tbuckley/cabot-search huggingface dataset:
Risk of oesophageal cancer by histology among patients hospitalised for gastroduodenal ulcers
Authors: S. Bahmanyar, K. Zendehdel, O. Nyren, W. Ye
Journal: Gut (2006)

The mechanism behind the epidemiologically evident inverse relation between Helicobacter pylori seropositivity and risk of oesophageal adenocarcinoma (OAC) remains obscure. Severe corpus gastritis is unlikely to be in the causal pathway. With the hypothesis of a uniformly low risk, the associations of OAC with duodenal ulcer and gastric ulcer were explored, both linked to H pylori infection but with different patterns of bacterial colonisation and intragastric acidity. Possible associations of oesophageal squamous cell carcinoma (OSCC) with these ulcer types were also addressed.Retrospective cohorts of 61,548 and 81,379 unoperated patients with duodenal ulcer and gastric ulcer, respectively, recorded in the Swedish Inpatient Register since 1965, were followed from the first hospitalisation until the date of any cancer, death, emigration, definitive surgery, or 31 December 2003. Standardised incidence ratios (SIRs), with 95% CIs, expressed relative risk of oesophageal cancer, compared with the Swedish population matched for age, sex and calendar period.Contrary to expectation, patients with duodenal ulcer had a significant 70% excess risk of OAC (SIR 1.7, 95% CI 1.1 to 2.5). Gastric ulcer was unrelated to OAC (SIR 1.1, 95% CI 0.6 to 1.7). Although duodenal ulcer was non-significantly associated with a small excess of OSCC (SIR 1.3, 95% CI 0.96 to 1.8), gastric ulcer was linked to 80% increased risk (SIR 1.8, 95% CI 1.4 to 2.3).The inverse association between H pylori and OAC does not pertain to all infections. The pattern of gastric colonisation and/or impact on acidity may be important. With the reservation for the possibility of confounding, this study also provides some support for the importance of intragastric environment in the aetiology of OSCC.
Use of Implantable Cardioverter-Defibrillators Among Medicare Patients—Reply
Authors: Sean D. Pokorney, Eric D. Peterson, Tracy Y. Wang
Journal: JAMA (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
TNF-induced osteoclastogenesis and inflammatory bone resorption are inhibited by transcription factor RBP-J
Authors: Baohong Zhao, Shannon N. Grimes, Susan Li, Xiaoyu Hu, Lionel B. Ivashkiv
Journal: The Journal of Experimental Medicine (2012)

Tumor necrosis factor (TNF) plays a key role in the pathogenesis of inflammatory bone resorption and associated morbidity in diseases such as rheumatoid arthritis and periodontitis. Mechanisms that regulate the direct osteoclastogenic properties of TNF to limit pathological bone resorption in inflammatory settings are mostly unknown. Here, we show that the transcription factor recombinant recognition sequence binding protein at the Jκ site (RBP-J) strongly suppresses TNF-induced osteoclastogenesis and inflammatory bone resorption, but has minimal effects on physiological bone remodeling. Myeloid-specific deletion of RBP-J converted TNF into a potent osteoclastogenic factor that could function independently of receptor activator of NF-κB (RANK) signaling. In the absence of RBP-J, TNF effectively induced osteoclastogenesis and bone resorption in RANK-deficient mice. Activation of RBP-J selectively in osteoclast precursors suppressed inflammatory osteoclastogenesis and arthritic bone resorption. Mechanistically, RBP-J suppressed induction of the master regulator of osteoclastogenesis (nuclear factor of activated T cells, cytoplasmic 1) by attenuating c-Fos activation and suppressing induction of B lymphocyte–induced maturation protein-1, thereby preventing the down-regulation of transcriptional repressors such as IRF-8 that block osteoclast differentiation. Thus, RBP-J regulates the balance between activating and repressive signals that regulate osteoclastogenesis. These findings identify RBP-J as a key upstream negative regulator of osteoclastogenesis that restrains excessive bone resorption in inflammatory settings.
Sorafenib and pegylated interferon-α2b in advanced metastatic melanoma: a multicenter phase II DeCOG trial
Authors: F Egberts, R Gutzmer, S Ugurel, J C Becker, U Trefzer, A Degen, F Schenck, L Frey, T Wilhelm, J C Hassel, D Schadendorf, E Livingstone, C Mauch, C Garbe, C Berking, K Rass, P Mohr, K C Kaehler, M Weichenthal, A Hauschild
Journal: Annals of Oncology (2011)
Role of Postmarketing Surveillance in Contemporary Medicine
Authors: Janet Woodcock, Rachel E. Behrman, Gerald J. Dal Pan
Journal: Annual Review of Medicine (2010)

