Bacteria grown in the presence of 2.1 per cent tween gave rise to the same number of colonies, in vitro, as bacteria grown in ordinary media. Their oxygen uptake was increased as compared with that of bacilli grown in media containing less tween. Virulent bacteria grown in the presence of high amounts of tween 80 decolorized methylene blue in a test in which organisms from the same virulent strain but cultured without tween, or with only small proportions of the detergent in the medium, did not reduce the dye. A positive methylene blue test is typical of non-virulent tubercle bacilli and of saprophytic mycobacteria. Essentially the same changes occurred when virulent tubercle bacilli were grown in the presence of 0.5 microg./ml. of para-formacetanilide thiosemicarbazone (TBI). This small amount of the substance was not sufficient to prevent the growth of bacteria, or to reduce the number of viable cells in a culture, but it reduced the virulence of the bacteria considerably and rendered them capable of decolorizing methylene blue. Cord factor, a lipid constituent of virulent bacteria which is toxic for mice, was shown to be present in filtrates from cultures of virulent bacteria when the media contained 2 per cent tween 80, but no such material could be recovered from culture filtrates containing the usual 0.05 per cent tween. On the other hand, no toxic material could be extracted from bacteria grown in the presence of 0.5 microg./ml. TBI.
Abstract 2600: <i>SLX4</i> mutation in hereditary breast cancer
Authors: Sohela Shah, Frank Lach, Yonghwan Kim, Kara Sarrel, Rohini Rau-Murthy, Nichole Hansen, Justin Rendleman, Tomas Kirchhoff, Vijai Joseph, Kenneth Offit, Agata Smogorzewska
Journal: Cancer Research (2012)

Abstract SLX4 is a DNA repair protein that serves as a docking platform for three structure-specific endonucleases. Recent studies have reported mutations in SLX4 in a new subtype of Fanconi Anemia (FA-P). Monoallelic defects in several Fanconi Anemia genes are known to confer susceptibility to breast and ovarian cancer. Therefore, we resequenced the entire SLX4 coding region in 739 (288 Ashkenazi Jewish and 480 Non-Ashkenazi Jewish) breast cancer patients with 3 or more family members affected by breast cancer and no known BRCA1/BRCA2 mutations, to determine if SLX4 is involved in breast cancer susceptibility. We found a novel nonsense (p.W823*) mutation in one patient. We are sequencing the gene in the breast tumor from the patient to determine the status of the wild-type allele. In addition we also found 8 novel, 33 rare (MAF&amp;lt;1%), and 3 common (MAF&amp;gt; 0.5) missense variants, of which 12 (5 novel and 10 rare) are predicted as damaging by Polyphen2. Functional analysis of these missense mutations is being performed to determine their role in the pathogenicity of the SLX4 gene. Acknowlegements- This project was funded by The Starr Cancer Consotium (Agata Smorgorzewska and Kenneth Offit), The Rita Allen Foundation Scholars Program Grant (Agata Smorgorzewska) and Burroughs Wellcome Fund Career Award for Medical Scientists (Agata Smorgorzewska). We would like to thank the Geoffrey Beene Translational Oncology and Diagnostic Molecular Genetics laboratories for their help with the study. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2600. doi:1538-7445.AM2012-2600
Carnitine deficiency in chronic obstructive pulmonary disease patients
Authors: Adel Attia, Moosa Suleman
Journal: European Respiratory Journal (2013)

