tbuckley/cabot-search huggingface dataset:
Are selective COX 2 inhibitors superior to traditional non steroidal anti-inflammatory drugs?
Authors: P. Juni
Journal: BMJ (2002)

Selective cyclo-oxygenase 2 (COX 2) inhibitors, including celecoxib (Celebrex) and rofecoxib (Vioxx), are hypothesised to have a lower risk of gastrointestinal complications than traditional non-steroidal anti-inflammatory drugs.1 In September 2000 the celecoxib long term arthritis safety study, better known as CLASS, was published in JAMA .2 This trial, widely cited and distributed, concluded that a COX 2 inhibitor was associated with a lower incidence of complications than traditional non-steroidal anti-inflammatory drugs. What was much less widely publicised were criticisms that contradicted this conclusion.

CLASS was reported as a three arm trial comparing celecoxib 800 mg/day with ibuprofen 2400 mg/day and diclofenac 150 mg/day in osteoarthritis or rheumatoid arthritis. Clinically relevant upper gastrointestinal ulcer complications (bleeding, perforation, or obstruction) and symptomatic ulcers during the first six months of treatment were described as the two main outcome measures, comparing incidence rates for celecoxib and a traditional non-steroidal anti-inflammatory drug (fig 1). It was concluded that, compared with the traditional non-steroidal anti-inflammatory drug, celecoxib “was associated with a lower incidence of symptomatic ulcers and ulcer complications combined.”3 The trial was funded by celecoxib's manufacturer Pharmacia.

An article in the Washington Post in August 20013 and two letters published in JAMA in November 2001 4 5 drew attention to the fact that complete information available to the United States Food and Drug Administration contradicted these conclusions. The paper reporting CLASS2 actually referred to the combined analysis of the results …
The impact of follicular lymphoma on health-related quality of life
Authors: R. Pettengell, C. Donatti, P. Hoskin, C. Poynton, P.J. Kettle, B. Hancock, S. Johnson, M.J.S. Dyer, S. Rule, M. Walker, D. Wild
Journal: Annals of Oncology (2007)

BackgroundThe purpose of this study was to determine whether there was a relationship between disease activity and health functioning, as measured by a range of patient-reported outcome (PRO) measures in patients with follicular lymphoma (FL).Patients and methodsA total of 222 patients with FL were recruited from eight sites across the UK and they completed a number of PRO measures. The participants were analyzed across five disease states: ‘active disease—newly diagnosed’, ‘active disease—relapsed’, ‘partial response’, ‘complete response’ and ‘disease free’. The relationship between these disease states and their level of health functioning was assessed as well as the relationship between being ‘on’ or ‘off’ chemotherapy and disease state.ResultsIn terms of health-related quality of life (HRQoL), participants in the relapsed category had the lowest mean physical well-being, emotional well-being, functional well-being and social well-being score. In a regression analysis, the ‘active disease–relapsed’ group acted as a significant predictor for each PRO variable. In addition, the remission group acted as a significant predictor of high anxiety scores as measured by the Hospital Anxiety and Depression Scale.ConclusionThe results of this study demonstrate that various aspects of patient-reported health outcomes differ according to disease state in patients with FL. For those patients who have relapsed, they are more likely to experience worse HRQoL and other patient-reported health outcomes than patients newly diagnosed, in partial or complete remission or when completely disease free.
Surreptitious manipulation of the human host by<i>Helicobacter pylori</i>
Authors: Dawn A. Israel, Richard M Peek, Jr
Journal: Gut Microbes (2010)

Microbial pathogens contribute to the development of more than 1 million cases of cancer per year. Gastric adenocarcinoma is the second leading cause of cancer-related death in the world, and gastritis induced by Helicobacter pylori is the strongest known risk factor for this malignancy. H. pylori colonizes the stomach for years, not days or weeks, as is usually the case for bacterial pathogens and it always induces inflammation; however, only a fraction of colonized individuals ever develop disease. Identification of mechanisms through which H. pylori co-opts host defenses to facilitate its own persistence will not only improve diagnostic and therapeutic modalities, but may also provide insights into other diseases that arise within the context of long-term pathogen-initiated inflammatory states, such as chronic viral hepatitis and hepatocellular carcinoma.
Risk of malignant neoplasms of liver and biliary tract in diabetic patients with different age and sex stratifications
Authors: Hua-Fen Chen, Peter Chen, Chung-Yi Li
Journal: Hepatology (2010)