Contemporary medicine is a large and complex system involving many participants, all of whom play a critical role in managing the risks intrinsic to medical product use. Despite the robust premarket review and approval process of the U.S. Food and Drug Administration (FDA), new information will inevitably be learned in the postmarketing period about the safety of medicines and how they are and should be used. For much of this information, FDA relies on public reports about possible adverse events. In turn, the public depends on FDA to communicate the most up-to-date safety information on medical products to better inform treatment decisions. Expanding the scope and strengthening the capabilities of the drug safety surveillance system are among key FDA projects designed to reduce avoidable injury and death from medication use. Although improving drug safety is our goal and obligation to the public, FDA cannot protect the public adequately without the active involvement of all participants in healthcare.
Analysis of Metabolic Parameters as Predictors of Risk in the RENAAL Study
Authors: Gerald B. Appel, Jai Radhakrishnan, Morrell M. Avram, Ralph A. DeFronzo, Fernando Escobar-Jimenez, M.M. Campos, Ellen Burgess, Darcy A. Hille, Tania Z. Dickson, Shahnaz Shahinfar, Barry M. Brenner
Journal: Diabetes Care (2003)

OBJECTIVE—Metabolic factors such as glycemic control, hyperlipidemia, and hyperkalemia are important considerations in the treatment of patients with type 2 diabetes and nephropathy. In the RENAAL (Reduction of End Points in Type 2 Diabetes With the Angiotensin II Antagonist Losartan) study, losartan reduced renal outcomes in the patient population. This post hoc analysis of the RENAAL study reports the effects of losartan on selected metabolic parameters and assesses the relationship between baseline values of metabolic parameters and the primary composite end point or end-stage renal disease (ESRD). RESEARCH DESIGN AND METHODS—Glycemic control (HbA1c) and serum lipid, uric acid, and potassium levels were compared between the losartan and placebo groups over time, and baseline levels were correlated with the risk of reaching the primary composite end point (doubling of serum creatinine, ESRD, or death) or ESRD alone. RESULTS—Losartan did not adversely affect glycemic control or serum lipid levels. Losartan-treated patients had lower total (227.4 vs. 195.4 mg/dl) and LDL (142.2 vs. 111.7 mg/dl) cholesterol. Losartan was associated with a mean increase of up to 0.3 mEq/l in serum potassium levels; however, the rate of hyperkalemia-related discontinuation was similar between the placebo and losartan groups. Univariate analysis revealed that baseline total and LDL cholesterol and triglyceride levels were associated with increased risk of developing the primary composite end point. Similarly, total and LDL cholesterol were also associated with increased risk of developing ESRD. CONCLUSIONS—Overall, losartan was well tolerated by patients with type 2 diabetes and nephropathy and was associated with a favorable effect on the metabolic profile of this population.
Impact of gastro-oesophageal reflux disease symptoms on COPD exacerbation
Authors: K Terada, S Muro, S Sato, T Ohara, A Haruna, S Marumo, D Kinose, E Ogawa, Y Hoshino, A Niimi, T Terada, M Mishima
Journal: Thorax (2008)

<h3>Background:</h3> The association between gastro-oesophageal reflux disease (GORD) and chronic obstructive pulmonary disease (COPD) exacerbation has so far remained unclear. <h3>Objective:</h3> To prospectively establish the clinical significance of GORD symptoms on exacerbation. <h3>Methods:</h3> 82 patients with COPD and 40 age matched controls were enrolled in this study. Symptoms were evaluated by a questionnaire using the Frequency Scale for the Symptoms of GORD (FSSG). Patients with COPD were prospectively surveyed for 6 months, and episodes of exacerbation were identified using a diary based on modified Anthonisen’s criteria. Exhaled breath condensate (EBC) pH was measured in both groups, and induced sputum was evaluated in patients with COPD. <h3>Results:</h3> Positive GORD symptoms were reported in 22 (26.8%) patients with COPD and in five (12.5%) controls (p = 0.10). The frequency of exacerbations was significantly associated with the FSSG score (p = 0.03, r = 0.24, 95% CI 0.02 to 0.43). Multiple regression analysis revealed that GORD symptoms were significantly associated with the occurrence of exacerbations (p&lt;0.01; relative risk 6.55, 95% CI 1.86 to 23.11). EBC pH was inversely correlated with FSSG score in both groups (p = 0.01, r = –0.37, 95% CI –0.55 to −0.14 in patients with COPD, and p&lt;0.01, r = –0.45, 95% CI –0.67 to −0.16 in control subjects). <h3>Conclusions:</h3> GORD symptoms were identified as an important factor associated with COPD exacerbation.
Alternative ways of expressing FEV<sub>1</sub>and mortality in elderly people with and without COPD
Authors: Claudio Pedone, Simone Scarlata, Nicola Scichilone, Francesco Forastiere, Vincenzo Bellia, Raffaele Antonelli-Incalzi
Journal: European Respiratory Journal (2012)