Introduction: Chronic Obstructive Pulmonary Disease (COPD) is increasingly recognized as a systemic disease characterized by progressive airflow limitation as well as respiratory and peripheral muscle weakness. Deficiency in the levels of carnitine, an essential nutrient for optimal muscle function, has been associated with peripheral and respiratory muscle weakness in other diseases, but has not yet been examined in COPD patients. The aim of this study was to investigate whether plasma acyl carnitine fractions were reduced in patients with COPD, and examine if the deficiency correlated with COPD severity.  Patients and methods: A prospective case control study to compare acyl carnitine levels and other parameters in 81 COPD patients treated at the Pulmonology Department, King Fahad Specialist Hospital Dammam, with 48 age and sex matched healthy controls. All subjects participating in the study underwent a complete physical examination and detailed pulmonary function tests (PFTs). Blood samples were taken for acyl carnitine profiles as well as a panel of other tests including albumin, total protein, Iron, CRP and pre-albumin. Acyl carnitine profile was determined using LC-MS/MS analysis.  Results: COPD patients had significantly lower total carnitine levels compared to controls (43.9 ± 6.5 and 22.7 ± 11.9 respectively). Furthermore there was a significantly greater reduction in carnitine levels in patients with very severe COPD compared to patients with mild COPD.  Conclusion: Our study demonstrated a significant deficiency in carnitine levels in COPD patients, and the degree  of deficiency correlated with the severity of COPD.
ABC of monitoring drug therapy. Patient compliance.
Authors: J. K. Aronson, M. Hardman
Journal: BMJ (1992)

Doctors assume that when they give a patient a prescription the drug willfbe taken, as directed.But patients do not always take their prescribed drugs, and if there is no therapeutic response to a given dosage regimen poor compliance must be considered.Hippocrates warned that patients may 'often lie about taking their medicines.Up to 20% of patients fail to collect their prescribed drugs within one month of issue and are therefore non-compliant from the start.'Even patients who collect their drugs may not take them.Rates of compliance have been variously estimated at between 10% and 90% and depend on Patients don't always take their drugs in the many factors, including the enthusiasm of the doctor, the disease being recommended fashion.This tin contains drugs t 2 belonging to a patient and his wife; there are several treated, and the patient's perception of the importance of the disease.full bottles of warfarin, antibiotics, and a range of psychotropic drugs. Methods of assessing complianceMethods of assessing compliance Method Description Comments _ *~~~~~~~~~Recording devices Tablet counting device.You may get some idea of * Measuring the concentration of the drug in body fluids compliance by counting the number of tablets in the 0 Measuring a marker substance added to the drug bottle and comparing this with the prescribed number of tablets.* Measuring the pharmacological effect.
Epidemiologic studies of electric and magnetic fields and cancer: strategies for extending knowledge.
Authors: D A Savitz
Journal: Environmental Health Perspectives (1993)

Epidemiologic research concerning electric and magnetic fields in relation to cancer has focused on the potential etiologic roles of residential exposure on childhood cancer and occupational exposure on adult leukemia and brain cancer. Future residential studies must concentrate on exposure assessment that is enhanced by developing models of historical exposure, assessment of the relation between magnetic fields and wire codes, and consideration of alternate exposure indices. Study design issues deserving attention include possible biases in random digit dialing control selection, consideration of the temporal course of exposure and disease, and acquisition of the necessary information to assess the potential value of ecologic studies. Highest priorities are comprehensive evaluation of exposure patterns and sources and examination of the sociology and geography of residential wire codes. Future occupational studies should also concentrate on improved exposure assessment with increased attention to nonutility worker populations and development of historical exposure indicators that are superior to job titles alone. Potential carcinogens in the workplace that could act as confounders need to be more carefully examined. The temporal relation between exposure and disease and possible effect modification by other workplace agents should be incorporated into future studies. The most pressing need is for measurement of exposure patterns in a variety of worker populations and performance of traditional epidemiologic evaluations of cancer occurrence. The principal source of bias toward the null is nondifferential misclassification of exposure with improvements expected to enhance any true etiologic association that is present. Biases away from the null might include biased control selection in residential studies and chemical carcinogens acting as confounders in occupational studies.
Metabolism and Excretion of Exogenous Thyrotropin-Releasing Hormone in Humans
Authors: Rahim M. Bassiri, Robert D. Utiger
Journal: Journal of Clinical Investigation (1973)

