tbuckley/cabot-search huggingface dataset:
Statin discontinuation and risk of acute myocardial infarction in patients with rheumatoid arthritis: a population-based cohort study
Authors: Mary A De Vera, Hyon Choi, Michal Abrahamowicz, Jacek Kopec, Maria Victoria Goycochea-Robles, Diane Lacaille
Journal: Annals of the Rheumatic Diseases (2011)

Objectives Screening for cardiovascular risk factors and treating hyperlipidaemia with statins are recommended to reduce the increased cardiovascular risk in individuals with rheumatoid arthritis (RA). However, poor compliance with statins may limit their therapeutic benefit. Our objective was to evaluate the impact of statin discontinuation on risk of acute myocardial infarction (AMI) among RA patients. Methods The authors conducted a population-based cohort study of RA patients with incident statin use followed from May 1996 to March 2006 using administrative health data. Primary exposure was statin discontinuation for ≥3 months at any time during therapy course. The authors used Cox's proportional hazards models and modelled statin discontinuation as a time-dependent variable, while adjusting for age, sex, comorbidities, use of other medications influencing cardiac risk, and proxy indicators of RA severity. Results During 15 669 person-years of follow-up in 4102 incident-statin users with RA, the authors identified 264 AMI events. Statin discontinuation was associated with 67% increased risk of AMI (adjusted HR 1.67; 95% CI 1.24 to 2.25). There was a 2% increase in risk of AMI with each 1-month increase in the duration of discontinuation (adjusted HR 1.02; 95% CI 1.01 to 1.03). These associations were not modified by timing of first statin prescription, prior AMI status, sex and age (p values for interactions &gt;0.17). Conclusions These population-based data indicate that RA patients who discontinue statins have increased risk of AMI. Findings emphasise the need to raise awareness, among health professionals and people with RA, of the importance of compliance with statin therapy in RA.
Temporal Variability of Urinary Phthalate Metabolite Levels in Men of Reproductive Age
Authors: Russ Hauser, John D. Meeker, Sohee Park, Manori J. Silva, Antonia M. Calafat
Journal: Environmental Health Perspectives (2004)

Phthalates are a family of multifunctional chemicals widely used in personal care and other consumer products. The ubiquitous use of phthalates results in human exposure through multiple sources and routes, including dietary ingestion, dermal absorption, inhalation, and parenteral exposure from medical devices containing phthalates. We explored the temporal variability over 3 months in urinary phthalate metabolite levels among 11 men who collected up to nine urine samples each during this time period. Eight phthalate metabolites were measured by solid-phase extraction–high-performance liquid chromatography–tandem mass spectrometry. Statistical analyses were performed to determine the between- and within-subject variance apportionment, and the sensitivity and specificity of a single urine sample to classify a subject's 3-month average exposure. Five of the eight phthalates were frequently detected. Monoethyl phthalate (MEP) was detected in 100% of samples; monobutyl phthalate, monobenzyl phthalate, mono-2-ethylhexyl phthalate (MEHP), and monomethyl phthalate were detected in > 90% of samples. Although we found both substantial day-to-day and month-to-month variability in each individual's urinary phthalate metabolite levels, a single urine sample was moderately predictive of each subject's exposure over 3 months. The sensitivities ranged from 0.56 to 0.74. Both the degree of between- and within-subject variance and the predictive ability of a single urine sample differed among phthalate metabolites. In particular, a single urine sample was most predictive for MEP and least predictive for MEHP. These results suggest that the most efficient exposure assessment strategy for a particular study may depend on the phthalates of interest.
Statins in lymphangioleiomyomatosis: a word of caution
Authors: S. El-Chemaly, A. Taveira-DaSilva, M. P. Stylianou, J. Moss
Journal: European Respiratory Journal (2009)

