tbuckley/cabot-search huggingface dataset:
Sequence variation in the guillemot (Alcidae: Cepphus) mitochondrial control region and its nuclear homolog
Authors: M. G. Kidd, V. L. Friesen
Journal: Molecular Biology and Evolution (1998)

We describe sequence variation in the mitochondrial control region and its nuclear homolog in three species and seven subspecies of guillemots (Cepphus spp.). Nuclear homologs of the 5' end of the control region were found in all individuals. Nuclear sequences were approximately 50% divergent from their mitochondrial counterparts and formed a distinct phylogenetic clade; the mitochondrial-nuclear introgression event must have predated the radiation of Cepphus. As in other vertebrates, the guillemot control region has a relatively conserved central block flanked by hypervariable 5' and 3' ends. Mean pairwise interspecific divergence values among control regions were lower than those in other birds. All individuals were heteroplasmic for the number of simple tandem nucleotide repeats (A(n)C) at the 3' end of the control region. Phylogenetic analyses suggest that black guillemots are basal to pigeon and spectacled guillemots, but evolutionary relationships among subspecies remain unresolved, possibly due to incomplete lineage sorting. Describing molecular variation in nuclear homologs of mitochondrial genes is of general interest in phylogenetics because, if undetected, the homologs may confound interpretations of mitochondrial phylogenies.
Phase III trial of dacarbazine versus dacarbazine with interferon alpha-2b versus dacarbazine with tamoxifen versus dacarbazine with interferon alpha-2b and tamoxifen in patients with metastatic malignant melanoma: an Eastern Cooperative Oncology Group study.
Authors: C I Falkson, J Ibrahim, J M Kirkwood, A S Coates, M B Atkins, R H Blum
Journal: Journal of Clinical Oncology (1998)

PURPOSE To investigate the response rate, time to treatment failure (TTF), overall survival, and toxicity in patients with metastatic melanoma treated with dacarbazine alone, dacarbazine plus interferon (IFN), dacarbazine plus tamoxifen (TMX), or dacarbazine plus IFN plus TMX. MATERIALS AND METHODS Two hundred seventy-one patients (258 were eligible) were randomized in a 2 x 2 factorial design to receive one of the above treatments. The trial was designed to detect a 50% improvement in survival with 83% power. RESULTS Nine complete (CRs) and 18 partial responses (PRs) were observed in the patients who received treatments that contained IFN compared with four CRs and 18 PRs in the patients who received treatments that did not contain IFN. Five CRs and 20 PRs occurred in patients treated with TMX compared with eight CRs and 16 PRs in those treated without TMX. Response differences were nonsignificant. The overall median TTF was 2.6 months, and the overall median survival was 8.9 months. There was no significant difference in TTF or survival among any of the different treatments. Poor performance status (PS), hepatic metastases, and weight loss were significant adverse prognostic factors. Twenty-three patients had a TTF greater than 20 months, and these durable responses were evenly distributed among the treatment arms. Significantly more severe and life-threatening toxic events occurred with treatments that contained IFN. CONCLUSION Neither IFN, TMX, nor the combination significantly improved the response rate, TTF, or survival when added to dacarbazine, but IFN significantly increased toxicity.
Cerebral metabolic effects of exogenous lactate supplementation on the injured human brain
Authors: Pierre Bouzat, Nathalie Sala, Tamarah Suys, Jean-Baptiste Zerlauth, Pedro Marques-Vidal, François Feihl, Jocelyne Bloch, Mahmoud Messerer, Marc Levivier, Reto Meuli, Pierre J. Magistretti, Mauro Oddo
Journal: Intensive Care Medicine (2014)
Enhanced neutrophil response in chronic obstructive pulmonary disease
Authors: A Noguera
Journal: Thorax (2001)

