tbuckley/cabot-search huggingface dataset:
Use of clarithromycin and roxithromycin and risk of cardiac death: cohort study
Authors: H. Svanstrom, B. Pasternak, A. Hviid
Journal: BMJ (2014)

To assess the risk of cardiac death associated with the use of clarithromycin and roxithromycin.Cohort study.Denmark, 1997-2011.Danish adults, 40-74 years of age, who received seven day treatment courses with clarithromycin (n = 160,297), roxithromycin (n = 588,988), and penicillin V (n = 4,355,309).The main outcome was risk of cardiac death associated with clarithromycin and roxithromycin, compared with penicillin V. Subgroup analyses were conducted according to sex, age, risk score, and concomitant use of drugs that inhibit the cytochrome P450 3A enzyme, which metabolises macrolides.A total of 285 cardiac deaths were observed. Compared with use of penicillin V (incidence rate 2.5 per 1000 person years), use of clarithromycin was associated with a significantly increased risk of cardiac death (5.3 per 1000 person years; adjusted rate ratio 1.76, 95% confidence interval 1.08 to 2.85) but use of roxithromycin was not (2.5 per 1000 person years; adjusted rate ratio 1.04, 0.72 to 1.51). The association with clarithromycin was most pronounced among women (adjusted rate ratios 2.83 (1.50 to 5.36) in women and 1.09 (0.51 to 2.35) in men). Compared with penicillin V, the adjusted absolute risk difference was 37 (95% confidence interval 4 to 90) cardiac deaths per 1 million courses with clarithromycin and 2 (-14 to 25) cardiac deaths per 1 million courses with roxithromycin.This large cohort study found a significantly increased risk of cardiac death associated with clarithromycin. No increased risk was seen with roxithromycin. Given the widespread use of clarithromycin, these findings call for confirmation in independent populations.
Pleural effusions in an overlap syndrome of idiopathic hypereosinophilic syndrome and erythema elevatum diutinum
Authors: JF Cordier, M Faure, C Hermier, J Brune
Journal: European Respiratory Journal (1990)

We report a patient with idiopathic hypereosinophilic syndrome presenting with bilateral eosinophilic pleural effusions. He also had erythema elevatum diutinum, a rare skin disease of the vasculitic type. No cardiomyopathy was present. Pleural effusions, skin lesions, and blood eosinophilia disappeared with prolonged corticosteroid treatment.
THE SUBMICROSCOPIC ORGANIZATION OF AXON MATERIAL ISOLATED FROM MYELIN NERVE FIBERS
Authors: E. De Robertis, C. M. Franchi
Journal: The Journal of Experimental Medicine (1953)

A technique has been developed for the extrusion of axon material from myelinated nerve fibers. This material is then compressed and prepared for observation with the electron microscope. All the stages of preparation and purification of the axon material can be checked microscopically and in the present paper they are illustrated with phase contrast photomicrographs. Observation with the electron microscope of the compressed axons showed the presence of the following components: granules, fibrils, and a membranous material. Only the larger granules could be seen with the ordinary microscope. A considerable number of dense granules were observed. Of these the largest resemble typical mitochondria of 250 mmicro by 900 mmicro. In addition rows or small clusters of dense granules ranging in diameter from 250 to 90 mmicro were present. In several specimens fragments of a membrane 120 to 140 A thick and intimately connected with the axon were found. The entire axon appeared to be constituted of a large bundle of parallel tightly packed fibrils among which the granules are interspersed. The fibrils are of indefinite length and generally smooth. They are rather labile structures, less resistant in the rat than in the toad nerve. They varied between 100 and 400 A in diameter and in some cases disintegrated into very fine filaments (less than 100 A thick). The significance is discussed of the submicroscopic structures revealed by electron microscopy of the material prepared in the way described.
Acquired <i>TNFRSF14</i> Mutations in Follicular Lymphoma Are Associated with Worse Prognosis
Authors: K-John J. Cheung, Nathalie A. Johnson, Joslynn G. Affleck, Tesa Severson, Christian Steidl, Susana Ben-Neriah, Jacqueline Schein, Ryan D. Morin, Richard Moore, Sohrab P. Shah, Hong Qian, Jessica E. Paul, Adele Telenius, Thomas Relander, Wan Lam, Kerry Savage, Joseph M. Connors, Carolyn Brown, Marco A. Marra, Randy D. Gascoyne, Douglas E. Horsman
Journal: Cancer Research (2010)

