tbuckley/cabot-search huggingface dataset:
Full-thickness biopsy findings in chronic intestinal pseudo-obstruction and enteric dysmotility
Authors: G. Lindberg, H. Tornblom, M. Iwarzon, B. Nyberg, J. E. Martin, B. Veress
Journal: Gut (2009)

<h3>Background and Aims:</h3> Small bowel manometry is increasingly used in the clinical investigation of patients with symptoms of intestinal motor dysfunction. Enteric dysmotility (ED) has been suggested as a new diagnostic term for patients with abnormal intestinal motor activity but no radiological signs of chronic intestinal pseudo-obstruction (CIP). Histopathological features of adult patients with ED and CIP have been compared in a large case series to study differences and similarities between the two diagnostic groups. <h3>Methods:</h3> Routine staining and an extensive panel of immunohistochemical stains on transversal and tangential cuts from full-thickness biopsies of the small bowel were used. <h3>Results:</h3> 39 females and 11 males with CIP and 58 females and 7 males with ED were investigated. The underlying lesion was more often a visceral myopathy (22% vs 5%) or neuromyopathy (30% vs 12%) in patients with CIP than in those with ED, whereas the predominant lesion in ED was neuropathy with inflammation. <h3>Conclusion:</h3> CIP in adults is associated with very different underlying pathology, whereas ED is more homogeneously associated with neuropathy in the enteric nervous system. Neuropathy of enteric ganglia with inflammation seems to be the most common cause for measurable disturbances of intestinal motor function.
Relation of Characteristics of Metabolic Syndrome to Short-Term Prognosis and Effects of Intensive Statin Therapy After Acute Coronary Syndrome
Authors: Gregory G. Schwartz, Anders G. Olsson, Michael Szarek, William J. Sasiela
Journal: Diabetes Care (2005)

OBJECTIVE—We examined relations between characteristics of the metabolic syndrome, early cardiovascular risk, and effect of early, intensive statin therapy after acute coronary syndrome. RESEARCH DESIGN AND METHODS—A total of 3,038 patients in the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) trial were characterized by the presence or absence of a history of diabetes, a history of hypertension and/or blood pressure ≥130/≥85, BMI &amp;gt;30 kg/m2, HDL cholesterol &amp;lt;40 mg/dl (men) or &amp;lt;50 mg/dl (women), and triglycerides ≥150 mg/dl. Patients with three or more of these characteristics were categorized as having metabolic syndrome. RESULTS—A total of 38% of patients (n = 1,161) met criteria for metabolic syndrome as defined in this study and had a 19% incidence of a primary end point event (death, nonfatal myocardial infarction, cardiac arrest, or recurrent unstable myocardial ischemia) during the 16-week trial. Patients with two or fewer characteristics (n = 1,877) were classified as not having metabolic syndrome and had a 14% incidence of a primary end point event. In univariate analysis, the individual characteristics that bore a significant relation to risk were diabetes and low HDL cholesterol. In a multivariable model including age, sex, and randomized treatment assignment, presence of metabolic syndrome was associated with a hazard ratio of 1.49 (95% CI 1.24–1.79, P &amp;lt; 0.0001). Relative risk reduction with 80 mg atorvastatin daily compared with placebo was similar in patients with and without metabolic syndrome. CONCLUSIONS—Metabolic syndrome, as defined in the context of this clinical trial, is a strong predictor of early recurrent ischemic events after acute coronary syndrome.
CD28-dependent Rac1 activation is the molecular target of azathioprine in primary human CD4+ T lymphocytes
Authors: Imke Tiede, Gerhard Fritz, Susanne Strand, Daniela Poppe, Radovan Dvorsky, Dennis Strand, Hans Anton Lehr, Stefan Wirtz, Christoph Becker, Raja Atreya, Jonas Mudter, Kai Hildner, Brigitte Bartsch, Martin Holtmann, Richard Blumberg, Henning Walczak, Heiko Iven, Peter R. Galle, Mohammad Reza Ahmadian, Markus F. Neurath
Journal: Journal of Clinical Investigation (2003)

