tbuckley/cabot-search huggingface dataset:
Acute reoxygenation injury in the isolated rat heart: role of resident cardiac mast cells.
Authors: A M Keller, R M Clancy, M L Barr, C C Marboe, P J Cannon
Journal: Circulation Research (1988)

Leukocyte-mediated myocardial reperfusion injury is characterized by the progressive migration and accumulation of polymorphonuclear leukocytes within the myocardium. In this study, we hypothesized that leukocytes normally resident to the myocardium also contribute to myocardial injury in the absence of migration and accumulation of peripheral polymorphonuclear leukocytes. In isolated crystalloid-perfused rat hearts, we found numerous resident cardiac leukocytes that were identified primarily as macrophages and mast cells, the latter staining avidly for peroxidase. When hypoxic perfused hearts (60 minutes, n = 16) were reoxygenated there was a prompt release of this peroxidase activity, the extent of which correlated closely with the degree of myocardial injury (total creatine kinase release, r = 0.96). When reoxygenation associated mast cell degranulation was prevented in six additional hypoxic hearts using 10 microM Lodoxamide Tromethamine, peroxidase release was reduced 7.8-fold (p less than 0.001) and creatine kinase release (injury) was reduced 5.9-fold (p less than 0.001). These results demonstrate that the isolated crystalloid-perfused rat heart is not a leukocyte-free preparation and suggest that mast cells resident to the heart play an important role in acute reoxygenation injury.
Silencing of Pellino1 improves post-infarct cardiac dysfunction and attenuates left ventricular remodelling in mice
Authors: Wei Wu, Yuanping Hu, Jiantao Li, Weina Zhu, Tuanzhu Ha, Linli Que, Li Liu, Quan Zhu, Qi Chen, Yong Xu, Chuanfu Li, Yuehua Li
Journal: Cardiovascular Research (2014)

Pellino1 is an evolutionally conserved immune regulator and participates in the regulation of Toll-like receptor/interleukin-1 receptor (TLR/IL-1R)-mediated signalling. Recent studies have shown that TLR/IL-1R contributes to the left ventricular (LV) remodelling after myocardial infarction (MI). However, the role of Pellino1 in LV remodelling following MI has not been investigated. This study examined the effect of Pellino1 silencing on cardiac function and LV remodelling after MI. Male C57BL/6 mice were subjected to permanent ligation of left anterior descending coronary artery (LAD) to induce MI. The levels of Pellino1 were significantly increased in the myocardium 3 days and sustained for 4 weeks after MI, when compared with the sham control. Hypoxia increased Pellino1 expression in cultured cardiomyocytes and fibroblasts. To examine whether Pellino1 plays a role in MI-induced cardiac dysfunction and the LV remodelling, we suppressed the expression of Pellino1 either by intramyocardial delivery of adenovirus expressing siRNA for Pellino1 (AdsiPeli1) or by Cre-LoxP-mediated conditional deletion of Pellino1 from the myocardium. In both models, silencing of Pellino1 significantly attenuated MI-induced cardiac dysfunction, decreased scar size, and reduced collagen deposition, when compared with the control groups. Pellino1 silencing in mice also attenuated MI-induced Pellino1 E3 ligase activity, receptor-interacting protein 1 and tumor necrosis factor receptor associated factor 6 (TRAF6) ubiquitination, nuclear factor Kappa B (NF-κB) activity, cytokine production, and inflammatory cell infiltration into the myocardium when compared with the MI group. Our data demonstrate that Pellino1 plays an important role in the pathogenesis of MI. Targeting Pellino1 may ameliorate cardiac dysfunction and remodelling following MI.
Adjuvant Radiation Therapy Is Associated With Improved Survival in Merkel Cell Carcinoma of the Skin
Authors: Pablo Mojica, David Smith, Joshua D.I. Ellenhorn
Journal: Journal of Clinical Oncology (2007)

