tbuckley/cabot-search huggingface dataset:
Eligibility for Lipid-Lowering Drug Therapy in Primary Prevention
Authors: Antonio M. Gotto, Lewis H. Kuller
Journal: Circulation (2002)

May 2001, the Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program issued revised guidelines for diagnosing and treating high blood cholesterol. 1These guidelines represent a major advance in risk assessment.They were preceded by the ATP I guidelines (1988), which focused on primary prevention of coronary heart disease (CHD), and by the ATP II guidelines (1993), 2 which discussed primary and secondary prevention.In the ATP II and ATP III guidelines, low-density lipoprotein cholesterol (LDL-C) is the primary target of risk-reduction therapy. See p 152The ATP II recommendations were based on epidemiological, preclinical, and incomplete clinical trial evidence.Within a few years after their publication, the results of 5 large-scale trials of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (ie, "statins") were reported.Two of these (West of Scotland Coronary Prevention Study [WOSCOPS] and Air Force/Texas Coronary Atherosclerosis Prevention Study [AFCAPS/TexCAPS]) were primaryprevention trials. 3,46][7] Based on these epic trials and other laboratory, epidemiological, and clinical evidence, the ATP III guidelines were developed (Tables 1 and2). Clinical Trial EvidenceThe major statin trials and resulting meta-analyses provided a firm foundation for a truly evidence-based approach to guideline revision.Involving 5 different populations with widely varying absolute risk levels and using 3 different statins (simvastatin, pravastatin, lovastatin), they produced remarkably consistent reductions of 24% to 37% in relative risk for major CHD events.In WOSCOPS, 6595 men with moderate hypercholesterolemia (LDL-Cϭ192 mg/dLϮSD) received pravastatin 40 mg/day for up to 4.9 years.Results indicated a 31% relative decrease in major CHD events, with a 26% reduction in LDL-C levels.AFCAPS/TexCAPS evaluated lovastatin 20 to 40 mg/day for up to 5.2 years in 6605 generally healthy men and women with average LDL-C levels (150 mg/dLϮSD) and below-average levels of highdensity lipoprotein cholesterol (HDL-C) (Ͻ36 mg/dL in men, Ͻ40 mg/dL in women, ϮSD).There was a 37% relative reduction in major CHD events and a 25% decrease in LDL-C levels.Just 17% of participants would have qualified for drug therapy under the ATP II criteria then guiding clinical practice.This indicates the merit of reducing LDL-C levels to targets below those recommended for primary prevention.
Antibiotic Therapy for Vibrio vulnificus Infection
Authors: J. Glenn Morris
Journal: JAMA (1985)

<h3>To the Editor.—</h3> We read with interest your recent review of current research on<i>Vibrio vulnificus</i>.<sup>1</sup>However, we are concerned that there are inadequate clinical data on antibiotic efficacy to support fully the recommendation that "physicians presented with a case of<i>V vulnificus</i>infection should use penicillin or tetracycline, since the bacterium is susceptible to most antibiotics.<sup>1</sup>These recommendations appear to be based on in vitro sensitivity data. In the absence of clinical confirmation of efficacy, such in vitro data can be misleading: to take a recent, well-publicized example, methicillin-resistant<i>Staphylococcus aureus</i>is sensitive in vitro to cephalosporins, but patients have no clinical response to these drugs. Unfortunately, the available clinical data on<i>V vulnificus</i>are sketchy, with the one published report of a series of cases noting only that "there was little difference between patients who died and those who survived in the types of antibiotics used."<sup>2</sup>
Prolonged Corrected QT Interval Is Associated With Acute and Chronic Hyperinsulinemia in Nondiabetic Subjects
Authors: Tomi Laitinen, Ilkka Vauhkonen, Leo Niskanen, Juha Hartikainen, Matti Uusitupa, Markku Laakso
Journal: Diabetes Care (2003)

Foussas et al. (1) observed that in type 2 diabetic patients intensive insulin treatment during acute coronary syndrome was associated with decreased QT dispersion, while the heart rate–corrected QT (QTc) interval tended to increase. This may be of concern because QTc prolongation is known to increase the risk of ventricular arrhythmia and sudden death. However, prognosis of diabetic patients with acute myocardial infarction can be improved by treatment of hyperglycemia with insulin (2).