We prospectively investigated 615,532 diabetic patients and 614,871 age-matched and sex-matched control subjects selected from National Health Insurance claims for malignant neoplasms of liver and biliary tract (International Statistical Classification of Diseases and Related Health Problems, 9th edition, codes 155 and 156, respectively) between 2000 and 2006. The person-year approach with Poisson assumption was used to estimate the hazard rates. We also evaluated the age-specific and sex-specific relative risks of these two malignancies in relation to diabetes with Cox proportional hazard regression model with adjustment for potential confounders. The overall hazard rate of malignant neoplasm of the liver was 32.76 and 17.41 per 10,000 patient-years, respectively, for diabetic men and women; the corresponding figures for biliary tract neoplasm were much lower at 1.42 and 1.60 per 10,000 patient-years. Compared with control subjects, diabetic patients had a two-fold increased risk of malignant neoplasm of the liver, but this risk was attenuated by adjusting for selected clinical risk factors (hazard ratio [HR] 1.21; 95% confidence interval [CI] 1.17-1.25). Additionally, diabetic patients were associated with increased risk of biliary neoplasms with an approximate magnitude of 20%-30%, but the HR was attenuated and became insignificant after adjustment for clinical risk factors (HR 1.07; 95% CI 0.95-1.21). Diabetic patients with cirrhosis had the highest relative risk of liver neoplasm (HR 85.25; 95% CI 76.84-94.58), whereas those with cholangitis had the highest risk of biliary tract neoplasm (HR 70.30; 95% CI 51.95-95.12) compared with control subjects without any clinical risk factors. Conclusion: This population-based study confirms the association of diabetes with liver neoplasm and suggests that diabetic patients with certain clinical risk factors should be educated for strict adherence of liver neoplasm screening. (Hepatology 2010)
Attachment of Giardia lamblia to rat intestinal epithelial cells.
Authors: P M Inge, C M Edson, M J Farthing
Journal: Gut (1988)

<h3>Abstract</h3> The application of high throughput technologies has enabled unravelling of unique differences between healthy mares and mares with endometritis at transcriptomic and proteomic levels. However, differences in the uterine microbiome are yet to be investigated. The present study was aimed at evaluating the differences in uterine microbiome between healthy mares and mares with endometritis. Low-volume lavage (LVL) samples were collected from the uterus of 30 mares classified into healthy (n=15) and endometritis (n=15) based on their reproductive history, intrauterine fluid accumulation, gross appearance of LVL samples, endometrial cytology, and bacterial culture. The samples were subjected to metagenomic analysis using 16S rRNA sequencing. Notable differences in the uterine microbiome were observed between healthy mares and mares with endometritis at various taxonomic levels. In healthy mares, the most abundant phylum, class, order, and family were Firmicutes, Bacilli, Bacillales, and Paenibacillaceae, respectively. In contrast, the most abundant corresponding taxonomic levels in mares with endometritis were Proteobacteria, Gammaproteobacteria, Enterobacterales, and Enterobacteriaceae, respectively. At the genus level, <i>Brevibacillus</i> and <i>Paenibacillus</i> were more abundant in healthy mares, whereas <i>Escherichia, Salmonella</i>, and <i>Klebsiella</i> were more abundant in mares with endometritis. In healthy mares, <i>Brevibacillus brevis</i> was the most abundant species, followed by <i>Brevibacillus choshinensis</i> and <i>Paenibacillus sp JDR-2</i>. However, in mares with endometritis, <i>Escherichia coli</i> was the most abundant species, followed by <i>Salmonella enterica</i> and <i>Klebsiella pneumoniae</i>. These results indicate novel differences in the uterine microbiome between healthy mares and mares with endometritis. The findings can potentially help formulate new approaches to prevent or treat equine endometritis.
The Effects of an Indigenous Muscarinic Drug, Betel Nut (<i>Areca catechu</i>), on the Symptoms of Schizophrenia: A Longitudinal Study in Palau, Micronesia
Authors: Roger J. Sullivan, Sylvia Andres, Caleb Otto, Wayne Miles, Robert Kydd
Journal: American Journal of Psychiatry (2007)

