tbuckley/cabot-search huggingface dataset:
Mutation of NRAS but not KRAS significantly reduces myeloma sensitivity to single-agent bortezomib therapy
Authors: George Mulligan, David I. Lichter, Alessandra Di Bacco, Stephen J. Blakemore, Allison Berger, Erik Koenig, Hugues Bernard, William Trepicchio, Bin Li, Rachel Neuwirth, Nibedita Chattopadhyay, Joseph B. Bolen, Andrew J. Dorner, Helgi van de Velde, Deborah Ricci, Sundar Jagannath, James R. Berenson, Paul G. Richardson, Edward A. Stadtmauer, Robert Z. Orlowski, Sagar Lonial, Kenneth C. Anderson, Pieter Sonneveld, Jesús F. San Miguel, Dixie-Lee Esseltine, Matthew Schu
Journal: Blood (2013)
Frontline-Treatment Of Acute Lymphoblastic Leukemia (ALL) In Older Adolescents and Young Adults (AYA) Using a Pediatric Regimen Is Feasible: Toxicity Results of the Prospective US Intergroup Trial C10403 (Alliance)
Authors: Anjali S. Advani, Ben Sanford, Selina Luger, Meenakshi Devidas, Eric C. Larsen, Michaela Liedtke, Peter M Voorhees, Matthew C. Foster, David F. Claxton, Susan Geyer, Edy Parker, Kristin Coffan, William L. Carroll, Naomi J. Winick, Steven E. Coutre, Martin S Tallman, Frederick R. Appelbaum, Harry Paul Erba, Richard M. Stone, Stephen P. Hunger, Richard A. Larson, Wendy Stock
Journal: Blood (2013)
A Program for Normal Glycemic Control of Insulin-dependent Diabetes
Authors: John R Williams, Katharine Alling
Journal: Diabetes Care (1980)

A method of instruction enabling patients to control their diabetes is described. The patients learn through home glucose monitoring how their blood sugar levels vary with changes in diet, exercise, and insulin. They learn to chart accurately all the factors influencing their control in a manner that enables them, as well as the physician, to analyze them quickly. From this information they learn to anticipate the results of various changes in life-style and, thus, to live beyond the customary constraints of the disease without loss of glycemic control. Significant improvements in neuritis, impotence, and creatinine clearance rates are reported.
<scp>d</scp>-Dimers in the Diagnosis of Pulmonary Embolism
Authors: DEBORAH A. QUINN, ROBERT B. FOGEL, CYNTHIA D. SMITH, MICHAEL LAPOSATA, B. TAYLOR THOMPSON, STEPHEN M. JOHNSON, ARTHUR C. WALTMAN, CHARLES A. HALES
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

The aim of this study was to determine if the absence of circulating d-dimers, as determined by latex agglutination assays, can correctly exclude the presence of pulmonary embolism using pulmonary angiography as the diagnostic endpoint. Blood samples were obtained prospectively at the time of angiography for suspicion of acute pulmonary embolism. Plasma was assayed for d-dimer by five different latex agglutination assays. Angiographic evidence of pulmonary emboli was found in 34% (35/ 103) of patients. The latex agglutination assays had sensitivities of 97 to 100% and specificities of 19 to 29%. The negative predictive value was 94 to 100%. However, a negative d-dimer was rare in patients with recent surgery, malignancy, or total bilirubin > 34 μ mol/L ( > 2 mg/dl). In 31 patients suspected of pulmonary emboli but without these confounding factors, the five d-dimer assays were negative in 46 to 55% of patients with normal pulmonary angiograms. The negative predictive value in these patients was 100% by all five latex agglutination assays tested. The latex agglutination assays for d-dimer, when the pulmonary angiogram is used as the diagnostic endpoint and in the absence of recent surgery, malignancy, or liver disease, appears to be a clinically useful test in the diagnosis of acute pulmonary embolism.
Morphine Sans the Gift of Morpheus
Authors: Leroy D. Vandam
Journal: New England Journal of Medicine (1977)

