tbuckley/cabot-search huggingface dataset:
Relationship Between Interleukin 6 and Mortality in Patients With Unstable Coronary Artery Disease
Authors: Eva Lindmark, Erik Diderholm, Lars Wallentin, Agneta Siegbahn
Journal: JAMA (2001)

Inflammatory activity is associated with high rates of long-term mortality in unstable coronary artery disease (CAD). Interleukin 6 (IL-6) induces C-reactive protein and fibrinogen, systemic markers of inflammation.To determine whether plasma levels of IL-6 are predictive of mortality and to evaluate the interaction of IL-6 levels with the effects of invasive vs noninvasive treatment strategies in unstable CAD patients.The prospective, randomized Fragmin and Fast Revascularisation During Instability in Coronary Artery Disease II trial, conducted among 3489 patients, 3269 of whom had plasma samples analyzed for IL-6 levels, with diagnosed unstable CAD (67% male; median age, 67 years) at 58 Scandinavian hospitals between June 1996 and August 1998.Patients were randomly assigned to receive either an early invasive (n = 1222) or a noninvasive treatment strategy (n = 1235). The latter group, as well as 666 patients with contraindications to invasive therapy, were further randomized to 90-day treatment with low-molecular-weight heparin (dalteparin, 5000-7500 IU twice per day; n = 1140) or placebo (n = 1127).Mortality at 6 and 12 months in the medically and interventionally randomized cohorts, respectively, in relation to IL-6 levels, measured at randomization.Plasma levels of IL-6 that were at least 5 ng/L compared with levels lower than 5 ng/L were associated with greatly increased mortality in the noninvasive group (7.9% vs 2.3%; relative risk [RR], 3.47; 95% confidence interval [CI], 1.94-6.21) and in the placebo-treated group (7.9% vs 2.5%; RR, 3.19; 95% CI, 1.77-5.74). The association remained significant after adjustment for most established risk indicators. An early invasive treatment strategy strongly reduced 12-month mortality among those with elevated IL-6 levels (5.1% absolute reduction; P =.004) whereas mortality was not reduced among patients without elevated IL-6 concentrations. Those taking dalteparin with elevated IL-6 levels experienced lower 6-month mortality than those who did not take dalteparin (3.5% absolute reduction; P =.08).Circulating IL-6 is a strong independent marker of increased mortality in unstable CAD and identifies patients who benefit most from a strategy of early invasive management.
Genetics of Risk Factors for Melanoma: an Adult Twin Study of Nevi and Freckles
Authors: V Bataille, H Snieder, A J MacGregor, P Sasieni, T D Spector
Journal: JNCI Journal of the National Cancer Institute (2000)

We sought by use of an adult twin study to investigate the relative contribution of genetic and environmental effects on the expression of nevi and freckles, which are known risk factors for melanoma, and to determine if age and sun exposure influence the heritability of nevi.Total nevus and freckle counts were conducted on 127 monozygotic twin pairs and 323 dizygotic twin pairs. Intraclass correlations were calculated by use of analysis of variance. Model-fitting analyses were performed to quantify the genetic and environmental components of the variance for nevus and freckle counts.The intraclass correlation for total nevus counts was.83 in monozygotic pairs compared with.51 in dizygotic pairs. Quantitative genetic analyses showed that the contribution of genetic factors on nevi expression varied according to age. For twins less than 45 years old, the additive genetic variance on total nevus count was 36% (95% confidence interval [CI] = 0.8%-63%), with 38% (95% CI = 14%-61%) and 26% (95% CI = 16%-42%) of the remaining variance attributed to common environment and unique environmental effects, respectively. In twins aged 45 years or older, common environmental effects on total nevus count became negligible, with the additive genetic variance increasing to 84% (95% CI = 77%-88%). Body site was also found to affect the heritability estimates for nevus counts, with a statistically significant difference between sun-exposed and sun-protected sites. The polychoric correlation (i.e., the correlation in liability within twins for more than two categories) for total freckle counts was.91 in monozygotic twin pairs compared with.54 in dizygotic twin pairs. Additive genetic effects explained 91% (95% CI = 86%-94%) of the variance in freckle counts.The contribution of genetic factors on the variance for total nevus counts increased with age, and sun exposure appears to influence the expression of nevi. The results of this study highlight the need to take into account the age and site of nevus counts for future genetic linkage or association studies in the search for new melanoma genes.
Reproducibility of oxidative stress biomarkers in breath condensate: are they reliable?
Authors: I. Rahman
Journal: European Respiratory Journal (2004)