To study the metabolism of thyrotropin-releasing hormone (TRH) in vivo, 400 mug TRH was administered intravenously to eight normal male subjects. Multiple plasma and urine samples were obtained before and after TRH administration. Serum TSH concentrations increased after TRH administration in all subjects. Plasma TRH levels, measured by radioimmunoassay, were undetectable (< 0.4 ng/ml) before TRH administration. Plasma TRH concentrations averaged 33+/-7 ng/ml (mean +/-SEM) 2 min after TRH injection. Thereafter, they decreased rapidly so that the mean plasma TRH level was 2.9 ng/ml 20 min after TRH administration. The fall in plasma TRH levels was linear during this interval. Thereafter TRH levels declined more slowly. The mean half-life (t(1/2)) of TRH was 5.3+/-0.5 min. The mean distribution volume was 15.7+/-3.8 liters, an average of 16.5% of body weight in these subjects. In the urine, 5.5+/-0.9% of the administered TRH was recovered in the 3 h after TRH administration. Of the total urinary TRH recovered, 84.9% was excreted in the first 30 min. These results indicate that TRH is distributed in a large volume, that it is rapidly metabolized and that a significant quantity of administered TRH is excreted in the urine.
Anaemia in Infancy and Childhood
Authors: J. H. Hutchison
Journal: BMJ (1965)

Any discussion of anaemic states in infancy and childhood must pay regard to the fact that the normal blood picture during this period is different from that of the healthy adult.In the first year of life in particular the peripheral blood undergoes several major changes.In the newborn infant a further factor of importance is that haemoglobin levels and red-cell counts may vary considerably between venous and capillary (" heel-prick ") blood, the latter giving higher values.However, certain flexible figures can be given because in clinical practice only relatively large departures from normal are likely to be significant.The modern haematologist uses many refined techniques, including serological, histochemical, and radio-isotopic methods, which are outside the competence of the ordinary physician.Nevertheless, the common anaemias of childhood can usually be dealt with by simple methods which are within the reach of any physician prepared to devote some time and care to their per- formance.In general practice the most useful single test is
NRF2 Pathway Activation and Adjuvant Chemotherapy Benefit in Lung Squamous Cell Carcinoma
Authors: David W. Cescon, Desmond She, Shingo Sakashita, Chang-Qi Zhu, Melania Pintilie, Frances A. Shepherd, Ming-Sound Tsao
Journal: Clinical Cancer Research (2015)

Genomic profiling of lung squamous cell carcinomas (SCC) has identified NRF2 pathway alterations, which activate oxidative response pathways, in one third of tumors. Preclinical data suggest these tumors may be resistant to platinum-based chemotherapy. We evaluated the clinical relevance of these findings and assessed whether NRF2 activation predicts benefit from adjuvant chemotherapy in SCC.Logistic regression (LR) and significance analysis of microarrays (SAM) were applied to all 104 TCGA (The Cancer Genome Atlas) SCC cases that had microarray gene expression and mutation data to identify genes associated with somatic NRF2 pathway alterations. The resulting signature (NRF2(ACT)) was tested in 3 independent SCC datasets to evaluate its prognostic and predictive effects. IHC and sequencing for NRF2 and KEAP1 were evaluated in one cohort (n = 43) to assess the relationship between gene expression, mutational status, and protein expression.Twenty-eight genes were identified by overlap between LR (291 genes) and SAM (30 genes), and these consistently separated SCC into 2 groups in all datasets, corresponding to putatively NRF pathway-activated and wild-type (WT) tumors. NRF2(ACT) was not prognostic. However, improved survival with adjuvant chemotherapy in the JBR.10-randomized trial appears limited to patients with the WT signature (HR 0.32, P = 0.16; NRF2(ACT) HR 2.28, P = 0.48; interaction P = 0.15). NRF2(ACT) was highly correlated with mutations in NRF2 and KEAP1, and with high NRF2 protein expression.A gene expression signature of NRF2 pathway activation is associated with benefit from adjuvant cisplatin/vinorelbine in SCC. Patients with NRF2 pathway-activating somatic alterations may have reduced benefit from this therapy.