Expressing forced expiratory volume in 1 s (FEV1) as % predicted relies on the assumption of proportional variability and generalisability of prediction equations that may be unrealistic, especially for elderly people. We evaluated the prognostic implications of alternative ways of expressing FEV1. We enrolled 318 patients with chronic obstructive pulmonary disease (COPD) and 475 controls in the Salute Respiratoria nell'Anziano (SARA) study. The risk for 5-, 10- and 15-year mortality associated with FEV1 was studied by expressing FEV1 % pred, standardised by height cubed (FEV1 · Ht(-3)) and as a multiple of the sex-specific first percentile (FEV1 quotient (FEV1Q)). In the group with COPD, the incidence rate ratio for the worst versus the best quintile of FEV1Q was 4.65 (95% CI 2.33-10.37), compared to 2.98 (1.53-6.27) for FEV1 % pred and 3.95 (2.01-8.45) for FEV1 · Ht(-3). The corresponding incidence rate ratios at 15 years were 4.52 (2.84-7.43), 3.16 (2.02-5.07) and 3.52 (2.25-5.63), respectively. In the control group, even moderate reduction of FEV1Q was associated with long-term mortality, while FEV1 % pred was not associated with the outcome. FEV1Q may be more informative about prognosis in an elderly population compared to FEV1 % pred.
Viruses and asthma exacerbations
Authors: N G PAPADOPOULOS, S L JOHNSTON
Journal: Thorax (1998)

The diseases of cystic fibrosis, chronic obstructive pulmonary disease (COPD), and chronic bronchitis are characterized by mucus-congested and inflamed airways. Anti-inflammatory agents that can simultaneously restore or enhance mucociliary clearance through cystic fibrosis transmembrane conductance regulator (CFTR) activation may represent new therapeutics in their treatment. Herein, we report the activation of CFTR-mediated chloride secretion by phosphodiesterase (PDE) 4 inhibitors in T84 monolayer using <sup>125</sup>I anion as tracer. In the absence of forskolin, the iodide secretion was insensitive to PDE4 inhibitor L-826,141 [4-[2-(3,4-bis-difluoromethoxyphenyl)-2-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-ethyl]-3-methylpyridine-1-oxide], roflumilast, or to PDE3 inhibitor trequinsin. However, these inhibitors potently augmented iodide secretion after forskolin stimulation, with efficacy coupled to the activation states of adenylyl cyclase. The iodide secretion from PDE3 or PDE4 inhibition was characterized at first by a prolonged efflux duration, followed by progressively elevated peak efflux rates at higher inhibitor concentrations. Paralleled with an increased phosphor-cAMP response element-binding protein formation, the CFTR activation dissociated from a global cAMP elevation and was blocked by H89 [<i>N</i>-[2-((<i>p</i>-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide]. 2-(4-Fluorophenoxy)-<i>N</i>-[(1<i>S</i>)-1-(4-methoxyphenyl)ethyl]nicotinamide, a stereoselective PDE4D inhibitor, augmented iodide efflux more efficiently than its less potent (<i>R</i>)-isomer. The peak efflux from maximal PDE4 and PDE3 inhibition matched that from full adenylyl cyclase activation. These data suggest that PDE3 and PDE4 (mainly PDE4D) form the major cAMP diffusion barrier in T84 cells to ensure a compartmentalized CFTR signaling. Together with their potent anti-inflammatory properties, the potentially enhanced airway mucociliary clearance from CFTR activation may have contributed to the efficacy of PDE4 inhibitors in COPD and asthmatic patients. PDE4 inhibitors may represent new opportunities to combat cystic fibrosis and other respiratory diseases in future.
Goals of asthma treatment: how high should we go?
Authors: H.K. Reddel
Journal: European Respiratory Journal (2004)

H.K. Reddel is supported by the Ann J. Woolcock Fellowship from the Asthma Foundation of NSW.

