tbuckley/cabot-search huggingface dataset:
Discontinuation of Statins in Routine Care Settings
Authors: Piet C. de Groen
Journal: Annals of Internal Medicine (2013)

LettersJuly 2, 2013Discontinuation of Statins in Routine Care SettingsPiet C. de Groen, MDPiet C. de Groen, MDFrom Mayo Clinic College of Medicine, Rochester, Minnesota.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-159-1-201307020-00020 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:As Zhang and colleagues (1) show, discontinuation of statins in routine care settings is common. Increased liver enzyme levels and perceived adverse effects are frequent reasons for discontinuation. Yet, sometimes statin therapy is the best treatment option for hyperlipidemia in patients with these abnormalities and prior statin-associated adverse effects.A 63-year-old woman was diagnosed at age 50 years with severe hyperlipidemia; her total cholesterol levels were 400 to 500 mg/dL (10.36 to 12.95 mmol/L). Her parents, 3 sisters, and brother had hyperlipidemia. Her father died at age 54 years of a myocardial infarction; her mother had survived ...References1. Zhang H, Plutzky J, Skentzos S, Morrison F, Mar P, Shubina M, et al. Discontinuation of statins in routine care settings: a cohort study. Ann Intern Med. 2013;158:526-34 LinkGoogle Scholar2. Guyatt GH, Keller JL, Jaeschke R, Rosenbloom D, Adachi JD, and Newhouse MT. The n-of-1 randomized controlled trial: clinical usefulness. Our three-year experience. Ann Intern Med. 1990;112:293-9 LinkGoogle Scholar Author, Article, and Disclosure InformationAuthors: Piet C. de Groen, MDAffiliations: From Mayo Clinic College of Medicine, Rochester, Minnesota.Disclosures: Consultancy: Invendo-Medical; Patents (planned, pending, or issued), royalties, stock/stock options (money to institution): Endometric; Travel/accommodations/meeting expenses unrelated to activities listed: Johns Hopkins. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoDiscontinuation of Statins in Routine Care Settings Huabing Zhang , Jorge Plutzky , Stephen Skentzos , Fritha Morrison , Perry Mar , Maria Shubina , and Alexander Turchin Discontinuation of Statins in Routine Care Settings Thomas W. LeBlanc , Jean S. Kutner , Christine S. Ritchie , and Amy P. Abernethy Discontinuation of Statins in Routine Care Settings Huabing Zhang , Jorge Plutzky , and Alexander Turchin Discontinuation of Statins in Routine Care Settings Danijela Gnjidic , David G. Le Couteur , and Sarah N. Hilmer Metrics July 2, 2013Volume 159, Issue 1Page: 74KeywordsAcidsAutoimmune hepatitisCardiovascular diseasesCholesterolEnzymesHepatitisHyperlipidemiaLipidsLiverLiver diseasesMusclesMyocardial infarctionOverlap syndromeSafetyStatins ePublished: 2 July 2013 Issue Published: July 2, 2013 Copyright & PermissionsCopyright © 2013 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
A5.23 Multiparameter Phospho-Flow Analysis of B Cells from Patients with Rheumatoid Arthritis
Authors: Daniel Szili, Judit Pozsgay, Zsuzsanna Banko, Tamas Gati, Gyorgy Nagy, Bernadett Rojkovich, Gabriella Sarmay
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background and Objectives</h3> Rheumatoid arthritis (RA) is a common, relapsing autoimmune disease, which affects approximately 1% of the population worldwide. While the specific molecular events that lead to initiation and onset of RA are not known, an uncontrolled activation of the immune system is considered to be a critical component of the disease. B lymphocytes undoubtedly play a critical role in disease aetiology. Antigen binding to B-cell receptor (BCR) triggers B cell activation, although the threshold of activation can be influenced by other receptors, such as TLR9. TLR9 has received substantial attention as a pathogenic co-stimulator of autoreactive B cell responses. Our aim was to compare basal activity and induced phosphorylation of AKT, ERK, p38 MAPK and CREB after stimulation of B cells from RA patients and healthy individuals via BCR and/or TLR9. <h3>Materials and Methods</h3> Blood samples were collected from healthy donors and RA patients having moderate (DAS28 3.2 &lt; 5.1) and active (DAS28 &gt; 5.1) disease. B cells were stimulated with anti-Ig (Fab')<sub>2</sub> and/or CpG ODN. Naive and memory B cells were identified by anti-CD20-A647 and anti-CD27-PE Phosphorylation level of AKT, ERK, p38 and CREB was detected before and after the stimuli by specific phospho-antibodies using multiparameter phospho-flow analysis. Results were evaluated by the FlowJo software. <h3>Results</h3> The basal level of phosphorylation of signalling molecules was significantly higher in RA patients as compared to healthy donors. The induced level of phosphorylation was also higher in RA samples in most of cases, CpG stimulated memory B cells from patients with active disease have shown the highest values. In anti-Ig plus CpG ODN stimulated samples phosphorylation of all molecules was significantly higher in both naïve and memory RA B cells as compared to healthy controls. However, when compared to unstimulated cells, the increment of phosphorylation in the stimulated cells was the same or lower in RA samples. <h3>Conclusions</h3> We have shown differences in the activation state of AKT, ERK, p38 and CREB in B cells from healthy individuals and RA patients. The higher basal phosphorylation level indicates the activated state of RA B cells. The lower capability of activation-induced phosphorylation may be a result of lower responsiveness of RA B cells. The analysis of phosphorylation signature in RA B-cells may provide new information to a better understanding of the disease.
Obesity and Risk of Recurrence or Death After Adjuvant Endocrine Therapy With Letrozole or Tamoxifen in the Breast International Group 1-98 Trial
Authors: Marianne Ewertz, Kathryn P. Gray, Meredith M. Regan, Bent Ejlertsen, Karen N. Price, Beat Thürlimann, Hervé Bonnefoi, John F. Forbes, Robert J. Paridaens, Manuela Rabaglio, Richard D. Gelber, Marco Colleoni, István Láng, Ian E. Smith, Alan S. Coates, Aron Goldhirsch, Henning T. Mouridsen
Journal: Journal of Clinical Oncology (2012)