Apart from myocardial ischemia and infarction, different factors in diabetic patients contribute to the duration of QTc interval, such as insulin resistance, glucose …
Prevalence of anti-neutrophil antibody in primary sclerosing cholangitis and ulcerative colitis using an alkaline phosphatase technique.
Authors: S K Lo, K A Fleming, R W Chapman
Journal: Gut (1992)

The detection of a nuclear anti-neutrophil antibody in patients with primary sclerosing cholangitis (PSC), using an immunoperoxidase technique, was recently reported by us. Subsequently, detection of a cytoplasmic anti-neutrophil antibody was reported by others, using a two stage procedure of enzyme linked immunosorbent assay followed by an immunofluorescent method. Detection of cytoplasmic anti-neutrophil antibody in PSC, which, in contrast to that two stage procedure, uses a simple one step immuno-alkaline phosphatase method is now reported. Normal human neutrophils were cytocentrifuged, ethanol fixed, and then incubated with coded patients' sera. Rabbit anti-human immunoglobulin conjugated with alkaline phosphatase was used to detect the bound antibody. Fast red was used to visualise the reaction. Twenty three of 30 (77%) PSC patients showed positive granular cytoplasmic staining (with some perinuclear accentuation) with a network of cytoplasmic filaments. Fifteen of 45 (33%) ulcerative colitis patients and 1 of 3 chronic active hepatitis patients showed similar staining. Thirty five of 152 patients with ulcerative colitis, chronic active hepatitis, and a variety of other liver diseases showed a different pattern of cytoplasmic labelling, with no surrounding filaments. Seventy nine patients, including seven PSC patients and 33 normal subjects, were negative. In comparison, 86% of PSC patients, 57% of patients with primary biliary cirrhosis, 50% of normal subjects, and well over 60% of patients with ulcerative colitis, Crohn's disease, alcoholic liver disease, and chronic active hepatitis were positive using the one step immunofluorescent method. This method is more specific for PSC than those described in recent reports and may be of diagnostic importance.
REGULATORY MECHANISMS IN CELL-MEDIATED IMMUNE RESPONSES
Authors: Susan Solliday Rich, Robert R. Rich
Journal: The Journal of Experimental Medicine (1974)

Regulatory effects of alloantigen-activated thymus-derived lymphocytes in mixed lymphocyte reactions have been demonstrated. Mice were injected into foot pads with allogeneic spleen cells; 4 days following sensitization spleen or regional lymph node cells from these animals were treated with mitomycin C and incorporated into MLR as regulator populations syngeneic to the responder cell type. Activated spleen cells suppressed MLR responses 60-90% whereas activated lymph node cells from the same animals enhanced MLR responses. Suppression by activated spleen cells was not due to cytotoxic effects nor to altered kinetics of the proliferative response. Studies of splenic suppressor cell generation in vivo revealed peak activity four days after alloantigen stimulation with no activity demonstrable at 7 days or at later times. Suppressor cell activity was abrogated by treatment with anti-thetaC3H serum and complement, and was not alloantigen specific.
Ca2+-transport ATPases of vascular smooth muscle.
Authors: J A Eggermont, M Vrolix, L Raeymaekers, F Wuytack, R Casteels
Journal: Circulation Research (1988)

