tbuckley/cabot-search huggingface dataset:
A Global Increase in 5‐Hydroxymethylcytosine Levels Marks Osteoarthritic Chondrocytes
Authors: Sarah E. B. Taylor, Piera Smeriglio, Lakshmi Dhulipala, Madhusikta Rath, Nidhi Bhutani
Journal: Arthritis & Rheumatology (2013)

To investigate the role of the newly discovered epigenetic mark 5-hydroxymethylcytosine (5hmC) and its regulators in altered gene expression in osteoarthritis (OA).Cartilage was obtained from OA patients undergoing total knee arthroplasty and from control patients undergoing anterior cruciate ligament reconstruction. Global levels of 5hmC and 5-methylcytosine (5mC) were investigated using immunoblotting, enzyme-linked immunosorbent assays, and cellular staining. Gene expression changes were monitored by quantitative polymerase chain reaction (PCR) analysis. Levels of locus-specific 5hmC and 5mC at CpG sites in the matrix metalloproteinase 1 (MMP-1), MMP-3, ADAMTS-5, and hypoxanthine guanine phosphoribosyltransferase 1 (HPRT-1) promoters were quantified using a glucosylation and enzyme digestion-based method followed by quantitative PCR analysis. Global and locus-specific 5hmC levels and gene expression changes were monitored in normal chondrocytes stimulated with inflammatory cytokines to identify the effect of joint inflammation.A global 5-6-fold increase in 5hmC concomitant with a loss of TET1 was observed in human OA chondrocytes compared to normal chondrocytes. Enrichment of 5hmC was observed in promoters of enzymes critical to OA pathology, MMP-1 and MMP-3. Short-term treatment of normal chondrocytes with inflammatory cytokines induced a rapid decrease in TET1 expression but no global or locus-specific 5hmC enrichment.This study provides the first evidence of an epigenetic imbalance of the 5hmC homeostasis in OA leading to TET1 down-regulation and 5hmC accumulation. Our experiments identify 5hmC and its regulators as potential diagnostic and therapeutic targets in OA.
Abstract 9257: The Effect of Massachusetts Health Reform on Racial Disparities in 30-Day Readmissions for Acute Myocardial Infarction
Authors: Karen E Lasser, Danny McCormick, Chieh Chu, Meredith D'Amore, Nancy Kressin, Amresh Hanchate
Journal: Circulation (2011)

Background: Following Massachusetts (MA) health reform, the percent of uninsured residents fell from 8.4% to 3.4%, with larger gains among minorities. Prior studies have not examined the effect of this policy change on 30-day readmission rates for myocardial infarction (MI). We hypothesized that racial disparities in such admissions would decline in MA among adults age 18-64 following the reform. Methods: Using MA inpatient discharge data from 2004-2009, we compared 30-day readmissions after hospitalization for acute MI among white and black patients, prior to and following reform implementation. We defined the pre-reform period as 2004-2006, and the post-reform period as 2008-2009. We used chi-square tests to compare 30-day readmissions for MI between groups. Controlling for age, gender, and Charlson Comorbidity Score, we used multiple logistic regression to calculate risk-adjusted odds of 30-day readmission. Treating adults &gt; 65 (who are mostly covered by Medicare and thus unaffected by the reform) as the comparison cohort, we used difference-in-difference specification to identify the post-reform change adjusted for secular changes unrelated to reform. Results: Pre-reform, black patients age 18-64 had higher readmission rates than white patients (18.1% vs. 11.2%; p=0.001), this difference persisted post-reform (17.0% vs. 10.2%; p &lt;0.001). Among patients age ≥65, in the pre-reform period, black patients also had higher readmission rates than whites (29.2% vs. 23.9%; p=0.02); this also persisted post-reform (27.8% vs. 22.2%; p=0.01). The readmission rate for blacks age18-64 did not change significantly from pre-reform to post-reform (18.1% vs. 17.0%, adjusted OR (AOR), 0.9; 95% CI, 0.6- 1.3); nor did the readmission rate for blacks, age ≥65, change significantly (29.2% vs. 27.8%, AOR, 0.8; 95% CI, 0.6- 1.2). The difference in the change in AOR for blacks pre- and post- reform, age 18-64, and the change in AOR for blacks pre- and post- reform, age &gt; 65 (“difference-in-difference”) was not significant (p=0.6). Conclusions: Black patients were more likely than whites to be readmitted after hospitalization for MI, both before and after health reform. MA health reform had no measurable impact on disparities in 30-day readmissions for MI.
Increased Incidence of Cardiovascular Disease in Middle-aged Men with Obstructive Sleep Apnea
Authors: Yüksel Peker, Jan Hedner, Jeanette Norum, Holger Kraiczi, Jan Carlson
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