To examine the association of baseline body mass index (BMI) with the risk of recurrence or death in postmenopausal women with early-stage breast cancer receiving adjuvant tamoxifen or letrozole in the Breast International Group (BIG) 1-98 trial at 8.7 years of median follow-up.This report analyzes 4,760 patients with breast cancer randomly assigned to 5 years of monotherapy with letrozole or tamoxifen in the BIG 1-98 trial with available information on BMI at randomization. Multivariable Cox modeling assessed the association of BMI with disease-free survival, overall survival (OS), breast cancer-free interval, and distant recurrence-free interval and tested for treatment-by-BMI interaction. Median follow-up was 8.7 years.Seventeen percent of patients have died. Obese patients (BMI ≥ 30 kg/m(2)) had slightly poorer OS (hazard ratio [HR] = 1.19; 95% CI, 0.99 to 1.44) than patients with normal BMI (< 25 kg/m(2)), whereas no trend in OS was observed in overweight (BMI 25 to < 30 kg/m(2)) versus normal-weight patients (HR = 1.02; 95% CI, 0.86 to 1.20). Treatment-by-BMI interactions were not statistically significant. The HRs for OS comparing obese versus normal BMI were HR = 1.22 (95% CI, 0.93 to 1.60) and HR = 1.18 (95% CI, 0.91 to 1.52) in the letrozole and tamoxifen groups, respectively.There was no evidence that the benefit of letrozole over tamoxifen differed according to patients' BMI.
Hepcidin and ferritin blood level as noninvasive tools for predicting breast cancer
Authors: R. Orlandi, M. De Bortoli, C.M. Ciniselli, E. Vaghi, D. Caccia, V. Garrisi, S. Pizzamiglio, S. Veneroni, C. Bonini, R. Agresti, M.G. Daidone, D. Morelli, C. Camaschella, P. Verderio, I. Bongarzone
Journal: Annals of Oncology (2013)
The Relationship of Clozapine and Haloperidol Treatment Response to Prefrontal, Hippocampal, and Caudate Brain Volumes
Authors: Celso Arango, Alan Breier, Robert McMahon, William T. Carpenter, Robert W. Buchanan
Journal: American Journal of Psychiatry (2003)