The leading edge of discovery on pain moves forward in one of its recurrent accelerations. Several phenomena have contributed to this resurgence. The first is the perennial human fascination with the sensation of pain and the natural impulse to relieve suffering. Secondly, some of the older ideas concerning pain perception, the specificity and pattern theories, have been supplanted by a hypothesis based on a gating mechanism in the spinal cord, which regulates traffic in pain impulses. Even acupuncture, that once hailed, now disparaged, therapeutic measure, has added to the ferment through attempts to comprehend its mechanism. Thirdly, and rationally so, . . .
Abstract 3305: Glucocorticoid differentially regulates gene expression in luminal and basal subtypes of breast cancer
Authors: Jun Ling, Zenaida Lopez-Dee, Shagufta H. Khan, Raj Kumar
Journal: Cancer Research (2014)

Abstract Steroid hormone receptors (SHRs), such as estrogen- and progesterone- receptors, are well-validated drug targets and prognostic indicators for breast cancer (BC). When targeting SHRs for BC therapy, the major challenge is how to increase the selectivity of drugs against SHRs in specific cell/tissue. While estrogen- and progesterone- receptors are well studied in BC, glucocorticoid (GC) as a ubiquitous stress activated steroid hormone is less investigated. However, the elevated GC circadian dynamics is associated with poor prognosis, and GC receptor (GR) is highly expressed in metastatic BC. GCs are used successfully as an adjuvant therapy to induce apoptosis of leukemia and lymphoma. However, when applied to BC, the results are controversial with most GCs showing either pro-survival or no effects. To analyze the underlying mechanisms, gene expression profiling was performed in this study using qRT-PCR array that covers the genes as the drivers of BC. Our results showed that compared to MCF7 (luminal subtype) cells, MDA-MB-231(basal B subtype) cells are more responsive to Dexamethasone (Dex; a synthetic GC) treatment with the higher number of genes that were either up- or down-regulated. Shared by both MCF7 and MDA-MB-231 cells, the Dex-regulated genes are highly related to cell adhesion and epithelial-mesenchymal transition (EMT), followed by the genes involved in signal transduction, cell division and apoptosis, including SERPIN-E1, CDKN2A, c-Myc, THBS1, Snai2 and E-cadherin. However, the up- and down-regulation patterns are different between MDA-MB-231 and MCF7 cells. Using a real-time label-free cell assay, we identified that Dex promotes MDA-MB-231 cell adhesion and migration but only the spreading for MCF7 cells, suggesting that there are cell-specific effects of GC/GR in different subtypes of breast cancer. Citation Format: Jun Ling, Zenaida Lopez-Dee, Shagufta H. Khan, Raj Kumar. Glucocorticoid differentially regulates gene expression in luminal and basal subtypes of breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3305. doi:10.1158/1538-7445.AM2014-3305
Endotoxin in Cerebrospinal Fluid
Authors: George H. McCracken, Larrie D. Sarff
Journal: JAMA (1976)

The<i>Limulus</i>lysate assay was used to measure endotoxin in 307 cerebrospinal fluid (CSF) specimens from 84 infants with meningitis caused by Gram-negative bacteria. Endotoxin was detected in 117 CSF samples (38%), and its presence was correlated with recovery of bacteria from CSF cultures. A direct relationship was demonstrated between the presence, persistence, and concentration of endotoxin in CSF and outcome from meningitis. Measurement of CSF endotoxin by the<i>Limulus</i>assay and of CSF K1 antigen by counterimmunoelectrophoresis (CIE) showed a significant correlation between the presence and amount of these two<i>Escherichia coli</i>K1 capsular substances. Endotoxin was detected in 72% of infants, and 52% had K1 antigen in CSF specimens obtained within 24 hours of diagnosis. Combining the results of the<i>Limulus</i>assay and CIE, 81% of patients with<i>E coli</i>K1 meningitis had endotoxin or K1 or both in initial CSF samples. (<i>JAMA</i>235:617-620, 1976)
Road Trauma, a socially accepted horror movie
Authors: Guy Mazairac
Journal: BMJ (2004)

Ihave the incredible good fortune to have been born in a rich, peaceful country. I know nothing of war or terrorism, apart from the images I see on the television news. But if television wars have any “justification,” then what of the war that I have to attend to—a war that kills every day? Absurdly, in my country, Belgium, a total of 1500 people die each year, with a cortege of thousands mentally or physically disabled. Worldwide, my war kills millions.

I cannot count the number of dead or disabled people that I have dealt with over the past 20 years in the mobile intensive care unit or in the emergency room.