Statins in lymphangioleiomyomatosis: a word of cautionTo the Editors:Lymphangioleiomyomatosis (LAM) is a rare progressive cystic lung disease affecting primarily females, characterised by the proliferation of neoplastic LAM cells with mutations in the tuberous sclerosis complex (TSC)1 or TSC2 genes.There is no proven therapy for LAM, but results of studies with sirolimus, an inhibitor of the mammalian target of rapamycin (mTOR), have been promising [1].Motivated by the finding [2] that in vitro, statins, which inhibit 3-hydroxy-3-methyl-glutarycoenzyme-A (HMG-CoA) reductase, inhibited the growth of TSC2 -/-cells, we evaluated the effects of statins on the decline of lung function in 335 patients with LAM. METHODSWe conducted a retrospective chart review on 504 patients with LAM referred to the National Institutes of Health since 1996, and enrolled in the National Heart, Lung, and Blood Institute (NHLBI) protocol 95-H-0186, approved by the NHLBI Institutional Review Board.All patients gave informed consent before enrollment.Patients were excluded if they were: 1) recipients of lung or kidney transplant; 2) receiving off-label sirolimus, or enrolled in the Multicenter International Lymphangioleiomyomatosis Efficacy of Sirolimus trial, or taking another mTOR inhibitor; 3) taking doxycycline [3]; 4) not followed long enough to calculate rates of decline in lung function; or 5) taking statins for an unknown length of time.Complete data for analysis were available for 335 patients.Univariate and multivariate analysis were conducted, comparing LAM patients receiving statins with the general LAM patient population.
Distinguishing Adolescents With ADHD From Their Unaffected Siblings and Healthy Comparison Subjects by Neural Activation Patterns During Response Inhibition
Authors: Daan van Rooij, Pieter J. Hoekstra, Maarten Mennes, Daniel von Rhein, Andrieke J.A.M. Thissen, Dirk Heslenfeld, Marcel P. Zwiers, Stephen V. Faraone, Jaap Oosterlaan, Barbara Franke, Nanda Rommelse, Jan K. Buitelaar, Catharina A. Hartman
Journal: American Journal of Psychiatry (2015)

Dysfunctional response inhibition is a key executive function impairment in attention deficit hyperactivity disorder (ADHD). Still, behavioral response inhibition measures do not consistently differentiate affected from unaffected individuals. The authors therefore investigated neural correlates of response inhibition and the familial nature of these neural correlates.Functional MRI measurements of neural activation during the stop-signal task and behavioral measures of response inhibition were obtained in adolescents and young adults with ADHD (N=185), their unaffected siblings (N=111), and healthy comparison subjects (N=124).Stop-signal task reaction times were longer and error rates were higher in participants with ADHD, but not in their unaffected siblings, while reaction time variability was higher in both groups than in comparison subjects. Relative to comparison subjects, participants with ADHD and unaffected siblings had neural hypoactivation in frontal-striatal and frontal-parietal networks, whereby activation in inferior frontal and temporal/parietal nodes in unaffected siblings was intermediate between levels of participants with ADHD and comparison subjects. Furthermore, neural activation in inferior frontal nodes correlated with stop-signal reaction times, and activation in both inferior frontal and temporal/parietal nodes correlated with ADHD severity.Neural activation alterations in ADHD are more robust than behavioral response inhibition deficits and explain variance in response inhibition and ADHD severity. Although only affected participants with ADHD have deficient response inhibition, hypoactivation in inferior frontal and temporal-parietal nodes in unaffected siblings supports the familial nature of the underlying neural process. Activation deficits in these nodes may be useful as endophenotypes that extend beyond the affected individuals in the family.
Inhibition of Src Tyrosine Kinase Impairs Inherent and Acquired Gemcitabine Resistance in Human Pancreatic Adenocarcinoma Cells
Authors: Mark S. Duxbury, Hiromichi Ito, Michael J. Zinner, Stanley W. Ashley, Edward E. Whang
Journal: Clinical Cancer Research (2004)

