tbuckley/cabot-search huggingface dataset:
Methoxyflurane and Nitrous Oxide as Obstetric Analgesics. II.--A Comparison by Self-administered Intermittent Inhalation
Authors: P. L. Jones, M. Rosen, W. W. Mushin, E. V. Jones
Journal: BMJ (1969)

Methoxyflurane (0·35%) in air and nitrous oxide/oxygen (50%/50%) self-administered intermittently in the usual way have been compared as analgesics for labour. There were 25 patients in each group. Objective assessment by an anaesthetist showed that methoxyflurane is the more effective analgesic, and this was supported by the opinion of the multiparae. Nausea and vomiting were significantly less with methoxyflurane. Fifty per cent. nitrous oxide in oxygen given intermittently does not appear to be the best analgesic concentration. Nevertheless, since a considerable variation in sensitivity exists, it would probably be unwise to consider the introduction of higher concentrations for use by unsupervised midwives. This trial confirms the predictions made by us using a method for screening inhalational analgesics, in which methoxyflurane and nitrous oxide were given continuously.
A Novel Paradigm to Trigger Apoptosis in Chronic Lymphocytic Leukemia
Authors: Sandra Loeder, Thorsten Zenz, Andrea Schnaiter, Daniel Mertens, Dirk Winkler, Hartmut Döhner, Klaus-Michael Debatin, Stephan Stilgenbauer, Simone Fulda
Journal: Cancer Research (2009)

Evasion of apoptosis is a hallmark of chronic lymphocytic leukemia (CLL), calling for new strategies to bypass resistance. Here, we provide first evidence that small-molecule X-linked inhibitor of apoptosis (XIAP) inhibitors in combination with the death receptor ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) present a novel approach to trigger apoptosis in CLL, including subgroups with resistant disease or unfavorable prognosis. XIAP, cellular IAP (cIAP) 1, and cIAP2 are expressed at high levels in primary CLL samples. Proof-of-concept studies in CLL cell lines show that subtoxic concentrations of XIAP inhibitors significantly enhance TRAIL-induced apoptosis and also sensitize for CD95-mediated apoptosis. Importantly also in primary CLL samples, XIAP inhibitor acts in concert with TRAIL to trigger apoptosis in 18 of 27 (67%) cases. This XIAP inhibitor-induced and TRAIL-induced apoptosis involves caspase-3 activation and is blocked by the caspase inhibitor zVAD.fmk. The cooperative interaction of XIAP inhibitor and TRAIL is even evident in distinct subgroups of patients with poor prognostic features (i.e., with 17p deletion, TP53 mutation, chemotherapy-refractory disease, or unmutated V(H) genes). Interestingly, cases with unmutated V(H) genes were significantly more sensitive to XIAP inhibitor-induced and TRAIL-induced apoptosis compared with V(H) gene-mutated samples, pointing to a role of B-cell receptor signaling in apoptosis regulation. By showing that XIAP inhibitors in combination with TRAIL present a new strategy to trigger apoptosis even in resistant forms and poor prognostic subgroups of CLL, our findings have important implications for the development of apoptosis-based therapies in CLL.
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Authors: C. Oliver
Journal: BMJ (1999)

B: Patients with pulmonary hypertension (PH) on stable background therapy are often able to live a life with only few restrictions. Quality of life includes flights for many people. But the hypobaric hypoxia present during high altitude can have major impact on the medical condition of these patients. Evidence is lacking and the recommendations in the current guidelines are derived from other chronic lung disease. We aim to fill this gap of knowledge. M+R: PEGASUS is a prospective, multicenter, multinational observational study which started in 2017 and is open until 2019. Primary endpoint is the safety of commercial air travel for patients with PH. In addition, adverse events will be associated with clinical parameters before flight to detect possible risk factors. Up to February 2018, 200 patients were prospectively included and 22 flights were documented. No adverse event with the need for medical intervention occurred so far. The flying participants had a pulmonary vascular resistance of 5.6 Wood units (median, interquartile range(IQR) 1.8), oxygen saturation at the end of six-minute-walking-test was 93% (IQR 7). 35% use oxygen at home. 7 of the 22 flying patients had a desaturation during flight below 91% measured by pulsoxymeter, three below 86%. 8 patients did not use oxygen while on the airplane and had more severe desaturations down to 78% while the minimum oxygen saturation was 88% in patients using oxygen on board. C: We are expecting important safety data for PH patients who travel by plane. Every PH patient is cordially invited to register before flying: pegasus.studie@gmx.de
The Exomes of the NCI-60 Panel: A Genomic Resource for Cancer Biology and Systems Pharmacology
Authors: Ogan D. Abaan, Eric C. Polley, Sean R. Davis, Yuelin J. Zhu, Sven Bilke, Robert L. Walker, Marbin Pineda, Yevgeniy Gindin, Yuan Jiang, William C. Reinhold, Susan L. Holbeck, Richard M. Simon, James H. Doroshow, Yves Pommier, Paul S. Meltzer
Journal: Cancer Research (2013)