The study was designed to assess the predictive relationship between brain structure volume and positive and negative symptom response to clozapine and haloperidol.Partially responsive outpatients with schizophrenia who participated in a 10-week, parallel-group, double-blind comparison of clozapine and haloperidol and who had an available magnetic resonance imaging scan were included in the current study. Prefrontal gray and white matter, hippocampal, and caudate volumes were manually measured. The Scale for the Assessment of Negative Symptoms (SANS) and the Brief Psychiatric Rating Scale (BPRS) were used to assess symptom changes. The Simpson-Angus Rating Scale was used to assess extrapyramidal symptoms.Twenty-two patients randomly assigned to clozapine and 23 patients assigned to haloperidol met study entry criteria. There were significant interactions between treatment and right prefrontal gray matter volume for BPRS total score and SANS total score. There were no significant treatment-by-brain structure interactions for BPRS positive symptom items. Right prefrontal gray matter volume was also related to differential treatment effects for the BPRS subscales of anxiety/depression and hostility and the Simpson-Angus Rating Scale akathisia item.These results suggest that there is a differential interaction among clozapine and haloperidol, brain structure, and treatment response. Partially responsive patients with larger brain volumes may be more likely to experience the benefits of clozapine treatment, but they may be more vulnerable to side effects and experience a subsequent worsening of their symptoms when treated with haloperidol.
Evaluation of Genetic Variants in MicroRNA-Related Genes and Risk of Bladder Cancer
Authors: Hushan Yang, Colin P. Dinney, Yuanqing Ye, Yong Zhu, H. Barton Grossman, Xifeng Wu
Journal: Cancer Research (2008)

Abstract MicroRNAs (miRNA) are small noncoding RNA molecules involved in a diversity of cellular functions. Although it has been reported that global suppression of the miRNA biogenesis pathway leads to enhanced tumorigenesis, the effect of common genetic variants of miRNA-related genes on cancer predisposition is unclear. To better understand this effect, we genotyped 41 single-nucleotide polymorphisms (SNP) from 24 miRNA-related genes in a case-control study conducted in 746 Caucasian patients with bladder cancer and 746 matched controls. The homozygous variant genotype of a nonsynonymous SNP in the GEMIN3 gene (rs197414) was associated with a significantly increased bladder cancer risk [odds ratios (OR), 2.40; 95% confidence interval (95% CI), 1.04–5.56]. Several additional miRNA-related SNPs were also identified that showed a borderline significant association with bladder cancer risk. Haplotype analysis indicated that a common haplotype of the GEMIN4 gene was associated with a significantly increased bladder cancer risk with an OR of 1.25 (95% CI, 1.01–1.54). To assess the aggregate effects of the promising SNPs, we performed a combined unfavorable genotype analysis that included all SNPs showing at least a borderline statistical significance. We found that, compared with the low-risk reference group with less than two unfavorable genotypes, the medium-risk group with two unfavorable genotypes exhibited a 1.29-fold (0.92–1.81) increased risk whereas the high-risk group with more than two unfavorable genotypes exhibited a 1.92-fold (1.36–2.71) increased risk (Ptrend &amp;lt; 0.0001). Overall, this is the first epidemiologic study showing that miRNA-related genetic variants may affect bladder cancer risk individually and jointly. [Cancer Res 2008;68(7):2530–7]
Match activity and physiological responses during a junior female singles tennis tournament
Authors: Jaime Fernandez-Fernandez, Alberto Mendez-Villanueva, Benjamin Fernandez-Garcia, Nicolas Terrados
Journal: British Journal of Sports Medicine (2007)