Merkel cell carcinoma (MCC) is a rare cutaneous malignancy. Because of the absence of randomized studies, the real benefit of adjuvant radiation therapy in MCC is unclear. The aim of this study was to better define the role of adjuvant radiation therapy in the management of MCC.The Surveillance, Epidemiology, and End Results (SEER) survey from the National Cancer Institute was queried from 1973 through 2002. Retrospective analysis was performed. The end point of the study was overall survival.There were 1,665 cases of MCC in the SEER registry. Presentation by stage were 55% stage I, 31% stage II, and 6% stage III. Eight percent of the cases could not be staged because of incomplete data. Surgical intervention was a component of therapy in 89% of the cases (n = 1,487). The median survival for the entire cohort was 49 months, and median follow-up was 40 months. Adjuvant radiation was a component of therapy in 40% of the surgical cases. The median survival for those patients receiving adjuvant radiation therapy was 63 months compared with 45 months for those treated without adjuvant radiation. The use of radiation was associated with an improved survival for patients with all sizes of tumors, but the improvement with radiation use was particularly prominent when analyzing those patients with primary lesions larger than 2 cm.The use of adjuvant radiation therapy is associated with improved survival in patients with MCC. Prospective evaluation of adjuvant radiation therapy in this setting is warranted.
THE PREDICTIVE VALUE OF THE BRIEF PSYCHIATRIC INTERVIEW
Authors: CECIL L. WITTSON, WILLIAM A. HUNT
Journal: American Journal of Psychiatry (1951)

The validity of predictions based upon the brief psychiatric interview has often been challenged. The present study reports 944 cases of naval personnel interviewed because of suspected neuropsychiatric symptomatology. On the basis of a brief psychiatric interview, these cases were separated into 3 classes—mild symptoms, treatment not indicated; moderate symptoms, shore duty indicated; and severe symptoms, hospitalization indicated. The subsequent naval careers of these 944 men were studied for one year. The neuropsychiatric discharge rates for the 3 groups during that year were in accord with the original prediction. The "mild" group lost 6.5% for neuropsychiatric reasons, the "moderate" group 20.2%, the "severe" group 89.7%. These data demonstrate the validity of the brief interview as a classificatory procedure.
Haematological manifestations in patients with severe acute respiratory syndrome: retrospective analysis
Authors: R. S M Wong
Journal: BMJ (2003)

To evaluate the haematological findings of patients with severe acute respiratory syndrome (SARS). Analysis of the demographic, clinical, and laboratory characteristics of patients with SARS. Prince of Wales Hospital, Hong Kong. Subjects All patients with a diagnosis of SARS between 11 March and 29 March 2003 who had no pre-existing haematological disorders. Clinical end points included the need for intensive care and death. Univariate and multivariate analyses were performed to examine factors associated with adverse outcome. 64 male and 93 female patients were included in this study. The most common findings included lymphopenia in 153 (98%) of the 157 patients, neutrophilia in 129 (82%), thrombocytopenia in 87 patients (55%), followed by thrombocytosis in 77 (49%), and isolated prolonged activated partial thromboplastin time in 96 patients (63%). The haemoglobin count dropped by more than 20 g/l from baseline in 95 (61%) patients. Four patients (2.5%) developed disseminated intravascular coagulation. Lymphopenia was shown in haemato-lymphoid organs at postmortem examination. Multivariate analysis showed that advanced age and a high concentration of lactate dehydrogenase at presentation were independent predictors of an adverse outcome. Subsets of peripheral blood lymphocytes were analysed in 31 patients. The counts of CD4 positive and CD8 positive T cells fell early in the course of illness. Low counts of CD4 and CD8 cells at presentation were associated with adverse outcomes. Abnormal haematological variables were common among patients with SARS. Lymphopenia and the depletion of T lymphocyte subsets may be associated with disease activity.
Effect of Postmenopausal Hormones on Inflammation-Sensitive Proteins
Authors: Mary Cushman, Claudine Legault, Elizabeth Barrett-Connor, Marcia L. Stefanick, Craig Kessler, Howard L. Judd, Pamela A. Sakkinen, Russell P. Tracy
Journal: Circulation (1999)