Abstract The NCI-60 cell lines are the most frequently studied human tumor cell lines in cancer research. This panel has generated the most extensive cancer pharmacology database worldwide. In addition, these cell lines have been intensely investigated, providing a unique platform for hypothesis-driven research focused on enhancing our understanding of tumor biology. Here, we report a comprehensive analysis of coding variants in the NCI-60 panel of cell lines identified by whole exome sequencing, providing a list of possible cancer specific variants for the community. Furthermore, we identify pharmacogenomic correlations between specific variants in genes such as TP53, BRAF, ERBBs, and ATAD5 and anticancer agents such as nutlin, vemurafenib, erlotinib, and bleomycin showing one of many ways the data could be used to validate and generate novel hypotheses for further investigation. As new cancer genes are identified through large-scale sequencing studies, the data presented here for the NCI-60 will be an invaluable resource for identifying cell lines with mutations in such genes for hypothesis-driven research. To enhance the utility of the data for the greater research community, the genomic variants are freely available in different formats and from multiple sources including the CellMiner and Ingenuity websites. Cancer Res; 73(14); 4372–82. ©2013 AACR.
Effect of Insulin on Acetylcholine-Induced Vasodilation in Normotensive Subjects and Patients With Essential Hypertension
Authors: Stefano Taddei, Agostino Virdis, Paola Mattei, Andrea Natali, Ele Ferrannini, Antonio Salvetti
Journal: Circulation (1995)

Background The present study was designed to directly test the vasodilation action of insulin and its relation to endothelium-dependent mechanisms. Methods and Results In 18 normotensive subjects and 27 patients with untreated mild to moderate essential hypertension, we studied the effect of intrabrachial insulin on the changes in forearm blood flow (strain-gauge plethysmography) induced by intrabrachial acetylcholine (at doses of 0.15, 0.45, 1.5, 4.5, and 15 μg · min −1 · dL −1 ), an endothelium-dependent vasodilator, or sodium nitroprusside (at doses of 1, 2, and 4 μg · min −1 · dL −1 ), an endothelium-independent vasodilator. Local hyperinsulinemia (deep venous plasma insulin, 48±6 and 51±5 μU/mL in control subjects and hypertensive patients, respectively) did not affect basal forearm blood flow and stimulated forearm glucose extraction (control subjects, 3±1% to 11±2%, P &lt;.001; hypertensive patients, 3±1% to 6±1%, P &lt;.001; P &lt;.01 for the between-group difference). In both normotensive and hypertensive subjects, insulin significantly potentiated acetylcholine-induced vasodilation, whereas it did not alter the vasodilatory response to sodium nitroprusside. N G -monomethyl- l -arginine, an inhibitor of endothelial nitric oxide synthesis, blunted insulin-induced facilitation of acetylcholine vasodilation in normotensive but not in hypertensive subjects. In contrast, in hypertensive patients but not in normotensive control subjects, the potentiation of the vascular response to acetylcholine induced by local hyperinsulinemia was abolished by intrabrachial ouabain, an inhibitor of Na + -K + pump. Conclusions In healthy humans and essential hypertensive patients alike, local physiological hyperinsulinemia per se does not increase forearm blood flow but potentiates the vasodilation induced by acetylcholine regardless of metabolic insulin resistance. This effect is endothelium-dependent because it is not seen with nitroprusside and is related to the l -arginine–nitric oxide pathway in normotensive subjects and to smooth muscle cell hyperpolarization in essential hypertensive patients.
Needle Biopsy of Skeletal Muscle in the Diagnosis of Myopathy and the Clinical Study of Muscle Function and Repair
Authors: Richard Edwards, Archie Young, Mark Wiles
Journal: New England Journal of Medicine (1980)

