tbuckley/cabot-search huggingface dataset:
Interleukin 1 beta induces the formation of nitric oxide by beta-cells purified from rodent islets of Langerhans. Evidence for the beta-cell as a source and site of action of nitric oxide.
Authors: J A Corbett, J L Wang, M A Sweetland, J R Lancaster, M L McDaniel
Journal: Journal of Clinical Investigation (1992)

Nitric oxide has recently been implicated as the effector molecule that mediates IL-1 beta-induced inhibition of glucose-stimulated insulin secretion and beta-cell specific destruction. The pancreatic islet represents a heterogeneous cell population containing both endocrine cells (beta-[insulin], alpha-]glucagon], gamma[somatostatin], and PP-[polypeptide] secreting cells) and non-endocrine cells (fibroblast, macrophage, endothelial, and dendritic cells). The purpose of this investigation was to determine if the beta-cell, which is selectively destroyed during insulin-dependent diabetes mellitus, is both a source of IL-1 beta-induced nitric oxide production and also a site of action of this free radical. Pretreatment of beta-cells, purified by FACS with IL-1 beta results in a 40% inhibition of glucose-stimulated insulin secretion that is prevented by the nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (NMMA). IL-1 beta induces the formation of nitric oxide by purified beta-cells as evidenced by the accumulation of cGMP, which is blocked by NMMA. IL-1 beta also induces the accumulation of cGMP by the insulinoma cell line Rin-m5F, and both NMMA as well as the protein synthesis inhibitor cycloheximide prevent this cGMP accumulation. Iron-sulfur proteins appear to be intracellular targets of nitric oxide. IL-1 beta induces the formation of an iron-dinitrosyl complex by Rin-m5F cells indicating that nitric oxide mediates the destruction of iron-sulfur clusters of iron containing enzymes. This is further demonstrated by IL-1 beta-induced inhibition of glucose oxidation by purified beta-cells, mitochondrial aconitase activity of dispersed islet cells, and mitochondrial aconitase activity of Rin-m5F cells, all of which are prevented by NMMA. IL-1 beta does not appear to affect FACS-purified alpha-cell metabolic activity or intracellular cGMP levels, suggesting that IL-1 beta does not exert any effect on alpha-cells. These results demonstrate that the islet beta-cell is a source of IL-1 beta-induced nitric oxide production, and that beta-cell mitochondrial iron-sulfur containing enzymes are one site of action of nitric oxide.
Frozen Section Diagnosis Of Endometrial Carcinoma
Authors: Frank R. Dutra
Journal: JAMA (1970)

To the Editor.—  In replying to an inquiry concerning endometrial adenocarcinoma, Dr. Alfred I. Sherman declares,  diagnosis of endometrial carcinoma by frozen section is... unreliable (210:2291, 1969). We do not agree with this statement.  Today, nearly all pathologists utilize modern reliable freezing microtome techniques for preparation of frozen sections for rapid diagnosis. Even before the advent of the cryotome, diagnosis of endometrial lesions was being made by many pathologists from frozen sections of curettings, and with great reliability.  The cryotome has brought the technique within the reach of any pathologist who has such an instrument and the ability to use it. This instrument is as essential to current practice of surgical pathology as the compound microscope.  Diagnosis of any lesion by frozen section examination is rarely unreliable; a competent surgical pathologist either recognizes the lesion and reports the diagnosis accordingly, or his examination of the frozen section (or
Survival after prolonged cardiac arrest and accidental hypothermia.
Authors: L Osborne, A S Kamal El-Din, J E Smith
Journal: BMJ (1984)

Un homme de 27 ans est trouve inconscient apres avoir passe la nuit a l'exterieur (et probablement absorbe alcool et barbituriques). Temperature œsophagienne 25°. Arret cardiaque prolonge, resistant aux premiers traitements (bicarbonate, lignocaine, cardioversion electrique, adrenaline et calcium en perfusions, massage cardiaque). Apres 4 h de rechauffement, oxygene, etc, la temperature arrive a 31° et la defibrillation est efficace. Recuperation totale apres un œdeme aigu du poumon et un syndrome de detresse respiratoire
Reducing HIV Risks
Authors: Bridget M. Kuehn
Journal: JAMA (2008)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
Observations on electrocardiogram and plasma catecholamines during dental procedures: the forgotten vagus.
Authors: P Taggart, R Hedworth-Whitty, M Carruthers, P D Gordon
Journal: BMJ (1976)