Observational studies in healthy women suggest postmenopausal hormone therapy reduces risk of coronary events. In contrast, in a recent clinical trial of women with coronary disease, a subgroup analysis demonstrated increased risk during the early months of therapy. Because higher levels of inflammation factors predict vascular disease outcomes, the effect of hormones on these factors is of interest.Four inflammation-sensitive factors, C-reactive protein, soluble E-selectin, von Willebrand factor antigen, and coagulation factor VIIIc were measured at baseline, 12, and 36 months in 365 participants of the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial, a randomized, placebo-controlled trial of the effects of 4 hormone preparations on cardiovascular disease risk factors. Compared with placebo, all 4 active preparations resulted in a large sustained increase in the concentration of C-reactive protein and a decrease in soluble E-selectin (P=0.0001). There were no effects of treatment on concentrations of von Willebrand factor or factor VIIIc. There were no differences in effects among treatment arms. Relative to placebo, when combining active treatment arms, final concentrations of C-reactive protein were 85% higher whereas E-selectin was 18% lower compared with baseline.Postmenopausal hormones rapidly increased the concentration of the inflammation factor C-reactive protein. Such an effect may be related to adverse early effects of estrogen therapy. In contrast, hormones reduced the concentration of soluble E-selectin, and this might be considered an anti-inflammatory effect. Because PEPI was not designed to assess clinical endpoints, studies of the impact of hormone-mediated changes in inflammation on risk of subsequent coronary events are needed.
Evolution of Flux Control in the Glucosinolate Pathway in Arabidopsis thaliana
Authors: Carrie F. Olson-Manning, Cheng-Ruei Lee, Mark D. Rausher, Thomas Mitchell-Olds
Journal: Molecular Biology and Evolution (2012)

Network characteristics of biochemical pathways are believed to influence the rate of evolutionary change in constituent enzymes. One characteristic that may affect rate heterogeneity is control of the amount of product produced by a biochemical pathway or flux control. In particular, theoretical analyses suggest that adaptive substitutions should be concentrated in the enzyme(s) that exert the greatest control over flux. Although a handful of studies have found a correlation between position in a pathway and evolutionary rate, these investigations have not examined the relationship between evolutionary rate and flux control. Given that genes with greater control will experience stronger selection and that the probability of fixation is proportional to the selective advantage, we ask the following: 1) do upstream enzymes have majority flux control, 2) do enzymes with majority flux control accumulate adaptive substitutions, and 3) are upstream enzymes under higher selective constraint? First, by perturbing the enzymes in the aliphatic glucosinolate pathway in Arabidopsis thaliana with gene insertion lines, we show that flux control is focused in the first enzyme in the pathway. Next, by analyzing several sequence signatures of selection, we also show that this enzyme is the only one in the pathway that shows convincing evidence of selection. Our results support the hypothesis that natural selection preferentially acts on enzymes with high flux control.
Cure of Helicobacter pylori infection in patients with reflux oesophagitis treated with long term omeprazole reverses gastritis without exacerbation of reflux disease: results of a randomised controlled trial
Authors: E J Kuipers, G F Nelis, E C Klinkenberg-Knol, P Snel, D Goldfain, J J Kolkman, H P M Festen, J Dent, P Zeitoun, N Havu, M Lamm, A Walan
Journal: Gut (2003)

<b>Background:</b><i>Helicobacter pylori</i> gastritis may progress to glandular atrophy and intestinal metaplasia, conditions that predispose to gastric cancer. Profound suppression of gastric acid is associated with increased severity of <i>H pylori</i> gastritis. This prospective randomised study aimed to investigate whether <i>H pylori</i> eradication can influence gastritis and its sequelae during long term omeprazole therapy for gastro-oesophageal reflux disease (GORD). <b>Methods:</b> A total of 231 <i>H pylori</i> positive GORD patients who had been treated for ⩾12 months with omeprazole maintenance therapy (OM) were randomised to either continuation of OM (OM only; n = 120) or OM plus a one week course of omeprazole, amoxycillin, and clarithromycin (OM triple; n = 111). Endoscopy with standardised biopsy sampling as well as symptom evaluation were performed at baseline and after one and two years. Gastritis was assessed according to the Sydney classification system for activity, inflammation, atrophy, intestinal metaplasia, and <i>H pylori</i> density. <b>Results:</b> Corpus gastritis activity at entry was moderate or severe in 50% and 55% of the OM only and OM triple groups, respectively. In the OM triple group, <i>H pylori</i> was eradicated in 90 (88%) patients, and activity and inflammation decreased substantially in both the antrum and corpus (p&lt;0.001, baseline <i>v</i> two years). Atrophic gastritis also improved in the corpus (p&lt;0.001) but not in the antrum. In the 83 OM only patients with continuing infection, there was no change in antral and corpus gastritis activity or atrophy, but inflammation increased (p&lt;0.01). <i>H pylori</i> eradication did not alter the dose of omeprazole required, or reflux symptoms. <b>Conclusions:</b> Most <i>H pylori</i> positive GORD patients have a corpus predominant pangastritis during omeprazole maintenance therapy. Eradication of <i>H pylori</i> eliminates gastric mucosal inflammation and induces regression of corpus glandular atrophy. <i>H pylori</i> eradication did not worsen reflux disease or lead to a need for increased omeprazole maintenance dose. We therefore recommend eradication of <i>H pylori</i> in GORD patients receiving long term acid suppression.
The relationship between leptin and proinflammatory cytokines with bone mineral density in patients with sarcoidosis (pts)
Authors: Elzbieta Puscinska, Michal Bednarek, Anna Goljan-Geremek, Anna Kowalczyk, Joanna Chorostowska-Wynimko, Paulina Jagus, Ada Rozy, Jacek Grudny, Dariusz Chmielewski, Dorota Gorecka
Journal: European Respiratory Journal (2012)