To characterize the Ca2+-transport properties of the plasma membrane and of the endoplasmic reticulum of bovine pulmonary artery, membrane vesicles are subfractionated by a procedure of density-gradient centrifugation that takes advantage of the selective effect of digitonin on the density of plasma-membrane vesicles. The obtained endoplasmic-reticulum fraction contains hardly any plasma-membrane vesicles, whereas the plasma-membrane fraction is still contaminated by a substantial amount of endoplasmic-reticulum vesicles. An adenosine 5'-triphosphate (ATP) energized Ca2+-transport system and a Ca2+-stimulated ATPase activity are present in both subcellular fractions. The Ca2+ transport by the plasma membrane is catalyzed by a (Ca2+,Mg2+)-ATPase of Mr 130,000. It binds calmodulin and it has a low steady-state phosphoprotein intermediate level. The endoplasmic-reticulum vesicles contain a Ca2+-transport ATPase of Mr 100,000 that is characterized by a high steady-state phosphointermediate level. It is antigenically related to the Ca2+-pump protein of cardiac sarcoplasmic reticulum. Phospholamban, the regulatory protein of the Ca2+-transport enzyme of cardiac sarcoplasmic reticulum, is also present in the endoplasmic reticulum of the pulmonary artery. A comparison of these fractions with the previously characterized fractions from porcine gastric smooth muscle reveals important differences in the basal Mg2-ATPase activity, in the ratio of the (Ca2+,Mg2+)-ATPase of the plasmalemma to that of the endoplasmic reticulum, and in the ratio of the (Na+,K+)-ATPase activity to the plasmalemmal (Ca2+,Mg2+)-ATPase activity. These differences can be ascribed in part to the species and in part to the tissue. These data suggest that in the bovine pulmonary artery the Ca2+ extrusion via the ATP-dependent Ca2+ pump may have a less predominant role, and that the Ca2+ uptake by the endoplasmic reticulum, and possibly also the Ca2+ extrusion via the Na+-Ca2+ exchanger could be more important in this tissue than in the porcine stomach.
Improved Exercise Performance Following Lung Volume Reduction Surgery for Emphysema
Authors: GARY T. FERGUSON, ENRIQUE FERNANDEZ, MARTIN R. ZAMORA, MARVIN POMERANTZ, JOHN BUCHHOLZ, BARRY J. MAKE
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Lung volume reduction surgery (LVRS) for emphysema has been suggested to improve patient lung function and activity. The short-term impact of LVRS on exercise performance was evaluated using maximal and submaximal steady-state exercise testing in 27 patients with severe hypoxemic chronic obstructive pulmonary disease (COPD), along with measurements of patient function, dyspnea, and quality of life. LVRS significantly improved exercise performance, due to ventilatory improvements associated with increased ventilatory reserve, enhanced tidal volume recruitment, and improved alveolar ventilation. Preoperative measurements of ventilatory reserve and dead space ventilation during exercise testing were closely associated with improved exercise performance. Improvements in patient dyspnea, walk distances, and quality of life also occurred following LVRS and were associated with improvements in exercise performance. Surgical mortality from LVRS was low (4%), but short-term all-cause mortality was increased (19%). Short-term mortality was associated with reduced expiratory muscle strength and markedly elevated dead space ventilation. We conclude that LVRS produces significant improvements in exercise performance, dyspnea, and quality of life in selected patients with COPD. Physiologic prediction of patients most likely to survive for an extended period and have significant benefit following LVRS may also be possible.
β-Cell Autoimmunity in Pediatric Celiac Disease: The Case for Routine Screening?
Authors: Giuseppe d'Annunzio, Alessandro Giannattasio, Elena Poggi, Emanuela Castellano, Angela Calvi, Angela Pistorio, Arrigo Barabino, Renata Lorini
Journal: Diabetes Care (2008)

To evaluate the prevalence of beta-cell autoimmunity and the usefulness of a type 1 diabetes screening in patients with celiac disease.We measured GAD antibodies (GADAs), insulinoma-associated protein 2 antigens (IA-2As), and insulin autoantibodies (IAAs) in 188 young Italian patients with celiac disease (66 male [35.1%]). Mean age at celiac disease diagnosis was 5.4 years (0.5-17.1), and mean celiac disease duration was 4.2 years (0-28.8). Celiac disease was diagnosed by jejunal biopsy after positivity for endomysial and tissue transglutaminase antibody was confirmed.GADAs were positive in seven patients (3.7%), and IA-2As were positive in two patients. IAAs were negative in all cases. Metabolic evaluation was normal, and no patients developed diabetes during follow-up. There was no significant association among beta-cell autoimmunity and sex, age, pubertal stage, family history, or coexistence of other autoimmune disorders; compliance to a gluten-free diet was confirmed.Our results showed a low prevalence of beta-cell autoimmunity and do not support a precocious screening for beta-cell autoimmunity in young celiac disease patients.
Beyond statin therapy: a review of the management of residual risk in diabetes mellitus
Authors: Eoin P Judge, D Phelan, Donal O'Shea
Journal: Journal of the Royal Society of Medicine (2010)