Abstract Clinical correlative studies have linked 1p36 deletions with worse prognosis in follicular lymphoma (FL). In this study, we sought to identify the critical gene(s) in this region that is responsible for conferring inferior prognosis. BAC array technology applied to 141 FL specimens detected a minimum region of deletion (MRD) of ∼97 kb within 1p36.32 in 20% of these cases. Frequent single-nucleotide polymorphism–detected copy-neutral loss of heterozygosity was also found in this region. Analysis of promoter CpGs in the MRD did not reveal differential patterns of DNA methylation in samples that differed in 1p36 status. Exon sequencing of MRD genes identified somatic alterations in the TNFRSF14 gene in 3 of 11 selected cases with matching normal DNA. An expanded cohort consisting of 251 specimens identified 46 cases (18.3%) with nonsynonymous mutations affecting TNFRSF14. Overall survival (OS) and disease-specific survival (DSS) were associated with the presence of TNFRSF14 mutation in patients whose overall treatment included rituximab. We further showed that inferior OS and DSS were most pronounced in patients whose lymphomas contained both TNFRSF14 mutations and 1p36 deletions after adjustment for the International Prognostic Index [hazard ratios of 3.65 (95% confidence interval, 1.35–9.878, P = 0.011) and 3.19 (95% confidence interval, 1.06–9.57, P = 0.039), respectively]. Our findings identify TNFRSF14 as a candidate gene associated with a subset of FL, based on frequent occurrence of acquired mutations and their correlation with inferior clinical outcomes. Cancer Res; 70(22); 9166–74. ©2010 AACR.
Dietary Factors and the Risk of Incident Kidney Stones in Men
Authors: Eric N. Taylor, Meir J. Stampfer, Gary C. Curhan
Journal: Journal of the American Society of Nephrology (2004)

Diet plays an important role in the pathogenesis of kidney stones. Because the metabolism of many dietary factors, such as calcium, may change with age, the relation between diet and kidney stones may be different in older adults. Uncertainty also remains about the association between many dietary factors, such as vitamin C, magnesium, and animal protein, and the risk of kidney stone formation. To examine the association between dietary factors and the risk of incident, symptomatic kidney stones in men and to determine whether these associations vary with age, a prospective cohort study was conducted of 45,619 men without a history of nephrolithiasis. Self-administered food frequency questionnaires were used to assess diet every 4 yr. A total of 1473 incident symptomatic kidney stones were documented during 477,700 person-years of follow-up. For men aged <60 yr, the multivariate relative risk (RR) for stone formation in the highest quintile of dietary calcium as compared with the lowest quintile was 0.69 (95% confidence interval [CI], 0.56 to 0.87; P = 0.01 for trend). By contrast, there was no association between dietary calcium and stone formation in men aged 60 yr or older. The multivariate RR for men who consumed 1000 mg or greater of vitamin C per day compared with those who consumed less than the recommended dietary allowance of 90 mg/d was 1.41 (95% CI, 1.11 to 1.80; P = 0.01 for trend). Other dietary factors showed the following multivariate RR among men in the highest quintile of intake compared with those in the lowest: magnesium, 0.71 (95% CI, 0.56 to 0.89; P = 0.01 for trend); potassium, 0.54 (95% CI, 0.42 to 0.68; P < 0.001 for trend); and fluid, 0.71 (95% CI, 0.59 to 0.85; P < 0.001 for trend). Animal protein was associated with risk only in men with a body mass index <25 kg/m2 (RR, 1.38; 95% CI, 1.05 to 1.81; P = 0.03 for trend). Sodium, phosphorus, sucrose, phytate, vitamin B6, vitamin D, and supplemental calcium were not independently associated with risk. In conclusion, the association between calcium intake and kidney stone formation varies with age. Magnesium intake decreases and total vitamin C intake seems to increase the risk of symptomatic nephrolithiasis. Because age and body size affect the relation between diet and kidney stones, dietary recommendations for stone prevention should be tailored to the individual patient.
Time Course of Hepatitis A Virus Antibody Titer After Active and Passive Immunization
Authors: Shigetoshi Fujiyama, Shiro Iino, Koichi Odoh, Shoji Kuzuhara, Hiroaki Watanabe, Masahiko Tanaka, Kyosuke Mizuno, Tatsuo Sato
Journal: Hepatology (1992)