Background: Sarcoidosis is a chronic inflammatory disease. Osteoporosis is a multifactor disorder of reduced bone mass. Body weight is commonly considered a significant predictor of bone mineral density (BMD) but obesity is also associated with chronic inflammation. Cytokines like TNF-α, IL-1 and IL-6 induce bone resorption and bone loss. Aim: The aim of the study was to investigate whether there is a relationship between leptin or cytokines and BMD in pts. Methods: 85 pts, none was treated with steroids, 46M and 39F, age 41±9y were enrolled. We evaluated BMI, serum leptin, TNF-α, IL-1 and IL-6, osteocalcin, alkaline phosphate and others. BMD was measured (DXA). Results: Pts with low BMI had decreased lumbar spine BMD(Tscore 30), p=0,00054. There were no such results for femoral neck BMD. The highest values of leptin were found in pts with obesity. The differences between pts with normal BMI compared to those with obesity was statistically significant (p=0,026). There was a weak correlation between leptin and BMI, R=0,25, leptin and IL-1,R=0,27, leptin and phosphate in urine, collected over 24h, R=0,31. No correlation was found between leptin and TNF-α or IL6. Conclusions: In our group BMD was related to BMI but not to leptin levels nor other cytokines. Obesity, through its mechanical loading effect have a protective influence on bone tissue metabolism. Leptin, cytokines have a role in bone growth, development and loss. Further research is required to ascertain the importance of adipokines or cytokines for BMD.
“Inapparent” hepatitis B virus infection and hepatitis C virus replication in alcoholic subjects with and without liver disease
Authors: Anna Linda Zignego, Marco Foschi, Giacomo Laffi, Monica Monti, Grazia Careccia, Roberto Giulio Romanelli, Enrichetta de Majo, Roberto Mazzanti, Giampiero Buzzelli, Giorgio la Villa, Paolo Gentilini
Journal: Hepatology (1994)

We evaluated hepatitis B virus DNA and hepatitis C virus RNA in sera from 110 HBsAg and IgM HBc antibody–negative heavy drinkers (50 cirrhosis, 13 chronic active hepatitis, 25 fatty liver with or without mild to moderate fibrosis, alcoholic hepatitis or both and 22 healthy alcoholic subjects) with polymerase chain reaction. Results of hepatitis C virus polymerase chain reaction were compared with those obtained with two tests (second generation recombinant immunoblot assay and enzyme-linked immunosorbent assay) used to detect hepatitis C virus antibodies. Hepatitis B virus DNA was found in three (2.7) patients. Hepatitis C virus RNA was detected in 29 (29.8) of the 97 subjects whose sera were well preserved for RNA extraction (42.5 cirrhosis, 83.3 chronic active hepatitis, 8 fatty liver and 0 healthy alcoholic subjects). Results obtained with second-generation recombinant immunoblot assay and enzyme-linked immunosorbent assay had a high degree of agreement with polymerase chain reaction as expected, the K indexes being 0.76 and 0.61, respectively. Nevertheless, five hepatitis C virus RNA-positive patients had negative recombinant immunoblot assay results, whereas all hepatitis C virus RNA-positive patients had positive or borderline enzyme-linked immunosorbent assay results. We conclude that, in Italian HBsAg-negative alcoholic patients, “inapparent” hepatitis B virus infection is rare. On the contrary, hepatitis C virus infection, as detected on hepatitis C virus polymerase chain reaction, is quite frequent, especially in patients who have cirrhosis and chronic active hepatitis. Second-generation enzyme-linked immunosorbent assay can be reliably used as initial test for the detection of hepatitis C virus infection in alcoholic patients; clearly positive results are very likely to correspond to viremia. Borderline results necessitate confirmation with polymerase chain reaction analysis. (Hepatology 1994;19:577–582).
Prednisolone response in patients with COPD * Authors' reply
Authors: I D Pavord
Journal: Thorax (2004)

