tbuckley/cabot-search huggingface dataset:
Human Skeletal Muscle Drug Transporters Determine Local Exposure and Toxicity of Statins
Authors: Michael J. Knauer, Bradley L. Urquhart, Henriette E. Meyer zu Schwabedissen, Ute I. Schwarz, Christopher J. Lemke, Brenda F. Leake, Richard B. Kim, Rommel G. Tirona
Journal: Circulation Research (2009)

The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, are important drugs used in the treatment and prevention of cardiovascular disease. Although statins are well tolerated, many patients develop myopathy manifesting as muscle aches and pain. Rhabdomyolysis is a rare but severe toxicity of statins. Interindividual differences in the activities of hepatic membrane drug transporters and metabolic enzymes are known to influence statin plasma pharmacokinetics and risk for myopathy. Interestingly, little is known regarding the molecular determinants of statin distribution into skeletal muscle and its relevance to toxicity.We sought to identify statin transporters in human skeletal muscle and determine their impact on statin toxicity in vitro.We demonstrate that the uptake transporter OATP2B1 (human organic anion transporting polypeptide 2B1) and the efflux transporters, multidrug resistance-associated protein (MRP)1, MRP4, and MRP5 are expressed on the sarcolemmal membrane of human skeletal muscle fibers and that atorvastatin and rosuvastatin are substrates of these transporters when assessed using a heterologous expression system. In an in vitro model of differentiated, primary human skeletal muscle myoblast cells, we demonstrate basal membrane expression and drug efflux activity of MRP1, which contributes to reducing intracellular statin accumulation. Furthermore, we show that expression of human OATP2B1 in human skeletal muscle myoblast cells by adenoviral vectors increases intracellular accumulation and toxicity of statins and such effects were abrogated when cells overexpressed MRP1.These results identify key membrane transporters as modulators of skeletal muscle statin exposure and toxicity.
Lower Effectiveness of Divalproex Versus Valproic Acid in a Prospective, Quasi-Experimental Clinical Trial Involving 9,260 Psychiatric Admissions
Authors: Adel A. Wassef, Diane E. Winkler, Ann L. Roache, Vivian Boma Abobo, Lina M. Lopez, John P. Averill, Ayesha I. Mian, John E. Overall
Journal: American Journal of Psychiatry (2005)

The authors examined clinical differences between divalproex sodium and generic immediate-release valproic acid.This 6-year prospective, quasi-experimental clinical trial compared the effectiveness and tolerability of divalproex and valproic acid. The dependent variables were length of hospital stay, rehospitalization rate, and adverse drug reactions in 9,260 psychiatric admissions.Inpatients who initially received divalproex sodium had a 32.7% longer hospital stay and 3.8% higher readmission rate than did patients who initially received valproic acid. Initial treatment with divalproex prolonged length of stay by 30.3% in patients treated with divalproex and valproic acid during different admissions. After other variables were controlled by multiway analysis of variance, the hospital stay of patients who continued the initial medication was 15.2% longer (2.0 days) for divalproex than valproic acid. Switching medications was more common for valproic acid, partly because of study design. Medication intolerance occurred in approximately 6.4% more patients taking valproic acid than divalproex. However, switching from valproic acid to divalproex did not significantly prolong length of stay, over that for continuous divalproex, or increase the rehospitalization rate.Lower peak valproate concentrations with divalproex sodium may have enhanced tolerability but may also explain the lower effectiveness. Extended-release divalproex could lower effectiveness further and require higher doses. Thus, inpatients are better served by beginning with generic valproic acid and by changing to delayed-release divalproex only if intolerance occurs. This would save up to one-third of inpatient costs and two-thirds of a billion dollars yearly in medication costs.
Prevalence of sensitization to the storage mites <i>Acarus siro, Tyrophagus putrescentiae</i>, and <i>Lepidoglyphus destructor</i> in allergic patients with different degrees of sensitization to the house‐dust mite <i>Dermatophagoides pteronyssinus</i>
Authors: S. van der Heide, N. R. Niemeijer, H. Hovenga, J. G. R. de Monchy, A. E. J. Dubois, H. F. Kauffman
Journal: Allergy (1998)

