tbuckley/cabot-search huggingface dataset:
What is the best predictor of spontaneous ventricular tachycardia and sudden death after myocardial infarction?
Authors: D A Richards, K Byth, D L Ross, J B Uther
Journal: Circulation (1991)

BACKGROUND Death during the first year after myocardial infarction is most commonly due to spontaneous ventricular tachycardia (VT) or fibrillation (VF). The purpose of this study was to compare, in a single cohort of patients, the values of inducible VT, delayed ventricular activation, low left ventricular ejection fraction, high-grade ventricular ectopy, and ST segment displacement on exercise in predicting electrical events (witnessed instantaneous death and spontaneous VT or VF) during the first year after myocardial infarction. METHODS AND RESULTS Three hundred sixty one patients aged less than 71 years underwent electrophysiological study, signal-averaged electrocardiogram, gated blood-pool scan, 24 hour ambulatory electrocardiographic monitoring, and exercise testing 1-2 weeks after myocardial infarction and were then followed up for at least 1 year. There were 34 deaths (eight witnessed instantaneous, 26 other), and nine patients survived one or more episodes of spontaneous VF or VT. Patients with inducible VT were 15.2 times more likely to suffer electrical events than patients without inducible VT. No proportional-hazards model excluding inducible VT was as good a predictor of electrical events as was inducible VT alone. CONCLUSIONS Inducible VT at electrophysiological study was the single best predictor of spontaneous VT and sudden death after myocardial infarction.
Acute Effects of Ozone on Mortality from the “Air Pollution and Health
Authors: Alexandros Gryparis, Bertil Forsberg, Klea Katsouyanni, Antonis Analitis, Giota Touloumi, Joel Schwartz, Evangelia Samoli, Sylvia Medina, H. Ross Anderson, Emilia Maria Niciu, H.-Erich Wichmann, Bohumir Kriz, Mitja Kosnik, Jiri Skorkovsky, Judith M. Vonk, Zeynep Dörtbudak
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

In the Air Pollution and Health: A European Approach (APHEA2) project, the effects of ambient ozone concentrations on mortality were investigated. Data were collected on daily ozone concentrations, the daily number of deaths, confounders, and potential effect modifiers from 23 cities/areas for at least 3 years since 1990. Effect estimates were obtained for each city with city-specific models and were combined using second-stage regression models. No significant effects were observed during the cold half of the year. For the warm season, an increase in the 1-hour ozone concentration by 10 mug/m3 was associated with a 0.33% (95% confidence interval [CI], 0.17-0.52) increase in the total daily number of deaths, 0.45% (95% CI, 0.22-0.69) in the number of cardiovascular deaths, and 1.13% (95% CI, 0.62-1.48) in the number of respiratory deaths. The corresponding figures for the 8-hour ozone were similar. The associations with total mortality were independent of SO2 and particulate matter with aerodynamic diameter less than 10 mum (PM10) but were somewhat confounded by NO2 and CO. Individual city estimates were heterogeneous for total (a higher standardized mortality rate was associated with larger effects) and cardiovascular mortality (larger effects were observed in southern cities). The dose-response curve of ozone effects on total mortality during the summer did not deviate significantly from linearity.
Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in the Treatment of Epidermal Growth Factor Receptor<i>–</i>Mutant Non–Small Cell Lung Cancer Metastatic to the Brain
Authors: Mariam Jamal-Hanjani, James Spicer
Journal: Clinical Cancer Research (2011)

Abstract Brain metastases are a common and devastating consequence of disease progression in patients with non–small cell lung cancer (NSCLC). The epidermal growth factor receptor (EGFR) inhibitors erlotinib and gefitinib have shown efficacy in patients with NSCLC and brain metastases. The cerebrospinal fluid (CSF) exposure to these drugs is a small fraction of the plasma levels achieved with standard doses, but disruption of the blood–brain barrier in the presence of central nervous system metastases is likely to lead to locally increased drug concentration, and dose escalation to boost CSF exposure has documented clinical efficacy. The use of gefitinib and erlotinib in this setting is reviewed here, including evidence from case reports, case series, and single-arm phase II trials. High response rates in the brain are seen in patients with EGFR mutation, or in populations in which this genotype is expected. By contrast, activity in the context of documented wild-type EGFR in disease metastatic to the brain is not common. These drugs may potentiate the effectiveness of radiotherapy to the brain, and their use may also delay development of disease within the brain. Clin Cancer Res; 18(4); 938–44. ©2011 AACR.
Therapeutic efficacy of azaindole-1 in experimental pulmonary hypertension
Authors: B.K. Dahal, D. Kosanovic, P.K. Pamarthi, A. Sydykov, Y-J. Lai, R. Kast, H. Schirok, J-P. Stasch, H.A. Ghofrani, N. Weissmann, F. Grimminger, W. Seeger, R.T. Schermuly
Journal: European Respiratory Journal (2010)

