tbuckley/cabot-search huggingface dataset:
The risk of colorectal cancer in ulcerative colitis: a meta-analysis
Authors: J A Eaden
Journal: Gut (2001)

<h3>BACKGROUND AND AIMS</h3> Controversy surrounds the risk of colorectal cancer (CRC) in ulcerative colitis (UC). Many studies have investigated this risk and reported widely varying rates. <h3>METHODS</h3> A literature search using Medline with the explosion of references identified 194 studies. Of these, 116 met our inclusion criteria from which the number of patients and cancers detected could be extracted. Overall pooled estimates, with 95% confidence intervals (CI), of cancer prevalence and incidence were obtained using a random effects model on either the log odds or log incidence scale, as appropriate. <h3>RESULTS</h3> The overall prevalence of CRC in <i>any</i> UC patient, based on 116 studies, was estimated to be 3.7% (95% CI 3.2–4.2%). Of the 116 studies, 41 reported colitis duration. From these the overall incidence rate was 3/1000 person years duration (pyd), (95% CI 2/1000 to 4/1000). The overall incidence rate for any child was 6/1000 pyd (95% CI 3/1000 to 13/1000). Of the 41 studies, 19 reported results stratified into 10 year intervals of disease duration. For the first 10 years the incidence rate was 2/1000 pyd (95% CI 1/1000 to 2/1000), for the second decade the incidence rate was estimated to be 7/1000 pyd (95% CI 4/1000 to 12/1000), and in the third decade the incidence rate was 12/1000 pyd (95% CI 7/1000 to 19/1000). These incidence rates corresponded to cumulative probabilities of 2% by 10 years, 8% by 20 years, and 18% by 30 years. The worldwide cancer incidence rates varied geographically, being 5/1000 pyd in the USA, 4/1000 pyd in the UK, and 2/1000 pyd in Scandinavia and other countries. Over time the cancer risk has increased since 1955 but this finding was not significant (p=0.8). <h3>CONCLUSIONS</h3> Using new meta-analysis techniques we determined the risk of CRC in UC by decade of disease and defined the risk in pancolitics and children. We found a non-significant increase in risk over time and estimated how risk varies with geography.
Coupled Gating Between Cardiac Calcium Release Channels (Ryanodine Receptors)
Authors: Steven O. Marx, Jana Gaburjakova, Marta Gaburjakova, Charles Henrikson, Karol Ondrias, Andrew R. Marks
Journal: Circulation Research (2001)

Excitation-contraction coupling in heart muscle requires the activation of Ca(2+)-release channels/type 2 ryanodine receptors (RyR2s) by Ca(2+) influx. RyR2s are arranged on the sarcoplasmic reticular membrane in closely packed arrays such that their large cytoplasmic domains contact one another. We now show that multiple RyR2s can be isolated under conditions such that they remain physically coupled to one another. When these coupled channels are examined in planar lipid bilayers, multiple channels exhibit simultaneous gating, termed "coupled gating." Removal of the regulatory subunit, the FK506 binding protein (FKBP12.6), functionally but not physically uncouples multiple RyR2 channels. Coupled gating between RyR2 channels may be an important regulatory mechanism in excitation-contraction coupling as well as in other signaling pathways involving intracellular Ca(2+) release.
Selection Footprint in the FimH Adhesin Shows Pathoadaptive Niche Differentiation in Escherichia coli
Authors: Evgeni V. Sokurenko, Michael Feldgarden, Elena Trintchina, Scott J. Weissman, Serine Avagyan, Sujay Chattopadhyay, James R. Johnson, Daniel E. Dykhuizen
Journal: Molecular Biology and Evolution (2004)

Spread of biological species from primary into novel habitats leads to within-species adaptive niche differentiation and is commonly driven by acquisition of point mutations in individual genes that increase fitness in the alternative environment. However, finding footprints of adaptive niche differentiation in specific genes remains a challenge. Here we describe a novel method to analyze the footprint of pathogenicity-adaptive, or pathoadaptive, mutations in the Escherichia coli gene encoding FimH—the major, mannose-sensitive adhesin. Analysis of distribution of mutations across the nodes and branches of the FimH phylogenetic network shows (1) zonal separation of evolutionary primary structural variants of FimH and recently derived ones, (2) dramatic differences in the ratio of synonymous and nonsynonymous changes between nodes from different zones, (3) evidence for replacement hot-spots in the FimH protein, (4) differential zonal distribution of FimH variants from commensal and uropathogenic E. coli, and (5) pathoadaptive functional changes in FimH brought by the mutations. The selective footprint in fimH indicates that the pathoadaptive niche differentiation of E. coli is either in its initial stages or undergoing an evolutionary "source/sink" dynamic.
Introduction: systemic effects in chronic obstructive pulmonary disease
Authors: E.F.M. Wouters
Journal: European Respiratory Journal (2003)

