tbuckley/cabot-search huggingface dataset:
Pulmonary function, smoking cessation and 30 year mortality in middle aged Finnish men
Authors: M. Pelkonen
Journal: Thorax (2000)

<h3>BACKGROUND</h3> Although it is well known that impaired pulmonary function is a strong predictor of mortality and that smoking decreases pulmonary function, little is known about the long term effect of smoking cessation on mortality at different levels of pulmonary function. We have studied the impact of smoking cessation on mortality over the entire range of baseline pulmonary function. <h3>METHODS</h3> The study subjects consisted of men aged 40–59 at entry who were the Finnish participants in the Seven Countries Study during 1959–89. <h3>RESULTS</h3> In all the participants (n = 1582) impaired forced expiratory volume in 0.75 seconds (FEV<sub>0.75</sub>) was significantly associated with increased all cause mortality. When those who gave up smoking during the follow up period were compared with continuous smokers (n = 860) all cause mortality was found to be decreased among those who quit. The relative adjusted hazard (HR) was 0.71 (95% confidence interval 0.50 to 1.00). The median survival time in those who stopped smoking compared with those who continued to smoke from 1969 onwards was 7.65, 7.59, and 6.30 years longer in the lowest, middle and highest tertiles of adjusted FEV<sub>0.75</sub> distribution, respectively. In those who gave up smoking, mortality from cardiovascular causes was significantly lower (HR 0.60 (95% CI 0.37 to 0.98)). <h3>CONCLUSIONS</h3> These findings suggest that smokers across the entire range of pulmonary function may increase their expectation of lifespan by giving up smoking.
Interleukin 9 promotes influx and local maturation of eosinophils
Authors: Jamila Louahed, Yuhong Zhou, W. Lee Maloy, Pyapalli U. Rani, Christine Weiss, Yaniv Tomer, Anne Vink, Jean-Christophe Renauld, Jacques Van Snick, Nicholas C. Nicolaides, Roy C. Levitt, Angela Haczku
Journal: Blood (2001)
The role of a masters degree as part of higher training in sports and exercise medicine or why do a masters?
Authors: Moira O'Brien, Nick Mahony
Journal: British Journal of Sports Medicine (2000)

Sports medicine is now recognised as a specialty in some European countries. As an emerging discipline, sports and exercise medicine needs to develop a solid academic footing if it is to gain acceptance by the Royal Colleges in Great Britain and Ireland. A higher professional university degree is a requirement for work in sports and exercise medicine clinics abroad, especially schemes associated with the Fellowship of the Australian College of Sports Medicine. Health insurance companies, professional athletes, and teams now demand a much higher standard of care from their sports physicians, and this makes the higher status of further postgraduate university qualifications even more important.

In Great Britain and Ireland, practitioners engaged in masters programmes develop an understanding of training methods from a wide variety of sports and the prerequisite knowledge to monitor and optimise the …
Incidence and prevalence of ulcerative colitis in Punjab, North India
Authors: A Sood
Journal: Gut (2003)

Ulcerative colitis occurs worldwide. It is considered common in most of Europe and North America and uncommon in most of the developing Asian countries. The incidence/prevalence of ulcerative colitis varies not only according to geographical region but also with race and ethnicity. There are no reported data from India on the incidence of the disease and its prevalence.A house to house survey was conducted by questionnaire, formulated to enquire about symptoms that are suggestive of ulcerative colitis. Those with prolonged diarrhoea with or without rectal bleeding were considered as suspected cases. These suspected cases were subjected to video sigmoidoscopy/colonoscopy and rectal biopsy. In addition, patients already diagnosed and receiving treatment for ulcerative colitis, encountered during the survey, were reviewed. Resurvey of the same areas was conducted after a one year interval to detect new cases. Using direct methods, standardised rates were calculated using world standard population weights 22, 18, 16, 12, 12, 9, 7, 3, and 1 for each 10 year age group. Standardised rates were also obtained separately for males, females, and combined populations, using the Punjab state 1991 population census data. Rates were also estimated according to UK 2000 population data. Ninety five per cent confidence intervals (95% CI) of prevalence and incidence rates of ulcerative colitis were estimated under the assumption that the distribution of cases followed a Poisson probability model.A total population of 51 910 were screened from January to March 1999. We identified 147 suspected cases and of these 23 were finally established as ulcerative colitis cases, giving a crude prevalence rate of 44.3 per 100 000 inhabitants (95% CI 29.4-66.6). A second visit to the same areas after one year identified 10 suspected cases in a population of 49 834. Of these, three were confirmed as "definite" ulcerative colitis giving a crude incidence rate of 6.02 cases per 100 000 inhabitants (95% CI 1.2-17.6).This is the first population based study from India reporting on the incidence and prevalence of ulcerative colitis. The disease frequency is not much less than that reported from Europe and North America.
Statin-induced fibrotic nonspecific interstitial pneumonia
Authors: S. Lantuejoul, E. Brambilla, C. Brambilla, G. Devouassoux
Journal: European Respiratory Journal (2002)