Objective: This study tested the findings of a prior study indicating a therapeutic relationship between consumption of betel nut and symptoms of schizophrenia. Method: The subjects were 65 outpatients with diagnoses of schizophrenia or schizoaffective disorder. Symptoms rated with the Positive and Negative Syndrome Scale were compared between high- and low-consumption betel chewers in a repeated-measures design. Movement disorders were assessed with the Abnormal Involuntary Movement Scale and Simpson-Angus Rating Scale. Global health and social functioning were assessed with the Medical Outcomes Study 12-item and 36-item Short-Form Health Surveys, respectively. Results: Male high-consumption betel chewers had significantly milder positive symptoms than low-consumption chewers over 1 year. Betel chewing was not associated with global health, social functioning, or movement disorders. Betel chewing was associated with tobacco use but not with cannabis or alcohol. Conclusions: These findings have clinical significance in betel-chewing regions and broader implications for theory of muscarinic neurophysiology in schizophrenia.
Proximal Tubular Cysts in Fetal Human Autosomal Recessive Polycystic Kidney Disease
Authors: KOICHI NAKANISHI, WILLIAM E. SWEENEY, KLAUS ZERRES, LISA M. GUAY-WOODFORD, ELLIS D. AVNER
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Standard texts describe human autosomal recessive polycystic kidney disease (ARPKD) as a cystic kidney disease in which lesions are localized to collecting tubules. Murine models of ARPKD consistently demonstrate an early phase of proximal tubular (PT) cystic involvement, which disappears shortly after birth. This is followed by a phase of collecting tubular (CT) cyst formation and progressive enlargement leading to compromise of renal function and death. Because the description of cystic lesions in human ARPKD has been largely based on postnatal specimens, PT cyst formation was hypothesized to be a characteristic feature of fetal human, as well as murine, ARPKD. This study examines nephron segment-specific cyst localization histochemically by lectin binding in 11 human ARPKD specimens obtained at different fetal and postnatal ages. PT cysts were found in human fetal specimens from gestational age 14 wk to 26 wk. The percentage of cysts involving PT segments ranged from 2 to 41%. The cystic index of PT cysts ranged from 2 to 5. In all specimens in which PT cysts were found, both the percentage of CT cysts and their cystic index were equal to or greater than the percentage of PT cysts and the associated PT cystic index. PT cysts were absent in all kidney specimens older than 34 wk gestational age. It is concluded that human ARPKD, like murine ARPKD, has a transient phase of PT cyst formation during early fetal development.
Stimulation of glucose oxidation protects against acute myocardial infarction and reperfusion injury
Authors: John R. Ussher, Wei Wang, Manoj Gandhi, Wendy Keung, Victor Samokhvalov, Tatsujiro Oka, Cory S. Wagg, Jagdip S. Jaswal, Robert A. Harris, Alexander S. Clanachan, Jason R.B. Dyck, Gary D. Lopaschuk
Journal: Cardiovascular Research (2012)

During reperfusion of the ischaemic myocardium, fatty acid oxidation rates quickly recover, while glucose oxidation rates remain depressed. Direct stimulation of glucose oxidation via activation of pyruvate dehydrogenase (PDH), or secondary to an inhibition of malonyl CoA decarboxylase (MCD), improves cardiac functional recovery during reperfusion following ischaemia. However, the effects of such interventions on the evolution of myocardial infarction are unknown. The purpose of this study was to determine whether infarct size is decreased in response to increased glucose oxidation. In vivo, direct stimulation of PDH in mice with the PDH kinase (PDHK) inhibitor, dichloroacetate, significantly decreased infarct size following temporary ligation of the left anterior descending coronary artery. These results were recapitulated in PDHK 4-deficient (PDHK4−/−) mice, which have enhanced myocardial PDH activity. These interventions also protected against ischaemia/reperfusion injury in the working heart, and dichloroacetate failed to protect in PDHK4−/− mice. In addition, there was a dramatic reduction in the infarct size in malonyl CoA decarboxylase-deficient (MCD−/−) mice, in which glucose oxidation rates are enhanced (secondary to an inhibition of fatty acid oxidation) relative to their wild-type littermates (10.8 ± 3.8 vs. 39.5 ± 4.7%). This cardioprotective effect in MCD−/− mice was associated with increased PDH activity in the ischaemic area at risk (1.89 ± 0.18 vs. 1.52 ± 0.05 μmol/g wet weight/min). These findings demonstrate that stimulating glucose oxidation via targeting either PDH or MCD decreases the infarct size, validating the concept that optimizing myocardial metabolism is a novel therapy for ischaemic heart disease.
Subdural haematoma associated with an arachnoid cyst after repetitive minor heading injury in ball games: Figure 1
Authors: A K Demetriades, A W McEvoy, N D Kitchen
Journal: British Journal of Sports Medicine (2004)