The incidence of a cardiovascular disease (CVD) was explored in a consecutive sleep clinic cohort of 182 middle-aged men (mean age, 46.8 +/- 9.3; range, 30-69 years in 1991) with or without obstructive sleep apnea (OSA). All subjects were free of hypertension or other CVD, pulmonary disease, diabetes mellitus, psychiatric disorder, alcohol dependency, as well as malignancy at baseline. Data were collected via the Swedish Hospital Discharge Register covering a 7-year period before December 31, 1998, as well as questionnaires. Effectiveness of OSA treatment initiated during the period as well as age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP) at baseline, and smoking habits were controlled. The incidence of at least one CVD was observed in 22 of 60 (36.7%) cases with OSA (overnight oxygen desaturations of 30 or more) compared with in 8 of 122 (6.6%) subjects without OSA (p < 0.001). In a multiple logistic regression model, significant predictors of CVD incidence were OSA at baseline (odds ratio [OR] 4.9; 95% confidence interval [CI], 1.8-13.6) and age (OR 23.4; 95% CI, 2.7-197.5) after adjustment for BMI, SBP, and DBP at baseline. In the OSA group, CVD incidence was observed in 21 of 37 (56.8%) incompletely treated cases compared with in 1 of 15 (6.7%) efficiently treated subjects (p < 0.001). In a multiple regression analysis, efficient treatment was associated with a significant risk reduction for CVD incidence (OR 0.1; 95% CI, 0.0-0.7) after adjustment for age and SBP at baseline in the OSA subjects. We conclude that the risk of developing CVD is increased in middle-aged OSA subjects independently of age, BMI, SBP, DBP, and smoking. Furthermore, efficient treatment of OSA reduces the excess CVD risk and may be considered also in relatively mild OSA without regard to daytime sleepiness.
Comparing cardiopulmonary responses to incremental exercise in patients with chronic thromboembolic pulmonary hypertension and idiopathic pulmonary arterial hypertension
Authors: Roberta Pulcheri Ramos, Fabricio Martins Valois, Juliana Moura, Thais Melatto, Eloara Ferreira, Jaquelina Sonoe Ota Arakaki, Luiz Eduardo Nery, J. Alberto Neder
Journal: European Respiratory Journal (2011)

Patients with chronic thromboembolic pulmonary hypertension (CTPH) are more likely to develop proximal obstructive lesions than those with idiopathic pulmonary arterial hypertension (IPAH). Therefore, CTPH might present with poorer right ventricle-pulmonary vascular coupling, worse ventilation-perfusion matching, and lower maximal exercise capacity compared to IPAH. We comparatively evaluated 26 patients with CTPH and 14 with IPAH who underwent a symptom-limited incremental exercise test on a cycle ergometer. Haemodynamic variables (systolic volume [SV] and cardiac index [CI]) were measured by impedance cardiography. Baseline characteristics were similar in CTPH and IPAH (age 48±16 vs 40±17 yrs; CI 2,0±0,5 vs 2,2±0,6 L/min/m2; pulmonary vascular resistance 14±5 vs 16±8 Wood; p>0,05). Metabolic, cardiovascular and haemodynamic parameters also did not differ between the groups (peak V'O2 11±3 vs 12±3 mL/kg/min; ΔV'O2/ΔW 7,3±1,7 vs 7,1±1,7; peak SV 84±13 vs 86±22 mL; peak CI 6,5±1,0 vs 6,9±1,6 L/min/m2; p>0,05). However, CTPH patients had higher ΔV'E/ ΔV'CO2 (75±26 vs 52±17; p<0,05), lower end-tidal CO2 pressure at the anaerobic threshold (21±5 vs 28±6 mmHg; p<0,05) and greater oxyhaemoglobin desaturation (peak SpO2 88±7 vs 93±5, p<0,05). In conclusion, patients with CTPH had higher sub-maximal ventilatory response to progressive exercise compared to those with IPAH. Although this difference did not impact upon peak exercise capacity, it indicates that CTPH led to more extensive pulmonary gas exchange abnormalities despite similar resting and exercise haemodynamic impairment.
Tracing paternal ancestry in mice, using the Y-linked, sex-determining locus, Sry.
Authors: B L Lundrigan, P K Tucker
Journal: Molecular Biology and Evolution (1994)

