tbuckley/cabot-search huggingface dataset:
Role of nasal interleukin-8 in neutrophil recruitment and activation in children with virus-induced asthma.
Authors: L M Teran, S L Johnston, J M Schröder, M K Church, S T Holgate
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Neutrophil infiltration is a major feature in the pathogenesis of the common cold, and respiratory viral infection is the major cause of asthma exacerbations. The factors regulating the neutrophil influx are unknown. Interleukin-8 (IL-8) is a potent neutrophil chemoattractant, which has been implicated in several inflammatory diseases. In this study, we investigated the presence of IL-8 chemokine in the nasal aspirates of asthmatic children (n = 12) in whom asthma was precipitated by proven viral infection. There were increased IL-8 levels in nasal aspirates from children during the virus-induced asthma exacerbations compared with samples from the same children when they had been asymptomatic for 2 wk (medians 863 and < 20 pg/ml, respectively, p < 0.01). Biological relevance was shown in that IL-8 levels correlate with increased nasal aspirate neutrophil myeloperoxidase levels and there was also a correlation between myeloperoxidase levels and upper respiratory symptom severity. Furthermore, we purified IL-8 from these samples, and demonstrated biological neutrophil chemotactic activity. These are the first in vivo data to suggest an important role for IL-8 in neutrophil influx in proven upper respiratory viral infection associated with asthma exacerbations. We suggest that IL-8 might provide a target for therapeutic intervention in virus-induced respiratory diseases.
Consistencies and inconsistencies underlying the quantitative assessment of leukemia risk from benzene exposure.
Authors: S H Lamm, A S Walters, R Wilson, D M Byrd, H Grunwald
Journal: Environmental Health Perspectives (1989)

This paper examines recent risk assessments for benzene and observes a number of inconsistencies within the study and consistencies between studies that should effect the quantitative determination of the risk from benzene exposure. Comparisons across studies show that only acute myeloid leukemia (AML) is found to be consistently in excess with significant benzene exposure. The data from the Pliofilm study that forms the basis of most quantitative assessments reveal that all the AML cases came from only one of the three studied plants and that all the benzene exposure data came from the other plants. Hematological data from the 1940s from the plant from which almost all of the industrial hygiene exposure data come do not correlate well with the originally published exposure estimates but do correlate well with an alternative set of exposure estimates that are much greater than those estimates originally published. Temporal relationships within the study are not consistent with those of other studies. The dose-response relationship is strongly nonlinear. Other data suggest that the leukemogenic effect of benzene is nonlinear and may derive from a threshold toxicity.
AN OPERATION FOR THE RADICAL CURE OF PRE-MASSETERIC FISTULAE OF STENSON'S DUCT
Authors: G. Chubb
Journal: BMJ (1921)

PRE-MASSETERIC FISTULAE OP STENSOWS DUCT. TmBIt does happen, lhowever, that the blood culture is per- sistently returned as negative in certain cases of indis- putably infective endocarditis.The explanation for tllis is
Malignant tumor of brown fat in patient with Turner's syndrome.
Authors: W S Lowry, P B Halmos
Journal: BMJ (1967)

Though we showed a positive correlation between the resting levels of circulating F.D.P. and the plasminogen activator in normal subjects the relation was not highly significant.This indicates that the concentration of circulating F.D.P. is probably the end-result of a complex dynamic system which will include fibrin deposition and active fibrinolysis associated with fibrino- lytic inhibition.It cannot be assumed that the results of our study necessarily represent definite proof of continuous in-vivo intravascular coagulation and fibrinolysis as envisaged by Astrup, though the exercise and adrenaline studies are very suggestive.More information is required on the rate of excretion of circulating F.D.P. in physiological circumstances, for if the present con- cept of a half-life of approximately nine hours is substantiated (Sherry, 1965), then the resting values obtained in this study could merely represent the end-product of transient episodes of exercise or anxiety which occurred several hours before the blood was withdrawn.Furthermore, we have no proof that these F.D.P. are derived from intravascular deposits of fibrin, for it is possible that they may represent a by-product of minute damage and repair within the tissues.Further work on these problems is in progress. SummaryFrom 106 apparently healthy subjects 147 serum samples were assayed for their fibrin degradation product (F.D.P.) con- tent by the tanned red cell haemagglutination inhibition immunoassay technique.In 98 %O of these samples it was possible to detect a measurable quantity of F.D.P., the mean value being 4.9 ± 2.8 ttg./ml.There was no significant sex difference or a consistent change during the menstrual cycle.Further studies with the use of exercise and intravenous adrenaline were carried out in order to evaluate the significance of these findings in relation to the concept of an in-vivo dynamic equilibrium between coagulation and fibrinolysis.
Milk Shows Potential as CT Contrast Agent
Authors: Mike Mitka
Journal: JAMA (2007)