We report the case of a chronic subdural haematoma caused by repetitive heading of a football which led to the diagnosis of a middle fossa arachnoid cyst. The association between arachnoid cysts and subdural haematoma is discussed as are safety implications in sporting injuries.
Bacterial lipopolysaccharide-mediated fetal death. Production of a newly recognized form of inducible cyclooxygenase (COX-2) in murine decidua in response to lipopolysaccharide.
Authors: R M Silver, S S Edwin, M S Trautman, D L Simmons, D W Branch, D J Dudley, M D Mitchell
Journal: Journal of Clinical Investigation (1995)

Maternal infection is a cause of spontaneous abortion and preterm labor in humans, but the pathophysiology is unclear. We hypothesized that eicosanoids play an important role in infection-driven pregnancy loss. To investigate this hypothesis, we administered lipopolysaccharide (LPS) to pregnant C3H/HeN mice and found that LPS administration caused fetal death in a dose-dependent fashion. Pretreatment with indomethacin significantly decreased the proportion of fetal death from 83% to < 25% in mice injected with 10 micrograms of LPS. Also, decidual explants from LPS-treated mice produced significantly more inflammatory eicosanoids, including prostaglandins E2 and F2 alpha and thromboxane B2, than controls. We investigated the regulatory mechanisms responsible for increased decidual prostanoid production in response to LPS. Western and Northern blots demonstrated that decidual protein and mRNA levels of a recently recognized highly inducible form of cyclooxygenase, COX-2, were substantially increased in mice treated with LPS. Induction of COX-2 was rapid: mRNA was detected 30 min after LPS injection. In contrast, another form of cyclooxygenase, COX-1, was only minimally induced in response to LPS. Our data indicate that LPS induces decidual prostanoid production via increased COX-2 expression. Since LPS-mediated fetal death is markedly diminished by pretreatment with indomethacin, COX-2-mediated eicosanoid production is likely a key pathophysiologic event in LPS-mediated fetal death.
ON THE TREATMENT OF FRACTURE OF THE FEMUR IN THE NEWLY-BORN
Authors: R. Jones
Journal: BMJ (1908)

whilst the remaining 3 deas were due to exhaustion on the fourth or filth dale.Of the remaining 62 patients, 33 were not seen after they left hospital, 18 were seen with recurrence, and 11 free from disease.In 11 of the 18, disemae reourred within the year.O those seen free trom diosee, 2 were seen within the year, 1 alter fifteen months, 1 after three yeasr, 2 after four years, 2 after seven yeas, and 3 alter eight years.The last 6 were all Instances of the more
Randomized, Placebo-Controlled Trial of Fluoxetine for Acute Treatment of Minor Depressive Disorder
Authors: Lewis L. Judd, Mark Hyman Rapaport, Kimberly A. Yonkers, A. John Rush, Ellen Frank, Michael E. Thase, David J. Kupfer, John M. Plewes, Pamela J. Schettler, Gary Tollefson
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: Minor depressive disorder is both common and associated with significant psychosocial impairment. This study examined antidepressant treatment efficacy in a large group of patients with minor depressive disorder. METHOD: One hundred sixty-two patients with minor depressive disorder were randomly assigned to receive fluoxetine or placebo in a 12-week, double-blind study; 73% (59 of 81) of the patients in each treatment group completed the study. Patients were evaluated weekly with standard depression rating instruments and measures of psychosocial impairment. Hypotheses were tested by last-observation-carried-forward analysis of variance (ANOVA) and confirmed by mixed (random-effects) regression analysis. RESULTS: At baseline, minor depressive disorder patients were mildly to moderately depressed, with a corresponding degree of functional impairment. Over 12 weeks of treatment, both ANOVA and mixed regression showed fluoxetine to be superior to placebo as indicated by significantly greater improvement of fluoxetine-treated patients in scores on the 30-item clinician-rated Inventory of Depressive Symptomatology, the 17-item and 21-item Hamilton Depression Rating Scale, the Beck Depression Inventory, and the Clinical Global Impression severity scale. Improvement in Global Assessment of Functioning Scale score was significantly greater for the fluoxetine group in mixed regression analysis only. Patients in both treatment groups reported a similar number and severity of adverse events during the 12-week treatment period. CONCLUSIONS: Clinicians frequently encounter minor depressive disorder either as a prodromal or residual phase of illness in major depressive disorder or as de novo minor depressive disorder episodes. Fluoxetine is significantly superior to placebo in reducing minor depressive disorder symptoms within a 12-week period. Improvement in psychosocial function with fluoxetine may take longer than 12 weeks.
An Apoptosis-inducing Isoform of Neu Differentiation Factor (NDF) Identified Using a Novel Screen for Dominant, Apoptosis-inducing Genes
Authors: Stefan Grimm, Philip Leder
Journal: The Journal of Experimental Medicine (1997)