In the textbook “Respiratory Diseases”, published in 1981, Crofton and Douglas 1 commenced the discussion of asthma management with the comment “It must be admitted that the treatment of asthma is largely palliative”. The chapter provides a bleak picture of high mortality, frequent symptoms,and disabling side-effects of treatment. The use of inhaled corticosteroids (ICS) and, later, long-acting β2-agonists, has produced extraordinary improvements in asthma outcomes, particularly in the burden of disease for patients. More recent attention has focussed on fine-tuning asthma treatment, the aim being to return the patient towards the disease-free state, i.e. not just to improve lung function, which has long been the preferred outcome variable for clinical trials, but to improve the whole spectrum of asthma features, summarised in the expression “asthma control”.

These concepts have been addressed by Bateman et al . 2, reporting the results of the Gaining Optimal Asthma controL (GOAL) study. The GOAL study 2 arose from scientific and clinical interest in determining the proportion of asthma patients who could achieve a stringent definition of asthma control. The commercial setting within which this question was examined was a double-blind randomised controlled trial comparing salmeterol and fluticasone combination (SFC) and fluticasone propionate (FP), given b.i.d by Diskus/Accuhaler for 12 months in patients with suboptimally controlled asthma at entry. The GOAL study 2 has raised several interesting issues relating to optimal asthma management, and the way in which response to treatment should be assessed.

The GOAL study 2 was planned in the late 1990s, when there was considerable interest in the potential impact of high doses of ICS, with or without long-acting β2-agonists, in achieving better outcomes in asthma. At the time, international asthma …
Cigarette smoke inhalation and lung damage in smoking volunteers
Authors: KD Clark, N Wardrobe-Wong, JJ Elliott, PT Gill, NP Tait, PD Snashall
Journal: European Respiratory Journal (1998)

Cigarette smoking is the dominant risk factor for chronic obstructive pulmonary disease (COPD) but only 10-15% of smokers develop the condition. Risk does not relate closely to cumulative cigarette consumption, perhaps because smokers vary in the degree and depth of smoke inhalation. This study examined the role of smoke inhalation in the development of COPD. Eighty current smokers and 20 lifetime nonsmoking volunteers (aged 35-65 yrs) were recruited. Lung function variables were measured and high-resolution computed tomography (HRCT) scans performed. Smoke inhalation was assessed by CO boost (the increment of expired carbon monoxide 5 min after smoking a cigarette) and serum cotinine. Mean CO boost was 6.3 parts per million (ppm) in smokers with low CO transfer coefficients (KCO) and 2.9 ppm in those with normal KCO (p=0.006); 7.2 ppm in smokers with both HRCT-defined emphysema and a low KCO and 2.6 ppm in those with neither abnormality (p=0.002); 4.5 ppm in smokers with HRCT-defined emphysema alone and 2.8 ppm in those without (p=0.08). Mean serum cotinine was 328 ng x mL(-1) in smokers with chronic productive cough and 243 ng x mL(-1) in those without (p=0.005). Lifetime nonsmokers had normal HRCT scans, lung function and serum cotinine. Emphysema is associated with high alveolar smoke exposure as measured by CO boost. Productive coughing is associated with high nicotine uptake, probably from airway smoke particle deposition.
Cardiovascular Complications in Diabetes
Authors: Alin O. Stirban, Diethelm Tschoepe
Journal: Diabetes Care (2008)

Cardiovascular complications are mainly responsible for the high morbidity and mortality in people with diabetes. The awareness of physicians for the importance of primary prevention increased lately and numerous strategies have been developed. The spectrum ranges from pharmacologic treatment to vitamins and dietetic interventions. Some interesting concepts such as focusing on exogenous advanced glycation end products have emerged, but definitive results on their clinical relevance are still lacking. A major problem of the primary prevention is the choice of the method applied for screening, the criteria used to classify risk patients, as well as the choice of therapy. Guidelines provide goals to be achieved and offer alternatives for treatment, but the medical decision has to be made on an individualized basis. In this overview, we will comprehensively focus on the most important pathomechanisms and clinically relevant approaches, aiming at the early diagnosis and treatment of diabetes along with coronary heart disease. When primary prevention fails, we advocate a more aggressive treatment of critically ill patients, followed by optimal secondary prevention meeting on-target goals precisely.
Increased expression of mRNA for matrix metalloproteinases-1 and -3 and tissue inhibitor of metalloproteinases-1 in intestinal biopsy specimens from patients with coeliac disease
Authors: S Daum, U Bauer, H-D Foss, D Schuppan, H Stein, E-O Riecken, R Ullrich
Journal: Gut (1999)