The molecular evolution of mammalian Y-linked DNA sequences is of special interest because of their unique mode of inheritance: most Y-linked sequences are clonally inherited from father to son. Here we investigate the use of Y-linked sequences for phylogenetic inference. We describe a comparative analysis of a 515-bp region from the male sex-determining locus, Sry, in 22 murine rodents (subfamily Murinae, family Muridae), including representatives from nine species of Mus, and from two additional murine genera--Mastomys and Hylomyscus. Percent sequence divergence was < 0.01% for comparisons between populations within a species and was 0.19%-8.16% for comparisons between species. Our phylogenetic analysis of 12 murine taxa resulted in a single most-parsimonius tree that is highly concordant with phylogenies based on mitochondrial DNA and allozymes. A total evidence tree based on the combined data from Sry, mitochondrial DNA, and allozymes supports (1) the monophyly of the subgenus Mus, (2) its division into a Palearctic group (M. musculus, M. domesticus, M. spicilegus, M. Macedonicus, and M. spretus) and an Oriental group (M. cookii++, M. cervicolor, and M. caroli), and (3) sister-group relationships between M. spicilegus and M. macedonicus and between M. cookii and M. cervicolor. We argue that Y-chromosome DNA sequences represent a valuable new source of characters for phylogenetic inference.
A negative result of airway reversibility test in obstructive airway disease does not mean no reserve of lung function
Authors: Seok Jeong Lee, Shun Nyung Lee, Myoung Kyu Lee, Kye Chul Shin, Suk Joong Yong, Sang-Ha Kim, Won-Yeon Lee
Journal: European Respiratory Journal (2011)

Introduction:  The airway reversibility test (ART) is performed to diagnose obstructive airway disease (OAD) such as asthma and COPD. The ART revealed negative results in some asthma patients. It can be made insufficient treatment (Tx) for those patients.   Objectives:  We reviewed the patients9 data to evaluate the characteristics of the patients who have marked improvement of spirometry (SPM) after regular Tx among patients with SPM below COPD stage II by GOLD guideline.   Method:  We reviewed SPM records of 1072 patients who performed ART to evaluate dyspnea from 1st September 2009 to 30th August 2010. Finally we reviewed the pre and post-Tx SPM data and characteristics of 121 patients who have pre-bronchodilator (BD) FEV 1 /FVC 1     Results:  Twenty four patients (19.8%) showed improved FEV 1  >80% after regular Tx with ICS and/or tiotropium (group 1). Four patients showed improvement of FEV 1 /FVC >70% and FEV 1  > 80% (group 2). The mean increments of FEV 1  are 0.47 L and 0.61 L in group 1 and 2. The increment of FEV 1  after Tx slightly correlated with initial post-BD FEV 1  change in ART (R=0.213, p=0.019). But, the post-BD FEV 1  change (%) was not different between group 1 and non-responder group (5.29±6.35 vs. 6.71±5.41, p = 0.33).   Conclusion:  The results of this study show about 20% of patients with SPM fitted in moderate COPD had FEV 1  improvement >80% after Tx. But we could not find specific characteristics in those patients. Collectively, physicians may consider active initial Tx including ICS when managing patients of OAD even though initial BD response is minimal. And further study to find the predictor of favorable Tx outcome will be needed.
Oral Mucositis and the Clinical and Economic Outcomes of Hematopoietic Stem-Cell Transplantation
Authors: Stephen T. Sonis, Gerry Oster, Hank Fuchs, Lisa Bellm, Williamson Z. Bradford, John Edelsberg, Vanessa Hayden, June Eilers, Joel B. Epstein, Francis G. LeVeque, Carole Miller, Douglas E. Peterson, Mark M. Schubert, Frederik K.L. Spijkervet, Mary Horowitz
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To explore the relationship between oral mucositis and selected clinical and economic outcomes in blood and marrow transplant patients. PATIENTS AND METHODS: Subjects consisted of 92 transplant patients from eight centers who participated in a multinational pilot study of a new oral mucositis scoring system (Oral Mucositis Assessment Scale [OMAS]). In the pilot study, patients were evaluated for erythema and ulceration/pseudomembrane formation beginning on the first day of conditioning and continuing for 28 days. We examined the relationship between patients’ peak OMAS scores and days with fever (body temperature &gt; 38.0°C), the occurrence of significant infection, days of total parenteral nutrition (TPN), and days of injectable narcotic therapy (all over 28 days), days in hospital (over 60 days), total hospital charges for the index admission, and vital status at 100 days. RESULTS: Patients’ peak OMAS scores spanned the full range of possible values (0 to 5) and were significantly (P &lt; .05) correlated with all of the outcomes of interest except days with fever (P = .21). In analyses controlling for type of graft (autologous v allogeneic) and study center, a 1-point increase in peak OMAS score was associated with (1) 1.0 additional day with fever (P &lt; .01), (2) a 2.1-fold increase in risk of significant infection (P &lt; .01), (3) 2.7 additional days of TPN (P &lt; .0001), (4) 2.6 additional days of injectable narcotic therapy (P &lt; .0001), (5) 2.6 additional days in hospital (P &lt; .01), (6) $25,405 in additional hospital charges (P &lt; .0001), and (7) a 3.9-fold increase in 100-day mortality risk (P &lt; .01). Mean hospital charges were $42,749 higher among patients with evidence of ulceration compared with those without (P = .06). CONCLUSION: Oral mucositis is associated with significantly worse clinical and economic outcomes in blood and marrow transplantation.
Impact of prior ketoconazole therapy on response proportion to abiraterone acetate, a 17-alpha hydroxylase C17,20-lyase inhibitor in castration resistant prostate cancer (CRPC)
Authors: C. Ryan, M. R. Smith, J. E. Rosenberg, A. M. Lin, M. Taplin, P. W. Kantoff, V. Huey, J. Kim, E. J. Small
Journal: Journal of Clinical Oncology (2008)