According to the definition of the European Respiratory Society, chronic obstructive pulmonary disease (COPD) is a disorder characterised by reduced maximum expiratory flow and slow forced emptying of the lungs 1. The clinical syndrome of COPD, manifested clinically by dyspnoea, cough and impaired exercise tolerance, encompasses different disease conditions, varying from chronic obstructive bronchitis with obstruction of small airways, to emphysema characterised by enlargement of air spaces and destruction of lung parenchyma, loss of lung elasticity, and closure of small airways. The outcome of this differentiation in COPD subtypes in the natural history of the COPD process still remains largely unexplored although imaging strategies easily allow a better characterisation of the pathological consequences of this disorder. Most attention is still focused on adequate diagnosis of COPD per se by lung function testing especially in …
Construct and criterion validity of several proposed DAS28-based rheumatoid arthritis flare criteria: an OMERACT cohort validation study
Authors: Aatke van der Maas, Elisabeth Lie, Robin Christensen, Ernest Choy, Yaël A de Man, Piet van Riel, Thasia Woodworth, Alfons A den Broeder
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> To describe rheumatoid arthritis (RA) worsening that leads to change or re-initiation of treatment, several Disease Activity Score 28 (DAS28)-based flare criteria have been described, but none validated. <h3>Methods</h3> Six previously published DAS28-based flare criteria ((1) increase in DAS28 &gt;1.2, or &gt;0.6 if DAS28 &gt;5.1; (2) increase in DAS28 &gt;1.2, or &gt;0.6 if DAS28 ≥3.2; (3) increase &gt;0.6 or DAS28 &gt;3.2; (4) increase in DAS28 &gt;1.2; (5) DAS28 &gt;3.2; (6) DAS28 &gt;2.6) were tested against five hypotheses concerning criterion and construct validity: (1+2) Sensitivity and specificity &gt;70% compared with patient9s/physician9s judgment; (3) difference in proportion with disease modifying anti-rheumatic drug/corticosteroid initiation/increase &gt;0.2; (4) mean difference in C-reactive protein (CRP) &gt;10 mg/l; and (5) no statistical difference in Short Form-36 Mental Health subscale change. Three different RA patient databases in which flare might occur were used. Sensitivity/specificity, χ<sup>2</sup> and two-sample student t test analyses were done. <h3>Results</h3> The analyses included 51, 147 and 744 RA patients, from the three databases. Criterion 2 fulfilled most hypotheses: 4 out of 5. Sensitivity and specificity varied between 63%–78% and 84%–92%. Construct validity was demonstrated with 23% more treatment change, higher mean CRP (11.4 mg/l) and depression scale change of −5. Criteria 3, 5 and 6 were more sensitive, criteria 1, 2 and 4 more specific. <h3>Conclusions</h3> An increase in DAS28 &gt;1.2 or &gt;0.6 if DAS28 ≥3.2 appears most discriminating and valid by our predefined validation criteria. Considering the other criteria, sensitivity and specificity shown here might facilitate use in different settings.
Influence of parasympatheitc dysfunction and hyperinsulinemia on the hemodynamic response to an isometric exercise in non—insulin-dependent diabetic patients
Authors: P. Valensi, T.N. Nguyen, S. Idriss, P. Cazes, G. Karam, J. Paries, P. Miossec, J.R. Attali
Journal: Metabolism (1998)
Randomized Comparison Between Stenting and Off-Pump Bypass Surgery in Patients Referred for Angioplasty
Authors: Frank Eefting, Hendrik Nathoe, Diederik van Dijk, Erik Jansen, Jaap Lahpor, Pieter Stella, Willem Suyker, Jan Diephuis, Harry Suryapranata, Sjef Ernst, Cornelius Borst, Erik Buskens, Diederick Grobbee, Peter de Jaegere
Journal: Circulation (2003)