Background-Neutrophils are likely to play a major role in the inflammatory response seen in chronic obstructive pulmonary disease (COPD).This study sought to address the hypothesis that an enhanced neutrophil response to proinflammatory agents in COPD may contribute to their recruitment and activation in the lungs.Methods-Circulating neutrophils were obtained from 10 patients with COPD, eight long term smokers with normal lung function, and eight healthy never smoking controls.The in vitro production of reactive oxygen species (ROS) was measured by the NADPH oxidase method (respiratory burst) and the surface expression of several adhesion molecules (Mac-1, LFA-1 and L-selectin) was measured by flow cytometry.Measurements were obtained under basal conditions and after stimulation with phorbol myristate acetate (PMA) and tumour necrosis factor alpha (TNF ). mRNA levels of p22-phox (a subunit of NADPH oxidase) and Mac-1 (CD11b) were also determined by reverse transcriptase polymerase chain reaction (RT-PCR).Results-Patients with COPD showed enhanced respiratory burst compared with smokers with normal lung function, both under basal conditions (mean (SE) fluorescence intensity (MFI) 15.1 (0.5) v 11.6 (0.5); mean diVerence -3.4 (95% CI of the diVerence -5.1 to -1.8), p<0.01) and after PMA stimulation (MFI 210 (7) v 133 (10); mean diVerence -77 (95% CI of the diVerence -102 to -52), p<0.01).Mac-1 surface expression was also enhanced in patients with COPD, both under basal conditions (MFI 91 (5) v 45 (3); mean diVerence -46 (95% CI of the diVerence -61 to -31), p<0.001) and after stimulation with TNF (MFI 340 (15) v 263 (11); mean diVerence -77 (95% CI of the diVerence -119 to -34), p=0.001).These diVerences were also apparent when patients with COPD were compared with non-smokers (p<0.05).The mRNA levels of p22-phox and Mac-1 (CD11b) were similar in patients with COPD and smokers with normal lung function, suggesting that the observed differences were due to post-transcriptional regulation.Conclusions-These results demonstrate an enhanced neutrophil response to proinflammatory agents in patients with COPD which may contribute to their enhanced recruitment and activation in the lungs of these patients.These findings support those of other studies which have indicated that the neutrophil is likely to play a major role in the pathogenesis of this disease.
Prediction of the Clinical Course of Chronic Obstructive Pulmonary Disease, Using the New GOLD Classification
Authors: Peter Lange, Jacob Louis Marott, Jørgen Vestbo, Kim Rose Olsen, Truls Sylvan Ingebrigtsen, Morten Dahl, Børge Grønne Nordestgaard
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

The new Global Initiative for Obstructive Lung Disease (GOLD) stratification of chronic obstructive pulmonary disease (COPD) into categories A, B, C, and D is based on symptoms, level of lung function, and history of exacerbations.To investigate the abilities of this stratification to predict the clinical course of COPD.Two similar population studies were performed in an area of Copenhagen including 6,628 individuals with COPD.The patients were monitored for an average period of 4.3 years regarding COPD exacerbations, hospital admissions, and mortality. The percentages of individuals experiencing a COPD exacerbation during the first year of observation were 2.2% in group A, 5.8% in group B, 25.1% in group C, and 28.6% in group D. One- and 3-year mortality rates were 0.6 and 3.8%, respectively, in group A, 3.0 and 10.6% in group B, 0.7 and 8.2% in group C, and 3.4 and 20.1% in group D. Groups B and D, characterized by a higher degree of dyspnea than groups A and C, had five to eight times higher mortality from cardiovascular disease and cancer than did groups A and C.The new stratification performs well by identifying individuals at risk of exacerbations. Surprisingly, subgroup B, characterized by more severe dyspnea, had significantly poorer survival than group C, in spite of a higher FEV(1) level. This subgroup warrants special attention, as the poor prognosis could be caused by cardiovascular disease or cancer, requiring additional assessment and treatment.
Role of the Endothelin-1 Gene Locus for Renal Impairment in the General Nondiabetic Population
Authors: Sara-Joan Pinto-Sietsma, Stefan-Martin Herrmann, Klaus Schmidt-Petersen, Tianhua Niu, Hans L. Hillege, Wilbert M.T. Janssen, Dick de Zeeuw, Paul de Jong, Reinhold Kreutz
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. A decreased GFR in the range of mild renal insufficiency and an increased urinary albumin excretion (UAE) rate in the range of microalbuminuria are important cardiovascular risk factors. Endothelin-1 (ET-1) has been suggested to be a major disease promoting factor in renal disease. The role of the ET-1 gene locus (EDN1) for renal function in the general nondiabetic population was evaluated. To explore the overall relevance of EDN1, two suitable single-nucleotide polymorphisms, EDN1 K198N and EDN1 T-1370G, were selected, and haplotype analysis was performed. Determined were genotypes in 7291 nondiabetic subjects from the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study. Genetic analysis was related to UAE and GFR as continuous variables and to microalbuminuria and diminished filtration as dichotomous traits. In a logistic regression analysis, no significant higher risk for increased UAE, microalbuminuria, decreased GFR, or diminished filtration could be observed for either single-nucleotide polymorphism separately. Haplotype analysis revealed that individuals with the homozygous G-N haplotype (compound EDN1 −1370GG/198NN genotype) have a lower GFR than the remaining subjects (P < 0.05) and exhibit a significant higher risk for the presence of a diminished filtration (relative risk, 2.4; 95% confidence interval, 1.07 to 5.33; P < 0.05). Further analysis demonstrated no association between this haplotype and UAE or plasma ET-1 levels. Although a functional relevance of the EDN1 G-N haplotype itself remains unclear, the data demonstrate that genetic variation at the EDN1 locus has a significant effect on glomerular filtration but not on UAE in the general nondiabetic population. E-mail: [email protected]
The Polymeal: a more natural, safer, and probably tastier (than the Polypill) strategy to reduce cardiovascular disease by more than 75%
Authors: Oscar H Franco, Luc Bonneux, Chris de Laet, Anna Peeters, Ewout W Steyerberg, Johan P Mackenbach
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objective</b> Although the Polypill concept (proposed in 2003) is promising in terms of benefits for cardiovascular risk management, the potential costs and adverse effects are its main pitfalls. The objective of this study was to identify a tastier and safer alternative to the Polypill: the Polymeal. <b>Methods</b> Data on the ingredients of the Polymeal were taken from the literature. The evidence based recipe included wine, fish, dark chocolate, fruits, vegetables, garlic, and almonds. Data from the Framingham heart study and the Framingham offspring study were used to build life tables to model the benefits of the Polymeal in the general population from age 50, assuming multiplicative correlations. <b>Results</b> Combining the ingredients of the Polymeal would reduce cardiovascular disease events by 76%. For men, taking the Polymeal daily represented an increase in total life expectancy of 6.6 years, an increase in life expectancy free from cardiovascular disease of 9.0 years, and a decrease in life expectancy with cardiovascular disease of 2.4 years. The corresponding differences for women were 4.8, 8.1, and 3.3 years. <b>Conclusion</b> The Polymeal promises to be an effective, non-pharmacological, safe, cheap, and tasty alternative to reduce cardiovascular morbidity and increase life expectancy in the general population.
Mechanism of Ventricular Rate Control After Radiofrequency Modification of Atrioventricular Conduction in Patients With Atrial Fibrillation
Authors: Steven M. Markowitz, Kenneth M. Stein, Bruce B. Lerman
Journal: Circulation (1996)