The prevalence of sensitization to the storage mites Acarus siro (AS), Tyrophagus putrescentiae (TP), and Lepidoglyphus destructor (LD) was studied in 250 sera of patients with different degrees of sensitization to the house‐dust mite Dermatophagoides pteronyssinus (DP) by measuring IgE binding to extracts of the storage mites. Additionally, allergenic cross‐reactivity between DP and the storage mite species was studied by RAST inhibition with five individual sera (and a pool of these sera) with moderate IgE levels to all three storage mites and to DP. Increased serum IgE to storage mites was found in 46% of the 200 patients sensitized to DP. Increased prevalence rates of IgE titers to storage mites were associated with higher IgE levels to DP In 50 sera without sensitization to DP, only five sera showed increased IgE to one of the storage mites. Extracts of TP almost completely inhibited the IgE binding to AS, and vice versa. DP inhibited IgE binding to all storage mites up to 60%, whereas IgE binding to DP was only minimally inhibited by extracts of storage mites. In conclusion, cosensitization to storage mites is a frequent finding in patients sensitized to DP. Although this is largely the result of cross‐reactivity between different mite species, it may nevertheless be of clinical significance in patients exposed to storage mites.
259 DYNAMIC BEHAVIOUR OF HEPATOCYTE IS ORCHESTRATED BY DYNAMIC ENROLMENT OF HNF4-DEPENDENT ACTIVATOR AND/OR REPRESSOR COMPLEXES
Authors: L. Amicone, L. Santangelo, C. Cicchini, A. Conigliaro, F. Garibaldi, A. Marchetti, M. Tripodi
Journal: Journal of Hepatology (2011)
Hydrogen peroxide: A link between acetaldehyde-elicited α1(i) collagen gene up-regulation and oxidative stress in mouse hepatic stellate cells
Authors: Patricia Greenwel, José-Alfredo Domínguez-Rosales, Gurjeet Mavi, A. M. Rivas-Estilla, Marcos Rojkind
Journal: Hepatology (2000)

Ethanol induces liver fibrosis by several means that include, among others, the direct fibrogenic actions of acetaldehyde and the induction of an oxidative stress response. However, the mechanisms responsible for these activities, and the possible connections between oxidative stress and acetaldehyde-induced fibrosis are not well understood. In this communication we investigated the molecular mechanisms whereby acetaldehyde induces mouse α1(I) procollagen ( col1a1 ) gene expression in cultured hepatic stellate cells. Transfection assays using reporter plasmids driven by different segments of the col1a1 promoter localized an acetaldehyde-responsive element (AcRE) between nucleotides −370 and −345. We also show that acetaldehyde enhances binding of a CCAAT/enhancer binding protein-β (C/EBPβ)-containing complex to this element, and that this effect is due, at least in part, to an increase in the concentration of nuclear p35C/EBPβ protein. Although this element overlaps to a previously described transforming growth factor β1 (TGF-β1)-responsive element, the stimulatory effect of acetaldehyde is not mediated through this cytokine, because addition of neutralizing anti-TGF-β1 antibodies does not prevent acetaldehyde-elicited col1a1 up-regulation. On the other hand, this effect is blocked by the addition of catalase, an H 2 O 2 scavenger. Moreover, this ethanol metabolite stimulates production of H 2 O 2 in stellate cells. Thus, these results suggest that acetaldehyde-induced col1a1 up-regulation is mediated, at least in part, through H 2 O 2 . Altogether, these data suggest that the −370 to −344 region of the col1a1 gene is a point of convergence of the action of numerous extracellular stimuli that ultimately leads to col1a1 up-regulation. In addition, we have established a direct connection between oxidative stress and enhanced col1a1 expression induced by acetaldehyde.
Peptide Hormone Action and Membrane Receptors.
Authors: Martin Rodbell
Journal: Annals of Internal Medicine (1973)