Stenting improves cardiac outcome in comparison with balloon angioplasty. Compared with conventional surgery, off-pump bypass surgery on the beating heart without cardiopulmonary bypass may reduce morbidity, hospital stay, and costs. The purpose, therefore, was to compare cardiac outcome, quality of life, and cost-effectiveness 1 year after stenting and after off-pump surgery.Patients referred for angioplasty (n=280) were randomly assigned to stenting (n=138) or off-pump bypass surgery. At 1 year, survival free from stroke, myocardial infarction, and repeat revascularization was 85.5% after stenting and 91.5% after off-pump surgery (relative risk, 0.93; 95% CI, 0.86 to 1.02). Freedom from angina was 78.3% after stenting and 87.0% after off-pump surgery (P=0.06). Quality-adjusted lifetime was 0.82 year after stenting and 0.79 year after off-pump surgery (P=0.09). Hospital stay after the initial procedure was 1.43 and 5.77 days, respectively (P<0.01). Stenting reduced overall costs by 2933 dollars (26.2%) per patient (8276 dollars versus 11 209 dollars; P<0.01). Stenting was more cost-effective in 95% of the bootstrap estimates.At 1 year, stenting was more cost-effective than off-pump surgery while maintaining comparable cardiac outcome and quality of life. Stenting rather than off-pump surgery, therefore, can be recommended as a first-choice revascularization strategy in selected patients.
Epoprostenol therapy for primary pulmonary hypertension after rejection of a single donor lung
Authors: R.J. Roeleveld, A. Vonk Noordegraaf, W. van der Bij, P.E. Postmus, A. Boonstra
Journal: European Respiratory Journal (2003)

Before prostacyclins became available, lung or heart/lung transplantation was the only effective treatment for patients with primary pulmonary hypertension (PPH) who deteriorated under supportive medical treatment. Unfortunately, acute and chronic rejections occur in a large number of cases, limiting the average survival to 4.5 yrs. A female patient, age 35 yrs, was diagnosed with PPH and underwent single lung transplantation. Despite aggressive immunosuppressive therapy, the patient had several episodes of acute rejection. Eventually, chronic rejection with bronchiolitis obliterans developed. After 5 yrs, the donor lung was no longer functional. The patient was in New York Heart Association (NYHA) class 4, had a 6‐min walking distance of 50 m and a resting arterial oxygen tension ( P a,O 2 ) of 9.8 kPa (74 mmHg) when using 3 L·min −1 of oxygen. Epoprostenol treatment was started and the patient showed remarkable improvement. After 17 months the patient was NYHA class 2, walked 503 m in 6 min and had a resting P a,O 2 of 10.9 kPa (82 mmHg) without supplemental oxygen. In this patient, treatment with epoprostenol was effective after rejection of a single donor lung transplanted for primary pulmonary hypertension.
Absence of relationship between degree of nonspecific and specific bronchial responsiveness in occupational asthma due to platinum salts
Authors: R Merget, A Dierkes, A Rueckmann, EM Bergmann, G Schultze-Werninghaus
Journal: European Respiratory Journal (1996)

There is evidence that bronchial responsiveness to allergen is quantitatively correlated with bronchial responsiveness to nonspecific stimuli in subjects with allergic asthma. This association has been questioned in occupational asthma due to low molecular weight substances. It was the aim of this study to assess the quantitative association of bronchial responsiveness to methacholine (MCh) and platinum salts (Pt), in the form of hexachloroplatinic acid, in workers with occupational asthma due to platinum salts. Fifty seven subjects with exposure to Pt, work-related asthma, and a positive bronchial challenge with Pt, underwent skin prick tests with Pt and bronchial challenge with MCh. Using the provocation concentration causing a &gt; or = 50% fall in specific airway conductance (PC50sGaw(Pt)) as dependent variable, anamnestic data (period from first symptoms to removal, period between removal from exposure and diagnosis, and smoking), season of the investigation, skin prick tests with environmental allergens, total immunoglobulin E (IgE), skin reactivity to Pt (Pt concentration causing a 2 mm wheal), and PC50sGaw(MCh) were included as independent variables for regression analysis. Fifty two subjects (91%) showed a PC50sGaw(MCh) &lt; 8 mg.mL-1 (geometric mean for all subjects 1.6 mg.mL-1). Responsiveness to Pt varied widely between subjects (geometric mean of PC50sGaw 9 x 10-5 mol.L-1, range 2 x 10-7 to 10-2 mol.L-1). There was no univariate correlation between bronchial responsiveness to MCh and Pt, but there was a correlation between skin reactivity to Pt and PC50sGaw(Pt) (r = 0.6). This association could not be improved by considering PC50sGaw(MCh), the period from first symptoms to removal, or the period between removal from exposure and diagnosis. The parameters that showed the highest (negative) associations with PC50sGaw(Pt) were skin reactivity to Pt and the period between removal from exposure and diagnosis (r = 0.65). We conclude that there is a moderate association between bronchial responsiveness to platinum salts and skin reactivity to platinum salts. However, there is no association between methacholine responsiveness and bronchial responsiveness to allergen in occupational asthma due to platinum salts.
Ku70 Is Required for Late B Cell Development and Immunoglobulin Heavy Chain Class Switching
Authors: John P. Manis, Yansong Gu, Rusty Lansford, Eiichiro Sonoda, Roger Ferrini, Laurie Davidson, Klaus Rajewsky, Frederick W. Alt
Journal: The Journal of Experimental Medicine (1998)