Background Modification of atrioventricular (AV) conduction during atrial fibrillation (AF) may be achieved by radiofrequency ablation in the posteroseptal region of the tricuspid annulus. We tested the hypothesis that elimination of the posterior atrionodal input rather than direct damage to the compact AV node accounts for the decrease in ventricular rate after AV nodal modification. Methods and Results Twenty-four patients with the typical form of AV nodal reentrant tachycardia (AVNRT) underwent selective radiofrequency ablation of the slow AV nodal pathway in the posteroseptal tricuspid annulus. AF was induced before ablation (phase 1), 30 minutes after ablation (phase 2), and during follow-up 24 hours after ablation (phase 3), both with and without concurrent infusion of isoproterenol (4 μg/min). Successful elimination of AVNRT was achieved in all patients. During phase 3, 11 patients (46%) had residual dual pathway physiology. AV nodal Wenckebach cycle length (AVNW-CL) increased progressively during each phase of the protocol (356±72 versus 371±78 ms versus 432±104 ms, P &lt;.0001), as did the effective refractory period of the AV node (279±60 versus 304±67 ms versus 372±56 ms, P &lt;.0001). Minimal, mean, and maximal RR intervals during AF progressively increased immediately after ablation and 24 hours later (485±88 versus 533±116 ms versus 637±142 ms for mean RR, P &lt;.0001). The changes in AVNW-CL, AV nodal effective refractory period, and ventricular response during AF were independent of residual dual pathway physiology after ablation. Similar observations were observed during isoproterenol infusion. Conclusions Modification of AV nodal conduction during AF by radiofrequency ablation in the posteroseptal tricuspid annulus is independent of the presence or absence of a residual slow AV nodal pathway. On the basis of these observations, the mechanism of AV nodal modification is consistent with elimination of the posterior atrionodal input.
Prognostic Significance of Mitotic Rate in Localized Primary Cutaneous Melanoma: An Analysis of Patients in the Multi-Institutional American Joint Committee on Cancer Melanoma Staging Database
Authors: John F. Thompson, Seng-Jaw Soong, Charles M. Balch, Jeffrey E. Gershenwald, Shouluan Ding, Daniel G. Coit, Keith T. Flaherty, Phyllis A. Gimotty, Timothy Johnson, Marcella M. Johnson, Stanley P. Leong, Merrick I. Ross, David R. Byrd, Natale Cascinelli, Alistair J. Cochran, Alexander M. Eggermont, Kelly M. McMasters, Martin C. Mihm, Donald L. Morton, Vernon K. Sondak
Journal: Journal of Clinical Oncology (2011)