of these two bacteria may influence weight, the researchers performed biochemical and genomic analyses of the gut microbes in obese and lean mice. They found that the microbial genomes of the bacteria found in obese mice were rich in genes encoding enzymes that break down otherwise indigestible food. “Our results indicate that the obese microbiome has an increased capacity to harvest energy from the diet,” the authors wrote. Theyalso foundthat this traitcouldbe transferred, as germ-free mice receiving microbes fromthegutsofobesemiceexperiencedasignificantlygreater increase in totalbody fat (withoutany increase in foodconsumption) than those receiving microbes from lean mice. “These results identifythegutmicrobiotaasanadditional contributing factor to the pathophysiology of obesity,” the authors concluded. Therefore,gutmicrobialgenomesmight be considered as a set of genetic factors that, togetherwiththehostgenotypeand lifestyle, contribute to the development of obesity. Whilethefindingscouldinfluencehow researchersandcliniciansviewthecauses ofobesityandsuggest thatmanipulation of thegutmicrobialenvironmentmayofferanapproachto treatingobesity,many questions remain. For example, it is unclear whether microbial influences have a meaningful impact on body weight in the human population and are contributing to the current rise in the incidence ofobesity. Inobesemice, theeffectof“increasedcaloricintakeandreducedcaloric expenditureismanytimeslargerthanthe small difference in extraction that could beproducedbydifferences in themicrobiota,”wroteMatejBajzerandRandySeeley,PhD,of theUniversityofCincinnati, in Ohio, in an accompanying New and Viewsarticle (BajzerMandSeeleyR. Nature. 2006;444:1009-1010).
Combination Therapy with Montelukast and Antihistamines (desloratadine or Levocetirizine) Improves Quality of Life in Patients with Persistent Allergic Rhinitis: a Double Blind Placebo Controlled Study
Authors: M. Ciebiada, M. Górska–Ciebiada, L.M. DuBuske, P. Gorski
Journal: Journal of Allergy and Clinical Immunology (2006)
Acoustic Tumors, vol 1, Diagnosis; vol 2, Management
Authors: Edward Tarlov
Journal: JAMA (1980)

This important two-volume compendium of the experience of the Los Angeles Otologic Group deserves special attention. It is based on results with 500 acoustic neuromas that were surgically treated mainly by a translabyrinthine approach, from 1968 to 1975, with an operative mortality of 2.6%. Complete removal was accomplished in 85% of the large tumors. Complete facial paralysis followed in 21% of the large tumors and in 13% of the overall group. These are creditable results with the translabyrinthine approach, with which House and his group have had considerable experience. In 26 chapters the contributors have attempted to summarize current means of diagnosis in vol 1 and their views on the management of acoustic tumors in vol 2. Complete and up-to-date, the first is a timely volume. Early diagnosis, of course, influences the quality of result, and the diagnostic tests used for early detection of this lesion have been changing, bearing
Factors Influencing Gastroduodenal Mucosal Prostaglandin Concentrations: Roles of Smoking and Aging
Authors: Byron Oyer, Edward Lee, Mark Feldman
Journal: Annals of Internal Medicine (1992)