Summary Total cholesterol and low-density lipoprotein (LDL) cholesterol exhibit an independent, strong, continuous correlation with cardiovascular events. The effectiveness of hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) in the treatment and prevention of atherosclerosis is well-established. However, despite the lowering of LDL targets and the increased use of statins, patients with type 2 diabetes mellitus (DM) continue to experience a higher proportion of adverse coronary artery disease events. This is as a result of an atherogenic dyslipidaemia, characterized by low levels of high-density lipoprotein and elevated plasma triglyceride concentrations, often with high levels of cholesterol-rich remnant particles. This article will review dyslipidaemia and its role in DM, and will discuss available treatment modalities that address residual cardiovascular risk in this disease.
Postoperative Radiation Therapy Is Associated With Improved Overall Survival in Incompletely Resected Stage II and III Non–Small-Cell Lung Cancer
Authors: Elyn H. Wang, Christopher D. Corso, Charles E. Rutter, Henry S. Park, Aileen B. Chen, Anthony W. Kim, Lynn D. Wilson, Roy H. Decker, James Byunghoon Yu
Journal: Journal of Clinical Oncology (2015)

Purpose To review trends in the use of postoperative radiotherapy (PORT) for stage II and III incompletely resected non–small-cell lung cancer (NSCLC) and evaluate the association between PORT and survival in such patients. Patients and Methods We identified patients with pathologic stage N0-2, overall American Joint Committee on Cancer stage II or III NSCLC within the National Cancer Data Base who had undergone a lobectomy or pneumonectomy with positive surgical margins. Only patients coded as receiving external-beam PORT at 50 to 74 Gy or observation were included. To account for perioperative mortality, we excluded patients who survived less than 4 months after diagnosis. Multivariable logistic regression was used to determine factors associated with PORT receipt. Cox proportional hazards regression was performed for multivariable analyses of overall survival. Results Among 3,395 included patients, 1,207 (35.6%) received PORT. Predictors for the use of PORT among this patient population included age less than 60 years, treatment in a nonacademic facility, earlier year of diagnosis, decreased travel distance, lower nodal stage, and chemotherapy receipt. On multivariable analysis adjusting for demographic and clinicopathologic covariates, PORT (hazard ratio, 0.80; 95% CI, 0.70 to 092) was associated with improved survival. Subset analysis by nodal stage showed that PORT improved survival across all nodal stages. Conclusion PORT is associated with improved overall survival in patients with incompletely resected stage II or III N0-2 NSCLC. The use of PORT for this population in more recent years has been declining. In the absence of randomized trials evaluating PORT utilization for this patient population, our findings strongly support the delivery of PORT in patients with incompletely resected NSCLC.
High Constitutive Glucocorticoid Receptor β in Human Neutrophils Enables Them to Reduce Their Spontaneous Rate of Cell Death in Response to Corticosteroids
Authors: Ian Strickland, Kevin Kisich, Pia J. Hauk, Alessandra Vottero, George P. Chrousos, Dwight J. Klemm, Donald Y.M. Leung
Journal: The Journal of Experimental Medicine (2001)

Neutrophils are markedly less sensitive to glucocorticoids than T cells, making it difficult to control inflammation in neutrophil-mediated diseases. Development of new antiinflammatory strategies for such diseases would be aided by an understanding of mechanisms underlying differential steroid responsiveness. Two protein isoforms of the human glucocorticoid receptor (GR) exist, GRalpha and GRbeta, which arise from alternative splicing of the GR pre-mRNA primary transcripts. GRbeta does not bind glucocorticoids and is an inhibitor of GRalpha activity. Relative amounts of these two GRs can therefore determine the level of glucocorticoid sensitivity. In this study, human neutrophils and peripheral blood mononuclear cells (PBMCs) were studied to determine the relative amounts of each GR isoform. The mean fluorescence intensity (MFI) using immunofluorescence analysis for GRalpha was 475 +/- 62 and 985 +/- 107 for PBMCs and neutrophils, respectively. For GRbeta, the MFI was 350 +/- 60 and 1,389 +/- 143 for PBMCs and neutrophils, respectively (P < 0.05). After interleukin (IL)-8 stimulation of neutrophils, there was a statistically significant increase in intensity of GRbeta staining to 2,497 +/- 140 (P < 0.05). No change in GRalpha expression was observed. This inversion of the GRalpha/GRbeta ratio in human neutrophils compared with PBMCs was confirmed by quantitative Western analysis. Increased GRbeta mRNA expression in neutrophils at baseline, and after IL-8 exposure, was observed using RNA dot blot analysis. Increased levels of GRalpha/GRbeta heterodimers were found in neutrophils as compared with PBMCs using coimmunoprecipitation/Western analysis. Transfection of mouse neutrophils, which do not contain GRbeta, resulted in a significant reduction in the rate of cell death when treated with dexamethasone.We conclude that high constitutive expression of GRbeta by human neutrophils may provide a mechanism by which these cells escape glucocorticoid-induced cell death. Moreover, upregulation of this GR by proinflammatory cytokines such as IL-8 further enhances their survival in the presence of glucocorticoids during inflammation.
Efficacy and safety of a new combination of calcipotriol and betamethasone dipropionate (once or twice daily) compared to calcipotriol (twice daily) in the treatment of psoriasis vulgaris: a randomized, double-blind, vehicle-controlled clinical trial
Authors: L. Guenther, F. Cambazard, P.C.M. Van De Kerkhof, E. Snellman, K. Kragballe, A.C. Chu, E. Tegner, A. Garcia-Diez, J. Springborg
Journal: British Journal of Dermatology (2002)