Abstract Purpose: We tested the hypotheses that Src tyrosine kinase overactivity represents a chemoresistance mechanism and that Src inhibition may enhance gemcitabine cytotoxicity in pancreatic adenocarcinoma cells. Experimental Design: Pancreatic adenocarcinoma cells PANC1, MiaPaCa2, Capan2, BxPC3, and PANC1GemRes, a stably gemcitabine-resistant subline of PANC1, were exposed to combinations of gemcitabine and Src tyrosine kinase inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2). Src expression, phosphorylation (Tyr-416), and activity were analyzed by immunoblotting and in vitro kinase assay. Expression of the M2 subunit of ribonucleotide reductase (RRM2), a putative chemoresistance enzyme, was quantified by Northern and Western blot. Cellular proliferation was quantified by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis was characterized by YO-PRO-1/propidium iodide staining, fluorometric caspase profiling, and caspase inhibition (Z-Val-Ala-Asp-fluoromethyl ketone). The effects of constitutively active and dominant negative Src were determined. The therapeutic efficacy of PP2 in combination with gemcitabine was tested in nude mice orthotopically xenografted with PANC1GemRes. Results: Greater gemcitabine resistance was associated with higher Src phosphorylation and activity, both of which were higher in PANC1GemRes, relative to PANC1; total Src levels were alike. PANC1GemRes overexpressed RRM2. PP2 enhanced inherent gemcitabine chemosensitivity and attenuated gemcitabine resistance in PANC1GemRes. Constitutively active Src increased gemcitabine chemoresistance; dominant negative Src impaired gemcitabine chemoresistance. PP2 augmented gemcitabine-induced caspase-mediated apoptosis, suppressed RRM2 expression, and decreased activity of the RRM2-regulating transcription factor E2F1 in PANC1GemRes. PP2 and gemcitabine in combination substantially decreased tumor growth and inhibited metastasis in vivo. Conclusions: Increased Src tyrosine kinase activity represents a potential chemoresistance mechanism and a promising therapeutic target warranting further investigation in gemcitabine-resistant pancreatic adenocarcinoma.
Daunorubicin Versus Mitoxantrone Versus Idarubicin As Induction and Consolidation Chemotherapy for Adults With Acute Myeloid Leukemia: The EORTC and GIMEMA Groups Study AML-10
Authors: Franco Mandelli, Marco Vignetti, Stefan Suciu, Roberto Stasi, Maria-Concetta Petti, Giovanna Meloni, Petra Muus, Filippo Marmont, Jean-Pierre Marie, Boris Labar, Xavier Thomas, Francesco Di Raimondo, Roel Willemze, Vincenzo Liso, Felicetto Ferrara, Liliana Baila, Paola Fazi, Robert Zittoun, Sergio Amadori, Theo de Witte
Journal: Journal of Clinical Oncology (2009)

Purpose To compare the antitumor efficacy of three different anthracyclines in combination with cytarabine and etoposide in adult patients with newly diagnosed acute myeloid leukemia (AML). Patients and Methods We randomly assigned 2,157 patients (age range, 15 to 60 years) to receive intensive induction-consolidation chemotherapy containing either daunorubicin, idarubicin, or mitoxantrone. After achieving complete remission (CR), patients were assigned to undergo either allogeneic or autologous stem-cell transplantation (SCT), depending on the availability of a sibling donor. Results The overall CR rate (69%) was similar in the three groups. Autologous SCT was performed in 37% of cases in the daunorubicin arm versus only 29% and 31% in mitoxantrone and idarubicin, respectively (P &lt; .001). However, the disease-free survival (DFS) and survival from CR were significantly shorter in the daunorubicin arm: the 5-year DFS was 29% versus 37% and 37% in mitoxantrone and idarubicin, respectively. The proportion of patients who underwent allogeneic SCT (22%) was equivalent in the three treatment groups, and the outcome was similar as well: the 5-year overall survival rates were 34%, 34%, and 31%, respectively. Conclusion In adult patients with AML who do not receive an allogeneic SCT, the use of mitoxantrone or idarubicin instead of daunorubicin enhances the long-term efficacy of chemotherapy.
Intensive training in young athletes.
Authors: N Maffulli, E Pintore
Journal: British Journal of Sports Medicine (1990)