Meeting Abstracts1 May 1973Peptide Hormone Action and Membrane Receptors.Martin Rodbell, Ph.D.Martin Rodbell, Ph.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-78-5-813_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptA variety of peptide hormones derived from pituitary, hypothalamic, pancreatic, and intestinal endocrine cells initiate their actions at the surface or plasma membrane of target cells. Receptors, localized at the outer surface of these membranes, form specific and reversible complexes with the hormones. These complexes control a variety of membrane processes involved in electrical excitation and transport of amino acids, sugars, and ions. They also regulate the activities of certain enzymes imbedded in the matrix of the membrane. For example, adenylate cyclase, an enzyme that catalyzes the formation of cyclic AMP, is coupled to receptors for such varied hormones as... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Bethesda, Maryland PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1973Volume 78, Issue 5Page: 813-813KeywordsAdenosine monophosphateAmino acidsBlood plasmaCellsEnzymesHormonesPeptide hormones Issue Published: 1 May 1973 PDF downloadLoading ...
Guide to Organizing an International Scientific Conference
Authors: I. Capperauld
Journal: BMJ (1996)

Gideon Rivlin Karger, Sw Fr 78, pp 94 ISBN 3 8055 6151 2

An estimated pounds sterling100 million is spent annually on international conferences on a worldwide basis, so Gideon Rivlin's Guide to Organizing an International Scientific Conference is a welcome publication, coming as it does nearly 20 years after the BMJ first tackled the subject in its “How to do it” series (see How To Do It, 3rd edition, volume 2, 1995). Rivlin's book can be used in one of two ways: either as a do-it-yourself …
Hypersensitivity reactions to racemic calcium folinate (leucovorin) during FOLFOX and FOLFIRI chemotherapy administrations
Authors: Alicia Ureña-Tavera, Miriam Zamora-Verduga, Ricardo Madrigal-Burgaleta, Denisse Angel-Pereira, Maria Pilar Berges-Gimeno, Emilio Alvarez-Cuesta
Journal: Journal of Allergy and Clinical Immunology (2014)
Electric and magnetic field exposures for people living near a 735-kilovolt power line.
Authors: P Levallois, D Gauvin, J St-Laurent, S Gingras, J E Deadman
Journal: Environmental Health Perspectives (1995)

The purpose of this study was to assess the effect of a 735-kV transmission line on the electric and magnetic field exposures of people living at the edge of the line's right of way. Exposure of 18 adults, mostly white-collar workers, living in different bungalows located 190-240 feet from the line (exposed subjects) was compared to that of 17 adults living in similar residences far away from any transmission line. Each subject carried a Positron meter for 24 hr during 1 workday, which measured 60-Hz electric and magnetic fields every minute. All measurements were carried out in parallel for exposed and unexposed subjects during the same weeks between September and December. During measurements the average loading on the line varied between 600 and 1100 A. The average magnetic field intensity while at home was 4.4 times higher among exposed subjects than unexposed (7.1 versus 1.6 mG, p = 0.0001) and 6.2 times higher when considering only the sleeping period (6.8 versus 1.1 mG, p = 0.0001). Based on the 24-hr measurement, average magnetic field exposure was three times higher among the exposed. Electric field intensity was also higher among the exposed while at home (26.3 versus 14.0 V/m, p = 0.03). Magnetic field intensity among the exposed was positively correlated with the loading on the line (r = 0.8, p = 0.001). Percentage of time above a magnetic field threshold (2 mG or 7.8 mG) was a good indicator to distinguish the two types of exposure.(ABSTRACT TRUNCATED AT 250 WORDS)
Familial Neural Hearing Loss and Atopic Dermatitis
Authors: Bruce W. Konigsmark
Journal: JAMA (1968)

Three of four sibs were affected by a nonprogressive neural hearing loss and atypical atopic dermatitis. History, physical and neurological examinations revealed no causes other than familial for the hearing loss. Audiometric examinations suggested the hearing loss was cochlear in origin. A review of the literature describing types of familial hearing loss associated with skin disease showed no similar report. It is suggested that these three children have a type of recessive familial hearing loss differing from others in its association with atypical atopic dermatitis.
Current Status of the Chemotherapy of the Systemic Mycoses.
Authors: John P. Utz
Journal: Annals of Internal Medicine (1968)