Statins inhibit the 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase, reduce the serum level of low-density lipoprotein cholesterol, and are extensively prescribed to prevent cardiovascular mortality and morbidity. Few systemic adverse effects, such as pseudopolymyositis, lupus-like syndromes, and anecdotal hypersensitivity pneumonitis, have been reported. A simvastatin-induced diffuse interstitial pneumonia associated with a nonspecific interstitial pneumonia pattern at histological analysis is repoted here. Ultrastructural analysis showed a diffuse cytoplasmic accumulation of intralysosomial lamellar inclusions in type II pneumonocytes, histiocytes and endothelial cells, suggesting a shared pathogenesis with amphiphilic drug-induced toxic lung injury. Because statins are increasingly prescribed, statin-induced interstitial lung disorders may be more frequently observed and early recognition will be required.
The Pathophysiology of Asthma
Authors: Lee Maddox, David A. Schwartz
Journal: Annual Review of Medicine (2002)

▪ Abstract Asthma is a chronic disorder of the airways that is characterized by reversible airflow obstruction and airway inflammation, persistent airway hyperreactivity, and airway remodeling. The etiology of asthma is complex and multifactorial. Recent advances have demonstrated the importance of genetics in the development of asthma, particularly atopic asthma. Environmental stimuli, particularly early childhood infections, have also been associated with the development of asthma. Most current data seem to suggest that these factors drive the development of a Th-2 lymphocyte–predominant immune response, which has been associated with atopy and IgE-mediated inflammation. The concept of reversible airflow obstruction has also recently been challenged. It is now clear that chronic airway changes occur, which may contribute to progressive airflow obstruction. We discuss the important influence of genetic and environmental factors on the emergence of the asthmatic phenotype. The significance of Th-1 and Th-2 lymphocyte–mediated immunity are discussed, and the inflammatory processes leading to chronic airway inflammation are detailed.
Alopecia Areata in the Very Young
Authors: ROBERT D. MEHLMAN, ROBERT D. GRIESEMER
Journal: American Journal of Psychiatry (1968)

The authors report their investigation of possible relationships between the dermatologic condition of alopecia areata and the emotional state of the patient among a number of young children with the disorder. The clinical evidence suggests a dynamic formulation based upon symbolic loss at a very early age, subsequent symptomatic management of the loss, and, finally, collapse of the management system, precipitating the onset of rapid hair loss. Further physiologic and psychiatric studies may shed some light on the specific somatization process and support the authors' conclusion that this disease belongs in the category of psychosomatic entities.
Activating Transcription Factor 1 Directs Mhem Atheroprotective Macrophages Through Coordinated Iron Handling and Foam Cell Protection
Authors: Joseph J. Boyle, Michael Johns, Theresa Kampfer, Aivi T. Nguyen, Laurence Game, Dominik J. Schaer, Justin C. Mason, Dorian O. Haskard
Journal: Circulation Research (2011)