Azathioprine and its metabolite 6-mercaptopurine (6-MP) are immunosuppressive drugs that are used in organ transplantation and autoimmune and chronic inflammatory diseases such as Crohn disease. However, their molecular mechanism of action is unknown. In the present study, we have identified a unique and unexpected role for azathioprine and its metabolites in the control of T cell apoptosis by modulation of Rac1 activation upon CD28 costimulation. We found that azathioprine and its metabolites induced apoptosis of T cells from patients with Crohn disease and control patients. Apoptosis induction required costimulation with CD28 and was mediated by specific blockade of Rac1 activation through binding of azathioprine-generated 6-thioguanine triphosphate (6-Thio-GTP) to Rac1 instead of GTP. The activation of Rac1 target genes such as mitogen-activated protein kinase kinase (MEK), NF-κB, and bcl-xL was suppressed by azathioprine, leading to a mitochondrial pathway of apoptosis. Azathioprine thus converts a costimulatory signal into an apoptotic signal by modulating Rac1 activity. These findings explain the immunosuppressive effects of azathioprine and suggest that 6-Thio-GTP derivates may be useful as potent immunosuppressive agents in autoimmune diseases and organ transplantation.
Serum Calcification Propensity Predicts All-Cause Mortality in Predialysis CKD
Authors: Edward R. Smith, Martin L. Ford, Laurie A. Tomlinson, Emma Bodenham, Lawrence P. McMahon, Stefan Farese, Chakravarthi Rajkumar, Stephen G. Holt, Andreas Pasch
Journal: Journal of the American Society of Nephrology (2013)

Medial arterial calcification is accelerated in patients with CKD and strongly associated with increased arterial rigidity and cardiovascular mortality. Recently, a novel in vitro blood test that provides an overall measure of calcification propensity by monitoring the maturation time (T50) of calciprotein particles in serum was described. We used this test to measure serum T50 in a prospective cohort of 184 patients with stages 3 and 4 CKD, with a median of 5.3 years of follow-up. At baseline, the major determinants of serum calcification propensity included higher serum phosphate, ionized calcium, increased bone osteoclastic activity, and lower free fetuin-A, plasma pyrophosphate, and albumin concentrations, which accounted for 49% of the variation in this parameter. Increased serum calcification propensity at baseline independently associated with aortic pulse wave velocity in the complete cohort and progressive aortic stiffening over 30 months in a subgroup of 93 patients. After adjustment for demographic, renal, cardiovascular, and biochemical covariates, including serum phosphate, risk of death among patients in the lowest T50 tertile was more than two times the risk among patients in the highest T50 tertile (adjusted hazard ratio, 2.2; 95% confidence interval, 1.1 to 5.4; P=0.04). This effect was lost, however, after additional adjustment for aortic stiffness, suggesting a shared causal pathway. Longitudinally, serum calcification propensity measurements remained temporally stable (intraclass correlation=0.81). These results suggest that serum T50 may be helpful as a biomarker in designing methods to improve defenses against vascular calcification.
Dexamethasone, high-dose cytarabine, and oxaliplatin (DHAOx) as salvage treatment for patients with initially refractory or relapsed non-Hodgkin’s lymphoma
Authors: D. Machover, B. Delmas-Marsalet, S.C. Misra, Y. Gumus, E. Goldschmidt, A. Schilf, N. Frénoy, J.-F. Emile, B. Debuire, C. Guettier, P. Farrokhi, B. Boulefdaoui, F. Norol, N. Parquet, A. Ulusakarya, C. Jasmin
Journal: Annals of Oncology (2001)
Educational intervention decreases exhaled nitric oxide in farmers with occupational asthma
Authors: H. Dressel, C. Gross, D. de la Motte, J. Sültz, R. A. Jörres, D. Nowak
Journal: European Respiratory Journal (2007)

Allergic occupational asthma is frequent in farming populations. As educational interventions can improve disease management, the short-term effect of an educational intervention in asthmatic farmers was evaluated on the basis of spirometric indices and exhaled nitric oxide fraction ( F eNO ). Farmers with occupational asthma (n = 81), mostly sensitised against cow dander and storage mites, participated in a 1-day educational programme. Outcome measures were assessed at baseline and after 4–6 weeks, using F eNO , lung function and a questionnaire. Results were compared with those of a control group without intervention (n = 24). In the educational group, the proportion of subjects reporting work-related symptoms was reduced after the intervention. The F eNO decreased from a geometric mean of 28.2 to 25.7 ppb, and, in subjects with an elevated (&gt;35 ppb) baseline F eNO (n = 32), from 59.7 to 49.2 ppb. The corresponding changes in the control group were 25.6 versus 27.7 ppb and 49.5 versus 48.1 ppb. Spirometric results were unaltered in the two groups. Thus exhaled nitric oxide fraction, a marker of allergic airway inflammation, indicated a beneficial effect of a short-term educational intervention in farmers with occupational asthma. This suggests a potential for exhaled nitric oxide fraction in assessing the efficacy of preventive measures within a short time with higher sensitivity than spirometry.
A108: Linking Exercise, Activity and Pathophysiology in Childhood Arthritis: An Innovative Canadian Knowledge Translation Strategy
Authors: Michele Gibbon, Lori B. Tucker, Debbie Ehrmann Feldman, Heather A. McKay, Joanie Sims-Gould, Jennifer N. Stinson, Elizabeth Stringer, Shirley M. L. Tse, Ciarán M. Duffy
Journal: Arthritis & Rheumatology (2014)