s1 May 1968Current Status of the Chemotherapy of the Systemic Mycoses.John P. Utz, M.D., F.A.C.P.John P. Utz, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-68-5-1177_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptDespite the wide variety of antibiotic agents effective against bacterial diseases by the year 1957, no agent was available for the systemic mycoses until amphotericin B became available that year. Early experience with this drug was summarized in a presentation before the 40th Annual Session of the American College of Physicians in 1959. Since that time the serious toxic effects, especially on the bone marrow and the kidney, and the unpleasant general reactions in the form of nausea, vomiting, fever, and chills that the patient experiences have led to continuing search for better agents. One of these, the SFD preparation... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: John P. Utz, M.D., F.A.C.P.Affiliations: Richmond, Virginia PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byFluorinated Pyrimidines and Their NucleosidesPulmonary Candidiasis Treated with 5-FluorocytosineChapter 13. Antifungal AgentsVariant Forms of Pulmonary CryptococcosisBAYARD TYNES, M.D., F.A.C.P., KATHLEEN N. MASON, M.S., ANNE E. JENNINGS, JOHN E. BENNETT, M.D., F.A.C.P. 1 May 1968Volume 68, Issue 5Page: 1177-1178KeywordsAntibioticsBacterial diseasesBone marrowChemotherapyDrugsFeversKidneysNauseaSystemic mycosesVomiting ePublished: 1 December 2008 Issue Published: 1 May 1968 PDF downloadLoading ...
Myocardial blood flow at rest and during pharmacological vasodilation in cardiac transplants during and after successful treatment of rejection.
Authors: S Y Chan, J Kobashigawa, L W Stevenson, E Brownfield, R C Brunken, H R Schelbert
Journal: Circulation (1994)

BACKGROUND The relative intracoronary flow reserve has been found to be reduced during acute transplant rejection, but the effects of rejection on absolute flows at rest and during hyperemia have not been established previously. This has now become possible through noninvasive quantification of myocardial blood flow with positron emission tomography. METHODS AND RESULTS Myocardial blood flow (MBF) at rest and during dipyridamole-induced hyperemia was quantified in 10 transplant patients (group A) during an acute, biopsy-proven rejection episode and again after successful immunosuppressive treatment and in 6 transplant patients (group B) without prior rejection episode. In group A patients, MBF during rejection averaged 1.7 +/- 0.3 mL.min-1.g-1 at rest and 2.5 +/- 0.9 mL.min-1.g-1 during hyperemia; after recovery, MBF at rest had declined to 1.2 +/- 0.3 mL.-1.g-1 (P &lt; .001) but had increased to 3.9 +/- 1.1 mL.-1.g-1 (P &lt; .001) during hyperemia. Flows after recovery from rejection were similar to those in the group B patients (0.9 +/- 0.2 and 3.9 +/- 0.7 mL.min-1.g-1). Flow reserve in the group A patients was only 1.5 +/- 0.5 during rejection but improved to 3.4 +/- 0.9 at recovery (P &lt; .001) and thus remained lower than in the control patients (4.5 +/- 0.7, P &lt; .05). Minimal coronary resistance during dipyridamole vasodilation was elevated during rejection (40 +/- 11 mm Hg.mL-1.min-1.g-1); after recovery, it no longer differed from that in the group B patients (26 +/- 11 versus 22 +/- 4 mm Hg.mL-1.min-1.g-1). MBF during rejection was increased relative to cardiac work, as demonstrated by significantly higher ratios of blood flow to rate-pressure product than those at recovery and in the control patients. CONCLUSIONS A decrease in hyperemic and an increase in resting myocardial blood flow, in excess to cardiac work, account for the previously reported reduction in coronary flow reserve. Because both alterations improve with antirejection treatment, they may reflect reversible alterations, presumably of endothelial function, local coagulation, and edema. The compromise in flow reserve and hyperemic flows may contribute to acute and chronic injury from rejection and thus provides a rationale for exercise restriction during rejection. The results further suggest a potential role for serial noninvasive flow measurements to guide immunosuppressive therapy.
Coagulation, an ancestral serine protease cascade, exerts a novel function in early immune defense
Authors: Torsten G. Loof, Matthias Mörgelin, Linda Johansson, Sonja Oehmcke, Anders I. Olin, Gerhard Dickneite, Anna Norrby-Teglund, Ulrich Theopold, Heiko Herwald
Journal: Blood (2011)
Eradication rate of Helicobacter pylori.
Authors: J Labenz, B Tillenburg, U Peitz, H Kohl, G Borsch
Journal: Gut (1995)

since been shown to have impaired synthesis of metallothionein in culture fibroblasts.3In our case,4 however, basal and metal induced metallothionein synthesis in skin fibroblasts was normal,5 indicating that heterogeneity exists among cases of primary, non-environ- mental, non-Wilsonian copper toxicosis.
Interaction between environmental pollutants and respiratory infections.
Authors: R Ehrlich
Journal: Environmental Health Perspectives (1980)

