tbuckley/cabot-search huggingface dataset:
Geography of intestinal permeability and absorption
Authors: I S Menzies, M J Zuckerman, W S Nukajam, S G Somasundaram, B Murphy, A P Jenkins, R S Crane, G G Gregory
Journal: Gut (1999)

BACKGROUND Intestinal morphology and function vary geographically. AIMS These functions were assessed in asymptomatic volunteers in European, North American, Middle Eastern, Asian, African, and Caribbean countries. METHODS Five hour urine collections were obtained from each subject following ingestion of a 100 ml iso-osmolar test solution containing 3–0-methyl- d -glucose, d -xylose, l -rhamnose, and lactulose after an overnight fast, to assess active (3–0-methyl- d -glucose) and passive ( d -xylose) carrier mediated, and non-mediated ( l -rhamnose) absorption capacity, as well as intestinal permeability (lactulose:rhamnose ratio). RESULTS A comparison of results for subjects from tropical countries (n=218) with those resident in the combined temperate and subtropical region (Europe, United States, Qatar) (n=224) showed significant differences. Residents in tropical areas had a higher mean lactulose:rhamnose ratio and lower mean five hour recoveries of 3–0-methyl- d -glucose, d -xylose, and l -rhamnose, indicating higher intestinal permeability and lower absorptive capacity. Investigation of visiting residents suggested that differences in intestinal permeability and absorptive capacity were related to the area of residence. Subjects from Texas and Qatar, although comprised of several ethnic groups and resident in a subtropical area, showed no significant difference from European subjects. CONCLUSIONS There are clearly demarcated variations in intestinal permeability and absorptive capacity affecting asymptomatic residents of different geographical areas which correspond with the condition described as tropical enteropathy. Results suggest the importance of environmental factors. The parameters investigated may be relevant to the predisposition of the indigenous population and travellers to diarrhoeal illness and malnutrition. Intestinal function in patients from the tropics may be difficult to interpret, but should take into account the range of values found in the asymptomatic normal population.
Tumor Necrosis Factor Receptor 2 Contributes to Ozone-induced Airway Hyperresponsiveness in Mice
Authors: STEPHANIE A. SHORE, IGOR N. SCHWARTZMAN, BRIAN LE BLANC, G. G. KRISHNA MURTHY, CLAIRE M. DOERSCHUK
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

The purpose of this study was to determine whether tumor necrosis factor (TNF) contributes to airway hyperresponsiveness (AHR) and migration of polymorphonuclear leukocytes (PMN) into the airways following exposure to ozone (O3). Wild-type mice, TNF p55 or p75 receptor knockout mice (p55 TNFR −/− and p75 TNFR −/− ), as well as double receptor knockout mice (p55 / p75 TNFR −/− ), were exposed to O3. Three hours after cessation of O3, airway responses to inhaled methacholine were determined by whole body plethysmography using changes in enhanced pause (Penh) as an index of airway narrowing. In wild-type mice, O3 exposure (0.5 ppm, 3 h) caused a significant increase in airway responsiveness as indicated by a 1.2 log leftward shift in the methacholine dose– response curve. In contrast, in p55 / p75 TNFR −/− mice, O3 caused only a 0.5 log shift in the dose–response curve (p < 0.05 compared with wild-type). Similar results were obtained in p75 TNFR −/− mice. In contrast, O3-induced airway hyperresponsiveness was not different in WT and p55 TNFR −/− mice. During O3 exposure (1 pm, 3 h), minute ventilation (V˙ e) decreased by 64 ± 4% in wild-type, but only 24 ± 5% in p55 / p75 TNFR −/− mice, indicating that despite their reduced O3-induced AHR, the TNFR-deficient mice actually inhaled a greater dose of O3. Similar results were obtained in p75 −/− mice, whereas changes in V˙ e induced by O3 were the same in wild-type and p55 −/− mice. PMN numbers in bronchoalveolar lavage fluid recovered 21 h after cessation of exposure to O3 (2 ppm, 3 h) were significantly increased compared with after air exposure but were not different in wild-type and p55 / p75 TNFR −/− mice. Our results indicate that TNF contributes to the AHR but not the PMN emigration induced by acute O3 exposure.Keywords: whole body plethysmography; polymorphonuclear leukocytes; minute ventilation; knockout mice; methacholine
Possible role of the vitamin E solubilizer in topical diclofenac on matrix metalloproteinase expression in corneal melting
Authors: Sylvia L Hargrave, Jae Chang Jung, M.Elizabeth Fini, Henry Gelender, Christian Cather, Anne Guidera, Ira Udell, Stephen Fisher, James V Jester, R.Wayne Bowman, James P McCulley, H.Dwight Cavanagh
Journal: Ophthalmology (2002)
Neutrophil function in ischemic heart disease.
Authors: J Mehta, J Dinerman, P Mehta, T G Saldeen, D Lawson, W H Donnelly, R Wallin
Journal: Circulation (1989)