Background/Purpose:

We implemented a novel knowledge translation (KT) initiative called the LEAP Ambassador Program to disseminate findings from the “Linking Exercise, Activity and Pathophysiology (LEAP) in Children with JIA study.” The main hypothesis of the study is that increased levels of physical activity will improve the outcomes (such as quality of life) of youth with juvenile idiopathic arthritis (JIA). The aim of this initiative is to inspire youth with JIA to be physically active through the creation of a community of athletes and youth with JIA, who model different levels of physical activity.



Methods:

The LEAP Ambassador program was developed by the LEAP study program manager and approved by the LEAP Steering Committee. Various levels of athletes, ranging from international, national, college/university level, and local LEAP study participants (youth with JIA, aged 8–16 years), were sought. Individuals agreeing to participate signed consent for use of their personal photo(s) and interview on the LEAP website (www.leapjia.com). Participants were asked to provide a photo of themselves involved in a sport or physical activity, and to answer 6 brief questions about their motivation to engage in sport/physical activities, in the face of disease flares and/or injuries. Each of the participating LEAP sites was encouraged to seek local LEAP ambassadors through their clinics and community connections, to ensure representation across the country.



Results:

To date, 15 LEAP ambassadors have been engaged in the program, including 3 international/national level athletes, 2 college/provincial level athletes and 10 youth with JIA. Different levels of physical activity and sports, including freestyle skiing, soccer, walking, horseback riding, speed skating, hockey, cycling and rowing, have been represented. The 10 youth with JIA who have agreed to be LEAP ambassadors come from across the country. Both English and Frenchspeaking ambassadors have been included.



Conclusion:

The LEAP ambassador program is a unique KT initiative aimed at developing a robust community across the country to support the research messages of the LEAP study, relating to the promotion of physical activity in youth with arthritis. A supportive network is being developed, in which athletes act as role models, inspiring youth with JIA to engage in physical activity, and the youth themselves encourage and motivate each other through shared experiences. Future plans include expansion of the program to include more athletes and youth with JIA, and increased use of social media to connect patients and athletes. An evaluation of the effectiveness of the program is also planned.
Cutaneous neoplasia following PUVA therapy for psoriasis
Authors: K.E. McKENNA, C.C. PATTERSON, J. HANDLEY, S. McGINN, G. ALLEN
Journal: British Journal of Dermatology (1996)

To determine the risk of cutaneous neoplasia following photochemotherapy (PUVA), we reviewed patients with psoriasis treated at our unit between 1979 and 1991. Two hundred and forty-five patients were assessed, with a median duration of follow-up of 9.5 years. Fifty-nine per cent were male, and 41% female. The median number of exposures was 59, and the median total dose was 133 J/cm2 for the group as a whole. Non-melanoma skin cancers (NMSC) occurred in six individuals (2.4%). Basal cell carcinoma occurred in all six and one individual also developed four squamous cell carcinomas and Bowen's disease of the penis. No cases of malignant melanoma were recorded. Patients who developed NMSC received a median number of 225 exposures and a median cumulative dose of 654 J/cm2. Compared with a control study population in West Glamorgan, Wales, there was a 1.4 (95% confidence limits (CL) 0.5 and 3.1) times increased risk of NMSC. A statistically significant increased incidence of NMSC was found for patients who had received 100 or more exposures, and 250 or more J/cm2, with risks of 3.7 (95% CL 1.0 and 9.5), and 4.0 (95% CL 1.1 and 10), respectively. A PUVA dose of < 250 J/cm2 or < 100 exposures conferred a minimal increase in risk of NMSC in our study population.
Telomere shortening in smokers with and without COPD
Authors: M. Morlá, X. Busquets, J. Pons, J. Sauleda, W. MacNee, A. G. N. Agustí
Journal: European Respiratory Journal (2006)