To investigate the antibody titer necessary to prevent hepatitis A virus infection, either 15 or 7.5 mg/kg of immune serum globulin was injected into 10 antihepatitis A virus negative volunteers and their serum antihepatitis A virus titers were observed for 28 wk. In addition, antibody titers were observed for 96 wk in a phase 1 clinical trial of a hepatitis A vaccine. The two studies were then compared to assess the immunogenicity of the vaccine and the persistence of the antibody. Serum-neutralizing antibody titers that were greater than or equal to 4 (considered as positive) persisted for 18 wk and 14 wk after the injection of 15 and 7.5 mg/kg of globulin, respectively. Hepatitis A virus vaccine recipients showed adequate neutralizing antibody titers, with the groups receiving 1, 0.5 and 0.25 micrograms/dose showing titers of 4(5.5), 4(4.7) and 4(4), respectively, at 18 mo after the third inoculation. These findings suggested that effective blood antibody titers were likely to be retained in the 1.0 micrograms or 0.5 micrograms/dose groups for at least several years. Moreover, the serum antihepatitis A virus titers demonstrated by a modified radioimmunoassay changed in parallel with the neutralizing antibody titers in the volunteers injected with globulin.
FURTHER LABORATORY STUDIES ON THE CLASSIFICATION OF PSITTACOSIS-LIKE AGENTS
Authors: M. Dorthy Beck, Monroe D. Eaton, Rosemary O'Donnell
Journal: The Journal of Experimental Medicine (1944)