An increasing number of children take part in organized sporting activities, undergoing intensive training and high level competition from an early age. Although intensive training in children may foster health benefits, many are injured as a result of training, often quite seriously. This paper reviews some of the areas of research dealing with intensively trained young athletes, and focuses on physical, cardiovascular and muscular effects, sports injuries and psychological effects of intensive training. It is concluded that measures should be taken to modify present training and competition schemes to avoid the deleterious effects of intensive physical activity on these children.
Condom Use and the Risk of Genital Human Papillomavirus Infection in Young Women
Authors: Rachel L. Winer, James P. Hughes, Qinghua Feng, Sandra O'Reilly, Nancy B. Kiviat, King K. Holmes, Laura A. Koutsky
Journal: New England Journal of Medicine (2006)

To evaluate whether the use of male condoms reduces the risk of male-to-female transmission of human papillomavirus (HPV) infection, longitudinal studies explicitly designed to evaluate the temporal relationship between condom use and HPV infection are needed.We followed 82 female university students who reported their first intercourse with a male partner either during the study period or within two weeks before enrollment. Cervical and vulvovaginal samples for HPV DNA testing and Papanicolaou testing were collected at gynecologic examinations every four months. Every two weeks, women used electronic diaries to record information about their daily sexual behavior. Cox proportional-hazards models were used to evaluate risk factors for HPV infection.The incidence of genital HPV infection was 37.8 per 100 patient-years at risk among women whose partners used condoms for all instances of intercourse during the eight months before testing, as compared with 89.3 per 100 patient-years at risk in women whose partners used condoms less than 5 percent of the time (adjusted hazard ratio, 0.3; 95 percent confidence interval, 0.1 to 0.6, adjusted for the number of new partners and the number of previous partners of the male partner). Similar associations were observed when the analysis was restricted to high-risk and low-risk types of HPV and HPV types 6, 11, 16, and 18. In women reporting 100 percent condom use by their partners, no cervical squamous intraepithelial lesions were detected in 32 patient-years at risk, whereas 14 incident lesions were detected during 97 patient-years at risk among women whose partners did not use condoms or used them less consistently.Among newly sexually active women, consistent condom use by their partners appears to reduce the risk of cervical and vulvovaginal HPV infection.
Randomized Trial of Posaconazole and Benznidazole for Chronic Chagas' Disease
Authors: Israel Molina, Jordi Gómez i Prat, Fernando Salvador, Begoña Treviño, Elena Sulleiro, Núria Serre, Diana Pou, Sílvia Roure, Juan Cabezos, Lluís Valerio, Albert Blanco-Grau, Adrián Sánchez-Montalvá, Xavier Vidal, Albert Pahissa
Journal: New England Journal of Medicine (2014)

Current therapeutic options for Chagas' disease are limited to benznidazole and nifurtimox, which have been associated with low cure rates in the chronic stage of the disease and which have considerable toxicity. Posaconazole has shown trypanocidal activity in murine models.We performed a prospective, randomized clinical trial to assess the efficacy and safety of posaconazole as compared with the efficacy and safety of benznidazole in adults with chronic Trypanosoma cruzi infection. We randomly assigned patients to receive posaconazole at a dose of 400 mg twice daily (high-dose posaconazole), posaconazole at a dose of 100 mg twice daily (low-dose posaconazole), or benznidazole at a dose of 150 mg twice daily; all the study drugs were administered for 60 days. We assessed antiparasitic activity by testing for the presence of T. cruzi DNA, using real-time polymerase-chain-reaction (rt-PCR) assays, during the treatment period and 10 months after the end of treatment. Posaconazole absorption was assessed on day 14.The intention-to-treat population included 78 patients. During the treatment period, all the patients tested negative for T. cruzi DNA on rt-PCR assay beyond day 14, except for 2 patients in the low-dose posaconazole group who tested positive on day 60. During the follow-up period, in the intention-to-treat analysis, 92% of the patients receiving low-dose posaconazole and 81% receiving high-dose posaconazole, as compared with 38% receiving benznidazole, tested positive for T. cruzi DNA on rt-PCR assay (P<0.01 for the comparison of the benznidazole group with either posaconazole group); in the per-protocol analysis, 90% of the patients receiving low-dose posaconazole and 80% of those receiving high-dose posaconazole, as compared with 6% receiving benznidazole, tested positive on rt-PCR assay (P<0.001 for the comparison of the benznidazole group with either posaconazole group). In the benznidazole group, treatment was discontinued in 5 patients because of severe cutaneous reactions; in the posaconazole groups, 4 patients had aminotransferase levels that were more than 3 times the upper limit of the normal range, but there were no discontinuations of treatment.Posaconazole showed antitrypanosomal activity in patients with chronic Chagas' disease. However, significantly more patients in the posaconazole groups than in the benznidazole group had treatment failure during follow-up. (Funded by the Ministry of Health, Spain; CHAGASAZOL ClinicalTrials.gov number, NCT01162967.).
THE ENHANCING EFFECT OF THE MICROBIAL FLORA ON MACROPHAGE FUNCTION AND THE IMMUNE RESPONSE
Authors: Heinz Bauer, Fiorenzo Paronetto, Willard A. Burns, Albert Einheber
Journal: The Journal of Experimental Medicine (1966)