Neutrophils contribute to the healing of and scar formation in myocardium after ischemic injury. Many recent studies indicate that neutrophils may be involved in the genesis and propagation of myocardial ischemia. To characterize neutrophil function in ischemic heart disease, neutrophil chemotaxis, leukotriene B4 (LTB4) generation, and elastase release in plasma were measured in 20 patients with stable angina, 17 patients with unstable angina or acute myocardial infarction (AMI), and 20 age-matched control subjects. Neutrophils from patients with stable angina exhibited markedly increased chemotactic activity and LTB4 generation as compared with the age-matched control subjects (p less than 0.01). Neutrophils of nine of 17 patients with unstable angina or AMI clumped spontaneously ex vivo and exhibited marked pseudopod formation and granule extrusion on electron microscopy. Subsequent chemotactic activity and LTB4 generation by neutrophils from these patients was less than in patients with stable angina, suggesting previous in vivo activation. Plasma levels of peptide B beta, a product of fibrin degradation by human neutrophil elastase, were approximately 15-fold higher (p less than 0.001) in patients with unstable angina or AMI (588 +/- 171 pmol/l, mean +/- SEM) compared with those in patients with stable angina (37 +/- 25 pmol/l) or control subjects (40 +/- 22 pmol/l), confirming intense in vivo neutrophil activation. Our study shows enhanced neutrophil function in patients with ischemic heart disease. The increased neutrophil chemotactic activity and LTB4 generation may be markers of stable angina pectoris. Intense neutrophil activation in unstable angina or AMI, as manifested by morphologic changes in neutrophils and elastase release, may relate to ongoing in vivo cellular activation.
Bacterial antigens in synovial biopsy specimens in yersinia triggered reactive arthritis.
Authors: R Merilahti-Palo, K O Soderstrom, R Lahesmaa-Rantala, K Granfors, A Toivanen
Journal: Annals of the Rheumatic Diseases (1991)

Non-viable structures of Yersinia enterocolitica O:3 were shown at the site of inflammation within mononuclear cells in the synovial membrane of eight out of 10 patients with yersinia triggered reactive arthritis. An avidin-biotin-peroxidase complex method, with a rabbit antiserum specific for Y enterocolitica O:3, was used to visualise yersinia structures. All 13 control samples were negative except for one with non-specific mast cell staining. The findings emphasise the significance of foreign material in the initiation of synovitis in reactive arthritis.
Antiarrhythmic drug therapy in the Multicenter UnSustained Tachycardia Trial (MUSTT): drug testing and as-treated analysis
Authors: D.George Wyse, Mario Talajic, Gail E Hafley, Alfred E Buxton, L.Brent Mitchell, Teresa K Kus, Douglas L Packer, William H Kou, Robert Lemery, Peter Santucci, Denise Grimes, Kathleen Hickey, Carolyn Stevens, Steven N Singh
Journal: Journal of the American College of Cardiology (2001)
European multicentre study to define disease activity criteria for systemic sclerosis. II. Identification of disease activity variables and development of preliminary activity indexes
Authors: G Valentini
Journal: Annals of the Rheumatic Diseases (2001)