5018 Background: Abiraterone acetate (AA) is an inhibitor of CYP 17 (17 α hydroxylase and C17,20-Lyase), a dual enzyme responsible for androgen synthesis. The mechanism of action of abiraterone is similar to ketoconazole (keto), which inhibits multiple adrenal CYP enzymes including CYP17, and is also used in CRPC. The impact of prior keto therapy on AA response is examined in this analysis. Methods: Eligibility for this Phase I study required progressive CRPC by consensus criteria and normal organ and adrenal function. Dose escalation was performed in both fasted and fed states at doses of 250, 500, 750 and 1000 mg daily. Patients (pts) were evaluated monthly during therapy. Medical records were reviewed to identify which pts had received prior therapy with keto, whether a PSA decline had been achieved and the duration of therapy on keto. Reasons for discontinuing keto were classified as due to disease progression (PD) or toxicity. Results: 18 of 33 pts (55%) experienced a decline in PSA by >50%. Of 30 pts completing 12 weeks of therapy, 13 (43%) have experienced a decline in PSA by >50%. 6 of 12 (50%) pts treated at the 1000 mg dose (the recommended phase II dose) responded. Of 14 pts who had not received prior keto, 8 (61%) responded to AA. Of the 19 pts previously treated with keto, 10 (53%) experienced a 50% or greater decline in PSA while on AA and the median time to progression for these patients is 21 weeks. 3 of 4 pts who discontinued ketoconazole due to toxicity experienced a PSA decline on AA and 7/15 (47% ) patients who had experienced disease progression on ketoconzole experienced a PSA decline on abiraterone with a median time to progression in these patients is 17 weeks. 16 of 19 pts (84%) had previously experienced a 50% decline in PSA while on ketoconazole, 4 did not. 15/19 (79%) had discontinued keto due to progressive disease and four (21%) had discontinued ketoconazole due to toxicity. The median duration of keto therapy in these 19 patients was 15 months (range 4.2–38 months). Conclusions: Most pts treated with AA had a prior response to keto. AA exhibits anti-tumor activity in CRPC even in pts experiencing PD on keto. Despite overlapping mechanisms of action, responses to AA occur in pts with keto refractory disease. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Cougar Biotechnology
Comparison of a Dimethicone/Antacid (Asilone Gel) with an Alginate/Antacid (Gaviscon Liquid) in the Management of Reflux Oesophagitis
Authors: H L Smart, M Atkinson
Journal: Journal of the Royal Society of Medicine (1990)

