tbuckley/cabot-search huggingface dataset:
Markers of Endothelial Dysfunction and Inflammation in Type 1 Diabetic Patients With or Without Diabetic Nephropathy Followed for 10 Years
Authors: Anne Sofie Astrup, Lise Tarnow, Lotte Pietraszek, Casper G. Schalkwijk, Coen D.A. Stehouwer, Hans-Henrik Parving, Peter Rossing
Journal: Diabetes Care (2008)

OBJECTIVE—We evaluated the association of biomarkers of endothelial dysfunction and inflammation with all-cause mortality and cardiovascular mortality and morbidity and decline in glomerular filtration rate (GFR) in type 1 diabetic patients. RESEARCH DESIGN AND METHODS—We prospectively followed 199 type 1 diabetic patients with diabetic nephropathy and 192 patients with persistent normoalbuminuria. Biomarkers were measured at baseline. RESULTS—We constructed two Z scores: the mean inflammatory Z score combined C-reactive protein, interleukin-6, soluble intercellular adhesion molecule (sICAM-1), and secreted phospholipase A2 and the mean Z score for endothelial dysfunction combined soluble vascular cell adhesion molecule 1, plasminogen activator inhibitor-1, and sICAM-1. The mean Z score of inflammatory biomarkers was associated with mortality and the combined end point in patients with diabetic nephropathy after multivariate adjustment (hazard ratio 1.7 [95% CI 1.1–2.6]; P = 0.025 and 1.5 [1.1–2.2]; P = 0.017). The mean Z score for endothelial dysfunction biomarkers was associated with mortality in a model adjusting for age and sex in patients with diabetic nephropathy (1.6 [1.0–2.3]; P = 0.031). The mean Z score for endothelial dysfunction correlated with decline in GFR (r = −0.243; P = 0.001); the correlation persisted after multivariate adjustment (coefficient −1.38 [95% CI −2.27 to −0.50]; P = 0.002). CONCLUSIONS—Mean Z scores of inflammatory biomarkers are significantly associated with all-cause mortality and cardiovascular morbidity and mortality in patients with nephropathy after multivariate adjustment. These data suggest that the high risk of cardiovascular disease in type 1 diabetes may be explained in part by inflammatory activity. Mean Z score of endothelial dysfunction correlated after multivariate adjustment with the rate of decline in GFR.
Hemoglobin A1c as a Screen for Previously Undiagnosed Prediabetes and Diabetes in an Acute-Care Setting
Authors: Robert A. Silverman, Urvi Thakker, Tovah Ellman, Ivan Wong, Kelly Smith, Kazuhiko Ito, Kirsten Graff
Journal: Diabetes Care (2011)

Hemoglobin A(1c) (HbA(1c)) is recommended for identifying diabetes and prediabetes. Because HbA(1c) does not fluctuate with recent eating or acute illness, it can be measured in a variety of clinical settings. Although outpatient studies identified HbA(1c)-screening cutoff values for diabetes and prediabetes, HbA(1c)-screening thresholds have not been determined for acute-care settings. Using follow-up fasting blood glucose (FBG) and the 2-h oral glucose tolerance test (OGTT) as the criterion gold standard, we determined optimal HbA(1c)-screening cutoffs for undiagnosed dysglycemia in the emergency department setting.This was a prospective observational study of adults aged ≥18 years with no known history of hyperglycemia presenting to an emergency department with acute illness. Outpatient FBS and 2-h OGTT were performed after recovery from the acute illness, resulting in diagnostic categorizations of prediabetes, diabetes, and dysglycemia (prediabetes or diabetes). Optimal cutoffs were determined and performance data identified for cut points.A total of 618 patients were included, with a mean age of 49.7 (±14.9) years and mean HbA(1c) of 5.68% (±0.86). On the basis of an OGTT, the prevalence of previously undiagnosed prediabetes and diabetes was 31.9 and 10.5%, respectively. The optimal HbA(1c)-screening cutoff for prediabetes was 5.7% (area under the curve [AUC] = 0.659, sensitivity = 55%, and specificity = 71%), for dysglycemia 5.8% (AUC = 0.717, sensitivity = 57%, and specificity = 79%), and for diabetes 6.0% (AUC = 0.868, sensitivity = 77%, and specificity = 87%).We identified HbA(1c) cut points to screen for prediabetes and diabetes in an emergency department adult population. The values coincide with published outpatient study findings and suggest that an emergency department visit provides an opportunity for HbA(1c)-based dysglycemia screening.
Impaired mucosal immune responses in interleukin 4-targeted mice.
Authors: M Vajdy, M H Kosco-Vilbois, M Kopf, G Köhler, N Lycke
Journal: The Journal of Experimental Medicine (1995)