To develop criteria for disease activity in systemic sclerosis (SSc) that are valid, reliable, and easy to use.Investigators from 19 European centres completed a standardised clinical chart for a consecutive number of patients with SSc. Three protocol management members blindly evaluated each chart and assigned a disease activity score on a semiquantitative scale of 0-10. Two of them, in addition, gave a blinded, qualitative evaluation of disease activity ("inactive to moderately active" or "active to very active" disease). Both these evaluations were found to be reliable. A final disease activity score and qualitative evaluation of disease activity were arrived at by consensus for each patient; the former represented the gold standard for subsequent analyses. The correlations between individual items in the chart and this gold standard were then analysed.A total of 290 patients with SSc (117 with diffuse SSc (dSSc) and 173 with limited SSc (lSSc)) were enrolled in the study. The items (including Delta-factors-that is, worsening according to the patient report) that were found to correlate with the gold standard on multiple regression were used to construct three separate 10-point indices of disease activity: (a) Delta-cardiopulmonary (4.0), Delta-skin (3.0), Delta-vascular (2.0), and Delta-articular/muscular (1.0) for patients with dSSc; (b) Delta-skin (2.5), erythrocyte sedimentation rate (ESR) >30 mm/1st h (2.5), Delta-cardiopulmonary (1.5), Delta-vascular (1.0), arthritis (1.0), hypocomplementaemia (1.0), and scleredema (0.5) for lSSc; (c) Delta-cardiopulmonary (2.0), Delta-skin (2.0), ESR >30 mm/1st h (1.5), total skin score >20 (1.0), hypocomplementaemia (1.0), scleredema (0.5), digital necrosis (0.5), Delta-vascular (0.5), arthritis (0.5), TLCO <80% (0.5) for all patients with SSc. The three indexes were validated by the jackknife technique. Finally, receiver operating characteristic curves were constructed in order to define the value of the index with the best discriminant capacity for "active to very active" patients.Three feasible, reliable, and valid preliminary indices to define disease activity in SSc were constructed.
In Vivo and In Vitro Evidence for Impaired Arginine Transport in Human Heart Failure
Authors: David M. Kaye, Belinda A. Ahlers, Dominic J. Autelitano, Jaye P. F. Chin-Dusting
Journal: Circulation (2000)

Background —The clinical features of congestive heart failure (CHF) result from a complex interaction between reduced ventricular function, neurohormonal activation, and impaired endothelial function. Although endothelial dysfunction has been well documented, the mechanisms that contribute to this abnormality remain unknown. Recent studies, however, indicate a potential therapeutic role for supplemental l -arginine, suggesting the presence of an underlying disorder of l -arginine metabolism. Methods and Results —We used 2 complementary approaches to assess l -arginine transport in control subjects and patients with CHF. During a steady-state intra-arterial infusion of [ 3 H] l -arginine (100 nCi/min), forearm clearance of [ 3 H] l -arginine was significantly reduced in CHF patients compared with forearm kinetics in control subjects (64±2 versus 133±14 mL/min, P =0.002). In conjunction with this, [ 3 H] l -arginine uptake by peripheral blood mononuclear cells (PBMCs) was also substantially reduced in heart failure patients compared with controls (V max 10.1±1.3 versus 49.8±7.1 pmol/10 5 cells per 5 minutes, P &lt;0.001). In association with this finding, we observed a 76% ( P &lt;0.01) reduction in mRNA expression for the cationic amino acid transporter CAT-1, as assessed by ribonuclease protection assay. Conclusions —These data document both in vivo and in vitro evidence for a marked depression of l -arginine transport in human CHF and therefore provide an explanation for the restorative actions of supplemental l -arginine on vascular function in CHF.
The RNA-binding landscapes of two SR proteins reveal unique functions and binding to diverse RNA classes
Authors: Minna-Liisa Änkö, Michaela Müller-McNicoll, Holger Brandl, Tomaz Curk, Crtomir Gorup, Ian Henry, Jernej Ule, Karla M Neugebauer
Journal: Genome biology (2012)