Our hospital invests large amounts of money in staffing and equipment in order to improve the immediate on-site care of those injured in road traffic crashes. The hope is to minimise the consequences of major trauma. I know that this is not enough. For years our hospital has …
P188Lipopolysaccharide- and omega-3 fatty acids-induced changes in connexin40 expression in endothelium of normotensive rat aorta.
Authors: K Frimmel, I Bernatova, R Sotnikova, J Navarova, L Okruhlicova
Journal: Cardiovascular Research (2014)

The aim of our study was to investigate the effect of omega-3 fatty acids (FA) on expression of connexin40 (Cx40) in rat aorta during inflammation. Cxs are proteins of gap junction channels which regulate homeostasis and vasomotion through direct intercellular communication. FA are known for their anti-inflammatory and beneficial effects on the cardiovascular system. In 10-day-lasting experiment, we used adult Wistar rats divided into four groups: W(C) – controls, W(FA) - FA in dose 30mg/kg/day, W(L) – application of a single dose of lipopolysaccharide (LPS, 1 mg/kg, i.p), W(L+FA). Cx40 expression was analyzed in aortic tissue using Western blot, its distribution by immunofluorescence and morphometric image analysis. We studied NO dependent relaxation of aorta and NOS activity, together with biomarkers CRP, MDA, NAGA in plasma and CD68 in aorta. Immunofluorescence revealed changes only in endothelial Cx40 spatial expression. In W(L+FA) density of Cx40 spots was decreased when compared to W(L) which increased Cx40 density in comparision to W(C). Total Cx40 expression in aorta of W(L) was significantly higher than in W(C). In W(L+FA), Cx40 expression was lower than in W(L). LPS increased expression of CD68, while its expression was reduced in W(L+FA) group compared to W(L). FA did not affect LPS-induced impairment of NO-dependent relaxation of aorta, and they had no protective effect on NOS activity. FA diet reduced also LPS-induced increase in levels of biomarkers. Our results suggest that endothelial Cx40-gap junctions might represent one of potential targets of the anti-inflammatory effects of FA diet.
Effects of TA-3090, a new calcium channel blocker, on myocardial substrate utilization in ischemic and nonischemic isolated working fatty acid-perfused rat hearts.
Authors: N J Davies, J J McVeigh, G D Lopaschuk
Journal: Circulation Research (1991)

Experimental studies have shown that calcium channel blockade has a protective effect on the ischemic myocardium. Although these agents may act by decreasing intracellular Ca2+ accumulation during reperfusion or to reduce oxygen requirements by decreasing myocardial work load, recent evidence suggests that calcium blockers may also favorably alter energy substrate metabolism in ischemic and reperfused myocardium. In this study, TA-3090, a new calcium channel blocker with minimal effect on myocardial work load, was used to study the effect of calcium channel blockade on both myocardial substrate utilization and reperfusion recovery of ischemic hearts. Isolated working rat hearts were perfused at an 11.5 mm Hg preload and an 80 mm Hg afterload with Krebs-Henseleit buffer containing 11 mM glucose, 1.2 mM palmitate, and 500 microunits/ml insulin. In aerobically perfused spontaneously beating hearts, a 0.5 microM dose of TA-3090 had a mild depressant effect on heart rate but no effect on peak systolic pressure development. In paced hearts (250 beats/min), 0.5 microM TA-3090 had no effect on either peak systolic pressure development or contractility. Fatty acid and glucose oxidation was determined by measuring 14CO2 production in hearts perfused with either [14C]palmitate or [14C]glucose, respectively, whereas glycolysis was determined by measuring 3H2O production from [3H]glucose. Under aerobic conditions, fatty acid oxidation was not altered by TA-3090, but a significant decrease in glucose oxidation and glycolytic rates was observed. If hearts were subjected to a 30-minute period of no-flow ischemia, the addition of 0.5 microM TA-3090 to the perfusate before ischemia significantly improved reperfusion recovery of mechanical function. The protective effects of TA-3090 were not observed if TA-3090 was added at the time of reperfusion and were not related to a depression of function before ischemia. TA-3090, added before ischemia, significantly reduced glycogen and ATP depletion during no-flow ischemia and also significantly decreased glycolytic rates in hearts subjected to low-flow ischemia (coronary flow = 0.5 ml/min). Combined, our data suggest that the beneficial effects of calcium channel blockade on the ischemic myocardium are not related solely to a decrease in myocardial work load or metabolic demand before ischemia, but rather may in part be related to a decrease in myocardial energy demand during ischemia itself, resulting in preservation of ATP and a decrease in glycolysis. The decrease in glycolytic rates during ischemia may also result in a reduction of glycolytic product accumulation during ischemia.
A Clinical Trial of BZ 55
Authors: L. J. P. Duncan, J. D. Baird, D. M. Dunlop
Journal: BMJ (1956)