Emotional stress is conventionally considered to be associated with tachycardia and enhanced sympathetic activity. The electrocardiogram and plasma catecholamine and lipid concentrations were observed in 21 young healthy women undergoing dental procedures. Ten of these received premedication with the beta-blocking agent oxprenolol and 11 with a placebo, administered on a double-blind randomised basis. Mild tachycardia occurred in the placebo group a few minutes before and a few minutes after dentistry, but there was a reduction in heart rate immediately before and during the procedure. The pattern was similar in the group who received oxprenolol, though the heart rates at each stage were lower. Plasma adrenaline concentrations were much higher in the samples taken during the procedure than in those taken shortly before and after it. Plasma noradrenaline and lipid concentrations remained unchanged. A decrease in heart rate in the face of intense emotional arousal and an increased plasma adrenaline concentration suggest that the expectation or experience of pain may be associated with parasympathetic dominance despite greatly enhanced sympathetic activity.
A novel function for FOXP3 in humans: intrinsic regulation of conventional T cells
Authors: Alicia N. McMurchy, Jana Gillies, Maria Concetta Gizzi, Michela Riba, Jose Manuel Garcia-Manteiga, Davide Cittaro, Dejan Lazarevic, Sara Di Nunzio, Ignazio S. Piras, Alessandro Bulfone, Maria Grazia Roncarolo, Elia Stupka, Rosa Bacchetta, Megan K. Levings
Journal: Blood (2012)
Use of Electronic Health Records for Automated Screening of Growth Disorders in Primary Care
Authors: Ulla Sankilampi, Antti Saari, Tiina Laine, Päivi J. Miettinen, Leo Dunkel
Journal: JAMA (2013)

Monitoring of linear growth is a well-established part of pediatric health care in the developed world.Although monitoring aims to support early diagnosis and timely treatment of disorders affecting growth, such disorders are often diagnosed late. 1 This population-based study assessed the effectiveness of a novel computerized and automated growth monitoring (AGM) strategy integrated into an electronic health record (EHR) system in the primary care setting.Our hypothesis was that compared with standard growth monitoring (SGM), the AGM strategy would result in a better diagnostic yield and facilitate earlier diagnosis of disorders affecting growth.
Dangerous Complication of Temporary Floating Pacing Electrodes
Authors: David Pomfret, Burton J. Polansky, Andrew Huvos
Journal: New England Journal of Medicine (1969)

TRANSVENOUS intracardiac pacing by means of a temporary floating cardiac pacing electrode † is becoming more popular with the advent of cardiac-cure units, because of the simplicity and convenience that these electrodes afford. The temporary floating pacing electrode is positioned through a venipuncture with a No. 18 needle and advanced under electrocardiographic rather than fluoroscopic control into the right ventricle by means of the technic of Harris et al.1 It is used as an interim method for intracardiac pacing in atrioventricular block or may be positioned prophylactically in the right ventricle before the development of any evidence of impaired atrioventricular conduction. . . .
Nebulized Hypertonic Saline Decreases IL-8 in Sputum of Patients with Cystic Fibrosis
Authors: Emer P. Reeves, Michael Williamson, Shane J. O'Neill, Peter Greally, Noel G. McElvaney
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Rationale: Inflammation within the cystic fibrosis (CF) lung is mediated by inflammatory chemokines, such as IL-8. IL-8 is protected from proteolytic degradation in the airways by binding to glycosaminoglycans, while remaining active. Evidence that increased hypertonicity of airway secretions induced by hypertonic saline treatment alters levels of IL-8 is lacking.Objectives: To investigate the antiinflammatory effect of hypertonic saline (HTS) treatment within the CF lung by focusing on IL-8.Methods: Degradation of IL-8 in CF lung secretions after treatment with glycosaminoglycan lyases and HTS was analyzed by Western blot analysis and ELISA. The ex vivo chemotactic activity of purified neutrophils in response to CF airway secretions was evaluated post nebulization of HTS (7% saline).Measurements and Main Results: In vivo CF bronchoalveolar lavage fluid (BALF) IL-8 levels were significantly higher than the control group (P < 0.05). Digesting glycosaminoglycans in CF BALF displaced IL-8 from glycosaminoglycan matrices, rendering the chemokine susceptible to proteolytic cleavage. High sodium concentrations also liberate IL-8 in CF BALF in vitro, and in vivo in CF sputum from patients receiving aerosolized HTS, resulting in degradation of IL-8 and decreased neutrophil chemotactic efficiency.Conclusions: Glycosaminoglycans possess the ability to influence the chemokine profile of the CF lung by binding and stabilizing IL-8, which promotes neutrophil chemotaxis and activation. Nebulized hypertonic saline treatment disrupts the interaction between glycosaminoglycans and IL-8, rendering IL-8 susceptible to proteolytic degradation with subsequent decrease in neutrophil chemotaxis, thereby facilitating resolution of inflammation.
Sex-Based Outcomes of Darunavir–Ritonavir Therapy
Authors: Judith Currier
Journal: Annals of Internal Medicine (2010)