Telomeres are complex DNA–protein structures located at the end of eukaryotic chromosomes. Telomere length shortens with age in all replicating somatic cells. It has been shown that tobacco smoking enhances telomere shortening in circulating lymphocytes. The present study investigated whether this effect was further amplified in smokers who develop chronic obstructive pulmonary disease. Telomere length was determined by fluorescence in situ hybridisation in circulating lymphocytes harvested from 26 never-smokers, 24 smokers with normal lung function and 26 smokers with moderate-to-severe airflow obstruction (forced expiratory flow in one second 48±4% predicted). In contrast to never-smokers, telomere length significantly decreased with age in smokers. There was also a dose–effect relationship between the cumulative long-life exposure to tobacco smoking (pack-yrs) and telomere length. The presence and/or severity of chronic airflow obstruction did not modify this relationship. The results of the current study confirm that smoking exposure enhances telomere shortening in circulating lymphocytes. It also demonstrates a dose–effect relationship between exposure to tobacco smoking and telomere length, but failed to show that this effect is amplified in smokers who develop chronic obstructive pulmonary disease.
HDAC2 Provides a Critical Support to Malignant Progression of Hepatocellular Carcinoma through Feedback Control of mTORC1 and AKT
Authors: Ji Heon Noh, Hyun Jin Bae, Jung Woo Eun, Qingyu Shen, Se Jin Park, Hyung Seok Kim, Boas Nam, Woo Chan Shin, Eun Kyung Lee, Kyungbun Lee, Ja-Jun Jang, Won Sang Park, Jung Young Lee, Suk Woo Nam
Journal: Cancer Research (2014)

Aberrant regulation of histone deacetylase 2 (HDAC2) contributes to malignant progression in various cancers, but the underlying mechanism leading to the activation of oncogenic HDAC2 remains unknown. In this study, we show that HDAC2 expression is upregulated in a large cohort of patients with human hepatocellular carcinoma, and that high expression of HDAC2 was significantly associated with poor prognosis of patients with hepatocellular carcinoma. We found that mTORC1/NF-κBp50 signaling is necessary for the growth factor-induced HDAC2 and is sustained in hepatocellular carcinoma, but not in normal hepatic cells. Growth factor-induced mTORC1 activates the nuclear translocation of NF-κBp50, where it binds to the intragenic sequences of the HDAC2 gene and promotes its transcription. Hepatocellular carcinoma tissues derived from chemical-induced mouse and rat liver cancer models validated that mTORC1 activation and NF-κBp50 nuclear translocation are essential for the transcriptional activation of oncogenic HDAC2 in hepatocellular carcinoma. In addition, we demonstrate that HDAC2 is required to maintain mTORC1 activity by stabilizing the mTOR/RAPTOR complex. Elevated expression of HDAC2 triggers a positive feedback loop that activates AKT phosphorylation via the transcriptional modulation of phosphoinositide signaling molecules. Bioinformatics analysis of HDAC2 signature and immunoblot analysis of mesenchymal genes also evidenced that HDAC2 plays a role in the malignant behavior of tumor cells by Snail induction and simultaneously E-cadherin suppression in hepatocellular carcinoma cells. These findings establish a molecular mechanism responsible for the activation of oncogenic HDAC2, which explains how growth factor-induced HDAC2 maintains mitogenic signaling and function during hepatocellular malignant progression and provide a novel strategy for therapeutic intervention in liver cancer. Cancer Res; 74(6); 1728-38. ©2014 AACR.
Insulin Glargine in Continuous Enteric Tube Feeding
Authors: Darcy Putz, Udaya M. Kabadi
Journal: Diabetes Care (2002)

In comparison with the traditional long-acting insulins, i.e., NPH and Ultralente (1–3), insulin glargine, a novel insulin analogue has been documented to decrease the number of hypoglycemic episodes while achieving an adequate glycemic control. The decline in hypoglycemic events, especially nocturnal, is attributed to the ability of insulin glargine to attain a steady-state plasma insulin concentration without a peak for ∼24 h on a subcutaneous (SC) administration of a single dose (4). Therefore, insulin glargine may achieve an effect similar to that obtained by continuous intravenous (IV) or SC infusion of regular insulin in …
Outcomes and Predictors of Incisional Surgical Site Infection in Stoma Reversal
Authors: Mike K. Liang, Linda T. Li, Andres Avellaneda, Jennifer M. Moffett, Stephanie C. Hicks, Samir S. Awad
Journal: JAMA Surgery (2013)