An accumulating body of evidence incriminates Rho kinase (ROCK) in the pathogenesis of pulmonary hypertension (PH). The therapeutic efficacy of azaindole-1, a novel highly selective and orally active ROCK inhibitor, has not yet been investigated in PH. This study aimed to investigate the effects of azaindole-1 on 1) acute hypoxic pulmonary vasoconstriction (HPV), 2) proliferation of pulmonary arterial smooth muscle cells (PASMCs) and 3) animal models of PH. Azaindole-1 significantly inhibited HPV in isolated, ventilated and buffer-perfused murine lungs and proliferation of primary rat PASMCs in vitro. Azaindole-1 was administered orally from 21 to 35 days after monocrotaline (MCT) injection in rats and hypoxic exposure in mice. Azaindole-1 (10 and 30 mg per kg body weight per day in rats and mice, respectively) significantly improved haemodynamics and right ventricular hypertrophy. Moreover, the medial wall thickness and muscularisation of peripheral pulmonary arteries were ameliorated. Azaindole-1 treatment resulted in a decreased immunoreactivity for phospho-myosin phosphatase target subunit 1 and proliferating cell nuclear antigen in pulmonary vessels of MCT-injected rats, suggesting an impaired ROCK activity and reduced proliferating cells. Azaindole-1 provided therapeutic benefit in experimental PH, and this may be attributable to its potent vasorelaxant and antiproliferative effects. Azaindole-1 may offer a useful approach for treatment of PH.
TV programme raises fresh allegations about MMR doctor
Authors: Jackson Trevor
Journal: BMJ (2004)

The gastroenterologist Dr Andrew Wakefield had filed patent applications for a measles vaccine and a cure for autism nine months before his study on childhood chronic enterocolitis and autism was published in the Lancet in 1998, a television documentary claimed last week. Dr Wakefield's paper led to suggestions of a link between the MMR (measles, mumps, and rubella) vaccine and autism.

Channel 4's Dispatches also included an interview with a researcher in Dr …
Cognitive Therapy: Current Status and Future Directions
Authors: Aaron T. Beck, David J.A. Dozois
Journal: Annual Review of Medicine (2010)

Cognitive therapy is a system of psychotherapy with a powerful theoretical infrastructure, which has received extensive empirical support, and a large body of research attesting to its efficacy for a wide range of psychiatric and medical problems. This article provides a brief overview of the conceptual and practical components of cognitive therapy and highlights some of the empirical evidence regarding its efficacy. Cognitive therapy (often labeled generically as cognitive behavior therapy) is efficacious either alone or as an adjunct to medication and provides a prophylaxis against relapse and recurrence.
Intracoronary beta-radiation therapy for long lesions in native coronary vessels
Authors: Goran R. Stankovic, Antonio Colombo, Carlo Di Mario, Remo Albiero, Nicola Corvaja, Takuro Takagi, Konstantinos Toutouzas, Antonio Amato, Ginevra Sivieri, Roberto Orecchia
Journal: Journal of the American College of Cardiology (2002)
Family Wide Molecular Adaptations to Underground Life in African Mole-Rats Revealed by Phylogenomic Analysis
Authors: Kalina T.J. Davies, Nigel C. Bennett, Georgia Tsagkogeorga, Stephen J. Rossiter, Christopher G. Faulkes
Journal: Molecular Biology and Evolution (2015)