Women account for an increasing proportion of patients with HIV-1 but remain underrepresented in antiretroviral clinical trials.To evaluate sex-based differences in efficacy and adverse events in treatment-experienced, HIV-positive women and men receiving darunavir-ritonavir therapy over 48 weeks.Multicenter, open-label, phase 3b study designed to enroll a high proportion of women, with sample size determined on the basis of a noninferiority design with a maximum allowable difference of 15% in virologic response favoring men. (ClinicalTrials.gov registration number: NCT00381303)65 sites in the United States, Puerto Rico, and Canada.287 women and 142 men.Patients received darunavir-ritonavir, 600/100 mg twice daily, plus an investigator-selected optimized background regimen.Virologic response (HIV RNA <50 copies/mL using a time-to-loss of virologic response [TLOVR] algorithm) and adverse events were assessed over 48 weeks.67% of patients were women; 84% of patients were black or Hispanic. A higher proportion of women discontinued treatment than men (32.8% vs. 23.2%; P = 0.042); more women than men discontinued treatment for reasons other than virologic failure. Response rates in women and men at week 48 were 50.9% and 58.5%, respectively (intention-to-treat TLOVR), and 73.0% and 73.5%, respectively (TLOVR censored for patients who withdrew for reasons other than virologic failure). The absolute difference in response, based on logistic regression and adjusted for baseline log(10) viral load and CD4(+) cell count, was -9.6 percentage points (95% CI, -19.9 to 0.7 percentage points; P = 0.067) for intention-to-treat TLOVR and -3.9 percentage points (CI, -13.9 to 6.0 percentage points; P = 0.438) for TLOVR population that censored patients who withdrew for reasons other than virologic failure. Adverse events were similar between the sexes. The most common grade 2 to 4 adverse events that were considered at least possibly treatment related in women and men were nausea (5.2% and 2.8%, respectively), diarrhea (4.5% and 4.9%, respectively), and rash (2.1% and 2.8%, respectively).Baseline characteristics differed between sexes.Nonsignificant, sex-based differences in response were found during the 48-week study; however, these differences were probably due to higher discontinuation rates in women, suggesting that additional efforts are needed to retain women in clinical trials.
Influx of neutrophils into the walls of large epicardial coronary arteries in response to ischemia/reperfusion.
Authors: R A Kloner, F Giacomelli, K J Alker, S L Hale, R Matthews, S Bellows
Journal: Circulation (1991)

