tbuckley/cabot-search huggingface dataset:
Fibrates downregulate apolipoprotein C-III expression independent of induction of peroxisomal acyl coenzyme A oxidase. A potential mechanism for the hypolipidemic action of fibrates.
Authors: B Staels, N Vu-Dac, V A Kosykh, R Saladin, J C Fruchart, J Dallongeville, J Auwerx
Journal: Journal of Clinical Investigation (1995)

Epidemiological and transgenic animal studies have implicated apo C-III as a major determinant of plasma triglyceride metabolism. Since fibrates are very efficient in lowering triglycerides, it was investigated whether fibrates regulate apo C-III gene expression. Different fibrates lowered rat liver apo C-III mRNA levels up to 90% in a dose- and time-dependent manner, whereas intestinal apo C-III mRNA remained constant. This decrease in liver apo C-III mRNA was rapid (1 d) and reversible, since it was restored to control levels within 1 wk after cessation of treatment. In addition, fenofibrate treatment abolished the developmental rise of hepatic apo C-III mRNA observed during the suckling-weaning period. Administration of fibrates to rats induced liver and intestinal expression of the acyl CoA oxidase gene, the rate-limiting enzyme for peroxisomal beta-oxidation of fatty acids. In primary cultures of rat and human hepatocytes, fenofibric acid lowered apo C-III mRNA in a time- and dose-dependent manner. This reduction in apo C-III mRNA levels was accompanied by a decreased secretion of apo C-III in the culture medium of human hepatocytes. In rat hepatocytes fenofibric acid induced acyl CoA oxidase gene expression, whereas acyl CoA oxidase mRNA remained unchanged in human hepatocytes. Nuclear run-on and transient transfection experiments of a reporter construct driven by the human apo C-III gene promoter indicated that fibrates downregulate apo C-III gene expression at the transcriptional level. In conclusion, these studies demonstrate that fibrates decrease rat and human liver apo C-III gene expression. In humans the mechanisms appears to be independent of the induction of peroxisomal enzymes. This downregulation of liver apo C-III gene expression by fibrates may contribute to the hypotriglyceridemic action of these drugs.
Prolonged conservative care versus early surgery in patients with sciatica caused by lumbar disc herniation: two year results of a randomised controlled trial
Authors: Wilco C Peul, Wilbert B van den Hout, Ronald Brand, Ralph T W M Thomeer, Bart W Koes
Journal: BMJ (2008)

<b>Objectives</b> To evaluate the effects of early lumbar disc surgery compared with prolonged conservative care for patients with sciatica over two years of follow-up. <b>Design</b> Randomised controlled trial. <b>Setting</b> Nine Dutch hospitals. <b>Participants</b> 283 patients with 6-12 weeks of sciatica. <b>Interventions</b> Early surgery or an intended six months of continued conservative treatment, with delayed surgery if needed. <b>Main outcome measures</b> Scores from Roland disability questionnaire for sciatica, visual analogue scale for leg pain, and Likert self rating scale of global perceived recovery. <b>Results</b> Of the 141 patients assigned to undergo early surgery, 125 (89%) underwent microdiscectomy. Of the 142 patients assigned to conservative treatment, 62 (44%) eventually required surgery, seven doing so in the second year of follow-up. There was no significant overall difference between treatment arms in disability scores during the first two years (P=0.25). Improvement in leg pain was faster for patients randomised to early surgery, with a significant difference between “areas under the curves” over two years (P=0.05). This short term benefit of early surgery was no longer significant by six months and continued to narrow between six months and 24 months. Patient satisfaction decreased slightly between one and two years for both groups. At two years 20% of all patients reported an unsatisfactory outcome. <b>Conclusions</b> Early surgery achieved more rapid relief of sciatica than conservative care, but outcomes were similar by one year and these did not change during the second year. <b>Trial Registry</b> ISRCT No 26872154.
Fungal Meningitis From Injection of Contaminated Steroids
Authors: Lucy E. Wilson, David Blythe, Joshua M. Sharfstein
Journal: JAMA (2012)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Current indications for laparoscopy in day-case surgery
Authors: E. Cassinotti, E.M. Colombo, M. Di Giuseppe, F. Rovera, G. Dionigi, L. Boni
Journal: International Journal of Surgery (2008)