To evaluate behavioral, demographic, clinical, and histologic variables that independently influence gastroduodenal mucosal prostaglandin concentrations.Prospective study.A clinical research laboratory located in a Department of Veterans Affairs hospital.Fifty-two healthy adults who had no history of peptic ulcer disease and who were not receiving nonsteroidal anti-inflammatory drugs.Mucosal biopsy specimens were obtained endoscopically from the stomach (body and antrum) and the duodenum (bulb and postbulbar area). Mucosal extracts from each of these four regions were assessed by radioimmunoassay to determine prostaglandin E2 and prostaglandin F2 alpha concentrations. Specimens were also examined histologically for inflammation and the presence of Helicobacter pylori. A multivariate linear regression model was used to determine which behavioral, demographic, and histologic variables significantly and independently influenced gastroduodenal mucosal prostaglandin concentrations.Smoking and older age were independently associated with lower prostaglandin concentrations in all four mucosal regions (P = 0.0001 to P = 0.05). Compared with results in young nonsmokers, mucosal prostaglandin concentrations were reduced by 70% to 80% in older smokers. Gender, alcohol use, endoscopic appearance, dyspeptic symptoms, mucosal inflammation, and the presence of H. pylori had no consistent effect on prostaglandin content.Smoking and older age are associated with significantly reduced gastric and duodenal prostaglandin concentrations. These observations may help explain the predisposition to ulcer disease in smokers and older persons.
Customer exposure to MTBE, TAME, C6 alkyl methyl ethers, and benzene during gasoline refueling.
Authors: S Vainiotalo, Y Peltonen, A Ruonakangas, P Pfäffli
Journal: Environmental Health Perspectives (1999)

We studied customer exposure during refueling by collecting air samples from customers' breathing zone. The measurements were carried out during 4 days in summer 1996 at two Finnish self-service gasoline stations with "stage I" vapor recovery systems. The 95-RON (research octane number) gasoline contained approximately 2.7% methyl tert-butyl ether (MTBE), approximately 8.5% tert-amyl methyl ether (TAME), approximately 3.2% C6 alkyl methyl ethers (C6 AMEs), and 0.75% benzene. The individual exposure concentrations showed a wide log-normal distribution, with low exposures being the most frequent. In over 90% of the samples, the concentration of MTBE was higher (range &lt;0.02-51 mg/m3) than that of TAME. The MTBE values were well below the short-term (15 min) threshold limits set for occupational exposure (250-360 mg/m3). At station A, the geometric mean concentrations in individual samples were 3.9 mg/m3 MTBE and 2. 2 mg/m3 TAME. The corresponding values at station B were 2.4 and 1.7 mg/m3, respectively. The average refueling (sampling) time was 63 sec at station A and 74 sec at station B. No statistically significant difference was observed in customer exposures between the two service stations. The overall geometric means (n = 167) for an adjusted 1-min refueling time were 3.3 mg/m3 MTBE and 1.9 mg/m3 TAME. Each day an integrated breathing zone sample was also collected, corresponding to an arithmetic mean of 20-21 refuelings. The overall arithmetic mean concentrations in the integrated samples (n = 8) were 0.90 mg/m3 for benzene and 0.56 mg/m3 for C6 AMEs calculated as a group. Mean MTBE concentrations in ambient air (a stationary point in the middle of the pump island) were 0.16 mg/m3 for station A and 0.07 mg/m3 for station B. The mean ambient concentrations of TAME, C6 AMEs, and benzene were 0.031 mg/m3, approximately 0.005 mg/m3, and approximately 0.01 mg/m3, respectively, at both stations. The mean wind speed was 1.4 m/sec and mean air temperature was 21 degreesC. Of the gasoline refueled during the study, 75% was 95 grade and 25% was 98/99 grade, with an oxygenate (MTBE) content of 12.2%.
Disease Pathways and Novel Therapeutic Targets in Hypertrophic Cardiomyopathy
Authors: Houman Ashrafian, William J. McKenna, Hugh Watkins
Journal: Circulation Research (2011)

As described in earlier reviews in this series on the molecular basis of hypertrophic cardiomyopathy (HCM), HCM is one of the archetypal monogenic cardiovascular disorders to be understood at the molecular level. Twenty years after the discovery of the first HCM disease gene, genetic studies still confirm that HCM is principally a disease of the sarcomere. At the biophysical level, myofilament mutations generally enhance Ca 2+ sensitivity, maximal force production, and ATPase activity. These defects ultimately appear to converge on energy deficiency and altered Ca 2+ handling as major common paths leading to the anatomic (hypertrophy, myofiber disarray, and fibrosis) and functional features (pathological signaling and diastolic dysfunction) characteristic of HCM. In this review, we provide an account of the consequences of HCM mutations and describe how specifically targeting these molecular features has already yielded early promise for novel therapies for HCM. Although substantial efforts are still required to understand the molecular link between HCM mutations and their clinical consequences, HCM endures as an exemplar of how novel insights derived from molecular characterization of Mendelian disorders can inform the understanding of biological processes and translate into rational therapies.
TAT-apoptosis repressor with caspase recruitment domain protein transduction rescues mice from fulminant liver failure
Authors: Junfeng An, Christoph Harms, Gisela Lättig-Tünnemann, Gernot Sellge, Ana D. Mandić, Yann Malato, Arnd Heuser, Matthias Endres, Christian Trautwein, Stefan Donath
Journal: Hepatology (2012)