To assess physiological load in conjunction with individual patterns of match-play activity in junior female tennis players during actual singles tennis competition.Eight elite junior female tennis players (n = 8; mean (SD) age, 17.3 (1.9) years) took part in a 2 day invitational tournament. Activity pattern analysis was performed during competitive matches. Heart rate and blood lactate concentrations were measured during selected changeovers breaks in play.The activity profile of junior female players were: rally duration, (mean (SD)) 8.2 (5.2) s; rest time between rallies, 17.7 (6.5) s; effective playing time, 21.9 (3.8)%; strokes per rally, 2.7 (1.7); changes of direction per rally, 2.3 (1.4). The mean (SD) heart rate and blood lactate concentration recorded during the matches were 161 (5) beats/min and 2.0 (0.8) mmol/litre. Heart rate and blood lactate concentration values were influenced by the characteristics of the match and mean (SD) heart rate was significantly higher (p = 0.004) during service games (166 (15.4) beats/min) than in return games (156 (19.6) beats/min), while blood lactate concentrations were not significantly different (p = 0.83) between service (2.3 (0.6) mmol/litre) and return games (2.3 (0.9) mmol/litre). We found a significant (p<0.05) positive relationship between rally duration, strokes per rally, changes of direction and blood lactate and heart rate responses, with stronger correlations when the players were serving.The physiological (ie, blood lactate and heart rate) responses associated with match play were influenced by the characteristics of the match (rally duration, strokes per rally and changes of direction), with higher heart rate on service position. Training programs should reflect these demands placed on female players during competitive match play.
Antiimmunoglobulin-treated B cells respond to a B cell differentiation factor for IgG1.
Authors: P C Isakson
Journal: The Journal of Experimental Medicine (1986)

We have determined whether B cells previously activated by anti-Ig (anti-Ig blasts) are responsive to lymphokines that induce isotype switching. Culture of anti-Ig blasts with a mixture of lymphokines, including BSF-1, resulted in marked secretion of IgM and IgG1, but not other IgG isotypes. The IgG1 response of anti-Ig blasts to lymphokines was 13-fold greater than was observed with splenic B cells. B cell blasts induced by 8-mercaptoguanosine or dextran sulfate did not secrete high levels of any IgG isotype in response to lymphokines alone. An mAb against BSF-1 suppressed the IgG1 response of anti-Ig blasts, but not the IgM response to lymphokines. These data suggest that anti-Ig-treated B cells respond to at least one of the effects of BSF-1.
Innate lymphoid cells sustain colon cancer through production of interleukin-22 in a mouse model
Authors: Stefanie Kirchberger, Daniel J. Royston, Olivier Boulard, Emily Thornton, Fanny Franchini, Rose L. Szabady, Oliver Harrison, Fiona Powrie
Journal: The Journal of Experimental Medicine (2013)

Patients with inflammatory bowel disease (IBD) have an increased risk of colon cancer. However, the immune cells and cytokines that mediate the transition from intestinal inflammation to cancer are poorly understood. We show that bacteria-induced colon cancer is accompanied by differential accumulation of IL-17(+)IL-22(+) colonic innate lymphoid cells (cILCs), which are phenotypically distinct from LTi and NK-22 cells, and that their depletion in mice with dysplastic inflammation blocks the development of invasive colon cancer. Analysis of the functional role of distinct Type 17 cytokines shows that although blockade of IL-17 inhibits some parameters of intestinal inflammation, reduction in dysplasia and colorectal cancer (CRC) requires neutralization of IL-22 indicating a unique role for IL-22 in the maintenance of cancer in this model. Mechanistic analyses showed that IL-22 selectively acts on epithelial cells to induce Stat3 phosphorylation and proliferation. Importantly, we could detect IL-22(+)CD3(+) and IL-22(+)CD3(−) cells in human CRC. Our results describe a new activity of IL-22 in the colon as a nonredundant mediator of the inflammatory cascade required for perpetuation of CRC, highlighting the IL-22 axis as a novel therapeutic target in colon cancer.
Influence of systemic inflammation and hypoxaemia on bone metabolism in patients with chronic obstructive pulmonary disease (COPD)
Authors: Olga Mardanova, Vladimir T. Ivashkin
Journal: European Respiratory Journal (2013)