Day-surgery setting allows to combine patients' satisfaction to cost-saving policies that seems to be more and more important for a modern hospital management. Minimally invasive surgery seems to be the ideal surgical approach for day-case procedures since, reducing trauma to a minimal level, allows patients to return quick to a normal life with minimal nursing assistance. Extensive review of the most recent article has been performed in this article in order to define the current evidences that support the use of laparoscopic surgery in a day-case setting. Laparoscopic cholecystectomy, anti-reflux procedure and hernia repair seems to be justified according to the results of the published data. Patients' selection and hospital organization seem to be mandatory in order to obtain successful results.
CLINICAL AND ELECTROENCEPHALOGRAPHIC STUDIES OF CHANGES OF CEREBRAL FUNCTION ASSOCIATED WITH VARIATIONS IN THE BLOOD SUGAR
Authors: HANS STRAUSS, I. S. WECHSLER
Journal: American Journal of Psychiatry (1945)

1. The reaction of the EEG to hyperventilation is discussed with relation to blood sugar levels, to age and to diagnosis. A group of psychoneurotics is described showing an unusual lability of the EEG to hyperventilation in the presence of normal blood sugar values. 2. The relationship between the presence of nervous complaints in the early morning and the development of delta activity on hyperventilation in the fasting state was studied. Delta activity develops more frequently in subjects having such complaints than in subjects without them. 3. Patients developing delta activity on hyperventilation in the fasting state feel, in a larger percentage, better at later hours than patients without delta activity. 4. Two cases of spontaneous hypoglycemia with electroencephalographic studies are reported.
Melanonychia induced by topical 5-fluorouracil
Authors: R. BARAN, P. LAUGIER
Journal: British Journal of Dermatology (2006)

Journal Article Melanonychia induced by topical 5‐fluorouracil Get access R. BARAN, R. BARAN The Dermatological Unit, General Hospital, 06407 Cannes, France Search for other works by this author on: Oxford Academic Google Scholar P. LAUGIER P. LAUGIER Department of Dermatology, Hôpital Cantonal Universitaire, 1211 Geneve 4, Switzerland Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 112, Issue 5, 1 May 1985, Pages 621–625, https://doi.org/10.1111/j.1365-2133.1985.tb15274.x Published: 01 May 1985 Article history Accepted: 09 October 1984 Published: 01 May 1985
Population Pharmacokinetics of Troxacitabine, a Novel Dioxolane Nucleoside Analogue
Authors: Carlton K. K. Lee, Eric K. Rowinsky, Jing Li, Francis Giles, Malcolm J. Moore, Manuel Hidalgo, Edmund Capparelli, Jacques Jolivet, Sharyn D. Baker
Journal: Clinical Cancer Research (2006)

Abstract Purpose: To develop and validate a population pharmacokinetic model for troxacitabine, a novel l-nucleoside analogue, administered by short infusion; to characterize clinical covariates that influence pharmacokinetic variability; and to design a dosage rate for continuous infusion administration to achieve low micromolar concentrations, which may be more efficacious than shorter infusions. Experimental Design: Plasma samples from 111 cancer patients receiving troxacitabine (0.12-12.5 mg/m2) as a 30-minute infusion in phase I trials were used to develop the model with NONMEM. Clinical covariates evaluated included creatinine clearance, body surface area, age, and sex. From the model, a troxacitabine dosage rate of 2.0 to 3.0 mg/m2/d was expected to achieve a target concentration of 0.1 μmol/L; plasma samples were obtained during the infusion from eight patients receiving troxacitabine as a 3-day infusion. Results: Troxacitabine pharmacokinetics were characterized by a three-compartment linear model. The mean value for systemic clearance [interindividual variability (CV%)] from the covariate-free model was 9.1 L/h (28%). Creatinine clearance and body surface area accounted for 36% of intersubject variation in clearance. Troxacitabine 2.0 mg/m2/d (n = 3) and 3.0 mg/m2/d (n = 5) for 3 days produced mean ± SD end of infusion concentrations of 0.12 ± 0.03 and 0.15 ± 0.03 μmol/L, respectively. Conclusions: Renal function and body surface area were identified as sources of troxacitabine pharmacokinetic variability. The population pharmacokinetic model model–derived dosage rates for continuous infusion administration successfully achieved predetermined target plasma concentrations. The present model may be used to optimize treatment with troxacitabine by developing a dosing strategy based on both renal function and body size.
My altered self: cancer
Authors: Farhat Yaqub
Journal: The Lancet (2013)