Acute liver failure (ALF) is associated with massive hepatocyte cell death and high mortality rates. Therapeutic approaches targeting hepatocyte injury in ALF are hampered by the activation of distinct stimulus-dependent pathways, mechanism of cell death, and a limited therapeutic window. The apoptosis repressor with caspase recruitment domain (ARC) is a recently discovered death repressor that inhibits both death receptor and mitochondrial apoptotic signaling. Here, we investigated the in vivo effects of ARC fused with the transduction domain of human immunodeficiency virus 1 (HIV-1) (TAT-ARC) on Fas- and tumor necrosis factor (TNF)-mediated murine models of fulminant liver failure. Treatment with TAT-ARC protein completely abrogated otherwise lethal liver failure induced by Fas-agonistic antibody (Jo2), concanavalin A (ConA), or D-galactosamine/lipopolysaccharide (GalN/LPS) administration. Importantly, survival of mice was even preserved when TAT-ARC therapy was initiated in a delayed manner after stimulation with Jo2, ConA, or GalN/LPS. ARC blocked hepatocyte apoptosis by directly interacting with members of the death-inducing signaling complex. TNF-mediated liver damage was inhibited by two independent mechanisms: inhibition of jun kinase (JNK)-mediated TNF-α expression and prevention of hepatocyte apoptosis by inhibition of both death receptor and mitochondrial death signaling. We identified JNK as a novel target of ARC. ARC's caspase recruitment domain (CARD) directly interacts with JNK1 and JNK2, which correlates with decreased JNK activation and JNK-dependent TNF-α production. Conclusion : This work suggests that ARC confers hepatoprotection upstream and at the hepatocyte level. The efficacy of TAT-ARC protein transduction in multiple murine models of ALF demonstrates its therapeutic potential for reversing liver failure. (HEPATOLOGY 2012)
Ischemic Electrocardiographic Changes After Truncal Vagotomy
Authors: Gregory J. Gallivan
Journal: JAMA (1970)

Preoperative and postoperative evaluation (including clinical cardiac status, electrocardiograms, and serum enzyme levels) of 106 patients undergoing transabdominal truncal vagotomy during a 17-month period produced evidence of ischemic ECG abnormalities. Although ischemic ECG changes have been reported in patients with subarachnoid hemorrhage, as well as in those with metabolic and gastrointestinal disorders, such findings, to our knowledge, have not been previously documented in vagotomized humans. A 9% occurrence of moderate to marked ischemia with prolonged QT interval exceeds fourfold the highest reported incidence of postoperative myocardial infarction. The ECG abnormalities were noted primarily one day after vagotomy, lasted one to several weeks, and were not accompanied by correlative clinical or serum enzyme level changes. All patients undergoing vagotomy should have ECGs performed preoperatively and postoperatively.
Myocardial Rubidium-82 Tissue Kinetics Assessed by Dynamic Positron Emission Tomography as a Marker of Myocardial Cell Membrane Integrity and Viability
Authors: Juergen vom Dahl, Otto Muzik, Edwin R. Wolfe, Christine Allman, Gary Hutchins, Markus Schwaiger
Journal: Circulation (1996)