The aim of our study was to access the influence of systemic inflammation and hypoxaemia on bone metabolism in patients with chronic obstructive pulmonary disease (COPD).  Materials and methods. The prospective cohort study was conducted. 33 male and 10 female patients with COPD over 55 years old were included.  In patients was assessed bone mineral density, SpO2, the blood level of leukocytes, fibrinogen, C-reactive protein, TNF-alfa, IL-6, osteocalcin, C-telopeptids.  Results: In patients with COPD the negative correlation between the T-score of the femoral neck and the fibrinogen blood level (r=-0,43, p  Conclusions: either increased level of systemic inflammation markers or hypoxaemia causes decreasing of bone mineral density and depression of osteoblasts activity in patients with COPD.
Management of hypertensive disorders during pregnancy: summary of NICE guidance
Authors: C. Visintin, M. A. Mugglestone, M. Q. Almerie, L. M. Nherera, D. James, S. Walkinshaw
Journal: BMJ (2010)

Salbutamol is used widely by elite athletes in treatment of asthma and related conditions, such as exercise-induced bronchoconstriction. In competitive sport, salbutamol is permitted by inhalation at doses up to 1600 µg/day, not to exceed 800 µg in any 12 hour period. WADA has established a urinary salbutamol Decision Limit for a presumed adverse analytical finding (AAF) of 1200 ng/mL. Urine salbutamol levels greater than this are deemed to be a result of prohibited use or excessive supratherapeutic inhalation. Studies have shown that under dehydrated conditions, exercise increases the risk of exceeding the Decision Limit after single inhaled doses of 1600 µg. One means of explaining an AAF is a Pharmacokinetic (PK) Study to establish whether an athlete is an outlier with higher urine concentrations than typical. However, a recent salbutamol case from the 2017 Vuelta a España, deemed it impractical and impossible to conduct a valid PK study capable of recreating the complex conditions of an athlete competing in such an event. Another means of explanation is the 'Salbutamol Passport'. This is a statistical model derived from serial test data obtained from an event during periods of stable salbutamol use. After adjustment for dose and dosing frequency, the Salbutamol Passport can be used to predict an expected concentration range for days when an athlete might increase their salbutamol intake due to worsening symptoms. Since the number of tests during stable use is typically small, the method uses propagation of uncertainty in mean and variance of the log-transformed salbutamol concentrations to derive expected bands for any dose and frequency of interest. The method is demonstrated with data from a cyclist competing in the 2007 Giro d'Italia. The athlete provided four salbutamol tests whilst taking 400 ug/day with geometric mean 461 ng/mL (95% CL: 352–604) and one test of 1352 ng/mL after allegedly increasing his dose to 700 ug/day. Extrapolating the 400 ug/day data to 700 ug/day, and assuming an increase from twice-daily to three-times daily dosing, the Salbutamol Passport prediction is 1050 ng/mL (95%PI: 802–1375). Since the observed test falls within the 95% prediction interval, the result would not constitute an AAF. This conclusion is unchanged after adjustment of salbutamol levels to a urine specific gravity of 1.020.
Bacterial adhesion to oropharyngeal and bronchial epithelial cells in smokers with chronic bronchitis and in healthy nonsmokers
Authors: GC Riise, S Larsson, BA Andersson
Journal: European Respiratory Journal (1994)

