tbuckley/cabot-search huggingface dataset:
Efficacy and safety of adjunctive anticoagulation in patients with lung cancer without indication for anticoagulants: a systematic review and meta-analysis
Authors: Jing Zhang, Yue-Li Zhang, Kai-Xiang Ma, Jie-Ming Qu
Journal: Thorax (2013)

Patients with lung cancer are at high risk of venous thromboembolism (VTE), and VTE predicts a poor prognosis. Anticoagulation therefore might be beneficial for these patients. It is not clear whether anticoagulants could improve survival and other outcomes in patients with lung cancer with no indication for anticoagulation.We searched the Web of Science, Medline, EMBASE and Cochrane databases for relevant studies. Two reviewers evaluated the studies and extracted data independently. The primary outcomes were 1-year survival and incidence of VTE. Pooled risk ratios (RR) were calculated using control as a reference group and significance was determined by the Z test.Nine eligible studies with 2185 participants were included. Anticoagulation showed significant improvement in survival at 1 year (RR 1.18, 95% CI 1.06 to 1.32; p=0.004) and at 2 years (RR 1.27, 95% CI 1.04 to 1.56; p=0.02), but not at 6 months. Subgroup analysis showed a survival benefit for patients with small cell lung cancer (SCLC) and those with non-advanced/limited cancer. The incidence of VTE (RR=0.55, 95% CI 0.31 to 0.97; p=0.04) and thromboembolic events (RR=0.48, 95% CI 0.28 to 0.82; p=0.008) was reduced with anticoagulation. Both vitamin K antagonist (VKA) and subcutaneous heparin increased the risk of haemorrhage, but heparin did not increase the incidence of major bleeding.Anticoagulation showed a survival benefit, especially for those with SCLC and prolonged life expectancy, and reduced the risk of VTE in lung cancer patients with no indication for anticoagulants. Subcutaneous heparin is superior to VKA because of a potentially smaller risk of major bleeding.
Clonidine Maintenance Prolongs Opioid Abstinence and Decouples Stress From Craving in Daily Life: A Randomized Controlled Trial With Ecological Momentary Assessment
Authors: William J. Kowalczyk, Karran A. Phillips, Michelle L. Jobes, Ashley P. Kennedy, Udi E. Ghitza, Daniel A. Agage, John P. Schmittner, David H. Epstein, Kenzie L. Preston
Journal: American Journal of Psychiatry (2015)

The authors tested whether clonidine blocks stress-induced seeking of heroin and cocaine. The study was also intended to confirm translational findings from a rat model of drug relapse by using ecological momentary assessment of patients' stress to test hypotheses about clonidine's behavioral mechanism of action.The authors conducted a randomized double-blind placebo-controlled clinical trial with 208 opioid-dependent patients at an outpatient buprenorphine clinic. The 118 participants (57%) who maintained abstinence during weeks 5-6 were continued on buprenorphine and randomly assigned to receive clonidine (N=61) or placebo (N=57) for 14 weeks. Urine was tested thrice weekly. Lapse was defined as any opioid-positive or missed urine test, and relapse as two or more consecutive lapses. Time to lapse and relapse were examined with Cox regressions; longest period of abstinence was examined with a t test, and ecological momentary assessment data were examined with generalized linear mixed models.In an intent-to-treat analysis, clonidine produced the longest duration (in consecutive days) of abstinence from opioids during the intervention phase (34.8 days [SD=3.7] compared with 25.5 days [SD=2.7]; Cohen's d=0.38). There was no group difference in time to relapse, but the clonidine group took longer to lapse (hazard ratio=0.67, 95% CI=0.45-1.00). Ecological momentary assessment showed that daily-life stress was partly decoupled from opioid craving in the clonidine group, supporting the authors' hypothesized mechanism for clonidine's benefits.Clonidine, a readily available medication, is useful in opioid dependence not just for reduction of withdrawal signs, but also as an adjunctive maintenance treatment that increases duration of abstinence. Even in the absence of physical withdrawal, it decouples stress from craving in everyday life.
A <sub>1</sub> or A <sub>3</sub> Adenosine Receptors Induce Late Preconditioning Against Infarction in Conscious Rabbits by Different Mechanisms
Authors: Hitoshi Takano, Roberto Bolli, Richard G. Black, Eitaro Kodani, Xian-Liang Tang, Zequan Yang, Samita Bhattacharya, John A. Auchampach
Journal: Circulation Research (2001)