Two groups of German workers have recently reported the successful control of most elderly or middle-aged patients suffering from mild diabetes by BZ 55 (N-butyl-N' -sulphanilylurea) (Franke and Fuchs, 1955; Bertram et al., 1955).It is, however, difficult to assess the therapeutic value of the drug from these reports because the data given are inadequate.When exact figures for diets are stated they seem unduly high by British standards.Certainly many of the patients in whom control was successfully achieved with BZ 55 appeared to have the type of diabetes which would usually have responded to dietary restriction alone, without the use of insulin or an insulin substitute (British Medical Journal, 1955).It was therefore felt that further carefully planned and fully documented clinical trials were necessary to establish the place of these sulphonamide compounds in the management of diabetes. Selection of PatientsWe considered that orally administered BZ 55 would have its main practical use as a complete 'substitute for parenteral insulin.Since the German work emphasized that such a complete substitution was only rarely possible in the young diabetic, we limited this initial study to patients over the age of 45 suffering from mild diabetes who were not overweight by more than 10% of their ideal weight (Metropolitan Life Insurance Company, Statistical Bureau, 1943, quoted by Dunlop et a!., 1953), but who, on a fully restricted diet, continued to show significant hyperglycaemia and glycosuria, and to ex- perience diabetic symptoms in the absence of insulin therapy.From the diabetic out-patient clinic 65 active patients (5 male, 60 female) who appeared to be of this type were selected and observed as out-patients for periods varying from one to six weeks.None of these patients had anv active focus of infection, although many had retinopathy and neuropathy of the diabetic type.Only five were not currently receiving insulin, but they were inadequately controlled by diet alone.Control in those receiving insulin was good or moderate.At the first visit each patient was impressed with the necessity of adhering strictly to the diet which they were at that time supposed to be taking, and the administra- tion of insulin was stopped.Thereafter each was seen once or twice weekly, when the blood-glucose concen- tration was estimated, 24-hour and fasting urine samples were tested for glucose and ketone bodies, and weight and symptoms were recorded.It was possible to complete the trial of the drug in
Internists and Nicotine Gum
Authors: Steven R. Cummings
Journal: JAMA (1988)

Nicotine gum may be a useful aid to help patients quit smoking. The effectiveness of the gum and incidence of side effects may depend on using the gum properly. To describe internists' current practices of prescribing nicotine gum and other drugs for smoking cessation, we surveyed randomly selected internists. Most internists prescribe nicotine gum to fewer than 25% of patients who try to quit smoking. Contrary to current recommendations, nearly half of internists would suggest gum to help patients cut down on smoking, and a majority would limit its use to less than three months. There is no evidence that sedatives are useful for smoking cessation, but one fourth of internists had recently prescribed them for that purpose. There is a widespread need for physician education about how to use nicotine gum more effectively. (<i>JAMA</i>1988;260:1565-1569)
Letter: Preventing animal diseases.
Authors: R G Small
Journal: BMJ (1976)

antigens, as with sarcomas and melanomas,' acute leukaemias,5 and Burkitt's lymphoma (Drs Magrath and Ziegler), often retain good immune reactivity to common antigens; thus the general immune status often fails to correlate with the host-tumour relationship.We assume that in these cases suppressor cells specifically inhibit tumour rejection mechan- isms.For the demonstration of this activity suppression of lymphocyte blastogenesis to autologous tumour cells by a clone of lymphoid cells added to the mixture of reactor and tumour cells would be necessary.This oversimplified view is in need of experimental support, but the basic techniques for the detection of human suppressor cells are already available.' 2 Means of deactivating suppressor cells could develop into an innova- tive modality of tumour immunotherapy, whereas activation of suppressor cells (by administration of fetal antigens?)may be useful for organ transplant acceptance.The hormonal milieu of the immediate post-partum period, selective immunosuppression during tumour chemotherapy,6 and ablative procedures (splenectomy, lymphadenectomy, adult thymectomy) come to mind as possible procedures of deactivation and elimination of suppressor cells.
Weighing the Benefits and Burdens of Witnessed Resuscitation
Authors: Daniel B. Kramer, Susan L. Mitchell
Journal: New England Journal of Medicine (2013)