Bacterial adhesion is probably a prerequisite for colonization of mucous membranes, but adhesion to the bronchial mucosa has not been studied in detail. We investigated adhesion of respiratory pathogens to bronchial epithelial cells, and asked whether chronic bronchitis had an influence on bacterial adhesion. Oropharyngeal and bronchial cells were collected during bronchoscopy from 14 healthy nonsmokers, 22 smokers with nonobstructive chronic bronchitis, and 19 smokers with chronic bronchitis and chronic obstructive pulmonary disease (COPD). Patients with a forced expiratory volume in one second (FEV1) less than 50% predicted were excluded. Adhesion of highly adherent test strains of H. influenzae and S. pneumoniae to these cells were studied. The test strains of H. influenzae and S. pneumoniae were found to adhere well to both oropharyngeal and bronchial cells. H. influenzae showed a higher degree of adhesion both to ciliated and goblet cells from the patients with nonobstructive bronchitis than to cells from the healthy nonsmokers. No corresponding difference was found for S. pneumoniae. The patients with COPD did not differ from the controls in their adhesion values. Our results indicate that bacterial adhesion is of importance for the colonization and retention of H. influenzae in the human airways. For S. pneumoniae the role of adhesion is more uncertain.
Imprisonment of Cuban doctor
Authors: J.G. Foulks, J.G. Mclarnon, T.L. Perry, B. Sastry, E. Puil, D.V. Godin, B.A. Macleod, T.L. Perry, M.C. Sutter, R.A. Wall, C. Krieger, C.C.Y. Pang, D.M.J. Quastel, M.J.A. Walker, J.M. Wright
Journal: The Lancet (1991)
Pretreatment multi-biomarker disease activity score and radiographic progression in early RA: results from the SWEFOT trial
Authors: Karen Hambardzumyan, Rebecca Bolce, Saedis Saevarsdottir, Scott E Cruickshank, Eric H Sasso, David Chernoff, Kristina Forslind, Ingemar F Petersson, Pierre Geborek, Ronald F van Vollenhoven
Journal: Annals of the Rheumatic Diseases (2014)

Objectives Prediction of radiographic progression (RP) in early rheumatoid arthritis (eRA) would be very useful for optimal choice among available therapies. We evaluated a multi-biomarker disease activity (MBDA) score, based on 12 serum biomarkers as a baseline predictor for 1-year RP in eRA. Methods Baseline disease activity score based on erythrocyte sedimentation rate (DAS28-ESR), disease activity score based on C-reactive protein (DAS28-CRP), CRP, MBDA scores and DAS28-ESR at 3 months were analysed for 235 patients with eRA from the Swedish Farmacotherapy (SWEFOT) clinical trial. RP was defined as an increase in the Van der Heijde-modified Sharp score by more than five points over 1 year. Associations between baseline disease activity measures, the MBDA score, and 1-year RP were evaluated using univariate and multivariate logistic regression, adjusted for potential confounders. Results Among 235 patients with eRA, 5 had low and 29 moderate MBDA scores at baseline. None of the former and only one of the latter group (3.4%) had RP during 1 year, while the proportion of patients with RP among those with high MBDA score was 20.9% (p=0.021). Among patients with low/moderate CRP, moderate DAS28-CRP or moderate DAS28-ESR at baseline, progression occurred in 14%, 15%, 14% and 15%, respectively. MBDA score was an independent predictor of RP as a continuous (OR=1.05, 95% CI 1.02 to 1.08) and dichotomised variable (high versus low/moderate, OR=3.86, 95% CI 1.04 to 14.26). Conclusions In patients with eRA, the MBDA score at baseline was a strong independent predictor of 1-year RP. These results suggest that when choosing initial treatment in eRA the MBDA test may be clinically useful to identify a subgroup of patients at low risk of RP. Trial registration number WHO database at the Karolinska Institute: CT20080004; and clinicaltrials.gov: NCT00764725 .