Background Recent reports have demonstrated the clinical use of rubidium-82 chloride (Rb-82) in combination with positron emission tomography (PET) not only as a tracer of myocardial blood flow but also as a marker of cell membrane integrity using static imaging early and late after tracer injection. The purpose of this study was to compare myocardial Rb-82 kinetics assessed by dynamic PET imaging as a marker for tissue viability with regional fluorine-18 fluorodeoxyglucose (FDG) uptake in patients with coronary artery disease. Methods and Results Twenty-seven patients with angiographically proven coronary artery disease and 5 subjects with a low likelihood for coronary artery disease underwent dynamic PET imaging under resting conditions using Rb-82 and FDG. Both image sequences served as input data for a semiautomated regional analysis program. This program generated polar maps representing Rb-82 tissue half-life and FDG utilization assessed by Patlak’s approach. Myocardial tissue viability was visually determined from static Rb-82 and FDG images. Regions were categorized as normal, ischemically compromised, and scar tissue. Their coordinates were subsequently copied to the functional polar maps for further analyses. In normal subjects, Rb-82 tissue half-life was homogeneous throughout the left ventricle (90±11 seconds). In coronary patients, differences between Rb-82 tissue half-lives in normal and scar tissue were highly significant (95±10 and 57±15 seconds, respectively; P &lt;.0001). FDG uptake in these two tissue groups was 78±12% and 40±13%, respectively ( P &lt;.0001). Ischemically compromised tissue with reduced perfusion but maintained FDG uptake displayed an Rb-82 half-life of 75±9 seconds, indicating active cellular tracer retention, which was significantly different from scar tissue. Overall agreement of tissue categorization as either viable or scar was 86% between Rb-82 kinetics and FDG utilization. In a subgroup of 11 patients with all three tissue types within one image set, Rb-82 tissue half-life discriminated between normal, ischemic, and scar tissue (97±9, 75±9, and 60±15 seconds, respectively; P &lt;.01). Conclusions This study demonstrated a significant relationship between cell membrane integrity as assessed by dynamic Rb-82 PET imaging and myocardial glucose utilization as a marker for tissue viability. In regions with reduced perfusion, Rb-82 kinetics was different in compromised but metabolically active and irreversibly injured myocardium. The predictive value of this approach must be evaluated in follow-up studies.
Training doctors in the new English NHS: The real challenge to the medical profession
Authors: James Penston
Journal: BMJ (2006)

EDITOR—Hutchinson has done us all a favour.1 Her article—full of unfounded assumptions and opinion disguised as fact—merely draws attention to the poverty of the arguments of those promoting NHS reforms. Moreover, her case is poorly served by an excess of tiresome jargon. Apparently, if medical training is to assist the “cultural change,” we need to “role model …
Simvastatin as a Treatment for Pulmonary Hypertension Trial
Authors: M. R. Wilkins, O. Ali, W. Bradlow, J. Wharton, A. Taegtmeyer, C. J. Rhodes, H. A. Ghofrani, L. Howard, P. Nihoyannopoulos, R. H. Mohiaddin, J. S. R. Gibbs
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Rationale: In animal models of pulmonary hypertension, simvastatin has been shown to reduce pulmonary artery pressure and induce regression of associated right ventricular (RV) hypertrophy.Objectives: To assess the therapeutic value of simvastatin in patients with pulmonary arterial hypertension (PAH).Methods: Forty-two patients with PAH were randomized to receive either simvastatin (80 mg/d) or placebo in addition to current care for 6 months, and thereafter offered open-label simvastatin.The primary outcome was change in RV mass, assessed by cardiac magnetic resonance (CMR).Measurements and Main Results: At 6 months, RV mass decreased by 5.2 6 11 g in the statin group (P 5 0.045) and increased 3.9 6 14 g in the placebo group.The treatment effect was 29.1 g (P 5 0.028).N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels decreased significantly in the statin group (275 6 167 fmol/ml; P 5 0.02) but not the placebo group (49 6 224 fmol/ml; P 5 0.43; overall treatment effect 2124 fmol/ml; P 5 0.041).There were no significant changes in other outcome measures (including 6-minute walk test, cardiac index, and circulating cytokines).From 6 to 12 months, both RV mass and NT-proBNP increased toward baseline values in 16 patients on active treatment who continued with simvastatin but remained stable in 18 patients who switched from placebo to simvastatin.Two patients required a reduction in dose but not cessation of simvastatin.Conclusions: Simvastatin added to conventional therapy produces a small and transient early reduction in RV mass and NT-proBNP levels in patients with PAH, but this is not sustained over 12 months.Clinical trial registered with www.clinicaltrials.gov(NCT00180713).