<h3>Importance</h3>Surgical site infection following stoma reversal (SR) poses a substantial burden to the patient and health care system. Its overall incidence is likely underreported and poorly characterized. Improving our understanding of surgical site infection following stoma reversal may help us identify methods to decrease this complication.<h3>Objective</h3>To evaluate the incidence of surgical site infection (SSI) and identify predictors of SSI following SR.<h3>Design</h3>A review of computerized hospital records on SR performed from January 1, 2005, until February 27, 2011.<h3>Setting</h3>An integrated medical system at the Michael E. DeBakey Veterans Affairs Medical Center.<h3>Participants and Intervention</h3>All adults undergoing SR during the study period.<h3>Main Outcome Measures</h3>Rates of SSI and characteristics of patients with and without SSI were compared. A logistic regression model was developed to identify predictors of SSI.<h3>Results</h3>One hundred twenty-eight patients underwent SR; 46 patients (36.0%) had an SSI. In comparison with no SSI, the infection was associated with seromas (17.4% vs 2.4%, P = .004), fascial dehiscence (15.2% vs 2.4%, P = .01), intensive care unit admission (34.8% vs 17.1%, P = .03), increased hospital length of stay (20 vs 9 days, P = .02), readmission (32.6% vs 13.4%, P = .01), delayed wound healing (91 vs 66 days, P = .02), and reoperation (32.6% vs 13.4%, P = .01). On multivariate analysis, history of fascial dehiscence (odds ratio, 16.9; 95% CI, 1.94-387), colostomy (5.07; 2.12-13.0), thicker subcutaneous fat (2.02; 1.33-3.21), and black race (0.35; 0.13-0.86) were associated with incisional SSI. There was no significant difference in patient satisfaction or functional status in late follow-up (1-73 months).<h3>Conclusions and Relevance</h3>Surgical site infection is common following SR and is associated with significant morbidity. Four factors are strongly associated with increased risk of SSI in SR: history of fascial dehiscence, thicker subcutaneous fat, colostomy, and white race. Patients with none of these risk factors had a 0% SSI risk; patients with all 4 risk factors had a 100% risk of SSI.
Increasing incidence of Barrett's oesophagus in the general population
Authors: E M van Soest
Journal: Gut (2005)

<b>Background:</b> Barrett's oesophagus (BO) predisposes to oesophageal adenocarcinoma. Epidemiological data suggest that the incidence of BO is rising but it is unclear whether this reflects a true rise in incidence of BO or an increase in detection secondary to more upper gastrointestinal endoscopies performed. This study aimed to examine the changes in BO incidence relative to the number of upper gastrointestinal endoscopies performed in the general population. <b>Methods:</b> We conducted a cohort study using the Integrated Primary Care Information database. This general practice research database contains the complete and longitudinal electronic medical records of more than 500 000 persons. <b>Results:</b> In total, 260 incident cases of BO were identified during the study period. The incidence of BO increased from 14.3/100 000 person years in 1997 (95% confidence interval (CI) 8.6–22.4) to 23.1/100 000 person years (95% CI 17.2–30.6) in 2002 (<i>r</i><sup>2</sup> = 0.87). The number of upper gastrointestinal endoscopies decreased from 7.2/1000 person years (95% CI 6.7–7.7) to 5.7/1000 person years (95% CI 5.4–6.1) over the same time period. This resulted in an overall increase in detected BO per 1000 endoscopies from 19.8 (95% CI 12.0–31.0) in 1997 to 40.5 (95% CI 30.0–53.5) in 2002 (<i>r</i><sup>2</sup> = 0.93). The incidence of adenocarcinoma increased from 1.7/100 000 person years (95% CI 0.3–5.4) in 1997 to 6.0/100 000 person years (95% CI 3.3–10.2) in 2002 (<i>r</i><sup>2</sup> = 0.87). <b>Conclusion:</b> The incidence of diagnosed BO is increasing, independent of the number of upper gastrointestinal endoscopies that are being performed. This increase in BO incidence will likely result in a further increase in the incidence of oesophageal adenocarcinomas in the near future.