Fifty-three patients with symptomatic reflux oesophagitis were entered into a single centre randomized study comparing the effects of a dimethicone/antacid (Asilone Gel) and an alginate/antacid (Gaviscon liquid) on symptoms and endoscopic changes over an 8-week period. Both treatments significantly improved heartburn, acid regurgitation and flatulence. Dimethicone/antacid but not alginate/antacid, produced a significant improvement in oesophagitis, oesophageal ulceration and histological grade of inflammation over the 8-week treatment period so that 14 patients treated with dimethicone/antacid and 10 with alginate/antacid had normal endoscopic oesophageal appearances at the end of the study. The difference in improvement between the two patient groups did not reach significance however, except for dimethicone/antacid improving histological changes (P&lt;0.05). These findings suggest that dimethicone/antacid and alginate/antacid are equally effective in treating symptomatic reflux oesophagitis although dimethicone/antacid may have an advantage in improving oesophageal histological appearances.
Risk of Second Malignancy After Hodgkin’s Disease in a Collaborative British Cohort: The Relation to Age at Treatment
Authors: A.J. Swerdlow, J.A. Barber, G. Vaughan Hudson, D. Cunningham, R.K. Gupta, B.W. Hancock, A. Horwich, T.A. Lister, D.C. Linch
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To assess long-term site-specific risks of second malignancy after Hodgkin’s disease in relation to age at treatment and other factors. PATIENTS AND METHODS: A cohort of 5,519 British patients with Hodgkin’s disease treated during 1963 through 1993 was assembled and followed-up for second malignancy and mortality. Follow-up was 97% complete. RESULTS: Three hundred twenty-two second malignancies occurred. Relative risks of gastrointestinal, lung, breast, and bone and soft tissue cancers, and of leukemia, increased significantly with younger age at first treatment. Absolute excess risks and cumulative risks of solid cancers and leukemia, however, were greater at older ages than at younger ages. Gastrointestinal cancer risk was greatest after mixed-modality treatment (relative risk [RR] = 3.3; 95% confidence interval [CI], 2.1 to 4.8); lung cancer risks were significantly increased after chemotherapy (RR = 3.3; 95% CI, 2.4 to 4.7), mixed-modality treatment (RR = 4.3; 95% CI, 2.9 to 6.2), and radiotherapy (RR = 2.9; 95% CI, 1.9 to 4.1); breast cancer risk was increased only after radiotherapy without chemotherapy (RR = 2.5; 95% CI, 1.4 to 4.0); and leukemia risk was significantly increased after chemotherapy (RR = 31.6; 95% CI, 19.7 to 47.6) and mixed-modality treatment (RR = 38.1; 95% CI, 24.6 to 55.9). These risks were generally greater after treatment at younger ages: for patients treated at ages younger than 25 years, there were RRs of 18.7 (95% CI, 5.8 to 43.5) for gastrointestinal cancer after mixed-modality treatment, 14.4 (95% CI, 5.7 to 29.3) for breast cancer after radiotherapy, and 85.2 (95% CI, 45.3 to 145.7) for leukemia after chemotherapy (with or without radiotherapy). CONCLUSION: Age at treatment has a major effect on risk of second malignancy after Hodgkin’s disease. Although absolute excess risks are greater for older patients, RRs of several important malignancies are much greater for patients who are treated when young. The increased risk of gastrointestinal cancers may relate particularly to mixed-modality treatment, and that of lung cancer to chemotherapy as well as radiotherapy; there are also well-known increased risks of breast cancer from radiotherapy and leukemia from chemotherapy. The roles of specific chemotherapeutic agents in the etiology of solid cancers after Hodgkin’s disease require detailed investigation.
TBNA (submucosal) for diagnosis of mesothelioma (and ROSE for a faster one)
Authors: Michele Gallo, Laura Basile, Maria Grazia Stella, Claudia Cannizzaro
Journal: European Respiratory Journal (2011)

We describe a malignant pleural mesothelioma (MPM) case diagnosis obtained with submucosal (SM) TBNA (transbronchial needle aspiration) and ROSE (Rapid on site examination). A 64 year old man was admitted to our unit because of pneumonia and scanty pleural effusion (PE) on chest radiography (see figure, Thorax CT scan).  Thick fissures in the mediastinal pleura (MP) nodules and enhancement maximum diameter 2.0 cm. Minimal PE, lung atelectasis. Lymphnodes diameter   To our knowledge, this is the first time that a mediastinal involvement of MPM is approached via TBNA and ROSE was diagnostic for Epithelial MPM.
Abstract 16641: One-Stent Technique is Not Inferior to Two-Stents Technique for the Treatment of Coronary True Bifurcation Lesions in the Era of Drug-Eluting Stents for a Long-Term Period
Authors: Yoon-Seok Koh, Ki-Bae Seung, Byung Joo Shim, Eun Ho Choo, Chan Joon Kim, Tae Hoon Kim, Suk Min Seo, Sang-Hyun Ihm, Jong Min Lee, Hun Jun Park, Pum Joon Kim, Kiyuk Chang, Wook Sung Jeong, Hyun chul Kwon, Hyo Soo Kim, Myung Ho Jeong, Yang Soo Jang, Seung Jung Park
Journal: Circulation (2010)