Abstract —We investigated whether activation of A 1 or A 3 adenosine receptors (ARs) induces late preconditioning (PC) against infarction in conscious rabbits using the selective AR agonists 2-chloro- N 6 -cyclopentyladenosine (CCPA) and N 6 -3-iodobenzyladenosine-5′- N -methylcarboxamide (IB-MECA). In vitro radioligand binding and cAMP assays demonstrated CCPA to be ≈200- to 400-fold selective for the rabbit A 1 AR and IB-MECA to be ≈20-fold selective for the rabbit A 3 AR. We observed that (1) pretreatment of rabbits 24 hours earlier with CCPA (100 μg/kg IV bolus) or IB-MECA (100 or 300 μg/kg) resulted in an ≈35% to 40% reduction in the size of the infarct induced by 30 minutes of coronary artery occlusion and 72 hours of reperfusion compared with vehicle-treated rabbits, whereas pretreatment with the selective A 2A AR agonist CGS 21680 (100 μg/kg) had no effect; (2) the delayed cardioprotective effect of CCPA, but not that of IB-MECA, was completely blocked by coadministration of the highly selective A 1 AR antagonist N-0861; (3) inhibition of nitric oxide synthase (NOS) with N ω -nitro- l -arginine during the 30-minute occlusion abrogated the infarct-sparing action of CCPA but not that of IB-MECA; and (4) inhibition of ATP-sensitive potassium (K ATP ) channels with sodium 5-hydroxydecanoate during the 30-minute occlusion blocked the cardioprotective effects of both CCPA and IB-MECA. Taken together, these results indicate that activation of either A 1 ARs or A 3 ARs (but not A 2A ARs) elicits delayed protection against infarction in conscious rabbits and that both A 1 AR- and A 3 AR-induced cardioprotection involves opening of K ATP channels. However, A 1 AR-induced late PC uses an NOS-dependent pathway whereas A 3 AR-induced late PC is mediated by an NOS-independent pathway.
Mild iron overload in patients carrying the HFE S65C gene mutation: a retrospective study in patients with suspected iron overload and healthy controls
Authors: P Holmstrom
Journal: Gut (2002)

The role of the HFE S65C mutation in the development of hepatic iron overload is unknown. The aim of the present study was: (A) to determine the HFE S65C frequency in a Northern European population; and (B) to evaluate whether the presence of the HFE S65C mutation would result in a significant hepatic iron overload.Biochemical iron parameters and HFE mutation analysis (for the C282Y, H63D, and S65C mutations) were analysed in 250 healthy control subjects and collected retrospectively in 296 patients with suspected iron overload (elevated serum ferritin and/or transferrin saturation). The frequency of patients having at least mild iron overload, and mean serum ferritin and transferrin saturation values were calculated for each HFE genotype. For patients carrying the S65C mutation, clinical data, liver biopsy results, and amount of blood removed at phlebotomy were determined.The HFE S65C mutation was found in 14 patients and eight controls. In controls, the S65C allele frequency was 1.6%. The S65C allele frequency was enriched in non-C282Y non-H63D chromosomes from patients (4.9%) compared with controls (1.9%) (p<0.05). Serum ferritin was significantly increased in controls carrying the S65C mutation compared with those without HFE mutations. Fifty per cent of controls and relatives having the S65C mutation had elevated serum ferritin levels or transferrin saturation. The number of iron overloaded patients was significantly higher among those having HFE S65C compared with those without any HFE mutation. Half of patients carrying the S65C mutation (7/14) had evidence of mild or moderate hepatic iron overload but no signs of extensive fibrosis in liver biopsies. Screening of relatives revealed one S65C homozygote who had no signs of iron overload. Compound heterozygosity with S65C and C282Y or H63D did not significantly increase the risk of iron overload compared with S65C heterozygosity alone.The HFE S65C mutation may lead to mild to moderate hepatic iron overload but neither clinically manifest haemochromatosis nor iron associated extensive liver fibrosis was encountered in any of the patients carrying this mutation.
866-5 Coronary flow velocity reserve &lt;2.0 by transthoracic doppler echocardiography can detect myocardial ischemia assessed by 201-thallium schintigraphy in a large population with coronary risk factors
Authors: Yoshiki Matsumura, Takeshi Hozumi, Hiroyuki Watanabe, Kohei Fujimoto, Kenichi Sugioka, Yasuhiko Takemoto, Hiroyuki Yamagishi, Minoru Yoshiyama, Kazuhide Takeuchi, Junichi Yoshikawa
Journal: Journal of the American College of Cardiology (2004)
ACUTE HEPATIC NECROSIS INDUCED BY BRUCELLA INFECTION IN HYPERTHYROID MICE
Authors: G. Mary Bradley, Wesley W. Spink
Journal: The Journal of Experimental Medicine (1959)