Interleukin 4-targeted (IL-4-/-) mice are defective in T helper (Th)2 cytokine production as determined after nematode infection. As Th2 cells appear to be selectively induced by oral immunization we investigated the ability of IL-4-/- mice to respond to perorally administered antigen. We found that IL-4-/- mice failed to respond to soluble protein antigens given perorally together with cholera toxin (CT) as a mucosal adjuvant. In contrast to wild-type mice no or poor anti-keyhole limpet hemocyanin (KLH) or anti-ovalbumin (OVA) B cell responses were observed in gut lamina propria, spleen, or serum of IL-4-/- mice after oral immunization. In addition, mucosal immunization failed to stimulate antigen-specific T cell responses in these mice. The lack of responsiveness was specific for mucosal administration of antigen and was not seen after intravenous injections with antigen and CT-adjuvant. The systemic adjuvant effect of CT was not impaired in IL-4-/- mice as evidenced by the strong enhancement of anti-KLH responses after intravenous immunization with KLH plus CT as opposed to KLH alone. However, CT as an immunogen, in contrast to KLH or OVA, stimulated significant mucosal and systemic immune responses in IL-4-/- mice after oral immunization. Both serum and intestinal IgA anti-CT antibodies were demonstrable in IL-4-/- mice as well as in wild-type mice. Total IgA levels in gut lavage and in serum of immunized IL-4-/- mice were of similar magnitude as in wild-type mice, suggesting that the ability of naive B cells to undergo isotype switch-differentiation from IgM to IgA in IL-4-/- mice did not appear to be impaired. Immunohistochemical analysis of Peyer's patches demonstrated a complete inability to form germinal centers in IL-4-/- mice in contrast to wild-type mice. Our data suggest that IL-4-/- mice are unable to respond to oral/mucosal immunization due to a failure to stimulate antigen-specific cells required to induce germinal center reactions in the Peyer's patches. Our findings demonstrate that IL-4 and probably functional Th2 cells are required for induction of gut mucosal antibody responses.
Letter by Lumley et al Regarding Article, “Arterial Pulse Wave Dynamics After Percutaneous Aortic Valve Replacement: Fall in Coronary Diastolic Suction With Increasing Heart Rate as a Basis for Angina Symptoms in Aortic Stenosis”
Authors: Matthew Lumley, Kalpa De Silva, Divaka Perera
Journal: Circulation (2012)

Percutaneous Aortic Valve Replacement: Fall in Coronary Diastolic Suction With Increasing Heart Rate as a Basis for Angina Symptoms in Aortic Stenosis" 1 with great interest and would like to commend the authors for producing novel coronary wave intensity data in the aortic stenosis population.The microcirculatory decompression (suction) wave was reported to increase in proportion to the severity of aortic stenosis (rϭ0.59,Pϭ0.05), a change opposite to that which was reported previously by the same authors in patients with left ventricular hypertrophy. 2The severity of aortic stenosis in determining this relationship was judged by peak aortic gradient.The 11 patients included in the study had an aortic valve area of 0.6Ϯ0.1 cm 2 , suggesting a relatively homogeneous population with respect to aortic valve area.In contrast, a broad range of peak valve gradients was observed (81Ϯ24 mm Hg), which would be consistent with a range of left ventricular (LV) systolic function.It is therefore possible that the peak aortic gradient is a surrogate measure of LV function in this cohort, most of whom had an aortic valve area Ͻ0.8 cm 2 (2 SD above the mean).In this context, the magnitude of the microcirculatory decompression wave may, in fact, be a reflection of LV systolic and diastolic function rather than aortic stenosis per se.The authors state in their article that the extent of microcirculatory compression during systole is related to the rate and magnitude of decompression (recoil) in diastole.Hence, compared to those with impaired LV function, patients with preserved function would be expected to have greater systolic microcirculatory compression and consequently more pronounced recoil, leading to an increased microcirculatory decompression-associated wave energy.Given that simultaneous pressure and Doppler velocity were measured in the left main coronary artery rather than the left anterior descending or circumflex vessel, it would be surprising if septal and posterior wall thickening (individually or collectively) were found to correlate with the amplitude of the microcirculatory decompression wave.On the other hand, it would be interesting to assess the relationship between the left main coronary artery backward decom-(Circulation.
Effect of Bitopertin, a Glycine Reuptake Inhibitor, on Negative Symptoms of Schizophrenia
Authors: Daniel Umbricht, Daniela Alberati, Meret Martin-Facklam, Edilio Borroni, Eriene A. Youssef, Michael Ostland, Tanya L. Wallace, Frédéric Knoflach, Ernest Dorflinger, Joseph G. Wettstein, Alexander Bausch, George Garibaldi, Luca Santarelli
Journal: JAMA Psychiatry (2014)