Purpose The aim of this study was to assess the independent prognostic value of primary tumor mitotic rate compared with other clinical and pathologic features of stages I and II melanoma. Methods From the American Joint Committee on Cancer (AJCC) melanoma staging database, information was extracted for 13,296 patients with stages I and II disease who had mitotic rate data available. Results Survival times declined as mitotic rate increased. Ten-year survival ranged from 93% for patients whose tumors had 0 mitosis/mm 2 to 48% for those with ≥ 20/mm 2 (P &lt; .001). Mean number of mitoses/mm 2 increased as the primary melanomas became thicker (1.0 for melanomas ≤ 1 mm, 3.5 for 1.01 to 2.0 mm, 7.3 for 3.01 to 4.0 mm, and 9.6 for &gt; 8 mm). Ulceration was also associated with a higher mitotic rate; 59% of ulcerated melanomas had ≥ 5 mitoses/mm 2 compared with 16% of nonulcerated melanomas (P &lt; .001). In a multivariate analysis of 10,233 patients, the independent predictive factors for survival in order of statistical significance were as follows: tumor thickness (χ 2 = 104.9; P &lt; .001), mitotic rate (χ 2 = 67.0; P &lt; .001), patient age (χ 2 = 48.2; P &lt; .001), ulceration (χ 2 = 46.4; P &lt; .001), anatomic site (χ 2 = 34.6; P &lt; .001), and patient sex (χ 2 = 33.9; P &lt; .001). Clark level of invasion was not an independent predictor of survival (χ 2 = 3.2; P = .37). Conclusion A high mitotic rate in a primary melanoma is associated with a lower survival probability. Among the independent predictors of melanoma-specific survival, mitotic rate was the strongest prognostic factor after tumor thickness.
Alcohol Sensitivity and Ethnic Background
Authors: JOHN A. EWING, BEATRICE A. ROUSE, E. D. PELLIZZARI
Journal: American Journal of Psychiatry (1974)

Previous clinical studies have shown Oriental subjects to be significantly more sensitive to alcohol than Occidental subjects. The results of this study corroborated these findings: the 24 Oriental subjects tested showed significantly more skin flushing, increased heart rate, drop in blood pressure, and general discomfort with alcohol than the 24 Occidental subjects. In addition, the former more frequently reported family histories of flushing. The need for further studies to elucidate the mechanism is apparent. The evidence suggests that the low rates of alcohol abuse and alcoholism commonly found among Oriental people may have physiological rather than cultural origins.
Genetic susceptibility to atracurium-induced bronchoconstriction.
Authors: R C Levitt, S L Ewart
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

The goal of this study was to develop a murine model of atracurium-induced bronchoconstriction in which to evaluate the mechanism of action of this airway response. We evaluated nine inbred strains of mice for the development of atracurium-induced bronchoconstriction. The maximal difference in the magnitude of the airway response to atracurium noted between the highly responsive DBA/2 mice and the minimally responsive SJL mice was greater than 20-fold. This phenotype appears to reflect an intrinsic difference in the lungs of these animals because the extent of neuromuscular blockade was not significantly different in DBA/2 and SJL mice. Atracurium-induced airway hyperresponsiveness in DBA/2 mice was eliminated in a dose-dependent manner by pretreatment with atropine or pancuronium. These data are consistent with a postganglionic vagal efferent mechanism which produces a differential pulmonary response to this neuromuscular blocker. A genetic predisposition to atracurium-induced bronchoconstriction appears to exist in certain inbred strains of mice. Thus, a mouse model may be useful for mapping the gene(s) that control this trait and for suggesting responsible candidate genes. Our results suggest that the inbred laboratory mouse will be useful to study the mechanism by which atracurium produces bronchoconstriction.
A comparison of the efficacy and safety of once-daily fluticasone furoate/vilanterol with twice-daily fluticasone propionate/salmeterol in moderate to very severe COPD
Authors: Alvar Agustí, Luis de Teresa, Wilfried De Backer, Michael T. Zvarich, Nicholas Locantore, Neil Barnes, Jean Bourbeau, Courtney Crim
Journal: European Respiratory Journal (2013)