When small numbers of Brucella melitensis were inoculated into ABC mice, occasional hepatic granulomas without necrosis were demonstrated. The greatest multiplication of brucellae was detected in the spleens. Because it had been previously observed that ACTH or cortisone markedly accelerated the multiplication of brucellae in the livers of infected mice with destruction of liver cells, it was considered that triiodothyronine might likewise exaggerate a brucella infection by stimulating endogenous adrenal secretion. Although adrenal hypertrophy was produced, infection of mice treated with triiodothyronine resulted in severe hepatic necrosis or infarcts without the multiplication of brucellae in either the livers or spleens. The lesions were not encountered in untreated infected mice or in control mice treated with triiodothyronine. The necrosis was associated with minimal inflammatory reaction. The necrosis was not induced in mice treated with triiodothyronine and given brucella endotoxin. The precise genesis of the acute hepatic necrosis cited in these experiments remains undefined. Triiodothyronine did not cause deaths in mice infected with Br. melitensis. The infection was neither enhanced nor suppressed.
Subcutaneous and Visceral Adipose Tissue: Their Relation to the Metabolic Syndrome
Authors: Bernardo Léo Wajchenberg
Journal: Endocrine Reviews (2000)

Methods for assessment, e.g., anthropometric indicators and imaging techniques, of several phenotypes of human obesity, with special reference to abdominal fat content, have been evaluated. The correlation of fat distribution with age, gender, total body fat, energy balance, adipose tissue lipoprotein lipase and lipolytic activity, adipose tissue receptors, and genetic characteristics are discussed. Several secreted or expressed factors in the adipocyte are evaluated in the context of fat tissue localization. The body fat distribution and the metabolic profile in nonobese and obese individuals is discussed relative to lipolysis, antilypolysis and lipogenesis, insulin sensitivity, and glucose, lipid, and protein metabolism. Finally, the endocrine regulation of abdominal visceral fat in comparison with the adipose tissue localized in other areas is presented.
Production of granulocyte colony-stimulating factor by malignant mesothelioma
Authors: T Rikimaru, Y Ichikawa, Y Ogawa, E Higuchi, M Kinosita, K Oizumi, I Shima
Journal: European Respiratory Journal (1995)

We present the case of a male patient, aged 45 yrs, with malignant mesothelioma producing granulocyte colony-stimulating factor (G-CSF). The diagnosis was established by histopathological examination of the autopsied pleural tissues. Production of G-CSF was confirmed by immunoperoxidase staining, using a specific monoclonal antibody against recombinant G-CSF (rhG-CSF).
Erratum to: A multicenter study of septic shock due to candidemia: outcomes and predictors of mortality
Authors: Matteo Bassetti, Elda Righi, Filippo Ansaldi, Maria Merelli, Cecilia Trucchi, Gennaro De Pascale, Ana Diaz-Martin, Roberto Luzzati, Chiara Rosin, Leonel Lagunes, Enrico Maria Trecarichi, Maurizio Sanguinetti, Brunella Posteraro, Jose Garnacho-Montero, Assunta Sartor, Jordi Rello, Giorgio Della Rocca, Massimo Antonelli, Mario Tumbarello
Journal: Intensive Care Medicine (2014)
Symptomatic Improvement of Premenstrual Dysphoric Disorder With Sertraline Treatment
Authors: Kimberly A. Yonkers
Journal: JAMA (1997)