In schizophrenia, the severity of negative symptoms is a key predictor of long-term disability. Deficient signaling through the N-methyl-D-aspartate receptor is hypothesized to underlie many signs and symptoms associated with schizophrenia in particular negative symptoms. Glycine acts as an N-methyl-D-aspartate receptor coagonist. Blockade of the glycine transporter type 1 to inhibit glycine reuptake and elevate synaptic glycine concentrations represents an effective strategy to enhance N-methyl-D-aspartate receptor transmission.To determine the efficacy and safety of bitopertin (RG1678), a glycine reuptake inhibitor, in patients with schizophrenia and predominant negative symptoms who were stable while taking an antipsychotic treatment.This randomized, double-blind, placebo-controlled, phase 2 proof-of-concept trial involved 323 patients with schizophrenia and predominant negative symptoms across 66 sites worldwide.Bitopertin (10, 30, or 60 mg/d) or placebo added to standard antipsychotic therapy for a treatment duration of 8 weeks.Change from baseline in the Positive and Negative Syndrome Scale negative factor score.In the per-protocol population, 8 weeks of treatment with bitopertin was associated with a significant reduction of negative symptoms in the 10-mg/d (mean [SE] reduction in negative symptoms score, -25% [2%]; P = .049) and 30-mg/d (mean [SE], -25% [2%]; P = .03) bitopertin groups, a significantly higher response rate and a trend toward improved functioning in the 10-mg/d group when compared with placebo (mean [SE], -19% [2%]). Results reached trend-level significance in the intent-to-treat population. Estimates of bitopertin binding to glycine transporter type 1 showed that low to medium levels of occupancy yielded optimal efficacy in patients, consistent with findings in preclinical assays.Bitopertin-mediated glycine reuptake inhibition may represent a novel treatment option for schizophrenia, with the potential to address negative symptoms.clinicaltrials.gov Identifier: NCT00616798.
Diversification, not use, of the immunoglobulin VH gene repertoire is restricted in DiGeorge syndrome.
Authors: R N Haire, R D Buell, R T Litman, Y Ohta, S M Fu, T Honjo, F Matsuda, M de la Morena, J Carro, R A Good
Journal: The Journal of Experimental Medicine (1993)

Immunoglobulin (Ig) genes were isolated from unamplified conventional as well as polymerase chain reaction-generated cDNA libraries constructed from the peripheral blood cells of a patient with complete DiGeorge syndrome. Comparison of the sequences of 36 heavy chain clones to the recently expanded database of human VH genes permitted identification of the germline VH genes that are expressed in this patient as well as placement of 19 of these genes in a partially resolved 0.8-mb region of the human VH locus. The pattern of VH gene use does not resemble the fetal (early) repertoire. However, as in the fetal repertoire, there are a number of cDNAs derived from germline genes that previously have been identified as autoantibodies. Two D mu sequences also were identified, as was another sequence resulting from a unique recombination event linking JH to an unidentified sequence containing a recombination signal sequence-like heptamer. All of the DiGeorge cDNAs are closely related to germline VH genes, showing little or no evidence of somatic mutation. In contrast, comparably selected IgM VH sequences derived from normal adult and age-matched human libraries, and from a second DiGeorge syndrome patient in whom the degree of thymic dysfunction is much less severe, exhibit considerable evidence of somatic mutation. The absence of somatic mutation is consistent with the atypical development of functional antibody responses associated with complete DiGeorge syndrome and implicates a role for T cells in the generation of diversity within the B cell repertoire.
Chronic obstructive pulmonary disease: towards pharmacogenetics
Authors: Alice M Wood, See Ling Tan, Robert A Stockley
Journal: Genome Medicine (2009)

Chronic obstructive pulmonary disease (COPD) is a common problem worldwide, and it is recognized that the term encompasses overlapping sub-phenotypes of disease. The development of a sub-phenotype may be determined in part by an individual's genetics, which in turn may determine response to treatment. A growing understanding of the genetic factors that predispose to COPD and its sub-phenotypes and the pathophysiology of the condition is now leading to the suggestion of individualized therapy based on the patients' clinical phenotype and genotype. Pharmacogenetics is the study of variations in treatment response according to genotype and is perhaps the next direction for genetic research in COPD. Here, we consider how knowledge of the pathophysiology and genetic risk factors for COPD may inform future management strategies for affected individuals.
Foam cells after treatment with hydrocolloid dressings
Authors: M.S. Agren, L. Franzen
Journal: British Journal of Dermatology (1991)