The major aspects that must be considered in studies of the health effects of environmental pollutants are: the direct damage due to the exposure, the role of pre-existing disease, and effects of the exposure on the response to secondary stresses. In experimental studies at concentrations of air pollutants found in urban environments frank toxicological responses are rarely observed. However, exposure to a secondary stress, i.e. respiratory challenge with infectious bacteria, can exacerbate the response of the experimental host. Changes in the resistance to respiratory infections provide a highly sensitive experimental animal model system, which is increasingly used in studies of health effects of air pollutants. This model indicates the impairment of the basic defense mechanisms of the respiratory system by the combined exposure to low concentrations of pollutants and the superimposed bacterial infection. Changes in the resistance to respiratory infections were studied in various species of laboratory animals. S. pyogenes and K. pneumoniae are the bacteria of choice to induce the pulmonary infection. Included in the studies are short-term single and multiple exposures as well as long-term exposures to gaseous pollutants such as O3 and NO2 and particulate pollutants such as sulfates and nitrates. Changes in the resistance are measured as excess mortalities and reduced survival time as compared to those in infected animals not exposed to the pollutants. Other parameters measured ranged from changes in the immune response to changes in retention rates of bacteria in lungs.
The Silent World of Doctor and Patient
Authors: Stanley J. Reiser
Journal: JAMA (1985)

In this thoughtful and important book, Jay Katz takes us on a journey through medical and legal history to establish convincingly one point— that medical and legal relationships and entitlements up to the 20th century have developed in a manner that has kept patients out of the process of decision in which the harms and benefits of therapeutic alternatives concerning them were weighed and balanced. In medicine, for centuries, such exclusion was justified on the basis of things such as the medical ignorance of patients, their intolerance of uncertainty, the need to maintain the patient's hope that things would improve, the simplicity that unilateral decision making gave to the doctor's life, the painfulness of discussing with patients dreaded events and hopeless prognoses, and the authority that silence in the medical relationship gave to physicians. In the law, too, the rights given to patients up to the mid-20th century were basically
Abdominal Incisions, Sutures and Sacrilege
Authors: Ronald A. Malt
Journal: New England Journal of Medicine (1977)

The abdominal incision often used in this country to show proper credentials of training is paramedian and rectus-retracting — which, to complete the proof, is closed in layers with fine sutures close to the fascial edge and tied with a square knot and a half. Subcuticular closure of the skin is a popular finale. So ingrained are these doctrines in certain quarters that deviation is accompanied by the thrill of adventure. Now, like other things that used to be forbidden, these harmless excursions may no longer be sins.When tested on abdominal walls removed from cadavers, a midline incision closed . . .
Myoglobinuria with Acute Renal Failure and Hot Kidneys Seen on Bone Imaging
Authors: KUMUDCHANDRA J. SHETH, JOHN R. STY, FREDERICK JOHNSON, PATRICIA TISDALE
Journal: Clinical Nuclear Medicine (1984)

We report a case of myoglobinuria secondary to prolonged seizures. The child showed “hot kidneys” with bone scintigraphy. The disease entity and etiologies of nontraumatic rhabdomyolysis are discussed.
TCT-446 Effect of Intra-Aortic Balloon Counterpulsation on Short-Term Survival in Cardiogenic Shock due to Acute Coronary Syndromes
Authors: Truls Råmunddal, Oskar Angerås, Christian Dworeck, Inger Haraldsson, Dan Ioanes, Berglind Libungan, Göran Matejka, Jacob Odenstedt, Petur Petursson, Wilhelm Ridderstråle, Elmir Omerovic
Journal: Journal of the American College of Cardiology (2013)
A nurse's place is at the bedside
Authors: M Barton
Journal: BMJ (1995)

EDITOR,--I was impressed recently while reading a nursing journal to find an article written by an orthopaedic surgeon, Robert Hay.1 In keeping with this spirit of interprofessional communication I have chosen to reply to Hay's article in the BMJ.

While delighted that Hay chose to communicate directly with the nursing profession, I am dismayed by his comments concerning nursing in general, nursing research …