More than 80% of sudden cardiac arrests occur outside hospital settings.1 Less than 10% of these patients survive to hospital discharge, accounting for hundreds of thousands of deaths annually worldwide.2,3 Prior work on interventions for sudden cardiac arrest has largely focused on patients' immediate4 and postresuscitation5 care. However, sudden cardiac arrests affect not only the patients but also their family members, some of whom may have witnessed the arrest and resuscitative efforts. Minimizing the adverse mental health outcomes for these family members is an important component of easing the public health burden of sudden cardiac arrests.There are no . . .
Maximum Androgen Blockade Using LHRH Agonist Buserelin in Combination with Short-Term (Two Weeks) or Long-Term (Continuous) Cyproterone Acetate Is Not Superior to Standard Androgen Deprivation in the Treatment of Advanced Prostate Cancer
Authors: Herman J. de Voogt, Urs Studer, Fritz H. Schr&ouml;der, Jan G. Klijn, Marleen de Pauw, Richard Sylvester
Journal: European Urology (1998)
ANNOTATIONS ON THE THIRTEENTH RHEUMATISM REVIEW
Authors: CHARLEY J. SMYTH
Journal: Annals of Internal Medicine (1961)

Editorials1 January 1961ANNOTATIONS ON THE THIRTEENTH RHEUMATISM REVIEWCHARLEY J. SMYTH, M.D., F.A.C.P.CHARLEY J. SMYTH, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-54-1-160 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTwenty-five years ago the first systematic review of reports published in English on the various phases of the rheumatic diseases appeared in the ANNALS OF INTERNAL MEDICINE. The purpose, as stated by Dr. Philip S. Hench, the first editor, was "to prepare a correlated synopsis of the recent significant literature—including such editorial comments as may seem helpful." At intervals since that time a comprehensive analysis of clinical contributions and experimental investigations, with critical annotations prepared by an editorial committee of the American Rheumatism Association, has been published in this journal.There is general agreement that theRheumatism Reviewshave served... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: CHARLEY J. SMYTH, M.D., F.A.C.P. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 January 1961Volume 54, Issue 1 Page: 160-168 Keywords Systematic reviews ePublished: 1 December 2008 Issue Published: 1 January 1961 PDF downloadLoading ...
Vitamin B6 metabolism in chronic alcohol abuse The effect of ethanol oxidation on hepatic pyridoxal 5'-phosphate metabolism.
Authors: R L Vech, L Lumeng, T K Li
Journal: Journal of Clinical Investigation (1975)

Individuals with chronic alcohol abuse frequently exhibit lowered plasma levels of pyridoxal 5'-phosphate, the coenzyme form of vitamin B6. Because the liver is the primary source of this coenzyme in plasma and also the principal organ that oxidizes ethanol, the effect of ethanol on hepatic pyridoxal phosphate metabolism was studied in the rat. The chronic feeding of ethanol (36 percent of the total dietary calories) for 6 wk significantly decreased the hepatic pyridoxal phosphate content both in animals given a sufficient amount of vitamin B6 in their diet and in those rendered vitamin B6 deficient. In isolated perfused livers, the addition of 18 mM ethanol lowered the pyridoxal phosphate content of livers from vitamin B6-sufficient animals and deceased the net synthesis of pyridoxal phosphate from pyridoxine by the livers of vitamin B6-deficient animals. Ethanol also diminished the rate of release of pyridoxal phosphate into the perfusate by the livers of vitamin B6-deficient rats. These effects of ethanol, in vitro, were abolished by 4-methyl pyrazole, an inhibitor of alcohol dehydrogenase. Thus the derangement of pyridoxal phosphate metabolism produced by ethanol is dependt upon its oxidation. These data support previous findings whic indicate that acetaldehyde is the responsible agent which acts by accelerating the degradation of intracellular pyridoxal phosphate.