Rationale: Intraplaque hemorrhage (IPH) drives atherosclerosis through the dual metabolic stresses of cholesterol-enriched erythrocyte membranes and pro-oxidant heme/iron. When clearing tissue hemorrhage, macrophages are typically seen storing either iron or lipid. We have recently defined hemorrhage-associated macrophages (HA-mac) as a plaque macrophage population that responds adaptively to IPH. Objective: This study aimed to define the key transcription factor(s) involved in HO-1 induction by heme. Methods and Results: To address this question, we used microarray analysis and transfection with siRNA and plasmids. To maintain physiological relevance, we focused on human blood-derived monocytes. We found that heme stimulates monocytes through induction of activating transcription factor 1 (ATF-1). ATF-1 coinduces heme oxygenase-1 (HO-1) and Liver X receptor beta (LXR-β). Heme-induced HO-1 and LXR-β were suppressed by knockdown of ATF-1, and HO-1 and LXR-β were induced by ATF-1 transfection. ATF-1 required phosphorylation for full functional activity. Expression of LXR-β in turn led to induction of other genes central to cholesterol efflux, such as LXR-α and ABCA1. This heme-directed state was distinct from known macrophage states (M1, M2, Mox) and, following the same format, we have designated them Mhem. Conclusions: These results show that ATF-1 mediates HO-1 induction by heme and drives macrophage adaptation to intraplaque hemorrhage. Our definition of an ATF-1–mediated pathway for linked protection from foam cell formation and oxidant stress may have therapeutic potential.
Physical-Chemical Methods for Determining Bilirubin Solubilities in Simulated Bile Systems
Authors: Martin C. Carey
Journal: Hepatology (1984)

This report describes a rigorous physical-chemical approach to determine the solubilities of unconjugated bilirubin in model bile systems. In the absence of calcium ions, metastable and equilibrium solubilities can be obtained by acidimetric (HC1) titration of excess unconjugated bilirubin in aqueous solutions of simple and mixed conjugated bile salt micelles. The experiments must be performed with degassed water under argon, in dim light and at constant temperature and ionic strength. This approach provides metastable and equilibrium solubilities of unconjugated bilirubin at a unique pH, i.e., the precipitation pH (pHppt) of bilirubin in the bile salt system. Because high levels of supersaturation can be acidimetrically induced, equilibration is usually complete in less than 20 min. To obtain equilibrium solubilities of bilirubin in simulated bile systems at other pH values (<pHppt>), it is necessary to perform equilibrium dissolution studies of crystalline diacid bilirubin in the presence of a strong buffer (at least 0.2 M). This method must, perforce, be the procedure of choice to estimate micellar bilirubin solubilities in the presence of calcium ions. Each dissolution experiment takes from 2 to 3 days, hence meticulous attention must be paid to the photochemical stability of bilirubin during the equilibration period, and appropriate precautions taken. Bilirubin solubilities obtained by both methods can be validated by titrating predetermined concentrations of unconjugated bilirubin spectrophotometrically in the model bile systems to the pH value at which saturation solubility was obtained. As a check of equilibration, it is imperative that bilirubin solubility values at the pHppt obtained by both dissolution and titra-metric methods display satisfactory agreement. For a complete description of the system, chemical and physical analyses of the excess solid-phase bilirubin that was in equilibrium with the bilirubin-saturated micellar phase should be performed.
Chronic, episodic, reversible airway obstruction after viral bronchiolitis in rats.
Authors: A Kumar, R L Sorkness, M R Kaplan, R F Lemanske
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Viral bronchiolitis in human infants has been associated with persistent airway abnormalities, but not proven as a cause. Previously we observed some adult rats had airway obstruction and hyperresponsiveness following bronchiolitis at an early age. The purpose of this study was to determine, via serial measurements of lung mechanics, whether the postbronchiolitis airway obstruction was episodic or continuous, and to determine the magnitude and duration of glucocorticoid effects. Rats were either virus- (n = 14) or sham-inoculated (n = 8) at 3 wks of age. Lung mechanics were measured 6 times in each rat at postinoculation Weeks 11-18. Half the rats in each group were treated with dexamethasone for 3 d at Week 15. The virus group had higher lung resistance (p = 0.03) and lower dynamic compliance (p = 0.005) than control rats, with airway obstruction occurring in an episodic pattern. Dexamethasone treatment had a transient effect in postbronchiolitis rats; lung resistance normalized in Week 15 (p = 0.006), then returned to pretreatment levels by Weeks 16-18. We conclude that viral bronchiolitis in rats can result in a chronic syndrome of intermittent, reversible airway obstruction which has multiple parallels with human asthma over a prolonged time period.
Gastroenterology in Romania: a fresh start in a new era.
Authors: M Acalovschi
Journal: Gut (1995)