Apoptosis is a genetically programmed series of events that results in cell death. As a consequence, it is difficult to identify dominant genes that play a role in this process using genetic selections in conventional cell culture systems. Accordingly, we have established an efficient expression screen to isolate dominant, apoptosis-inducing genes. The assay is based on the apoptotic morphology induced in the human kidney cell line 293 after transient transfection of small plasmid pools from normalized cDNA expression libraries. Using this assay, we isolated a novel isoform of the proto-oncogene Neu differentiation factor (NDF), a ligand for erbB receptor tyrosine kinases. Several lines of experimental evidence indicate that this gene kills in a cell-autonomous fashion and independently of known erbB receptors. This apoptotic property of an NDF isoform is readily contrasted with NDF's transforming potential and might balance the tendency to tumorigenesis in cells that overexpress NDF.
Oxidative Stress as a Regulator of Gene Expression in the Vasculature
Authors: Charles Kunsch, Russell M. Medford
Journal: Circulation Research (1999)

Abstract —Oxidative stress and the production of intracellular reactive oxygen species (ROS) have been implicated in the pathogenesis of a variety of diseases. In excess, ROS and their byproducts that are capable of causing oxidative damage may be cytotoxic to cells. However, it is now well established that moderate amounts of ROS play a role in signal transduction processes such as cell growth and posttranslational modification of proteins. Oxidants, antioxidants, and other determinants of the intracellular reduction-oxidation (redox) state play an important role in the regulation of gene expression. Recent insights into the etiology and pathogenesis of atherosclerosis suggest that this disease may be viewed as an inflammatory disease linked to an abnormality in oxidation-mediated signals in the vasculature. In this review, we summarize the evidence supporting the notion that oxidative stress and the production of ROS function as physiological regulators of vascular gene expression mediated via specific redox-sensitive signal transduction pathways and transcriptional regulatory networks. Elucidating, at the molecular level, the regulatory processes involved in redox-sensitive vascular gene expression represents a foundation not only for understanding the pathogenesis of atherosclerosis and other inflammatory diseases but also for the development of novel therapeutic treatment strategies.
Tissue-specific direct targets of Caenorhabditis elegans Rb/E2F dictate distinct somatic and germline programs
Authors: Michelle Kudron, Wei Niu, Zhi Lu, Guilin Wang, Mark Gerstein, Michael Snyder, Valerie Reinke
Journal: Genome biology (2013)

Abstract Background The tumor suppressor Rb/E2F regulates gene expression to control differentiation in multiple tissues during development, although how it directs tissue-specific gene regulation in vivo is poorly understood. Results We determined the genome-wide binding profiles for Caenorhabditis elegans Rb/E2F-like components in the germline, in the intestine and broadly throughout the soma, and uncovered highly tissue-specific binding patterns and target genes. Chromatin association by LIN-35, the C. elegans ortholog of Rb, is impaired in the germline but robust in the soma, a characteristic that might govern differential effects on gene expression in the two cell types. In the intestine, LIN-35 and the heterochromatin protein HPL-2, the ortholog of Hp1, coordinately bind at many sites lacking E2F. Finally, selected direct target genes contribute to the soma-to-germline transformation of lin-35 mutants, including mes-4 , a soma-specific target that promotes H3K36 methylation, and csr-1 , a germline-specific target that functions in a 22G small RNA pathway. Conclusions In sum, identification of tissue-specific binding profiles and effector target genes reveals important insights into the mechanisms by which Rb/E2F controls distinct cell fates in vivo .