Summary Background Calcipotriol and betamethasone dipropionate are both widely used, effective treatments for psoriasis. Vitamin D analogues and topical corticosteroids have different mechanisms of action in the treatment of psoriasis. A new vehicle has been developed in order to contain both calcipotriol (50 µg g−1) and betamethasone dipropionate (0·5 mg g−1) in an ointment form. By using calcipotriol and a corticosteroid together, greater efficacy may be achieved than by using either compound alone. Objectives The present study was conducted in order to compare the clinical efficacy and safety of the combined ointment formulation used once daily with the vehicle ointment used twice daily, calcipotriol ointment used twice daily and the combined formulation used twice daily in psoriasis vulgaris. Methods This was an international, multicentre, prospective, randomized, double-blind, vehicle-controlled, parallel group, 4-week study in patients with psoriasis vulgaris amenable to topical treatment. Patients were randomized to one of four treatment groups: combined formulation once daily, combined formulation twice daily, calcipotriol twice daily or vehicle twice daily. Efficacy and safety were assessed. Results There was no statistically significant difference in the mean percentage change in the Psoriasis Area and Severity Index (PASI) from baseline to end of treatment between the two combined formulation groups, but the difference in PASI reduction was significantly higher in the combined formulation groups (68·6% once daily, 73·8% twice daily) than in both the twice daily calcipotriol group (58·8%) and the vehicle group (26·6%). Safety data showed the frequency of adverse events to be less in the combined formulation groups than in both the calcipotriol group and the vehicle group. The proportion of patients with lesional/perilesional adverse reactions was less in the combined formulation groups and vehicle group than in the calcipotriol group (9·9% combined formulation once daily, 10·6% combined formulation twice daily, 19·8% calcipotriol, 12·5% vehicle). Conclusions No statistically significant nor clinically relevant difference in efficacy was seen between the combined formulation used once daily and twice daily. When compared to vehicle ointment or calcipotriol ointment alone, the combined formulation was shown to be clearly more efficacious.
Does traffic noise influence respiratory mortality?
Authors: Aurelio Tobías, Alberto Recio, Julio Díaz, Cristina Linares
Journal: European Respiratory Journal (2014)

To the Editor: 

Over the last decade, several studies have investigated the association between noise levels, primarily due to road traffic in large cities, and pathologies not related to either traditional hearing impairments or sleep disorders. These pathologies are mainly hypertension and cardiovascular, connective system and respiratory diseases [1]. Their impact on public health has been assessed in time series studies, indicating a traffic noise effect on both cardiovascular and respiratory hospital admissions rates similar to that attributed to air pollutants [2]. In addition, a recent study has shown an association of noise levels with cardiovascular mortality [3]. The description of the physiopathological mechanisms involved in this association reveal an actual impact of current road traffic noise levels on health [1]. Others question this because of the high correlation between traffic noise and air pollution [4], although a previous study in our setting showed an independent association between noise and cardiovascular mortality from the effect of the primary chemical air pollutants [5]. However, the effect of noise on respiratory mortality has not …