<h3>Context.</h3> —Premenstrual dysphoric disorder is an important cause of symptoms and functional impairment in menstruating women. <h3>Objective.</h3> —To evaluate the efficacy of sertraline hydrochloride for treatment of premenstrual dysphoria by measuring changes in symptom expression and functional impairment. <h3>Design.</h3> —Two screening cycles followed by 1 single-blind placebo cycle and 3 cycles of randomized, double-blind, placebo treatment. <h3>Setting.</h3> —Twelve university-affiliated outpatient psychiatry and gynecology clinics. <h3>Patients.</h3> —Of the 447 women who requested participation, 243 met criteria for premenstrual dysphoric disorder and were randomized; 200 women completed the study. <h3>Intervention.</h3> —A flexible (50-150 mg) daily dose of sertraline hydrochloride. <h3>Main Outcome Measures.</h3> —The Daily Record of Severity of Problems, Hamilton Rating Scale for Depression, Clinical Global Impression Scale, and Social Adjustment Scale. <h3>Results.</h3> —Mean (±SD) total daily symptom scores decreased significantly (<i>P</i>&lt;.001) in the sertraline-treated (64±22 to 44±19) compared with the placebotreated (62±22 to 54±24) groups. Significant improvement (<i>P</i>&lt;.05) was found for all clinically derived symptom clusters (depressive, physical, and anger/irritability symptoms). Hamilton Rating Scale for Depression scores decreased by 44% and 29% in the sertraline and placebo groups, respectively (<i>P</i>&lt;.002). End-point global ratings showed much or very much improvement in 62% of the active treatment group and 34% of the placebo treatment group (<i>P</i>&lt;.001). Reported functional impairment was substantial at baseline. Improvement in psychosocial functioning with treatment was similar to what is found in studies of major depression. <h3>Conclusions.</h3> —Sertraline was significantly better than placebo for treatment of premenstrual dysphoria as reflected by symptomatic improvement and change in reported functional impairment. Serotonin reuptake inhibitors such as sertraline are useful therapeutic options for women with premenstrual dysphoria.
Standardization of the measurement of transfer factor (diffusing capacity)
Authors: J.E. Cotes, D.J. Chinn, Ph.H. Quanjer, J. Roca, J.-C. Yernault
Journal: European Respiratory Journal (1993)

Interstitial lung diseases (ILDs) are a set of heterogeneous lung diseases characterised by inflammation and, in some cases, fibrosis. These lung conditions lead to dyspnoea, cough, abnormalities in gas exchange, restrictive physiology (characterised by decreased lung volumes), hypoxaemia and, if progressive, respiratory failure. In some cases, ILDs can be caused by systemic diseases or environmental exposures. The ability to treat or cure these ILDs varies based on the subtype and in many cases lung transplantation remains the only curative therapy. There is a growing body of evidence that both common and rare genetic variants contribute to the development and clinical manifestation of many of the ILDs. Here, we review the current understanding of genetic risk and ILD.
Polymorphonulcear leukocyte chemotaxis toward oxidized lipid components of cell membranes.
Authors: S R Turner, J A Campbell, W S Lynn
Journal: The Journal of Experimental Medicine (1975)

Polymorphonuclear leukocyte chemotaxis has been elicited by oxidized arachidonic acid and other oxidized polyenoic lipids in the Boyden micropore filter assay system. This chemotactic activity was observed in the absence of serum and chemotactic proteins. The esterfied arachidonic acid present in plasma membranes may be a precursor of chemotactic messages as well as prostaglandins in vivo.
Simeprevir with pegylated interferon alfa 2a or 2b plus ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1 infection (QUEST-2): a randomised, double-blind, placebo-controlled phase 3 trial
Authors: Michael Manns, Patrick Marcellin, Fred Poordad, Evaldo Stanislau Affonso de Araujo, Maria Buti, Yves Horsmans, Ewa Janczewska, Federico Villamil, Jane Scott, Monika Peeters, Oliver Lenz, Sivi Ouwerkerk-Mahadevan, Guy De La Rosa, Ronald Kalmeijer, Rekha Sinha, Maria Beumont-Mauviel
Journal: The Lancet (2014)
Critical issues in clinical periodontal research
Authors: Philip M. Preshaw
Journal: Periodontology 2000 (2012)

Abstract As periodontal researchers and clinicians, we are challenged every day to make decisions relating to the clinical management of our patients and about how best to conduct clinical periodontal research. This volume of Periodontology 2000 addresses some of the critical issues in contemporary clinical periodontics and periodontal research that are of direct relevance to clinicians, researchers, teachers and students. The 11 review articles in this volume of Periodontology 2000 focus on aspects of periodontal research methodology and clinical periodontology. In terms of research methodology, the articles aim to inform the reader on topics relating to randomized controlled trials in periodontal research, evidence‐based dentistry, calibration of clinical examiners and statistics relevant to periodontal research. The clinical periodontology articles address issues relating to decisions on retaining periodontally compromised teeth or replacing them with implants, periodontal management in the patient with osteoporosis, surgical approaches for root coverage and the emerging science of advanced regenerative technologies, including the use of stem cells, for periodontal regeneration. It is hoped that these critical reviews will address many of the dilemmas that confront us on a regular basis and provide practical guidance to those engaged in both clinical periodontology and clinical periodontal research.
Endoscopic surveillance of patients with Barrett's oesophagus
Authors: H Barr
Journal: Gut (2002)

I propose that a patient with a clinical diagnosis of Barrett’s oesophagus (BO) must have regularly endoscopic surveillance and protocol biopsy. BO is defined by endoscopically visible oesophageal columnar epithelium with intestinal metaplasia. The purpose of screening is detection of dysplastic change and early cancer, to allow early intervention and prevention of the suffering of symptomatic oesophageal adenocarcinoma and premature death.