1. It was demonstrated by pathogenicity and latency tests in mammals and birds that variations exist among a group of viruses, isolated from several sources and producing coccoid elementary bodies resembling those of psittacosis. 2. Active cross immunity tests emphasized these differences and confirmed their significance. 3. On the basis of the present experimental evidence the psittacosis-like viruses causing atypical pneumonia in man may be classified into three groups: psittacosis, ornithosis, and human pneumonitis (strain S-F) of undetermined origin.
A Randomized, Double-Blind, Phase II Study of Two Doses of Pemetrexed as First-Line Chemotherapy for Advanced Breast Cancer
Authors: Antonio Llombart-Cussac, Miguel Martin, Nadia Harbeck, Rodica M. Anghel, Alexandra E. Eniu, Mark W. Verrill, Patrick Neven, Jacques De Grève, Allen S. Melemed, Romnee Clark, Lorinda Simms, Christopher J. Kaiser, Doreen Ma
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Pemetrexed has shown varied response rates in advanced breast cancer. This randomized, double-blind, phase II study was conducted to assess the efficacy and safety of two doses of pemetrexed in a homogeneous population. A secondary objective was to identify molecular biomarkers correlating with response and toxicity. Experimental Design: Patients with newly diagnosed metastatic breast cancer or locally recurrent breast cancer received 600 mg/m2 (P600 arm) or 900 mg/m2 (P900 arm) of pemetrexed on day 1 of a 21-day cycle. All patients received folic acid and vitamin B12 supplementation. Results: The P600 (47 patients) and P900 (45 patients) arms had response rates of 17.0% (95% confidence interval, 7.7-30.8%) and 15.6% (95% confidence interval, 6.5-29.5%) with ∼50% stable disease per arm, median progression-free survival of 4.2 and 4.1 months, and median times to tumor progression of 4.2 and 4.6 months, respectively. Both arms exhibited minimal toxicity (grade 3/4 neutropenia &amp;lt;20%, leukopenia &amp;lt;9%, and other toxicities &amp;lt;5%). Tumor samples from 49 patients were assessed for the expression levels of 12 pemetrexed-related genes. Folylpolyglutamate synthetase and thymidine phosphorylase correlated with efficacy. Best response rates and median time to tumor progression for high versus low thymidine phosphorylase expression were 27.6% versus 6.3% (P = 0.023) and 5.4 versus 1.9 months (P = 0.076), and for folylpolyglutamate synthetase were 37.5% versus 10.0% (P = 0.115) and 8.6 versus 3.0 months (P = 0.019), respectively. γ-Glutamyl hydrolase expression correlated with grade 3/4 toxicities: 78.6% for high versus 27.3% for low γ-glutamyl hydrolase (P = 0.024). Conclusion: The two pemetrexed doses yielded similar efficacy and safety profiles. Exploratory biomarker analysis identified efficacy and toxicity correlations and warrants further evaluation.
Molecular Mechanisms of Cardiovascular Toxicity of Targeted Cancer Therapeutics
Authors: Hui Cheng, Thomas Force
Journal: Circulation Research (2010)

In 2002, Hoshijima and Chien drew largely theoretical parallels between the dysregulation of the signaling pathways driving cancer and those driving cardiac hypertrophy (Hoshijima M, Chien KR. J Clin Invest. 2002;109:849-855). On the surface, this statement appeared to stretch the limits of reason, given the fact that cancer cells are known for their proliferative capacity, and adult cardiomyocytes are, except under unusual circumstances, terminally differentiated and incapable of re-entering the cell cycle. However, on closer examination, there are numerous parallels between signaling pathways that drive tumorigenesis and signaling pathways that regulate hypertrophic responses and survival in cardiomyocytes. Indeed, this issue appears to be at the core of the cardiotoxicity (often manifest as a dilated cardiomyopathy) that can result from treatment with agents typically referred to as "targeted therapeutics," which target specific protein kinases that are dysregulated in cancer. Herein, we examine the cardiotoxicity of targeted therapeutics, focusing on the underlying molecular mechanisms, thereby allowing an understanding of the problem but also allowing the identification of novel, and sometimes surprising, roles played by protein kinases in the heart.
Complicated grief after death of a relative in the intensive care unit
Authors: Nancy Kentish-Barnes, Marine Chaize, Valérie Seegers, Stéphane Legriel, Alain Cariou, Samir Jaber, Jean-Yves Lefrant, Bernard Floccard, Anne Renault, Isabelle Vinatier, Armelle Mathonnet, Danielle Reuter, Olivier Guisset, Zoé Cohen-Solal, Christophe Cracco, Amélie Seguin, Jacques Durand-Gasselin, Béatrice Éon, Marina Thirion, Jean-Philippe Rigaud, Bénédicte Philippon-Jouve, Laurent Argaud, Renaud Chouquer, Mélanie Adda, Céline Dedrie, Hugues Georges, Eddy Lebas, Nathalie Rolin, Pierre-Edouard Bollaert, Lucien Lecuyer, Gérard Viquesnel, Marc Léone, Ludivine Chalumeau-Lemoine, Maïté Garrouste, Benoit Schlemmer, Sylvie Chevret, Bruno Falissard, Élie Azoulay
Journal: European Respiratory Journal (2015)