During their evolutionary radiation, mammals have colonized diverse habitats. Arguably the subterranean niche is the most inhospitable of these, characterized by reduced oxygen, elevated carbon dioxide, absence of light, scarcity of food, and a substrate that is energetically costly to burrow through. Of all lineages to have transitioned to a subterranean niche, African mole-rats are one of the most successful. Much of their ecological success can be attributed to a diet of plant storage organs, which has allowed them to colonize climatically varied habitats across sub-Saharan Africa, and has probably contributed to the evolution of their diverse social systems. Yet despite their many remarkable phenotypic specializations, little is known about molecular adaptations underlying these traits. To address this, we sequenced the transcriptomes of seven mole-rat taxa, including three solitary species, and combined new sequences with existing genomic data sets. Alignments of more than 13,000 protein-coding genes encompassed, for the first time, all six genera and the full spectrum of ecological and social variation in the clade. We detected positive selection within the mole-rat clade and along ancestral branches in approximately 700 genes including loci associated with tumorigenesis, aging, morphological development, and sociality. By combining these results with gene ontology annotation and protein–protein networks, we identified several clusters of functionally related genes. This family wide analysis of molecular evolution in mole-rats has identified a suite of positively selected genes, deepening our understanding of the extreme phenotypic traits exhibited by this group.
The Relationship Between Wheezing Patterns During Early Childhood and Six Year Asthma Diagnosis in a High Risk Birth Cohort
Authors: K.M. Hanson, M.D. Evans, C.J. Tisler, D.F. DaSilva, T.E. Pappas, R.A. Grabher, L.E.P. Salazar, K.T. Sullivan Dillie, E.L. Anderson, K.A. Roberg, R.E. Gangnon, J.E. Gern, R.F. Lemanske
Journal: Journal of Allergy and Clinical Immunology (2007)
The Direction of Rotation in Cerebellar Affections
Authors: J. S. R. Russell
Journal: BMJ (1897)

ERYTHROL TETRANITRATE IN ANGINA.[METHABLOUNAL 907 6. Gout is probably always preceded by some affection of the kidneys, functional or organic, which interferes with the proper excretion of uric acid.The probablp seat of the kidney affection giving rise to gout is in the epithelium of the coI- voluted tubes.7. In certain blood diseases and disorders accompanied by leucoeytosis uric acid is formed within the system from nuclein.Under such circumstances it passes at once into the blood and is rapidly eliminated by the kidneys.8. The solubility of uric acid in the blond is not affected by a diminished alkalinity of the blood produced by the addition of organic acids.9.The deposition of sodium biurate is not accelerated by a diminution of the alkalinity of the blood.IO.An increased alkalinity of the blood does not increase the solubility of deposits of sodium hiurate.i i.The saline constituents of vegetables exercise a remarkable inhibitory power over the decomposition of sodium quadriurate.12. The solubility of sodium biurate in the blood is increased by the presence of the saline constituents of veget- ables.13.The solubility of sodium biurate in the blood is diminished by the presence of the saline constituents of meat.14.The gout-inducing properties of certain wines are not due to their acidity.Probably they owe their gout-inducing action to the effect they exercise on the metabolism of the liver.
Maintenance of inspiratory muscle training in COPD patients: one year follow-up
Authors: P. Weiner, R. Magadle, M. Beckerman, M. Weiner, N. Berar-Yanay
Journal: European Respiratory Journal (2003)

In most chronic obstructive pulmonary disease (COPD) patients, dyspnoea and functional exercise capacity may improve as a result of inspiratory muscle training (IMT). However, the long-term benefits of IMT have been investigated to a much lesser extent. The present study investigated the short-term and long-term benefits of IMT on inspiratory muscle performance (strength and endurance), exercise capacity and the perception of dyspnoea. Thirty-eight patients with significant COPD had 3 months of basic IMT and were then randomised into a group that received maintenance IMT for the next year, and a group that got training with very low load. Following the basic training there was a statistically significant increase in inspiratory muscle performance, 6-min walk test (6MWT), and a decrease in the dyspnoea. During the second stage of the study, the training group continued to maintain the improvement in all parameters, while there was already deterioration in the inspiratory muscle performance, exercise capacity and dyspnoea in the low intensity group during the 6–12 month period. The present study concludes that, in patients with significant chronic obstructive pulmonary disease, inspiratory muscle training results in improvement in performance, exercise capacity and in the sensation of dyspnoea. The benefits of 12‐weeks of inspiratory muscle training decline gradually over 1 yr of follow-up if maintenance training is not performed.
Human tumor antigens recognized by T lymphocytes.
Authors: T Boon, P van der Bruggen
Journal: The Journal of Experimental Medicine (1996)

W e have come a long way since the identification of the first human tumor antigen recognized by autologous CTL.This report provides a brief appraisal of these antigens and their potential for cancer immunotherapy.Our comments will be restricted to nonviral antigens.The initial work carried out on mouse tumors revealed two possible mechanisms for generating new antigens that might be suflficiendy tumor-specific to be of relevance to immunotherapy.The first mechanism involved a point mutation, and the second involved the transcriptional activation ofa gene not expressed in normal tissues (1-3).Subsequent work on mouse tumors provided two interesting examples of tumor antigens resulting from point mutations (4, 5).Tumor-specific Shared Antigens.Three families of genes that appear to code for highly specific tumor antigens have been identified so far, namely, the MAGE, BAGE, and GAGE genes (6-9).These genes are frequently expressed in a wide range of tumor types such as melanoma, lung carcinoma, sarcoma, and bladder carcinoma, but very rarely in other tumor types such as brain tumors, renal carcinoma, and leukemia (7,(10)(11)(12).The only normal tissues where expression of these genes has been observed are testis and placenta (7).Starting from CTL clones obtained by stimulating lymphocytes with an autologous melanoma cell line, six antigens encoded by MAGE-1, BAGE, and GAGE have been identified (8,9,[13][14][15].For these six an-
Orientational Perception: III. Orientational Percept Distortions in Depersonalization
Authors: DANIEL CAPPON
Journal: American Journal of Psychiatry (1969)