Immunoglobulin (Ig) heavy chain (HC) class switch recombination (CSR) is a late B cell process that involves intrachromosomal DNA rearrangement. Ku70 and Ku80 form a DNA end-binding complex required for DNA double strand break repair and V(D)J recombination. Ku70−/− (K70T) mice, like recombination activating gene (RAG)-1– or RAG-2–deficient (R1T or R2T) mice, have impaired B and T cell development at an early progenitor stage, which is thought to result at least in part from defective V(D)J recombination (Gu, Y., K.J. Seidl, G.A. Rathbun, C. Zhu, J.P. Manis, N. van der Stoep, L. Davidson, H.L. Cheng, J.M. Sekiguchi, K. Frank, et al. 1997. Immunity. 7:653–665; Ouyang, H., A. Nussenzweig, A. Kurimasa, V.C. Soares, X. Li, C. Cordon-Cardo, W. Li, N. Cheong, M. Nussenzweig, G. Iliakis, et al. 1997. J. Exp. Med. 186:921–929). Therefore, to examine the potential role of Ku70 in CSR, we generated K70T mice that carry a germline Ig HC locus in which the JH region was replaced with a functionally rearranged VH(D)JH and Ig λ light chain transgene (referred to as K70T/HL mice). Previously, we have shown that B cells from R1T or R2T mice carrying these rearranged Ig genes (R1T/HL or R2T/HL mice) can undergo CSR to IgG isotypes (Lansford, R., J. Manis, E. Sonoda, K. Rajewsky, and F. Alt. 1998. Int. Immunol. 10:325–332). K70T/HL mice had significant numbers of peripheral surface IgM+ B cells, which generated serum IgM levels similar to those of R2T/HL mice. However, in contrast to R2T/HL mice, K70T/HL mice had no detectable serum IgG isotypes. In vitro culture of K70T/HL B cells with agents that induce CSR in normal or R2T/HL B cells did lead to the induction of germline CH transcripts, indicating that initial signaling pathways for CSR were intact in K70T/HL cells. However, treatment with such agents did not lead to detectable CSR by K70T/HL B cells, and instead, led to cell death within 72 h. We conclude that Ku70 is required for the generation of B cells that have undergone Ig HC class switching. Potential roles for Ku70 in the CSR process are discussed.
A PECULIAR FROM OF PURPURA.
Authors: A. PINEY
Journal: British Journal of Dermatology (1933)

Journal Article A PECULIAR FROM OF PURPURA. Get access A. PINEY, M.D., M.R.C.P. A. PINEY, M.D., M.R.C.P. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 45, Issue 7, 1 July 1933, Pages 309–310, https://doi.org/10.1111/j.1365-2133.1933.tb10183.x Published: 01 July 1933
IκBα deficiency in brain leads to elevated basal neuroinflammation and attenuated response following traumatic brain injury: implications for functional recovery
Authors: Hong Lian, David J Shim, Samson SK Gaddam, Jennifer Rodriguez-Rivera, Brittany R Bitner, Robia G Pautler, Claudia S Robertson, Hui Zheng
Journal: Molecular Neurodegeneration (2012)

Abstract Background The transcription factor NFκB is an important mediator of cell survival and inflammation in the immune system. In the central nervous system (CNS), NFκB signaling has been implicated in regulating neuronal survival following acute pathologic damage such as traumatic brain injury (TBI) and stroke. NFκB is normally bound by the principal inhibitory protein, IκBα, and sequestered in the cytoplasm. Activation of NFκB requires the degradation of IκBα, thereby freeing NFκB to translocate to the nucleus and activate the target genes. Mice deficient in IκBα display deregulated and sustained NFκB activation and early postnatal lethality, highlighting a critical role of IκBα in NFκB regulation. Results We investigated the role of IκBα in regulating NFκB activity in the brain and the effects of the NFκB/IκBα pathway in mediating neuroinflammation under both physiological and brain injury conditions. We report that astrocytes, but not neurons, exhibit prominent NFκB activity, and that basal NFκB activity in astrocytes is elevated in the absence of IκBα. By generating mice with brain-specific deletion of IκBα, we show that IκBα deficiency does not compromise normal brain development. However, basal neuroinflammation detected by GFAP and Iba1 immunoreactivity is elevated. This leads to impaired inflammatory responses following TBI and worsened brain damage including higher blood brain barrier permeability, increased injury volumes and enlarged ventricle volumes. Conclusions We conclude that, in the CNS, astrocyte is the primary cell type subject to NFκB regulation. We further demonstrate that IκBα plays an important role in regulating NFκB activity in the brain and a robust NFκB/IκBα-mediated neuroinflammatory response immediately following TBI is beneficial.
Survival estimates for adults with cystic fibrosis born in the United Kingdom between 1947 and 1967
Authors: P A Lewis, S Morison, J A Dodge, D Geddes, E C Coles, G Russell, J M Littlewood, M T Scott
Journal: Thorax (1999)