An increased proportion of deaths occur in the intensive care unit (ICU). We performed this prospective study in 41 ICUs to determine the prevalence and determinants of complicated grief after death of a loved one in the ICU. Relatives of 475 adult patients were followed up. Complicated grief was assessed at 6 and 12 months using the Inventory of Complicated Grief (cut-off score &gt;25). Relatives also completed the Hospital Anxiety and Depression Scale at 3 months, and the Revised Impact of Event Scale for post-traumatic stress disorder symptoms at 3, 6 and 12 months. We used a mixed multivariate logistic regression model to identify determinants of complicated grief after 6 months. Among the 475 patients, 282 (59.4%) had a relative evaluated at 6 months. Complicated grief symptoms were identified in 147 (52%) relatives. Independent determinants of complicated grief symptoms were either not amenable to changes (relative of female sex, relative living alone and intensivist board certification before 2009) or potential targets for improvements (refusal of treatment by the patient, patient died while intubated, relatives present at the time of death, relatives did not say goodbye to the patient, and poor communication between physicians and relatives). End-of-life practices, communication and loneliness in bereaved relatives may be amenable to improvements.
Collagen and elastin metabolism in hypertensive pulmonary arteries of rats.
Authors: G J Poiani, C A Tozzi, S E Yohn, R A Pierce, S A Belsky, R A Berg, S Y Yu, S B Deak, D J Riley
Journal: Circulation Research (1990)

We evaluated the processes controlling the accumulation of collagen and elastin in main pulmonary arteries of rats during an episode of hypoxic pulmonary hypertension. Explant cultures of main pulmonary arteries were incubated with [3H]proline to measure collagen and protein synthesis and percent collagen synthesis. Elastin synthesis was measured by [14C]valine incorporation into insoluble elastin. Relative collagen synthesis increased twofold (from 1.1 +/- 0.2 x 10(3) to 2.0 +/- 1.0 x 10(3) disintegrations per minute [14C]hydroxyproline/vessel/hr/mg protein), relative collagen synthesis doubled (from 2% to 4-5% of total protein synthesis), and elastin synthesis increased ninefold (from 0.4 +/- 0.2 x 10(4) to 3.6 +/- 0.6 x 10(4) dpm [14C]valine/vessel/hr/mg protein) in early hypertension. The level of pro alpha l(I) collagen RNA paralleled the relative collagen synthetic rate during the study period. Within 7 days of recovery from hypoxia, collagen and elastin contents were normal. We conclude that collagen and elastin in main pulmonary arteries are synthesized rapidly during an episode of hypoxic pulmonary hypertension and that collagen and elastin are rapidly removed from the hypertensive vessel during normoxic recovery.
Low reproducibility of many lactate markers during incremental cycle exercise
Authors: R Hugh Morton, Stephen R Stannard, Bartholomew Kay
Journal: British Journal of Sports Medicine (2011)

Reports on reproducibility of lactate markers usually considered only two trials. The authors assessed reproducibility of power output at seven markers in 11 fit subjects over at least six trials under tightly controlled conditions. Subjects undertook incremental exercises (50 W start, +50 W every 3 min to exhaustion) on a cycle ergometer. At each trial blood lactate concentration was determined at rest and within the final 30 s of each stage. The Rest+1, 2.0 and 4.0 mmol/l markers were determined by interpolation, the D-max and nadir using a quadratic model and the lactate slope index using an exponential plus constant model, and a visual turnpoint was determined empirically. Intraclass correlations and coefficients of variation assessed reproducibility. Power output at all markers differed significantly between subjects, but not between trials. Intraclass correlation coefficients were respectively 0.799, 0.794, 0.807, 0.903, 0.677, 0.769 and 0.648, and corresponding standard errors of measurement 11.9, 9.2, 9.1, 2.5, 9.2, 10.8 and 24.7 W. Statistical powers of detecting a 30 W increment at these markers were 0.30, 0.43, 0.42, 0.98, 0.58, 0.38 and 0.18 respectively. These results indicate that only the D-max marker has good reproducibility and that it alone can identify small but meaningful changes in training status with sufficient statistical power.
Validation and use of a parametric model for projecting cystic fibrosis survivorship beyond observed data: a birth cohort analysis
Authors: A. D. Jackson, L. Daly, A. L. Jackson, C. Kelleher, B. C. Marshall, H. B. Quinton, G. Fletcher, M. Harrington, S. Zhou, E. F. McKone, C. Gallagher, L. Foley, P. Fitzpatrick
Journal: Thorax (2011)