Our interpretation of the important data on corticosteroid responsiveness in chronic obstructive pulmonary disease (COPD) presented by Burge et al 1 is quite different from that of the authors. They have shown that those with an improvement in forced expiratory volume in 1 second (FEV1) of >20% following short term treatment with prednisolone had a more significant reduction in exacerbation frequency with longer term treatment with inhaled fluticasone than those without. Thus, arguably, the only important positive clinical outcome of long term treatment of COPD with inhaled corticosteroids is largely confined to those who are identified by a positive response to prednisolone. This is a powerful validation of the suggestion in current guidelines2 that decisions on …
What Makes a Good Reviewer and a Good Review for a General Medical Journal?
Authors: Nick Black
Journal: JAMA (1998)

Context.—Selecting peer reviewers who will provide high-quality reviews is a central task of editors of biomedical journals.Objectives.—To determine the characteristics of reviewers for a general medical journal who produce high-quality reviews and to describe the characteristics of a good review, particularly in terms of the time spent reviewing and turnaround time.Design, Setting, and Participants.—Surveys of reviewers of the 420 manuscripts submitted to BMJ between January and June 1997.Main Outcome Measures.—Review quality was assessed independently by 2 editors and by the corresponding author using a newly developed 7-item review quality instrument.Results.—Of the 420 manuscripts, 345 (82%) had 2 reviews completed, for a total of 690 reviews. Authors' assessments of review quality were available for 507 reviews. The characteristics of reviewers had little association with the quality of the reviews they produced (explaining only 8% of the variation), regardless of whether editors or authors defined the quality of the review. In a logistic regression analysis, the only significant factor associated with higher-quality ratings by both editors and authors was reviewers trained in epidemiology or statistics. Younger age also was an independent predictor for editors' quality assessments, while reviews performed by reviewers who were members of an editorial board were rated of poorer quality by authors. Review quality increased with time spent on a review, up to 3 hours but not beyond.Conclusions.—The characteristics of reviewers we studied did not identify those who performed high-quality reviews. Reviewers might be advised that spending longer than 3 hours on a review on average did not appear to increase review quality as rated by editors and authors.
Vegetables, fruit and risk of non-gallstone-related acute pancreatitis: a population-based prospective cohort study
Authors: Viktor Oskarsson, Omid Sadr-Azodi, Nicola Orsini, Åke Andrén-Sandberg, Alicja Wolk
Journal: Gut (2012)

<h3>Objective</h3> To examine the association of vegetable and fruit consumption with the risk of non-gallstone-related acute pancreatitis. <h3>Design</h3> A population-based prospective cohort of 80 019 women and men, aged 46–84 years, completed a food-frequency questionnaire at baseline and was followed up for incidence of non-gallstone-related acute pancreatitis from 1 January 1998 to 31 December 2009. Participants were categorised into quintiles according to consumption of vegetables and consumption of fruit. Cox proportional hazards models were used to estimate RRs and 95% CIs. <h3>Results</h3> In total, 320 incident cases (216 men and 104 women) with non-gallstone-related acute pancreatitis were identified during 12 years of follow-up (891 136 person-years). After adjustment for potential confounders, the authors observed a significant inverse linear dose–response association between vegetable consumption and risk of non-gallstone-related acute pancreatitis; every two additional servings per day were associated with 17% risk reduction (RR=0.83; 95% CI 0.70 to 0.98; p=0.03). Among participants consuming &gt;1 drink of alcohol per day and among those with body mass index ≥25 kg/m<sup>2</sup>, the RR for the highest compared with the lowest quintile of vegetable consumption was 0.29 (95% CI 0.13 to 0.67) and 0.49 (95% CI 0.29 to 0.85), respectively. Fruit consumption was not significantly associated with the risk of non-gallstone-related acute pancreatitis; the RR comparing extreme quintiles of consumption was 1.20 (95% CI 0.81 to 1.78). <h3>Conclusions</h3> Vegetable consumption, but not fruit consumption, may play a role in the prevention of non-gallstone-related acute pancreatitis.