The immune response to bacteria and to a soluble protein was compared in germfree and conventionalized mice. Sixty germfree and 59 conventionalized mice received a suspension of killed Serratia marcescens into one front foot-pad and sterile horse ferritin into the other and were sacrificed in groups from 2 hr to 14 days after inoculation. All mice had no pre-existing antibody to either antigen and the flora of the conventionalized mice never contained Serratia. Lymphatic tissue changes and the fate of the antigens were followed in axillary lymph nodes and the spleens by histologic, fluorescent antibody, and autoradiographic techniques after tritiated thymidine injection. Individual serum antibody titers for both antigens were determined at each time period. The cellular and serologic responses were slightly delayed in the germfree mice but later equaled and sometimes exceeded those of the conventional animals. In all animals, lymph nodes draining the site of Serratia injection showed a more vigorous response than those on the ferritin-injected side but the reaction was qualitatively the same for both antigens. All lymph nodes contained the antigens by 2 hr after foot-pad injection. With time, both antigens lost their particulate nature sooner in conventionalized than in germfree macrophages. In the latter, both antigens persisted throughout the study while no longer demonstrable with fluoresceinated antiserum in conventional macrophages after the first week. While phagocytosis is equal in germfree and conventional mice, a greater digestive capacity of macrophages for antigens seems to result from the continuous exposure of conventional animals to the immunologic effects of the microbial flora. Conversely, the lack of substantial antigenic stimulation of lymphatic tissue in germfree animals fails to develop these macrophage functions beyond their basic ability to degrade foreign substances. Although the onset of the immune response is delayed in germfree mice, the relatively prolonged antigen digestion and the presumably slower release of immunogenic antigen fragments result in a more sustained and sometimes greater response than in conventional animals. This modifying effect of the microflora on the function of macrophages during the immune response is independent of previous experience with, or the nature of, the antigen.
Incidence of sporting injury in New Zealand youths aged 6-15 years.
Authors: R G Pringle, P McNair, S Stanley
Journal: British Journal of Sports Medicine (1998)

To document the incidence of injury in 6-15 year olds playing rugby union, rugby league, and netball, and to identify the common mechanisms, sites, severity, and time of injury.Cross sectional data were collected by trained observers who watched 258 games of rugby union, netball, and rugby league over a four week period. The condition of the injured participants was monitored until recovery.In total, 5174 players were observed and an injury rate of 18 per 1000 player hours was calculated. Of all observed injuries, 29% required some form of medical treatment. A significant difference (p<0.05) in the distribution of injury over the four quarters of the games was recorded, most occurring in the first three quarters. In total, 81% of the injuries were classified as contact injuries, and these mainly occurred through direct contact with the opposition. Of all observed injuries, 27% were recurrent.The incidence of injury in rugby union, netball, and rugby league is low for children aged between 6 and 15 years relative to adult rates.