Having breast cancer instilled in Felicia Marie Knaul a resolve to use her personal and professional experience for the greater good. From the perspective of a patient, Knaul's book Beauty without the Breast is an intimate and detailed account of her life with breast cancer—or "altered-self" as she refers to herself with the cancer—from 2007 to 2012. The book is written in English and is a follow-up to Knaul's previous book Tómatelo a Pecho, a Spanish narrative of her first 20 months of life with cancer.
Fish Consumption Among Healthy Adults Is Associated With Decreased Levels of Inflammatory Markers Related to Cardiovascular Disease
Authors: Antonis Zampelas, Demosthenes B. Panagiotakos, Christos Pitsavos, Undurti N. Das, Christina Chrysohoou, Yannis Skoumas, Christodoulos Stefanadis
Journal: Journal of the American College of Cardiology (2005)
Human autoantibody to defensin: disease association with hyperreactive onchocerciasis (sowda).
Authors: M Y Gallin, A B Jacobi, D W Büttner, O Schönberger, T Marti, K D Erttmann
Journal: The Journal of Experimental Medicine (1995)

Chronic hyperreactive onchodermatitis (sowda) is a severe form of onchocerciasis observed in a subset of individuals infected with the filarial nematode Onchocerca volvulus. SDS-PAGE and immunoblot analyses of O. volvulus adult worm extracts were used to characterize the antigens of the marked antibody response of sowda patients. One 2.5-kD antigen was recognized by sera from all 35(100%) sowda patients that were studied. In comparison, only 7 of 44 (16%) patients with generalized onchocerciasis and 11 of 21 (52%) of exposed individuals with no microfilariae in skin snips and no signs of disease showed reactivity to this antigen. Microfilaricidal treatment of sowda patients with improvement of the clinical status was associated with a decrease or disappearance of antibodies to the 2.5-kD antigen. Amino acid sequencing of the antigen indicated identity to human defensins 1-3 of neutrophils. Defensin was demonstrated by immunohistochemical staining in onchocercal nodules on the surface of adult filariae and in the surrounding tissue. A similar staining pattern was observed for other proteins present in neutrophils such as myeloperoxidase, elastase, and the L-1 protein complex (MRP 8/MRP 14), indicating that neutrophils, macrophages, and their proteins predominate in the environment adjacent to the worms. These results demonstrate an association between the presence of autoantibodies to defensins and an infectious disease of known etiology. The association with a particular form of onchocerciasis, sowda, suggests a link between formation of autoantibodies to defensin and enhanced immune reactivity towards the parasite.
The Genetic Landscape of Clinical Resistance to RAF Inhibition in Metastatic Melanoma
Authors: Eliezer M. Van Allen, Nikhil Wagle, Antje Sucker, Daniel J. Treacy, Cory M. Johannessen, Eva M. Goetz, Chelsea S. Place, Amaro Taylor-Weiner, Steven Whittaker, Gregory V. Kryukov, Eran Hodis, Mara Rosenberg, Aaron McKenna, Kristian Cibulskis, Deborah Farlow, Lisa Zimmer, Uwe Hillen, Ralf Gutzmer, Simone M. Goldinger, Selma Ugurel, Helen J. Gogas, Friederike Egberts, Carola Berking, Uwe Trefzer, Carmen Loquai, Benjamin Weide, Jessica C. Hassel, Stacey B. Gabriel, Scott L. Carter, Gad Getz, Levi A. Garraway, Dirk Schadendorf
Journal: Cancer Discovery (2013)

Most patients with BRAF(V600)-mutant metastatic melanoma develop resistance to selective RAF kinase inhibitors. The spectrum of clinical genetic resistance mechanisms to RAF inhibitors and options for salvage therapy are incompletely understood. We performed whole-exome sequencing on formalin-fixed, paraffin-embedded tumors from 45 patients with BRAF(V600)-mutant metastatic melanoma who received vemurafenib or dabrafenib monotherapy. Genetic alterations in known or putative RAF inhibitor resistance genes were observed in 23 of 45 patients (51%). Besides previously characterized alterations, we discovered a "long tail" of new mitogen-activated protein kinase (MAPK) pathway alterations (MAP2K2, MITF) that confer RAF inhibitor resistance. In three cases, multiple resistance gene alterations were observed within the same tumor biopsy. Overall, RAF inhibitor therapy leads to diverse clinical genetic resistance mechanisms, mostly involving MAPK pathway reactivation. Novel therapeutic combinations may be needed to achieve durable clinical control of BRAF(V600)-mutant melanoma. Integrating clinical genomics with preclinical screens may model subsequent resistance studies.
Effects of Prenatal and Postnatal Methylmercury Exposure From Fish Consumption on Neurodevelopment
Authors: Philip W. Davidson, Gary J. Myers, Christopher Cox, Catherine Axtell, Conrad Shamlaye, Jean Sloane-Reeves, Elsa Cernichiari, Larry Needham, Anna Choi, Yining Wang, Maths Berlin, Thomas W. Clarkson
Journal: JAMA (1998)