Background Extracellular matrix (ECM) degradation may play a role in villus atrophy in coeliac disease (CD). Aims To compare the cellular expression of mRNA transcripts for the two major matrix degrading proteases, matrix metalloproteinase (MMP)-1 and MMP-3, their inhibitor, tissue inhibitor of metalloproteinases (TIMP)-1, and procollagen I in the intestinal mucosa of patients with untreated and treated CD and normal controls. Patients/Methods Duodenal biopsy specimens from ten untreated CD patients, from six of these after a gluten free diet, and from ten control patients were hybridised with 35 S-labelled RNA probes. The number of positive cells in the subepithelial region and lamina propria were counted microscopically. Results The numbers of cells positive for MMP-1 (p&lt;0.005), MMP-3 (p&lt;0.01), and TIMP-1 (p&lt;0.05) mRNA were higher in the subepithelial region of CD mucosa than in that from controls. In the lamina propria, only cells positive for MMP-1 mRNA were increased in CD patients compared with controls (p&lt;0.01). MMP-1 and MMP-3 mRNA expression returned to normal in CD patients after treatment with a gluten free diet (p&lt;0.05), while TIMP-1 mRNA expression remained elevated. The number of procollagen I mRNA expressing cells did not change. Expression of MMP-1 and MMP-3 mRNA was mainly localised to subepithelial fibroblasts and macrophages. Conclusions The decreased ratio of collagen I and TIMP-1 mRNA expressing cells to MMP-1 and MMP-3 mRNA expressing cells in untreated CD suggests a shift towards ECM degradation. ECM degradation by activated subepithelial fibroblasts and macrophages may be an important mechanism driving mucosal transformation in CD.
Plasmin Cleavage of von Willebrand Factor as an Emergency Bypass for ADAMTS13 Deficiency in Thrombotic Microangiopathy
Authors: Claudia Tersteeg, Steven de Maat, Simon F. De Meyer, Michel W.J. Smeets, Arjan D. Barendrecht, Mark Roest, Gerard Pasterkamp, Rob Fijnheer, Karen Vanhoorelbeke, Philip. G. de Groot, Coen Maas
Journal: Circulation (2014)

Von Willebrand factor (VWF) multimer size is controlled through continuous proteolysis by ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type I motif, member 13). This prevents spontaneous platelet agglutination and microvascular obstructions. ADAMTS13 deficiency is associated with thrombotic thrombocytopenic purpura, in which life-threatening episodes of microangiopathy damage kidneys, heart, and brain. Enigmatically, a complete ADAMTS13 deficiency does not lead to continuous microangiopathy. We hypothesized that plasmin, the key enzyme of the fibrinolytic system, serves as a physiological backup enzyme for ADAMTS13 in the degradation of pathological platelet-VWF complexes.Using real-time microscopy, we determined that plasmin rapidly degrades platelet-VWF complexes on endothelial cells in absence of ADAMTS13, after activation by urokinase-type plasminogen activator or the thrombolytic agent streptokinase. Similarly, plasmin degrades platelet-VWF complexes in platelet agglutination studies. Plasminogen directly binds to VWF and its A1 domain in a lysine-dependent manner, as determined by enzyme-linked immunosorbent assay. Plasma levels of plasmin-α2-antiplasmin complexes increase with the extent of thrombocytopenia in patients with acute episodes of thrombotic thrombocytopenic purpura, independent of ADAMTS13 activity. This indicates that plasminogen activation takes place during microangiopathy. Finally, we show that the thrombolytic agent streptokinase has therapeutic value for Adamts13(-/-) mice in a model of thrombotic thrombocytopenic purpura.We propose that plasminogen activation on endothelial cells acts as a natural backup for ADAMTS13 to degrade obstructive platelet-VWF complexes. Our findings indicate that thrombolytic agents may have therapeutic value in the treatment of microangiopathies and may be useful to bypass inhibitory antibodies against ADAMTS13 that cause thrombotic thrombocytopenic purpura.