Journal Article Foam cells after treatment with hydrocolloid dressings Get access M.S. ÅGren, M.S. ÅGren Department of Pathology, Faculty of Health Sciences, Linkoping, Sweden Search for other works by this author on: Oxford Academic Google Scholar L. Franzén L. Franzén Department of Pathology, Faculty of Health Sciences, Linkoping, Sweden Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 125, Issue 2, 1 August 1991, Page 193, https://doi.org/10.1111/j.1365-2133.1991.tb06076.x Published: 01 August 1991
Running a domiciliary nebuliser service
Authors: R. S. Wilson, M. F. Muers
Journal: Thorax (1997)

A nebuliser service should be provided locally, according to local needs. It should be centralised and administered by a designated consultant or consultants and written guidelines should be provided for medical and para-medical staff. The service should: (1) provide compressor/nebuliser units suitable for the prescribed treatment, (2) provide a system for equipment replacement, repair and maintenance, and (3) show patients how to use the equipment and give them comprehensive written instructions.
Hospital-acquired Infection with Vancomycin-resistant <i>Enterococcus faecium</i> Transmitted by Electronic Thermometers
Authors: Lawrence L. Livornese, Susan Dias, Carol Samel, Barbara Romanowski, Shirley Taylor, Phyllis May, Peter Pitsakis, Gail Woods, Donald Kaye, Matthew E. Levison, Caroline C. Johnson
Journal: Annals of Internal Medicine (1992)

Objectives: To describe an epidemic of vancomycinresistant Enterococcus faecium causing bacteremia and bacteriuria, to identify the source of infection, to delineate risk factors associated with acquisition of the organism, and to determine antibiotic sensitivities for the organism. Design: Investigation of an epidemic, including a case-control study. Setting: Medical-surgical intensive care unit and ward in a university medical center. Patients: Nine patients infected or colonized with vancomycin-resistant Enterococcus faecium and 20 noninfected controls. Measurements: Clinical data, environmental surveillance cultures, and in-vitro microbiologic studies. Results: Colonization or infection by vancomycinresistant E. faecium was associated with an increased duration of treatment with ceftazidime, 13.2 compared with 4.6 days, and a greater number of nonisolated days of hospitalization in the intensive care unit, 19.9 compared with 6.4 days for infected and noninfected patients, respectively (P < 0.05). Environmental surveillance cultures recovered the organism repeatedly from the rectal probe handles of three electronic thermometers used exclusively on nonisolated patients in the intensive care unit. Restriction endonuclease analysis of plasmid DNA showed that all clinical and environmental isolates were identical. Infection control measures, including isolation of colonized or infected patients and emoval of the rectal thermometer probes suspected to be responsible for transmission, resulted in termination of the outbreak. In-vitro, time-kill studies showed that the combination of ciprofloxacin, rifampin, and gentamicin resulted in bactericidal activity against the organism. Conclusions: This nosocomial outbreak of infection due to a highly vancomycin-resistant strain of Enterococcus is the first epidemic in which an electronic thermometer has been implicated as the vehicle of transmission for an infectious agent.
Effects of airway calibre on lung delivery of nebulised salbutamol
Authors: B. J. Lipworth, D. J. Clark
Journal: Thorax (1997)