CONSIDERABLE use has been made of needle biopsy for diagnostic and investigative purposes in recent years.1 However, many organs in man, including liver, kidney, and brain, are unsuitable for direct functional studies based on repeated biopsies, and hence the relation between structure, function, and underlying biochemical processes, particularly in disease, has remained obscure. An understanding of the essential "metabolic" function of many organs has evolved with an understanding of the underlying chemical processes, investigated in animals and determined in man generally by indirect methods. The function of muscle is to produce force and to do work — properties that may . . .
TCT-281 The Association Between Cholesterol Crystal And Features Of Plaque Vulnerability On Optical Coherence Tomography
Authors: Yu Kataoka, Julie Thornton, Kathy Wolski, Rishi Puri, James Harvey, Kiyoko Uno, Samir Kapadia, E. Murat Tuzcu, Steven Nissen, Stephen Nicholls
Journal: Journal of the American College of Cardiology (2012)
The relationship of dietary fish intake to level of pulmonary function in the first National Health and Nutrition Survey (NHANES I)
Authors: J Schwartz, ST Weiss
Journal: European Respiratory Journal (1994)

Eicosapentaenoic acid (EPA), which predominates in marine fish, tends to counteract and inhibit the uptake and incorporation of arachidonic acid and membrane phospholipids and dilute arachidonic acid as a potential substrate for oxidation. Thus, fish intake may be protective for the occurrence of asthma and other pulmonary diseases. We wanted to examine the relationship between the effect of chronic dietary intake to fish and its relationship to level of pulmonary function. We performed this analysis using data from the First National Health and Nutritional Examination Survey (NHANES I). A detailed subsample of 2,526 adults had a medical history questionnaire, that included a 24-hour dietary recall, and performed spirometric examination. Log of forced expiratory volume in one second (FEV1) served as a dependent variable in regression analysis which included an adjustment for height, age, cigarette smoking and gender. When added to the regression model including the above variables dietary fish intake showed a protective association with FEV1 (beta = 0.008 +/- 0.004, p = 0.028). When smokers were excluded from the analysis, the effect of fish intake on pulmonary function appeared to increase slightly (beta = 0.0108 +/- 0.006, p = 0.61). These data suggest that chronic dietary intake of fish is associated with higher levels of pulmonary function and is consistent with the hypothesis of an effect of fish oil on arachidonic acid metabolism.
A KNOWLEDGE TRANSLATION INITIATIVE TO ENHANCE EVIDENCE-INFORMED CLINICAL MANAGEMENT OF ACHILLES TENDINOPATHY: THE PURPOSE, PROCESS AND OUTCOMES OF THE BC TENDINOPATHY TOOLKIT
Authors: A M Hoens, A Ezzat, J Anthony, A Scott, M Yates, J R Justesen, D Hughes
Journal: British Journal of Sports Medicine (2013)

Introduction Translation of knowledge to practice in health care is a significant challenge.1 – 3 This presentation describes the purpose, process and preliminary outcomes of a knowledge translation (KT) initiative undertaken by a unique partnership of physical therapy researchers, educators and expert clinicians to address the gap between evidence and practice in the management of Achilles tendinopathy. Methods Physiotherapy clinicians in British Columbia requested evidence-informed guidance on the management of tendinopathy. To address this need, the provincial Physical Therapy Knowledge Broker assembled a team of researchers, educators and expert clinicians with the mandate to develop, disseminate and implement a toolkit of decision aids to guide clinical decision-making for Achilles Tendinopathy. The process to develop the toolkit involved the following components: (1) identification of the purpose and scope of the project (2) agreement on the processes for selection of content and format (3) creation of a mechanism for resolution of conflicting opinion (4) an iterative feedback process with stakeholders and (4) the incorporation of concepts and strategies from the knowledge translation and implementation science literature to support the stages of knowledge synthesis, dissemination and implementation.1 – 4 Results The ‘Tendinopathy Toolkit’ included: (1) a tabulated summary of the evidence for manual therapy, exercise, low level laser therapy, ultrasound, extracorporeal shock wave therapy, iontophoresis using dexamethasone, taping, orthotics, night splints and braces, heel raise inserts, needling techniques, and the appropriate outcome measures for this population (targeted ‘take home messages’ and clinical implications for each were also included); (2) an algorithm to guide the sequence of interventions; (3) and appendices including (a) exercise programmes (b) low level laser dosage calculation (c) tabulated details for each article reviewed and (d) a review of common medical interventions. The second phase of the initiative—utilization of strategies to enhance implementation and uptake of the toolkit—is currently being undertaken. Discussion Clinicians want to provide evidence-informed management of tendinopathy but many struggle with accessing, appraising and synthesising the vast array of literature available on this topic. This KT initiative highlights the need for, challenges associated with, evidence-informed process for and positive response to the development of decision aids synthesising the current evidence to guide clinical management of this patient population.
Inhibition of KIT Tyrosine Kinase Activity: A Novel Molecular Approach to the Treatment of KIT-Positive Malignancies
Authors: M. C. Heinrich
Journal: Journal of Clinical Oncology (2002)