The author reports a study of orientational percept (OP) distortions using 20 depersonalized and derealized patients and matched controls. His findings tend to support a heuristic theory of abnormal (verbal) behavior relating reports of OP distortions to the symptoms of depersonalization and derealization. The indices of OP and of depersonalization, derealization relate reliably to other more established predictors of psychiatric states and to the verbal behavior of patients and controls.
Genetic relatedness in sperm whales: Evidence and cultural implications
Authors: Sarah L. Mesnick
Journal: Behavioral and Brain Sciences (2001)

Results of genetic analyses show that social groups of female and immature sperm whales are comprised of multiple matrilines as evidenced by the presence of multiple mitochondrial (maternally inherited) control region haplotypes. These data suggest: (1) a social environment in which the transmission of cultural information, such as vocal dialects, is more likely to be horizontal or oblique rather than strictly vertical (mother-offspring) and (2) lead us to question the data presented to support gene-culture coevolution.
Achievement of Dual Low-Density Lipoprotein Cholesterol and High-Sensitivity C-Reactive Protein Targets More Frequent With the Addition of Ezetimibe to Simvastatin and Associated With Better Outcomes in IMPROVE-IT
Authors: Erin A. Bohula, Robert P. Giugliano, Christopher P. Cannon, Jing Zhou, Sabina A. Murphy, Jennifer A. White, Andrew M. Tershakovec, Michael A. Blazing, Eugene Braunwald
Journal: Circulation (2015)

Statins lower low-density lipoprotein cholesterol (LDL-C) and high-sensitivity C-reactive protein (hs-CRP); addition of ezetimibe to statins further reduces LDL-C and hs-CRP. An analysis of the relationship between achieved LDL-C and hs-CRP targets and outcomes for simvastatin and ezetimibe/simvastatin was prespecified in Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT).The IMPROVE-IT trial randomly assigned 18 144 patients stabilized after acute coronary syndrome to simvastatin or ezetimibe/simvastatin. LDL-C and hs-CRP were measured at baseline and 1 month after randomization. Outcomes were assessed in those achieving one or both of the prespecified targets of LDL-C<70 mg/dL and hs-CRP<2 mg/L versus achieving neither target, adjusting for differences in baseline characteristics. An exploratory analysis examined targets of LDL-C<50 mg/dL and hs-CRP<1 mg/L. Patients meeting both targets at baseline, with no 1-month values, or with end points before 1 month were excluded. Of 15 179 patients, 39% achieved the dual LDL-C (<70 mg/dL) and hs-CRP (<2 mg/L) targets at 1 month, 14% met neither target, 14% met only the hs-CRP target, and 33% met only the LDL-C target. Those achieving dual targets had lower primary end point rates than those meeting neither target (cardiovascular death, major coronary event, or stroke; 38.9% versus 28.0%; adjusted hazard ratio, 0.73; 0.66-0.81; P<0.001). More patients treated with ezetimibe/simvastatin met dual targets than those treated with simvastatin alone (50% versus 29%, P<0.001). The association of dual-target attainment with improved outcomes was similar irrespective of treatment assignment (P-interaction=0.65). Similar findings were observed using the exploratory targets.Significantly more patients treated with ezetimibe/simvastatin met prespecified and exploratory dual LDL-C and hs-CRP targets than patients treated with simvastatin alone. Reaching both LDL-C and hs-CRP targets was associated with improved outcomes after multivariable adjustment.URL: http://www.clinicaltrials.gov; Unique identifier: NCT00202878.
Siblings of patients with Crohn’s disease exhibit a biologically relevant dysbiosis in mucosal microbial metacommunities
Authors: Charlotte Hedin, Christopher J van der Gast, Geraint B Rogers, Leah Cuthbertson, Sara McCartney, Andrew J Stagg, James O Lindsay, Kevin Whelan
Journal: Gut (2015)