In this issue of the European Respiratory Journal , Van Hoydonck et al. 1 report a study about the reproducibility of oxidative stress biomarkers, such as hydrogen peroxide (H2O2) and 8‐isoprostane (a member of the F2‐isoprostane class) in nonconcentrated exhaled breath condensate (EBC) obtained from healthy male smokers. The aim of their study was to identify whether these biomarkers could reproducibly be measured on different days of collection to enable identification of a susceptible population to lung diseases and monitoring of disease severity. The authors collected the EBC samples at three time points within 1 week (day 0, day 3 or 4, day 7) from each healthy smoker. Their major findings were: 1) H2O2 and 8‐isoprostane were detected in only 47% and 36% of all EBC samples, respectively; 2) only three of 12 smokers had detectable 8‐isoprostane concentrations on all three occasions (mean 4.6 pg·mL−1; range 3.9–7.7 pg·mL−1), whereas H2O2 was not detected on all three occasions in any of the smokers within 1 week; and 3) 8‐isoprostane and H2O2 concentrations were below the limit of detection in many samples (<3.9 pg·mL−1 for 8‐isoprostane and 0.31 µM forH2O2). They concluded that the levels of H2O2 and 8‐isoprostane could not be reproducibly assessed in the EBCof healthy smokers because of their low concentration and/or the lack of sensitivity/specificity of the available assays. The other major factors that may affect the reproducibility would include intra- and inter-individual variability, sampling time and variability in dilution of respiratory droplets by water vapour 2 …
Another ten stories in antiviral drug discovery (part C): “Old” and “new” antivirals, strategies, and perspectives
Authors: Erik De Clercq
Journal: Medicinal Research Reviews (2009)

The ten stories told here deal with (i) ribavirin as an inhibitor of IMP dehydrogenase and (ii) ribavirin, in combination with pegylated interferon, as the present "standard of care" for hepatitis C; (iii) S-adenosylhomocysteine hydrolase inhibitors as antiviral agents; (iv) new adamantadine derivatives for the treatment of influenza A virus infections; (v) 5-substituted 2'-deoxyuridines (i.e. IDU, TFT) for the treatment of herpes simplex virus (HSV) infections; (vi) acyclic guanosine analogues (e.g. acyclovir) for the treatment of HSV infections; (vii) OMP decarboxylase inhibitors (i.e. pyrazofurin) and CTP synthetase inhibitors (i.e. cyclopentenylcytosine) as possible antiviral agents; (viii) the future of cidofovir (and alkoxyalkyl esters thereof) and ST-246 as potential antipoxvirus agents; (ix) the two decade journey from tivirapine to rilpivirine in the ultimate therapy of HIV infections; and (x) the extension of the therapeutic application of tenofovir disoproxil fumarate (Viread) to the treatment of hepatitis B virus infection, in addition to HIV infection.
Etanercept-induced pleuropericardial lupus-like syndrome
Authors: I. Porfyridis, I. Kalomenidis, I. Psallidas, G. Stratakos, C. Roussos, T. Vassilakopoulos, G. T. Stathopoulos
Journal: European Respiratory Journal (2009)