PURPOSE: Activation of the KIT tyrosine kinase by somatic mutation has been documented in a number of human malignancies, including gastrointestinal stromal tumor (GIST), seminoma, acute myelogenous leukemia (AML), and mastocytosis. In addition, paracrine or autocrine activation of this kinase has been postulated in numerous other malignancies, including small-cell lung cancer and ovarian cancer. In this review, we discuss the rationale for and development of KIT tyrosine kinase inhibitors for the treatment of human malignancies. MATERIALS AND METHODS: Studies were identified through a MEDLINE search, review of bibliographies of relevant articles, and review of abstracts from national meetings. RESULTS: Four tyrosine kinase inhibitors that have activity against KIT are currently being used in clinical trials, and one, STI571, has recently been approved by the United States Food and Drug Administration for treating patients with chronic myelogenous leukemia. The role of KIT inhibitors in treating KIT-positive malignancies is reviewed. CONCLUSION: Targeted therapy to inhibit the kinase activity of KIT is a rational approach to the treatment of KIT-positive malignancies. Two key factors are the potency of a given inhibitor and the relative contribution of KIT activation to the growth of the tumor. Given our current understanding of KIT activity in human malignancy, the best candidate diseases for treatment with KIT inhibitors are GIST, mastocytosis, seminoma and possibly some cases of AML. Additionally, KIT inhibitors may play an adjunctive role in diseases such as small-cell lung cancer, in which KIT activation is secondary to ligand binding rather than an acquired mutation.
What do general practitioners want from a dermatology department?
Authors: E.D. HARLOW, J.L. BURTON
Journal: British Journal of Dermatology (1996)

Four hundred and fifty-six practitioners (GPs) in Avon were asked what they required from their department of dermatology, and what improvements to the present service they could suggest. Most GPs preferred to manage the majority of dermatological problems themselves, with support from the department where necessary. They referred to a hospital department because they lacked the necessary expertise, but would prefer to receive training, advice and support in managing their patients rather than surrender long-term care to a specialist department. Despite this expressed willingness to shoulder more of the dermatological burden, only 31% of the GPs had received any postgraduate training in dermatology. In fact 57% said they had little interest in the subject and had not attended any form of dermatology teaching since qualifying. GPs would also like more guidance in the form of regularly updated guidelines and protocols, and easy access to dermatologists for telephone advice at regular fixed times. Some also felt that consultants should aim to provide diagnosis, investigation, and management guidelines for referred patients after a single visit. These findings should prompt a re-appraisal of the relative roles of GP and dermatologist, and emphasize the need for vocational training and continuing medical education in dermatology for all GPs.
HEMIPLEGIA FOLLOWING ACUTE INFECTIONS
Authors: W. A. JONES
Journal: JAMA (1910)

The cerebral palsies of childhood have received considerable attention in certain rather elaborate treatises; such as those of McNutt, Lovett, Osler, Sachs and Spiller in this country, and of several writers abroad, but aside from these not much has appeared on the subject. Thus, even in the most elaborate systems of medicine, paralysis of central origin in diphtheria is given the briefest consideration, or else is not mentioned at all. These facts are thought to justify the publication of the following reports of cases. <h3>Case 1.—History.—</h3> The patient, a schoolgirl, aged 9, was seen at the University Free Dispensary Feb. 8, 1908. Her father was living at 38 and well except that he was nervous; her mother was living and well at 36. She had had two miscarriages, both at about three months. Two brothers and one sister were living and well. A paternal aunt was paralyzed at 24, following
Serum Inorganic Sulphates In Addison's Disease
Authors: E. G. WAKEFIELD
Journal: Annals of Internal Medicine (1930)