<h3>Background</h3> The current lifetable approach to survival estimation is favoured by CF registries. Recognising the limitation of this approach, we examined the utility of a parametric survival model to project birth cohort survival estimates beyond the follow-up period, where short duration of follow-up meant median survival estimates were indeterminable. <h3>Methods</h3> Parametric models were fitted to observed survivorship data from the US CF Foundation (CFF) Patient Registry 1980–1994 birth cohort. Model-predicted median survival was estimated. The best fitting model was applied to a Cystic Fibrosis Registry of Ireland dataset to allow an evaluation of the model9s ability to estimate predicted median survival. This involved a comparison of birth cohort lifetable predicted and observed (Kaplan–Meier) median survival estimates. <h3>Results</h3> A Weibull model with main effects of gender and birth cohort was developed using a US CFF dataset (n=13 115) for which median survival was not directly estimable. Birth cohort lifetable predicted median survival for male and female patients born between 1985 and 1994 and surviving their first birthday was 50.9 and 42.4 years respectively. To evaluate the accuracy of a Weibull model in predicting median survival, a model was developed for the 1980–1984 Cystic Fibrosis Registry of Ireland birth cohort (n=243), which had an observed (Kaplan–Meier) median survival of 27.7 years. Model-predicted median survival estimates were calculated using data censored at different follow-up periods. The estimates converged to the true value as length of follow-up increased. <h3>Conclusions</h3> Accurate prognostic information that is clinically critical for care of patients affected by rare, life-limiting disorders can be provided by parametric survival models. Problems associated with short duration of follow-up for recent birth cohorts can be overcome using this approach, providing better opportunities to monitor survival and plan services locally.
Allergenicity suppression in natural latex surgical gloves
Authors: F. Leynadier, T. Tran Xuan, J. Dry
Journal: Allergy (1991)

By a revised manufacturing process we aimed to obtain latex surgical gloves without immediate allergenicity, and also to determine a simple physical technique by which to estimate this allergenicity. Five glove samples were evaluated for allergenicity by physical and biochemical methods and by skin texts at the University Allergy Centre, Three groups of allergic patients with documented anaphylaxis to surgical gloves, positive skin test to latex extract and specific IgE to latex (RAST Pharmacia &amp; class II), volunteered for the study. The protein content, the in vitro allergenic potency of glove supernatants (RAST inhibition) and the skin test results with glove supernatants were lower in washed gloves than in non‐washed samples ( P &lt; 0.02 to P &lt; 0.009). The supplementary effect of glove sterilization at 120°C (for 1 h in saturated steam) was obvious. The protein content became undetectable in four of the five glove supernatants, and skin tests results with sample supernatants were decreased (M±SEM = 0.68±0.29 mm vs 3.06±0.61 mm with non‐sterilized gloves), P &lt; 0.009 by Wilcoxon test. With the Spearman test there was a significant correlation ( P = 0.029) between the mean wheal size, obtained with supernatants (Groups 1 and 2) and electrical conductivity. Skin tests through pieces of gloves randomly distributed and coded were decreased by sterilization: 0.66±0.25 mm vs 2.86±00,45 mm, p 0.0001. Thus, it is possible to decrease glove allergenicity by washing them after mould forming and then sterilizing with steam. Electrical conductivity may be a simple parameter for revealing allergenicity.