Context.—Human neurodevelopmental consequences of exposure to methylmercury (MeHg) from eating fish remain a question of public health concern.Objective.—To study the association between MeHg exposure and the developmental outcomes of children in the Republic of Seychelles at 66 months of age.Design.—A prospective longitudinal cohort study.Participants.—A total of 711 of 779 cohort mother-child pairs initially enrolled in the Seychelles Child Development Study in 1989.Setting.—The Republic of Seychelles, an archipelago in the Indian Ocean where 85% of the population consumes ocean fish daily.Main Outcome Measures.—Prenatal and postnatal MeHg exposure and 6 age-appropriate neurodevelopmental tests: the McCarthy Scales of Children's Abilities, the Preschool Language Scale, the Woodcock-Johnson Applied Problems and Letter and Word Recognition Tests of Achievement, the Bender Gestalt test, and the Child Behavior Checklist.Results.—The mean maternal hair total mercury level was 6.8 ppm and the mean child hair total mercury level at age 66 months was 6.5 ppm. No adverse outcomes at 66 months were associated with either prenatal or postnatal MeHg exposure.Conclusion.—In the population studied, consumption of a diet high in ocean fish appears to pose no threat to developmental outcomes through 66 months of age.
Natriuretic hormone activity in the urine of cirrhotic patients
Authors: Giorgio La Villa, Mónica Asbert, Wladimiro Jiménez, Pere Ginés, Joan Claria, Clara Lopez, Ramon Planas, Josep Llach, Joan Gaya, Francisca Rivera, Paolo Gentilini, Vicente Arroyo, Joan Rodés
Journal: Hepatology (1990)

The ability of urine extracts to inhibit sodium and potassium-activated ATPase, cross-react with antidigoxin antibodies and induce natriuresis in rats was investigated in 10 healthy subjects, 10 cirrhotic patients without ascites (compensated cirrhotics), 27 nonazotemic cirrhotic patients with ascites and 10 cirrhotic patients with ascites and functional renal failure to assess whether reduced activity of natriuretic hormone contributes to sodium retention in cirrhosis. No significant differences were seen between healthy subjects and compensated cirrhotic patients in any of these parameters (sodium and potassium-activated ATPase inhibition = 178.5 ± 19.8 vs. 247.4 ± 48.7 nmol equivalent of ouabain/day; digoxinlike activity = 43.9 ± 6.1 vs. 48.0 ± 5.6 ng equivalent of digoxin/day; natriuretic activity = 0.36 ± 0.15 vs. 0.63 ± 0.27 μmol/min). Cirrhotic patients with ascites with and without functional renal failure showed significantly higher values of sodium and potassium-activated ATPase inhibition (708.1 ± 94.0 and 529.2 ± 53.9 nmol equivalent of ouabain/day, respectively), digoxinlike activity (136.9 ± 7.2 and 116.3 ± 7.9 ng equivalent of digoxin/day) and natriuretic activity (1.78 ± 0.48 and 1.93 ± 0.37 μmol/min) than healthy subjects and compensated cirrhotic patients. We saw no significant differences between these two groups of cirrhotic patients with ascites with respect to these parameters. In the cirrhotic patients studied, sodium and potassium-activated ATPase inhibition and antidigoxin antibodies directly correlated with the degree of impairment of hepatic and renal function, plasma renin activity and plasma levels of aldosterone and norepinephrine. These results show that natriuretic hormone activity is increased in cirrhotic patients with ascites and suggest that sodium retention in these patients cannot be attributed to a deficiency in this hormone. An alternate explanation, however, is that the increased activity of natriuretic hormone in patients with cirrhosis and ascites, which may represent a compensatory response, is not sufficient to antagonize the renal effects of sodium-retaining forces. (Hepatology 1990;12:467-475).
A Vaccine to Prevent Herpes Zoster and Postherpetic Neuralgia in Older Adults
Authors: M.N. Oxman, M.J. Levin, G.R. Johnson, K.E. Schmader, S.E. Straus, L.D. Gelb, R.D. Arbeit, M.S. Simberkoff, A.A. Gershon, L.E. Davis, A. Weinberg, K.D. Boardman, H.M. Williams, J. Hongyuan Zhang, P.N. Peduzzi, C.E. Beisel, V.A. Morrison, J.C. Guatelli, P.A. Brooks, C.A. Kauffman, C.T. Pachucki, K.M. Neuzil, R.F. Betts, P.F. Wright, M.R. Griffin, P. Brunell, N.E. Soto, A.R. Marques, S.K. Keay, R.P. Goodman, D.J. Cotton, J.W. Gnann, J. Loutit, M. Holodniy, W.A. Keitel, G.E. Crawford, S.-S. Yeh, Z. Lobo, J.F. Toney, R.N. Greenberg, P.M. Keller, R. Harbecke, A.R. Hayward, M.R. Irwin, T.C. Kyriakides, C.Y. Chan, I.S.F. Chan, W.W.B. Wang, P.W. Annunziato, J.L. Silber
Journal: New England Journal of Medicine (2005)