There are several clinical situations in which large epicardial coronary arteries are deprived of blood flow, such as occurs when an obstructing thrombus or embolus lodges within a vessel or during coronary dissection. There is little information concerning the effect of flow deprivation on large epicardial coronary arteries.We studied a model in which a segment of a large epicardial coronary artery was deprived of blood flow using both proximal and distal clamps for 3 hours followed by reperfusion. On examination by light microscopy of cross sections of the arteries, 19 +/- 6 neutrophils were present in the intima of ischemic/reperfused vessels, whereas only a mean of 4 +/- 3 (SEM) were present in the intima of nonischemic vessels (p less than 0.02). On average, there were 17 +/- 9 neutrophils just under the elastic lamina in ischemic/reperfused vessels versus none in the nonischemic vessels (p less than 0.05); there were 16 +/- 10 neutrophils present within the media of ischemic/reperfused vessels, and none (p less than 0.05) in the nonischemic vessels. Electron microscopic analysis revealed that neutrophils in the ischemic/reperfused vessels were often "sandwiched" between the endothelial cells and the elastic lamina. Ultrastructural abnormalities within the myocardium also revealed damage to the microvasculature, including the presence of neutrophils within the vessels and erythrocyte stasis. To rule out the possibility that findings in the large epicardial arteries were due to toxic substances from static blood within the isolated arterial segment, a protocol was performed in which blood was removed from the isolated segment. Again, neutrophil infiltration into the vessel was observed. Resting mean epicardial coronary artery blood flow before coronary occlusion was 19 +/- 3 ml/min; mean coronary blood flow 2.5 hours after reperfusion was identical at 19 +/- 3 ml/min. Response to both endothelial-dependent vasodilation (acetylcholine) and endothelial-independent vasodilation (nitroglycerin) challenges was normal early after reperfusion but was depressed late after reperfusion, suggesting progressive vascular dysfunction and hence a form of vascular reperfusion injury in this model.When large epicardial coronary arteries are deprived of blood flow, followed by reperfusion in this model, neutrophils migrate into the vessel wall as well as into the microvasculature. These abnormalities are associated with reduced endothelial-dependent and endothelial-independent coronary vasodilator reserve.
A Polymorphism in Interferon L3 Is an Independent Risk Factor for Development of Hepatocellular Carcinoma After Treatment of Hepatitis C Virus Infection
Authors: Kuo-Chin Chang, Po-Lin Tseng, Yi-Ying Wu, Hung-Chao Hung, Chao-Min Huang, Sheng-Nan Lu, Jing-Houng Wang, Chuan-Mo Lee, Chien-Hung Chen, Ming-Chao Tsai, Yi-Hao Yen, Ming-Tsung Lin, Cheng-Kun Wu, Chao-Cheng Huang, Hsiu-Hsi Chen, Tsung-Hui Hu
Journal: Clinical Gastroenterology and Hepatology (2014)

Background & AimsPolymorphisms in interferon (IFN)L3 (encodes IFNλ3 or interleukin 28B) are associated with outcomes of treatment for hepatitis C virus (HCV) infection. However, there is controversy regarding how polymorphisms in IFNL3 affect the risk for development of hepatocellular carcinoma (HCC) in patients treated with pegylated interferon and ribavirin.MethodsIn a retrospective study, we analyzed data from 1118 patients with HCV infection (589 men; median age, 60 y; 49.9% infected with genotype 1; 51.3% with advanced fibrosis) treated with pegylated interferon and ribavirin from March 2000 through October 2009 at the Chang Gung Memorial Hospital in Kaohsiung, Taiwan (71.64% achieved sustained virologic response [SVR]). Baseline samples were collected before therapy. Starting 24 weeks after treatment, clinical and biochemical features were assessed every 3 to 6 months and patients underwent ultrasound examinations. Lesions detected were examined by computed tomography, angiography, or fine-needle aspiration biopsy analyses. Patients were followed up from the initiation of HCV therapy until a diagnosis of HCC (based on published guidelines), death, or March 31, 2013 (median, 60 mo). DNA samples from each patient were analyzed for rs12979860 in IFNL3. Kaplan–Meier analysis was used to determine the risk for development of HCC.ResultsThe percentages of patients with the IFNL3 rs12979860 CC, CT, and TT genotypes were 86.4%, 13.2%, and 0.3%, respectively. A total of 108 patients (9.66%) developed HCC. The IFNL3 rs12979860 CT and TT genotypes correlated with high baseline levels of α-fetoprotein (AFP; ≥20 ng/mL), advanced stage of fibrosis, diabetes, or lack of an SVR (all P < .05). Based on multivariate Cox regression analysis, age 60 years and older, low platelet count (<15 × 109 cells/L), AFP level of 20 ng/mL or greater, advanced stage fibrosis, diabetes, lack of an SVR, and the IFNL3 rs12979860 CT and TT genotypes were significant risk factors for HCC (P < .05). Age 60 years and older, low numbers of platelets or high AFP level, and advanced fibrosis were risk factors for HCC among patients with a SVR. The IFNL3 rs12979860 genotype did not have a significant effect on risk for HCC among patients with SVRs, although some of these patients (with the CT or TT genotype) did develop HCC. Among patients without SVRs, only fibrosis stage and the IFNL3 rs12979860 CT and TT genotypes (hazard ratio, 1.80; 95% confidence interval, 1.06–3.07; P = .030) were independent risk factors for HCC.ConclusionsBased on a retrospective study of patients treated for HCV infection, the IFNL3 rs12979860 CT and TT polymorphisms are associated with a risk for HCC, especially in patients without a SVR.
Atropine Poisoning in Infancy
Authors: M. J. Purcell
Journal: BMJ (1966)