<h3>BACKGROUND</h3> The UK has published observed cohort survival figures for subjects with cystic fibrosis born since 1968. Prior to 1968 cohorts cannot be established directly from routine data as cystic fibrosis was classified with a number of unrelated conditions in ICD7. Reported here are interrupted survival curves from 1978 for patients with cystic fibrosis born before 1968. <h3>METHODS</h3> Life tables for the three year cohorts born between 1947 and 1967 were constructed by firstly estimating the numbers of patients with cystic fibrosis born in each cohort from live birth data and the disease incidence. The number of the estimated cohort that had survived to 1978 is known, which enables the proportion surviving to 1978 to be calculated. The survival of these cohorts after 1978 can be calculated in the usual way. <h3>RESULTS</h3> The survival for each successive cohort was better than that of the previous one, but most of the improvements appear to have taken place up to the age of about 20 years. Only 3% of the 1947–49 cohort survived to 30 years of age compared with 21% for the 1965–67 cohort, and 3% of the 1953–55 cohort survived to 40 years of age. For the later cohorts the mortality rate for those aged between 26 and 30 years appears to be about 50 per 1000 per year. <h3>CONCLUSIONS</h3> While the trend in the numbers surviving into later adulthood is upwards, the mortality rates for these ages does not appear to be improving. It is not possible to tell from these data whether the high mortality rates in adulthood will improve with better resourced adult clinics or with improved treatment during childhood.
Exercise-induced acute renal failure associated with ibuprofen, hydrochlorothiazide, and triamterene.
Authors: L R Sanders
Journal: Journal of the American Society of Nephrology (1995)

Nonsteroidal anti-inflammatory drugs predispose to acute renal failure in conditions associated with decreased RBF. Such conditions include advanced age, hypertension, chronic renal insufficiency, diuretic use, and any condition decreasing effective circulating volume. Strenuous exercise also causes marked reductions in RBF. The patient discussed developed severe acute renal failure after strenuous exercise and therapeutic doses of ibuprofen and hydrochlorothiazide-triamterene. Urinalysis showed a nephritic sediment with red blood cell casts. Renal biopsy showed acute tubular necrosis and arteriolar nephrosclerosis. Although exercise-associated acute renal failure is uncommon, susceptible patients with exercise-induced renal ischemia and prostaglandin inhibition may develop this complication.
Ca2+ responses to interleukin 1 and tumor necrosis factor in cultured human skin fibroblasts. Possible implications for Reye syndrome.
Authors: B E Corkey, J F Geschwind, J T Deeney, D E Hale, S D Douglas, L Kilpatrick
Journal: Journal of Clinical Investigation (1991)

Elevated concentrations of cytokines were found in the plasma of patients acutely ill with Reye syndrome (RS) but not in control subjects or recovered RS patients. To determine whether this disorder involves a genetically determined abnormal response to cytokines, the effects of tumor necrosis factor (TNF) and IL-1 on intracellular free Ca2+ were compared in cultured skin fibroblasts from control subjects and patients with RS. IL-1 and TNF caused rapid, transient, and concentration-dependent increases in cytosolic free Ca2+. The peak cytosolic free Ca2+ was greater and occurred at higher concentrations of IL-1 and TNF in patient cells than in cells from age-matched controls. In control cells, the Ca2+ transient diminished sharply with increasing amounts of IL-1 or TNF above the maximum stimulatory concentration. In contrast, in patient fibroblast this bell-shaped curve of concentration dependency was much less apparent. Bradykinin-stimulated Ca2+ transients were similar in the two groups and did not exhibit the bell-shaped concentration dependency. Thus, plasma cytokine levels are elevated in RS patients and the Ca2+ response to cytokines is increased in cells derived from these patients. We propose that the increased response reflects a genetic defect in cytokine receptor-modulated signal transduction.