The quandaries and uncertainties that occur in the minds of both the patient and their doctor when confronted with a diagnosis of BO illustrate the dilemmas of post modern evidence based medicine. Presentation of the facts leads to diverse interpretations. Surveillance can reveal ubiquitous human folly, best exposed by Swift’s wretched Struldbrugs decaying into immortality ( Gullivier’s Travels , 1726). I will argue that Barrett’s surveillance prolongs life not death, relieving suffering. The current myopic approach to patients with BO exposes the “shoulder shrug” of restrictive reactive medicine.

### Is the disease an “important” health problem?

To justify screening, the disease must meet …
<i>CDKN2A</i>mutations in melanoma families from Uruguay
Authors: A.L. Borges, F. Cuéllar, J.A. Puig-Butillé, M. Scarone, L. Delgado, C. Badenas, M. Milà, J. Malvehy, V. Barquet, J. Núñez, M. Laporte, G. Fernández, P. Levrero, M. Martínez-Asuaga, S. Puig
Journal: British Journal of Dermatology (2009)

Background Familial melanoma, a cluster of several cases within a single family, accounts for approximately 10% of cases of melanoma. Hereditary melanoma is defined as two or more first-degree relatives having melanoma. A member of a melanoma-prone family has a 35–70-fold increased relative risk of developing a melanoma. Genetic susceptibility is linked to the major susceptibility genes CDKN2A and CDK4, and the minor susceptibility gene MC1R. Objectives To determine the clinical and genetic characteristics of cutaneous melanoma in melanoma-prone families from Uruguay. Methods We studied 13 individuals from six melanoma-prone families living in Uruguay. Phenotype, familial and personal history were recorded. Molecular screening of CDKN2A and CDK4 was done by polymerase chain reaction–single strand conformational polymorphism analysis. The MC1R gene was sequenced. Results Mutations in CDKN2A were detected in five of six families: c.−34G>T, p.G101W and p.E88X. A novel germline mutation p.E88X, associated with hereditary melanoma in two unrelated families, is described. We hypothesize that a founder effect occurred probably in the Mediterranean region. No mutations in CDK4 were detected. Six different MC1R variants, all previously reported, were present in Uruguayan families. Conclusions The overall rate of deleterious CDKN2A mutations in our familial melanoma pedigrees, even though the sample size is small, was considerably higher (83%) than the often quoted range.
Irinotecan in combination with 5-fluorouracil and folinic acid or with cisplatin in patients with advanced gastric or esophageal-gastric junction adenocarcinoma: results of a randomized phase II study
Authors: C. Pozzo, C. Barone, J. Szanto, E. Padi, C. Peschel, J. Bükki, V. Gorbunova, V. Valvere, J. Zaluski, M. Biakhov, E. Zuber, C. Jacques, R. Bugat
Journal: Annals of Oncology (2004)
The Psychobiology of Depression and Resilience to Stress: Implications for Prevention and Treatment
Authors: Steven M. Southwick, Meena Vythilingam, Dennis S. Charney
Journal: Annual Review of Clinical Psychology (2005)

This review discusses neurobiological and psychosocial factors associated with stress-induced depression and compares these factors with those believed to characterize stress resilience. Neurobiological factors that are discussed and contrasted include serotonin, the 5-HT1A receptor, polymorphisms of the 5-HT transporter gene, norepinephrine, alpha-2 adrenergic receptors, neuropeptide Y, polymorphisms of the alpha-2 adrenergic gene, dopamine, corticotropin-releasing hormone (CRH), dehydroepiandrosterone (DHEA), cortisol, and CRH receptors. These factors are described in the context of brain regions believed to be involved in stress, depression, and resilience to stress. Psychosocial factors associated with depression and/or stress resilience include positive emotions and optimism, humor, cognitive flexibility, cognitive explanatory style and reappraisal, acceptance, religion/spirituality, altruism, social support, role models, coping style, exercise, capacity to recover from negative events, and stress inoculation. The review concludes with potential psychological, social, spiritual, and neurobiological approaches to enhancing stress resilience, decreasing the likelihood of developing stress-induced depression/anxiety, and treating stress-induced psychopathology.