in healthy men.2And even if these external conditions are comparable individual circum- stances like changes in the fluid balance (day and night rhythm, menstrual cycle in the female, salt or liquorice consumption, oedema, and the effects of the drug itself, such as diarrhoea and diuresis) might influence the results.This introduces an explanation for the wide diversity in the reported data of effective serum levels of antibiotics, and an explanation why drug toxicity may occur, although the dose given remained constant after changes in the fluid balance and the patient's mobility (digitalis).The relations of these postural changes in serum levels with effectual activity, elimina- tion, and excretion are not known; they might be important for establishing doses and frequency of administration of a number of drugs.-Weare, etc.,
Cardiovascular Effects of Sustained Norepinephrine Infusions in Dogs
Authors: ARTHUR J. MOSS, ERIC A. SCHENK
Journal: Circulation Research (1970)

Sustained infusions of norepinephrine (NE) are known to produce deleterious pathophysiologic effects on the circulatory system. The mechanisms responsible for these effects were investigated in 25 dogs; 17 were treated with selective block of alpha receptors by phenoxybenzamine or of beta receptors by propranolol, or by both agents, and then infused with NE (4 µg.kg -1 .min -1 ) for 4 hours; 8 control animals were given only adrenergic blocking agents. Left ventricular and systemic pressure, cardiac output and arterial blood gases were measured at selected intervals throughout the infusion period, and histologic examinations of the heart and other vital organs were performed at the conclusion of each study. In animals with alpha-receptor blockade, NE infusions were associated with extensive subendocardial hemorrhage and focal myofiber fatty degeneration, yet blood pressure, cardiac output, and derived cardiac work parameters were well maintained. In animals with beta-receptor blockade, NE caused minimal pathologic changes in the heart despite significant reduction in cardiac output, minute and stroke work, and significant increase in left ventricular end-diastolic pressure (LVEDP) and peripheral vascular resistance. In animals receiving combined alpha- and beta-receptor blockade, NE infusions were not associated with significant hemodynamic or morphologic abnormality. These findings indicate: (1) the hemodynamic abnormalities are the result of the action of NE mediated primarily through alpha receptors; (2) the morphologic changes are produced by NE mediated mostly through beta receptors; and (3) the reductions in cardiac output and minute and stroke work and the increase in LVEDP produced by sustained NE infusions are not necessarily a consequence of the pathologic changes which develop in the heart muscle.
3-Substituted GABA analogs with central nervous system activity: A review
Authors: Justin S. Bryans, David J. Wustrow
Journal: Medicinal Research Reviews (1999)

Gabapentin and Pregabalin are both 3-alkylated γ-amino butyric acid (GABA) analogs. Gabapentin was designed as a lipophilic GABA analog and was first synthesized as a potential anticonvulsant and was launched in 1994 as add-on therapy for the treatment of epilepsy. In this review the discovery and development of gabapentin as an anticonvulsant are discussed. During human trials and while in clinical use, it became apparent that gabapentin induced some other potentially useful therapeutic effects in chronic pain states and behavioral disorders. A review of animal and clinical data relating to these other potential therapeutic utilities is presented. Pregabalin was identified after an investigation into other 3-substituted GABA analogs. It has since been shown to have a similar pharmacological profile to gabapentin with greater potency in preclinical models of pain and epilepsy. Studies of the mechanism(s) of action of these compounds are discussed. Work towards identifying new analogs of both gabapentin and pregabalin is also reviewed. © 1999 John Wiley & Sons, Inc. Med Res Rev 19, 149–177, 1999.