Article1 January 1930Serum Inorganic Sulphates In Addison's DiseaseE. G. WAKEFIELD, M.D.E. G. WAKEFIELD, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-3-7-662 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIt has been shown2,3,5,6,7 that during the critical periods and terminal stages of Addison's disease renal insufficiency may be manifested and is evidenced by the retention of urea and by inability of the kidney to excrete water and phenolsulphonephthalein. The amount of total solids in the urine also may be lessened.The object of my study was to determine if the concentration of serum inorganic sulphates is increased in Addison's disease. Also, if serum inorganic sulphates were found to be increased I hoped to establish whether the increase is a constant feature of the disease or whether it occurs only...Bibliography1 MARSHALLDAVIS EKDM: The phates in blood serum, urine and other influence of the adrenals on the kidneys. Jour. Pharmacol. and Exper. Therap., 1916, viii, 525-550. Google Scholar2 ROSENOW G: Über die Nierenfunktion bei der Addisonschen. Med. Klin., 1925, xxi, 202-203. Google Scholar3 ROWNTREESNELL LGAM: Unpublished data. Google Scholar4 SWINGLEWENNER WWWF: Sulphate retention in dogs following bilateral adrenal extirpation. Physiol. Zoöl., 1928, i, 37-44. CrossrefGoogle Scholar5 WAKEFIELD EG: The colorimetric determination of total and inorganic sulbody fluids. Jour. Biol. Chem., 1929, lxxxi, 713-721. CrossrefGoogle Scholar6 WAKEFIELD EG: Inorganic serum sulphates in renal insufficiency. A comparative study with blood urea and creatinine. The effect of diuresis on serum sulphates. Arch. Int. Med., 1929, xliv, 244-251. CrossrefGoogle Scholar7 WAKEFIELDSMITH EGEE: Addison's disease, suprarenalopathies sclerosis of the glands of internal secretion. Am. Jour. Med. Sc., 1927, clxxiv, 343-357. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: E. G. WAKEFIELD, M.D.Affiliations: The Mayo Foundation Rochester, Minnesota*Work done in the Division of Medicine under the direction of Dr. L. G. Rowntree. Submitted for publication July 31, 1929. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byBeitrag zum Mechanismus der Säurebasenregulation im Harn bei Gestörter Nierenfunktion 1 January 1930Volume 3, Issue 7 Page: 662-666 Keywords Attention Renal diseases Urea Urine ePublished: 1 December 2008 Issue Published: 1 January 1930 PDF downloadLoading ...
Use of Tobramycin-Impregnated Calcium Sulphate Pellets in Addition to Oral Antibiotics
Authors: Eleanna V. Salgami, Frank L. Bowling, Richard W. Whitehouse, Andrew J.M. Boulton
Journal: Diabetes Care (2006)

To supplement surgical debridement, pellets of calcium sulfate (CS) were used as vehicles for local antibiotic delivery in treating osteomyelitis (1). We are aware of one case series in which diabetic pedal osteomyelitis was resolved with postoperatively implanted polymethylmethacrylate antibiotic beads and intravenous antibiotics (2). We now present a case of radiologically successful, nonsurgical management of diabetic foot osteomyelitis with tobramycin-impregnated CS pellets, in addition to oral antibiotic …
The Epidemiology of Lower Extremity Amputations in Diabetic Individuals
Authors: Randi S Most, Pomeroy Sinnock
Journal: Diabetes Care (1983)

The Diabetes Control Activity has established diabetes control programs in 20 states. Each has investigated the extent and nature of diabetes morbidity within its state by means of a descriptive analysis of selected health status indicators. Data from six states are included: 100% of hospital discharges from Rhode Island, South Carolina, and Maine and approximately 50% from Minnesota, Illinois, and Ohio were pooled to provide a profile of lower extremity amputations (LEA) in diabetic individuals. The purposes of this study were to identify diabetic persons at high risk of amputation for targeting preventive programs as well as to establish a baseline for monitoring trends over time. Discharge data provided by hospital abstracting services were examined for 1976–1978. Results indicate that 45% of all LEAs are performed on patients with diabetes. An age-adjusted LEA rate of 59.7/10,000 diabetic individuals was computed. Diabetes-related amputation rates increase with age and are higher in males. The overwhelming majority of LEAs are either toe or above the knee, with few performed on the foot. The relative risk of LEAs for the diabetic cqmpared with the nondiabetic population is highest in the under- 45 age group (28), although the attributable risk is highest in the older population (91.5/10,000 diabetic individuals). Overall, diabetic persons have a 15 times higher risk of LEA than nondiabetic individuals.