The incidence and severity of herpes zoster and postherpetic neuralgia increase with age in association with a progressive decline in cell-mediated immunity to varicella-zoster virus (VZV). We tested the hypothesis that vaccination against VZV would decrease the incidence, severity, or both of herpes zoster and postherpetic neuralgia among older adults.We enrolled 38,546 adults 60 years of age or older in a randomized, double-blind, placebo-controlled trial of an investigational live attenuated Oka/Merck VZV vaccine ("zoster vaccine"). Herpes zoster was diagnosed according to clinical and laboratory criteria. The pain and discomfort associated with herpes zoster were measured repeatedly for six months. The primary end point was the burden of illness due to herpes zoster, a measure affected by the incidence, severity, and duration of the associated pain and discomfort. The secondary end point was the incidence of postherpetic neuralgia.More than 95 percent of the subjects continued in the study to its completion, with a median of 3.12 years of surveillance for herpes zoster. A total of 957 confirmed cases of herpes zoster (315 among vaccine recipients and 642 among placebo recipients) and 107 cases of postherpetic neuralgia (27 among vaccine recipients and 80 among placebo recipients) were included in the efficacy analysis. The use of the zoster vaccine reduced the burden of illness due to herpes zoster by 61.1 percent (P<0.001), reduced the incidence of postherpetic neuralgia by 66.5 percent (P<0.001), and reduced the incidence of herpes zoster by 51.3 percent (P<0.001). Reactions at the injection site were more frequent among vaccine recipients but were generally mild.The zoster vaccine markedly reduced morbidity from herpes zoster and postherpetic neuralgia among older adults.
Carbocisteine inhibits rhinovirus infection in human tracheal epithelial cells
Authors: H. Yasuda, M. Yamaya, T. Sasaki, D. Inoue, K. Nakayama, M. Yamada, M. Asada, M. Yoshida, T. Suzuki, H. Nishimura, H. Sasaki
Journal: European Respiratory Journal (2006)

The aim of the study was to examine the effects of a mucolytic drug, carbocisteine, on rhinovirus (RV) infection in the airways. Human tracheal epithelial cells were infected with a major-group RV, RV14. RV14 infection increased virus titres and the cytokine content of supernatants. Carbocisteine reduced supernatant virus titres, the amount of RV14 RNA in cells, cell susceptibility to RV infection and supernatant cytokine concentrations, including interleukin (IL)-6 and IL-8, after RV14 infection. Carbocisteine reduced the expression of mRNA encoding intercellular adhesion molecule (ICAM)-1, the receptor for the major group of RVs. It also reduced the supernatant concentration of a soluble form of ICAM-1, the number and fluorescence intensity of acidic endosomes in the cells before RV infection, and nuclear factor-κB activation by RV14. Carbocisteine also reduced the supernatant virus titres of the minor group RV, RV2, although carbocisteine did not reduce the expression of mRNA encoding a low density lipoprotein receptor, the receptor for RV2. These results suggest that carbocisteine inhibits rhinovirus 2 infection by blocking rhinovirus RNA entry into the endosomes, and inhibits rhinovirus 14 infection by the same mechanism as well as by reducing intercellular adhesion molecule-1 levels. Carbocisteine may modulate airway inflammation by reducing the production of cytokines in rhinovirus infection.
<i>Traité International de Psychologie Pathologique</i>. Edited by Dr. A. Marie. Collaborators, Bechterew, Clouston, Dégerine, Grasset. Lugaro, Magnan, Pilcz, Raymond, Ziehen. Vol. II. Psychopathologie Clinique. (<i>Paris: Félix Alcan, 1911</i>.)
Authors: None Farrar
Journal: American Journal of Psychiatry (1912)
Prednisone prevents atrial fibrillation promotion by atrial tachycardia remodeling in dogs
Authors: A SHIROSHITATAKESHITA, B BRUNDEL, J LAVOIE, S NATTEL
Journal: Cardiovascular Research (2006)

Background: There is evidence suggesting involvement of oxidative stress, inflammation, and calcineurin/nuclear factor of activated T cell pathways in atrial fibrillation. This study evaluated the efficacy of anti-inflammatory and calcineurin-inhibitory drugs on promotion of atrial fibrillation by atrial tachycardia-induced remodeling in dogs.