Etanercept-induced pleuropericardial lupus-like syndromeTo the Editors:Tumour necrosis factor (TNF)-a is currently being targeted in autoimmune joint diseases, including rheumatoid arthritis (RA) and spondylarthropathies [1, 2].Widespread use of anti-TNF-a therapies (e.g.etanercept) has unveiled a spectrum of adverse effects, including infection [3] and a systemic lupus erythematosus (SLE)-like syndrome [4].The latter appears to be biologically based on perturbations in TNF-a-controlled homeostasis of interferon (IFN)-a [5], and is betrayed by seroconversion of SLE markers [6].With interest, we read the occurrence of pleural effusions associated with anti-TNF-a agents [7].We encountered a patient with RA taking etanercept, who developed alternating pleural effusions.We obtained measurements that suggested that a lupus-like syndrome and not a common drug reaction precipitated these pleural effusions.A 50-yr-old Greek ex-smoker presented with acute-onset fever (39uC), malaise and right-sided pleuritic pain.She had longstanding seropositive RA and was started on 25 mg bi-weekly subcutaneous etanercept 3 yrs earlier (when tuberculin skin test was 0 mm and chest radiograph negative).Her prior serology was: negative antinuclear antibody (ANA) and antidouble stranded (ds)DNA antibody and a rheumatoid factor (RF) of 35 U?L -1 .On admission, a free-floating right-sided pleural effusion (fig.1a, b andc), haemolytic anaemia (haematocrit 30%, positive indirect Coombs' test), leukocytopaenia (4,000 cells?mm -3 ) and microscopic haematuria (100 red cells?mm - , no casts) were found.Serum RF and ANA were 65 U?L -1 and 1:640, respectively; a tuberculin skin test was 12 mm, while thoracentesis yielded an exudate (pH 7.22; glucose 68 mg?dL -1 , lactate dehydrogenase (LDH) 704 U?L -1 , protein 4.6 g?dL -1 , 6400 nucleated cells?mm -3 , 80% neutrophils, 10% lymphocytes and 10% eosinophils) meeting all Light's criteria.Pleural fluid adenosine deaminase was low (22 U?L -1 ) and smears, cultures and cytology were negative, while thoracoscopy failed due to markedly thickened pleura.Etanercept was discontinued and parenteral piperacillin/ tazobactam and ciprofloxacin and oral isoniazide, rifampin, ethambutol and pyrazinamide were started.Despite treatment, fever and the effusion persisted, resolving spontaneously after 40 days.The pleurisy relapsed, 20 days later, on the left side accompanied by a small pericardial effusion (fig.1d, e andf).Thoracentesis revealed an exudate (pH 7.42, glucose 111 mg?dL -1 , LDH 210 U?L -1 , protein 3.3 g?dL -1 , 2,600 cells?mm -3 , 80% lymphocytes, 20% neutrophils) with low adenosine deaminase (21 U?L -1 ) and negative smears, cultures and cytology.Repeat serology was: RF 68 U?L -1 , ANA 1:1280, anti-dsDNA 9 U?L -1 , and anti-histone antibodies 3.7 U?L -1 .Pleural fluid
Jaundice as a presentation of heart failure
Authors: R van Lingen
Journal: Journal of the Royal Society of Medicine (2005)

On rare occasions the first manifestation of heart disease is jaundice, caused by passive congestion of the liver or acute ischaemic hepatitis. We looked for this presentation retrospectively in 661 patients referred over fifty-six months to a ‘jaundice hotline’ (rapid access) service. The protocol included a full clinical history, examination and abdominal ultrasound. Those with no evidence of biliary obstruction had a non-invasive liver screen for parenchymal liver disease and those with suspected heart disease had an electrocardiogram, chest X-ray and echocardiogram. 8 patients (1.2%), bilirubin 31–79 μmol/L, mean 46 μmol/L, had a primary cardiac cause for their jaundice. All had dyspnoea, an increased cardiothoracic ratio on chest X-ray and an abnormal electrocardiogram. The jugular venous pressure was raised in the 3 in whom it was recorded. In 6 patients the jaundice was attributed to hepatic congestion and in 2 to ischaemic hepatitis. All patients had severe cardiac dysfunction. Jaundice due to heart disease tends to be mild, and a key feature is breathlessness. The most common mechanism is hepatic venous congestion; ischaemic hepatitis is suggested by a high aminotransferase.
The effect of tiotropium on exacerbations and airflow in patients with COPD
Authors: D. Dusser, M-L. Bravo, P. Iacono
Journal: European Respiratory Journal (2006)