Gastroenterology in Romania: a fresh start in a new era This month's 'International Gastroenterology' section features an article on the difficulties associated with establishing a gastroenterology journal in Romania following the overthrow of the totalitarian regime in 1989.Clearly there are shared problems common to editors of all new journals: getting papers and readers, for a start.The liberal scientific tradition in the West, however, has always encouraged discussion, debate, and disagreement while the editorial process depends on vigorous (but constructive) peer review.This is not so in Romania where criticism has been regarded as hostile, personal, and potentially dangerous.Gut sends its best wishes to the Romanian Journal of Gastroenterology.Enthusiasm emanating from a group of Romanian professionals who had been controlled and silenced for several decades was the constructive force in the origin of the Romanian Journal of Gastroenterology.Dissatisfaction with the state of imposed apathy surrounding them generated a desire for change: to show that we exist and have something worthwhile to say in the medical field.In the free publishing history of Romania, which really only began in 1989, many medical journals have appeared -some have survived but many others have failed.The Romanian Journal of Gastroenterology is one of the survivors.
Collagen remodeling of the pressure-overloaded, hypertrophied nonhuman primate myocardium.
Authors: K T Weber, J S Janicki, S G Shroff, R Pick, R M Chen, R I Bashey
Journal: Circulation Research (1988)

Cardiac muscle is tethered within a fibrillar collagen matrix that serves to maximize force generation. In the human pressure-overloaded, hypertrophied left ventricle, collagen concentration is known to be increased; however, the structural and biochemical remodeling of collagen and its relation to cell necrosis and myocardial mechanics is less clear. Accordingly, this study was undertaken in a nonhuman primate model of left ventricular hypertrophy caused by gradual onset experimental hypertension. The amount of collagen, its light microscopic features, and proportions of collagen types I, III, and V were determined together with diastolic and systolic mechanics of the intact ventricle during the evolutionary, early, and late phases of established left ventricular hypertrophy (4, 35, and 88 weeks, respectively). In comparison to controls, we found 1) increased collagen at 4 weeks, as well as a greater proportion of type III, in the absence of myocyte necrosis; 2) collagen septae were thick and dense at 35 weeks, while the proportion of types I and III had converted to control; 3) necrosis was evident at 88 weeks, and the structural remodeling and proportion of collagen types I and III reflected the extent of scar formation; and 4) unlike diastolic myocardial stiffness, which was unchanged at 4, 35, or 88 weeks, the systolic stress-strain relation of the myocardium was altered in either a beneficial or detrimental manner in accordance with structural remodeling of collagen and scar formation. Thus, early in left ventricular hypertrophy, reactive fibrosis and collagen remodeling occur in the absence of necrosis while, later on, reparative fibrosis is present.(ABSTRACT TRUNCATED AT 250 WORDS)
Prediction of<i>BRCA</i>Mutations Using the BRCAPRO Model in Clinic-Based African American, Hispanic, and Other Minority Families in the United States
Authors: Dezheng Huo, Ruby T. Senie, Mary Daly, Saundra S. Buys, Shelly Cummings, Jacqueline Ogutha, Kisha Hope, Olufunmilayo I. Olopade
Journal: Journal of Clinical Oncology (2009)

BRCAPRO, a BRCA mutation carrier prediction model, was developed on the basis of studies in individuals of Ashkenazi Jewish and European ancestry. We evaluated the performance of the BRCAPRO model among clinic-based minority families. We also assessed the clinical utility of mutation status of probands (the first individual tested in a family) in the recommendation of BRCA mutation testing for other at-risk family members.A total of 292 minority families with at least one member who was tested for BRCA mutations were identified through the Breast Cancer Family Registry and the University of Chicago. Using the BRCAPRO model, the predicted likelihood of carrying BRCA mutations was generated. Area under the receiver operating characteristic curves (AUCs) were calculated.There were 104 African American, 130 Hispanic, 37 Asian-American, and 21 other minority families. The AUC was 0.748 (95% CI, 0.672 to 0.823) for all minorities combined. There was a statistically nonsignificant trend for BRCAPRO to perform better in Hispanic families than in other minority families. After taking into account the mutation status of probands, BRCAPRO performance in additional tested family members was improved: the AUC increased from 0.760 to 0.902.The findings support the use of BRCAPRO in pretest BRCA mutation prediction among minority families in clinical settings, but there is room for improvement in ethnic groups other than Hispanics. Knowledge of the mutation status of the proband provides additional predictive value, which may guide genetic counselors in recommending BRCA testing of additional relatives when a proband has tested negative.
Influence of Activation State of ErbB-2 (HER-2) on Response to Adjuvant Cyclophosphamide, Doxorubicin, and Fluorouracil for Stage II, Node-Positive Breast Cancer: Study 8541 From the Cancer and Leukemia Group B
Authors: Michael P. DiGiovanna, David F. Stern, Susan Edgerton, Gloria Broadwater, Lynn G. Dressler, Daniel R. Budman, I. Craig Henderson, Larry Norton, Edison T. Liu, Hyman B. Muss, Donald A. Berry, Daniel F. Hayes, Ann D. Thor
Journal: Journal of Clinical Oncology (2008)