Fluticasone furoate/vilanterol trifenatate (FF/VI) is a once-daily inhaled corticosteroid/long-acting β 2 -agonist combination in development for chronic obstructive pulmonary disease (COPD) treatment. We compared the efficacy and safety of FF/VI versus fluticasone propionate/salmeterol (FP/SAL) twice daily over 12 weeks. Moderate to very severe COPD patients received FF/VI 100/25 μg once daily in the morning (n=266) or FP/SAL 500/50 μg twice daily (n=262). The primary end-point was a change from baseline in 0–24 h weighted mean forced expiratory volume in 1 s (wmFEV 1 ) at 12 weeks. Additional end-points included time to 100 mL improvement from baseline on day 1 and a change from baseline in St George's Respiratory Questionnaire (SGRQ). Safety was also assessed. wmFEV 1 (mean 130 mL) was greater and time to 100 mL improvement shorter (median 16 min) with FF/VI than FP/SAL (weighted mean 108 mL, median 28 min). Health status (SGRQ total score) improved in both groups (FF/VI -4.3 units, FP/SAL -3.0 units). Differences between treatments were not statistically significant. Six patients in the FF/VI (2%) and three in the FP/SAL (1%) arm experienced serious adverse events, none of which were considered to be drug related. Improvements in lung function and health status were not significantly different between FF/VI 100/25 μg once daily and FP/SAL 500/50 μg twice daily; there was no apparent difference between the safety profiles of either therapy.
A Clinicopathologic Study of Thrombotic Microangiopathy in IgA Nephropathy
Authors: Khalil El Karoui, Gary S. Hill, Alexandre Karras, Christian Jacquot, Luc Moulonguet, Olivier Kourilsky, Véronique Frémeaux-Bacchi, Michel Delahousse, Jean-Paul Duong Van Huyen, Alexandre Loupy, Patrick Bruneval, Dominique Nochy
Journal: Journal of the American Society of Nephrology (2011)

Thrombotic microangiopathy (TMA) occurs in IgA nephropathy, but its clinical significance is not well described. We retrospectively examined a series of 128 patients diagnosed with IgA nephropathy between 2002 and 2008 who had a mean follow-up of 44±27 months. In our series, 53% presented with lesions of TMA, acute or organized, in arteries and/or arterioles. Among patients with TMA, 4% were normotensive, 25% had controlled hypertension, and 71% had uncontrolled hypertension. Of those with uncontrolled hypertension, 26% had malignant hypertension. Histologically, the group with TMA had a significantly greater percentage of sclerotic glomeruli and worse tubulointerstitial fibrosis than those of the group without TMA. However, a significant minority of patients had near-normal histology, with minimal tubular atrophy (20%) and/or <20% interstitial fibrosis (24%). TMA rarely occurred in the absence of significant proteinuria. During follow-up, a doubling of serum creatinine or ESRD occurred in all patients with laboratory evidence of TMA, in 42% of those with morphologic evidence but no laboratory evidence of TMA, and in 11% of those without TMA. In summary, lesions of TMA are frequent in IgA nephropathy and may occur in normotensive patients with near-normal renal histology. Although the pathophysiologic mechanisms involved remain undetermined, the current study rules out severe hypertension or advanced renal disease as sole causes.
Debanding and repair of ventricular septal defect: a new technique for older patients.
Authors: P Lauridsen, A Uhrenholdt, I H Rygg
Journal: Thorax (1979)

<h3>BACKGROUND AND PURPOSE:</h3> A large spectrum of neurologic disease has been reported in patients with coronavirus disease 2019 (COVID-19) infection. Our aim was to investigate the yield of neuroimaging in patients with COVID-19 undergoing CT or MR imaging of the brain and to describe associated imaging findings. <h3>MATERIALS AND METHODS:</h3> We performed a retrospective cohort study involving 2054 patients with laboratory-confirmed COVID-19 presenting to 2 hospitals in New York City between March 4 and May 9, 2020, of whom 278 (14%) underwent either CT or MR imaging of the brain. All images initially received a formal interpretation from a neuroradiologist within the institution and were subsequently reviewed by 2 neuroradiologists in consensus, with disputes resolved by a third neuroradiologist. <h3>RESULTS:</h3> The median age of these patients was 64 years (interquartile range, 50–75 years), and 43% were women. Among imaged patients, 58 (21%) demonstrated acute or subacute neuroimaging findings, the most common including cerebral infarctions (11%), parenchymal hematomas (3.6%), and posterior reversible encephalopathy syndrome (1.1%). Among the 51 patients with MR imaging examinations, 26 (51%) demonstrated acute or subacute findings; notable findings included 6 cases of cranial nerve abnormalities (including 4 patients with olfactory bulb abnormalities) and 3 patients with a microhemorrhage pattern compatible with critical illness–associated microbleeds. <h3>CONCLUSIONS:</h3> Our experience confirms the wide range of neurologic imaging findings in patients with COVID-19 and suggests the need for further studies to optimize management for these patients.