This randomised, double-blind, parallel-group, 1-yr study compared the effect of tiotropium 18 µg once daily (n = 500) and placebo (n = 510) on exacerbations, associated health resource use (HRU) and airflow limitation in chronic obstructive pulmonary disease (COPD) patients. The mean± sd number of exacerbations during the past year was 2.14±1.40, the mean weekly morning peak expiratory flow (PEF) was 259.6±96.1 L·min −1 and the mean forced expiratory volume in one second (FEV 1 ) was 1.37±0.45 L. Tiotropium significantly delayed the time to first exacerbation by ∼100 days, reduced the proportion of patients experiencing more than one exacerbation by 17%, and decreased the number of exacerbations by 35% and exacerbation days by 37% versus placebo. Tiotropium also decreased HRU versus placebo, as indicated by the significant reductions in the use of concomitant respiratory medications, antibiotics and oral steroids, and the number of unscheduled physician contacts. Mean weekly morning PEF improved significantly with tiotropium versus placebo from week 1 until the end of the study. At the end of the study, tiotropium significantly improved trough (pre-dose) FEV 1 , forced vital capacity, slow vital capacity and inspiratory capacity versus placebo. In conclusion, tiotropium reduced exacerbations and associated health resource use, and improved airflow over 1 yr in chronic obstructive pulmonary disease patients.
Heidelberg Center Works on Viruses, Genes, and a Swifter Computer
Authors: C. Vanchieri
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Heidelberg Center Works on Viruses, Genes, and a Swifter Computer Get access Cori Vanchieri Cori Vanchieri Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 21, 3 November 1993, Pages 1715–1717, https://doi.org/10.1093/jnci/85.21.1715 Published: 03 November 1993
Efficacy and safety of albendazole plus ivermectin, albendazole plus mebendazole, albendazole plus oxantel pamoate, and mebendazole alone against Trichuris trichiura and concomitant soil-transmitted helminth infections: a four-arm, randomised controlled trial
Authors: Benjamin Speich, Said M Ali, Shaali M Ame, Isaac I Bogoch, Rainer Alles, Jörg Huwyler, Marco Albonico, Jan Hattendorf, Jürg Utzinger, Jennifer Keiser
Journal: The Lancet Infectious Diseases (2015)
Effects of sympathetic tone on vagally induced phasic changes in heart rate and atrioventricular node conduction in the anesthetized dog.
Authors: J J Salata, R M Gill, R F Gilmour, D P Zipes
Journal: Circulation Research (1986)

We examined the effects of stellate ganglia stimulation on the phase-dependent chronotropic and dromotropic responses to brief vagal bursts in open-chest anesthetized dogs. Stellate stimulation affected the phasic vagal effects on heart rate by shortening the latent period, shifting the phase at which maximum decrease in heart rate occurred to earlier phases, and reducing the maximum decrease in heart rate. These effects were due primarily to an increase in the basic heart rate. No significant sympathetic-parasympathetic interaction occurred for heart rate, indicating that accentuated antagonism did not occur with brief vagal bursts. Stellate stimulation primarily decreased the amplitude of the phasic vagal effects on atrioventricular nodal conduction, regardless of the underlying heart rate, and a significant sympathetic-parasympathetic interaction was associated with this effect. The peak of the phase-dependent vagal effects on heart rate and atrioventricular nodal conduction were phase-shifted with one another. From these findings, we postulate the small changes in sympathetic tone might shift the predominant phase-dependent vagal effect from one on heart rate to one on atrioventricular nodal conduction. Furthermore, our results suggest that dynamic vagal control of heart rate and atrioventricular node conduction involves both phase-dependent and phase-independent factors. Sympathetic activity appears to affect only the phase-independent factor(s) in the control of heart rate, whereas it affects both phase-dependent and phase-independent factors in the control of atrioventricular node conduction.
Alemtuzumab Treatment of Intermediate-1 Myelodysplasia Patients Is Associated With Sustained Improvement in Blood Counts and Cytogenetic Remissions
Authors: Elaine M. Sloand, Matthew J. Olnes, Aarthie Shenoy, Barbara Weinstein, Carol Boss, Kelsey Loeliger, Colin O. Wu, Kenneth More, A. John Barrett, Phillip Scheinberg, Neal S. Young
Journal: Journal of Clinical Oncology (2010)

Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis and progression to leukemia. Clinical and experimental evidence suggests an immune-mediated pathophysiology in some patients, in whom immunosuppressive therapy (IST) with horse antithymocyte globulin (h-ATG) and cyclosporine (CsA) can be effective. Because of the toxicities associated with h-ATG/CsA, we investigated an alternative regimen with alemtuzumab in MDS.We conducted a nonrandomized, off-label, pilot, phase I/II study of alemtuzumab monotherapy in patients with MDS who were judged likely to respond to IST based on the following criteria: HLA-DR15-negative patients whose age plus the number of months of RBC transfusion dependence (RCTD) was less than 58; and HLA-DR15-positive patients whose age plus RCTD was less than 72. In total, 121 patients with MDS were screened, of whom 32 met eligibility criteria to receive alemtuzumab 10 mg/d intravenously for 10 days. Primary end points were hematologic responses at 3, 6, and 12 months after alemtuzumab.Seventeen (77%) of 22 evaluable intermediate-1 patients and four (57%) of seven evaluable intermediate-2 patients responded to treatment with a median time to response of 3 months. Four of seven evaluable responders with cytogenetic abnormalities before treatment had normal cytogenetics by 1 year after treatment. Five (56%) of nine responding patients evaluable at 12 months had normal blood counts, and seven (78%) of nine patients were transfusion independent.Alemtuzumab is safe and active in MDS and may be an attractive alternative to ATG in selected patients likely to respond to IST.
Toxicology of the fluoroalkenes: Review and research needs
Authors: J. Wesley Clayton
Journal: Environmental Health Perspectives (1977)