ErbB-2 (human epidermal growth factor receptor 2) overexpression may be predictive of relative resistance and/or sensitivity to specific chemotherapeutic agents. Results from a previous study from the Cancer and Leukemia Group B (CALGB 8541) demonstrated an interaction between ErbB-2 and increasing dose of adjuvant cyclophosphamide, doxorubicin, and fluorouracil (CAF) chemotherapy. Other studies have suggested that evaluation of the phosphorylated/activated form of ErbB-2 might be more precise in defining the impact of ErbB-2 in breast cancer. We have evaluated tumor tissue sections from CALGB 8541 patients to determine whether the interaction of ErbB-2 with CAF dose is dependent on ErbB-2 activation state, and whether phosphorylated ErbB-2 is an adverse prognostic factor in patients treated with CAF.Patients were randomly assigned to one of three dosing regimens of CAF. Paraffin samples from 992 of 1,572 patients who participated in CALGB 8541 were available. Of the 570 tumors with any staining for ErbB-2, 488 had tissue available for assay for phosphorylated ErbB-2, which was performed by immunohistochemistry.Of 910 total assessable cases, 112 of 488 ErbB-2-positive cases (23%) stained positively for phosphorylated ErbB-2. The previously described interaction of dosing regimen of CAF with ErbB-2 was not dependent on phosphorylation status of ErbB-2.Monitoring phosphorylation of ErbB-2 with an antiphospho-ErbB-2 antibody did not add further precision to identifying those patients most likely to benefit from increased dose of anthracycline-based adjuvant chemotherapy. Favorable outcomes are observed in ErbB-2-overexpressing patients treated with high-dose CAF regardless of ErbB-2 phosphorylation state.
Pulmonary Hypertension and Right Heart Failure in Pituitary Adenylate Cyclase–Activating Polypeptide Type I Receptor–Deficient Mice
Authors: Christiane Otto, Lutz Hein, Marc Brede, Roland Jahns, Stefan Engelhardt, Hermann-Josef Gröne, Günther Schütz
Journal: Circulation (2004)

Pituitary adenylate cyclase-activating polypeptide (PACAP), acting via 3 different G protein-coupled receptors, has been implicated in the regulation of several homeostatic systems in the body, including cardiopulmonary control. To define the physiologic role of the PACAP-preferring type I receptor, PAC1, in cardiopulmonary function, we developed a mutant mouse strain lacking functional PAC1 receptors.When PAC1-deficient mice were crossed onto a C57BL/6 background, almost all mutants died during the second postnatal week. Whereas mutant mice were indistinguishable from their wild-type littermates at birth, they showed progressive weakness and died from rapidly developing heart failure. Right ventricles of PAC1 mutants were massively dilated and showed cardiac myocyte hypertrophy, whereas left ventricular structure was unaltered. On direct cardiac catheterization, right ventricular pressure was elevated by 45% in PAC1-deficient mice, indicating increased pulmonary artery pressure, as no malformations were detected in the valves or outflow tract of the right ventricle. Consistent with elevated pulmonary pressure, lung capillary density was decreased by 30% and small pulmonary arteries of mutant mice had significant vascular smooth muscle cell hypertrophy compared with wild-type mice.Whereas PACAP induces vasodilation in isolated pulmonary vessels in wild-type mice, the absence of its specific receptor PAC1 causes pulmonary hypertension and right heart failure after birth. These in vivo findings demonstrate the crucial importance of PAC1-mediated signaling for the maintenance of normal pulmonary vascular tone during early postnatal life.