A study was undertaken to test the hypothesis that airway calibre may alter lung deposition and therefore lung bioavailability of inhaled drugs as a result of narrowed airways reducing peripheral drug delivery. This was evaluated using the early lung absorption profile of salbutamol over the first 30 minutes after inhalation.Three groups were compared: (1) 10 normal subjects with mean forced expiratory volume in one second (FEV1) 109.5% predicted and mid forced expiratory flow (FEF25-75) 103.0%, (2) 10 mild asthmatic patients with FEV1 102.0% and FEF25-75 82.6%, and (3) 10 severe asthmatic patients with FEV1 49.2% and FEF25-75 27.5% predicted. Each subject had one study visit where a single dose of nebulised salbutamol was given (40 micrograms/kg) via a Ventstream nebuliser with mouthpiece followed by mouth rinsing. Plasma salbutamol levels were measured at five, 10, 20, and 30 minutes after the end of nebulisation with calculation of maximal (Cmax) and average (Cav) concentration over 0-30 minutes. Systemic beta 2 responses (plasma potassium, tremor and heart rate) and airway responses (FEV1, FEF25-75) were measured before and 30 minutes after nebulisation.For Cav over 0-30 minutes the severe asthmatic patients had a lower plasma salbutamol concentration (1.31 ng/ml) than either the normal subjects (2.40 ng/ml) or those with mild asthma (2.45 ng/ml): normal subjects versus severe asthmatics 95% CI 0.30 to 1.88, mild versus severe asthmatics 95% CI 0.07 to 2.21. Airway responses as delta FEF25-75 were lower in the severe asthmatic subjects (0.30 l/s) than in either the normal subjects (0.69 l/s) or those with mild asthma (0.74 l/s): normal subjects versus severe asthmatic subjects 95% CI 0.09 to 0.88, mild versus severe asthmatics 95% CI 0.04 to 0.93. Values for delta log tremor also showed attenuated responses in those with severe asthma (1.22 mg2/s) compared with normal subjects (2.00 mg2/s) or those with mild asthma (2.02 mg2/s): normal subjects versus those with severe asthma 95% CI -0.02 to 3.30, mild versus severe asthmatics 95% CI 0.02 to 3.30.These results show that baseline airway calibre significantly alters the early lung absorption profile of salbutamol in patients with severe asthma. This may have implications in terms of optimising dose and delivery of inhaled beta 2 agonists in these patients.
Transmission of <i>Mycobacterium tuberculosis</i> to Contacts of HIV-infected Tuberculosis Patients
Authors: ANNA C. C. CARVALHO, KATHRYN DeRIEMER, ZOELETE B. NUNES, MARNEILI MARTINS, MARIO COMELLI, ALESSANDRA MARINONI, AFRNIO L. KRITSKI
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

We assessed the infectiousness of human immunodeficiency virus (HIV)-seropositive and HIV-seronegative individuals with pulmonary tuberculosis (TB) in a prospective cohort study. We enrolled, evaluated, and followed 104 close contacts of HIV-seropositive pulmonary TB patients and 256 close contacts of HIV-seronegative pulmonary TB patients using a standardized questionnaire, symptom review, chest radiograph, HIV serology, and tuberculin skin testing (TST). Contacts were followed for ⩾ 12 mo. TB infection at enrollment was 27% (28/104) among contacts of HIV-seropositive TB patients and 35% (90/256) among contacts of HIV-seronegative TB patients (odds ratio [OR] = 0.68, 95% confidence interval [CI] 0.41 to 1.12; p = 0.130). TST conversion occurred in 21% (42/ 204) of subjects; 8% (5/63) of contacts of HIV-seropositive index cases and 26% (37/141) of contacts of HIV-seronegative index cases (OR = 0.24, 95% CI 0.09 to 0.65; p = 0.003). TB was diagnosed in nine contacts; eight were contacts of HIV-seronegative index cases. HIV seropositivity in the index case was independently associated with a lower risk of TB infection among contacts, even among household contacts younger than 15 yr of age. Contacts of HIV-seropositive persons with pulmonary TB were less likely to have a positive TST response at 1 yr of follow-up than contacts of HIV-seronegative persons.
Misoprostol inhibits gastric mucosal release of endogenous prostaglandin E2 and thromboxane B2 in healthy volunteers.
Authors: A Mertz-Nielsen, O Eskerod, K Bukhave, J Rask-Madsen
Journal: Gut (1995)

Prostaglandin analogues of the E-series theoretically offer the ideal antiulcer drugs. Peptic ulcer healing with prostaglandin analogues is, however, no better than would be predicted from their ability to inhibit gastric acid secretion and they are less effective than histamine H2 receptor antagonists in preventing ulcer relapse. It could be that prostaglandin analogues inhibit gastric mucosal synthesis or release of endogenous eicosanoids, thereby abrogating their own effects. This study, therefore, examined how a single therapeutic dose (200 micrograms) of misoprostol, a synthetic analogue of prostaglandin E1, influences gastric mucosal release of endogenous prostaglandin E2 (PGE2), thromboxane B2 (TXB2), and chemotactic leukotriene B4 (LTB4) during basal conditions and in response to gastric luminal acidification (0.1 M HCl; 5 ml/min for 10 minutes). Nine healthy volunteers were studied in a single blind, cross over design. In each subject misoprostol or placebo was instilled in randomised order into the stomach, which was subsequently perfused with isotonic mannitol. Misoprostol significantly decreased basal as well as acid stimulated output of PGE2 and TXB2, without affecting output of LTB4. These data show that misoprostol inhibits gastric mucosal synthesis of prostanoids. Decreased concentrations, or even a changed profile, of native eicosanoids modulating the release of inflammatory mediators from immune cells might explain why prostaglandin analogues have a comparatively poor clinical performance in ulcer healing and prevention.