<h3>Objective</h3> To determine the existence of mucosal dysbiosis in siblings of patients with Crohn9s disease (CD) using 454 pyrosequencing and to comprehensively characterise and determine the influence of genotypical and phenotypical factors, on that dysbiosis. Siblings of patients with CD have elevated risk of developing CD and display aspects of disease phenotype, including faecal dysbiosis. Whether the mucosal microbiota is disrupted in these at-risk individuals is unknown. <h3>Design</h3> Rectal biopsy DNA was extracted from 21 patients with quiescent CD, 17 of their healthy siblings and 19 unrelated healthy controls. Mucosal microbiota was analysed by 16S rRNA gene pyrosequencing and were classified into core and rare species. Genotypical risk was determined using Illumina Immuno BeadChip, faecal calprotectin by ELISA and blood T-cell phenotype by flow cytometry. <h3>Results</h3> Core microbiota of both patients with CD and healthy siblings was significantly less diverse than controls. Metacommunity profiling (Bray–Curtis (S<sub>BC</sub>) index) showed the sibling core microbial composition to be more similar to CD (S<sub>BC</sub>=0.70) than to healthy controls, whereas the sibling rare microbiota was more similar to healthy controls (S<sub>BC</sub>=0.42). <i>Faecalibacterium prausnitzii</i> contributed most to core metacommunity dissimilarity both between siblings and controls, and between patients and controls. Phenotype/genotype markers of CD risk significantly influenced microbiota variation between and within groups, of which genotype had the largest effect. <h3>Conclusions</h3> Individuals with elevated CD-risk display mucosal dysbiosis characterised by reduced diversity of core microbiota and lower abundance of <i>F. prausnitzii</i>. This dysbiosis in healthy people at risk of CD implicates microbiological processes in CD pathogenesis.
Combination Immunotherapy for Tumors via Sequential Intratumoral Injections of Oncolytic Herpes Simplex Virus 1 and Immature Dendritic Cells
Authors: Christopher J. Farrell, Cecile Zaupa, Zachary Barnard, Jason Maley, Robert L. Martuza, Samuel D. Rabkin, William T. Curry
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Oncolytic herpes simplex virus 1 (oHSV) vectors treat tumors in preclinical models and have been used safely in phase I clinical trials for patients with cancer. Infection of tumors with oHSV also induces specific antitumor immunity. We investigated whether this immunotherapeutic effect is enhanced by combining oHSV infection with intratumoral administration of immature myeloid dendritic cells (iDC). Experimental Design: Subcutaneous neuroblastoma tumors were established in syngeneic immunocompetent mice and sequentially treated with oHSV(G47Δ) and intratumoral iDCs. Tumor volumes and survival were monitored. Antitumor immune responses were evaluated by immunohistochemistry, IFN-γ ELISPOT, and CTL assay. Treatment was also evaluated in immunodeficient NOD-SCID mice. Results: We observed significant reductions in tumor volumes in mice receiving G47Δ + iDCs compared with those treated with G47Δ or iDC monotherapy. Survival was prolonged, with ∼90% of tumors eradicated in the combination group. Combination therapy led to enhancement of antitumor immune responses, confirmed by increases in IFN-γ expression by splenocytes harvested from G47Δ + iDC-treated mice. Splenocytes harvested from G47Δ + iDC-treated mice were effective against neuroblastoma tumor cells in a CTL assay. Immunohistochemistry of combination-treated tumors revealed robust lymphocytic infiltrates. Adding iDCs to G47Δ infection in tumors in NOD-SCID mice did not reduce the rate of growth. Substitution of lipopolysaccharide-matured dendritic cells abrogated the enhanced tumor volume reduction seen with combination therapy with iDCs. Conclusions: Combination treatment of murine tumors with oHSV and iDCs reduces the volume of established tumors and prolongs survival via enhancement of antitumor immunity.
Destructive herpetic whitlow in AIDS: report of three cases
Authors: M.G. ROBAYNA, P. HERRANZ, F.A. RUBIO, P. PEÑA, J.M. PEÑA, J. GONZÁLEZ, M. CASADO
Journal: British Journal of Dermatology (1997)

Herpes simplex virus infection in immunocompromised individuals, including AIDS patients, is characterized by its tendency for atypical presentations and unusual locations, often resulting in delayed diagnosis and treatment. Three HIV-infected patients who developed prolonged cutaneous lesions of the fingers are presented. These lesions were unmodified by previous antibiotic treatment, and rapidly progressed to the complete destruction of nail structures in two patients. Viral culture confirmed the diagnosis of herpetic whitlow in all cases, and treatment with oral acyclovir resulted in complete recovery. Surgical treatment was not necessary.