In this review of the published literature on the toxicology of fluoroalkenes several features emerge and research needs are evident. The fluoroalkenes vary widely in acute inhalation toxicity. Those, such as perfluoroisobutylene, PFIB, the most highly toxic member, attacks the pulmonary epithelium of rats eventuating in edema and death after a delay of about one day. Other fluoroalkenes, such as hexafluoropropylene (HFP) or chlorotrifluoroethylene (CTFE), also cause pulmonary injury but at lower concentrations produce concentration dependent changes in the renal concentrating mechanism of the rat. Changes in the CNS of rats and rabbits have also been reported for CTFE. CTFE, in repeated exposures, has produced blood pressure changes in dogs, CNS effects and changes in the erythropoietic system. This variety of responses indicates the need for investigation. Chronic effects have not been sufficiently studied for PFIB and HFP. Thus pointing up the desirability for study. Mechanisms of action research for fluoroalkenes is an important area of need. While several ideas have been suggested, there are no data to support them. The nucleophilic sensitivity of the fluoroalkenes and the potential carcinogenic effects stemming therefrom suggests a need field for investigation. We also can readily perceive the needs for the evaluation of effects on reproduction (including mutagenesis and teratogenesis), metabolism pulmonary functions, cellular function and structure. Epidemiologic studies on occupationally exposed populations are desirable in order to adequately define human health hazard from these fluorocarbons.
Further care home scandals like Winterbourne are likely without action, warn campaigners
Authors: A. O'Dowd
Journal: BMJ (2012)

Abuse scandals at care homes for people with learning disabilities similar to that at Winterbourne View are likely to recur if the government fails to act, campaigners have warned.

The warning comes at the same time as a multiagency report described as painting a “horrifying picture of abuse” called for more investment in community based care for people with learning disabilities.

The focus of both reports is the case of the former Winterbourne View private hospital in south Gloucestershire, owned and operated by Castlebeck Limited.

In May last year the BBC’s Panorama programme broadcast undercover filming of staff at the privately run assessment and treatment centre as they physically abused residents.1 2 …
MicroRNA and Mechanisms of Impaired Angiogenesis in Diabetes Mellitus
Authors: Nicholas J. Leeper, John P. Cooke
Journal: Circulation (2011)

D iabetes mellitus impairs physiological angiogenesis, which may be manifested as nonhealing foot ulcers or refractory angina.Multiple molecular mechanisms have been proposed.Hyperglycemia induces the generation of reactive oxygen species that cause endothelial derangements, 1 including the reduced synthesis 2 and accelerated degradation 3 of endothelium-derived nitric oxide (NO).The bioactivity of NO is critical for angiogenic processes such as the survival, proliferation, and migration of endothelial cells. 4The impairment in NO bioactivity may also explain in part the reduced expression of a major angiogenic cytokine, vascular endothelial growth factor (VEGF), in hyperglycemic states, because NO and VEGF have a reinforcing and reciprocal relationship. 5Glucose intolerance also reduces the number and function of bone marrow-derived endothelial progenitor cells, 6 circulating cells that participate in the angiogenic response.In addition to generating reactive oxygen species, hyperglycemia may impair cytoprotective mechanisms against oxidative stress.In particular, the thioredoxins play a key role in angiogenic processes by maintaining endothelial redox homeostasis, with favorable effects on protein folding, activity of reductive and metabolic enzymes, energy utilization, and transcription factor activity. 7Emerging evidence indicates that hyperglycemia upsets this cytoprotective mechanism by increasing the expression of the endogenous inhibitor thioredoxin-interacting protein (TXNIP). Article see p 282Is it possible that these and other disparate mechanisms for the impaired angiogenesis in diabetes mellitus have a common genomic basis?This question logically follows from the work of Caporali and colleagues in the current issue of Circulation. 8They have discovered a novel genomic mechanism for hyperglycemia-induced impairment of angiogenesis, ie, the increased expression of a specific microRNA (miRNA) that appears to orchestrate a pathophysiological response in diabetes mellitus.