Abstract Background The SR proteins comprise a family of essential, structurally related RNA binding proteins. The complexity of their RNA targets and specificity of RNA recognition in vivo is not well understood. Here we use iCLIP to globally analyze and compare the RNA binding properties of two SR proteins, SRSF3 and SRSF4, in murine cells. Results SRSF3 and SRSF4 binding sites mapped to largely non-overlapping target genes, and in vivo consensus binding motifs were distinct. Interactions with intronless and intron-containing mRNAs as well as non-coding RNAs were detected. Surprisingly, both SR proteins bound to the 3' ends of the majority of intronless histone transcripts, implicating SRSF3 and SRSF4 in histone mRNA metabolism. In contrast, SRSF3 but not SRSF4 specifically bound transcripts encoding numerous RNA binding proteins. Remarkably, SRSF3 was shown to modulate alternative splicing of its own as well as three other transcripts encoding SR proteins. These SRSF3-mediated splicing events led to downregulation of heterologous SR proteins via nonsense-mediated decay. Conclusions SRSF3 and SRSF4 display unique RNA binding properties underlying diverse cellular regulatory mechanisms, with shared as well as unique coding and non-coding targets. Importantly, CLIP analysis led to the discovery that SRSF3 cross-regulates the expression of other SR protein family members.
Pressure studies in the moving knee.
Authors: M I Jayson, A S Dixon
Journal: Annals of the Rheumatic Diseases (1969)

Obesity was found to have no influence on prognosis in the series, as 60 per cent. of the patients were less than 7 lb.over their ideal weight for height and age, and there was no correlation between deterioration and excess of weight.It was shown that 68 per cent. of the patients left in the trial had deteriorated after 5 years; i.e. eighteen patients needed increased time for stairs and 39 required surgery.32 per cent. of patients had shown no deterioration in any way which could be measured.Finally, it was suggested that all patients with primary osteoarthrosis of the hips did not inevitably deteriorate, although those with radiological cysts when first seen were more likely to do so and might be suitable for surgery at an early stage.
First-Line Treatment of Advanced Breast Cancer With Sunitinib in Combination With Docetaxel Versus Docetaxel Alone: Results of a Prospective, Randomized Phase III Study
Authors: Jonas Bergh, Igor M. Bondarenko, Mikhail R. Lichinitser, Annelie Liljegren, Richard Greil, Nataliya L. Voytko, Anatoly N. Makhson, Javier Cortes, Alain Lortholary, Joachim Bischoff, Arlene Chan, Suzette Delaloge, Xin Huang, Kenneth A. Kern, Carla Giorgetti
Journal: Journal of Clinical Oncology (2012)

To investigate whether sunitinib plus docetaxel improves clinical outcomes for patients with human epidermal growth factor receptor 2 (HER2)/neu-negative advanced breast cancer (ABC) versus docetaxel alone.In this phase III study, patients were randomly assigned to open-label combination therapy (sunitinib 37.5 mg/d, days 2 to 15 every 3 weeks; and docetaxel 75 mg/m(2), day 1 every 3 weeks) or monotherapy (docetaxel 100 mg/m(2) every 3 weeks). Progression-free survival (PFS) was the primary end point.Two hundred ninety-six patients were randomly assigned to combination therapy, and 297 patients were assigned to monotherapy. Median PFS times were 8.6 and 8.3 months with combination therapy and monotherapy, respectively (hazard ratio, 0.92; one-sided P = .265). The objective response rate (ORR) was significantly higher with the combination (55%) than with monotherapy (42%; one-sided P = .001). Duration of response was similar in both arms (7.5 months with the combination v 7.2 months with monotherapy). Median overall survival (OS) times were 24.8 and 25.5 months with combination therapy and monotherapy, respectively (one-sided P = .904). There were 107 deaths with the combination and 91 deaths with monotherapy. The frequency of common adverse events (AEs) was higher with the combination, as were treatment discontinuations caused by AEs.The combination of sunitinib plus docetaxel improved ORR but did not prolong either PFS or OS compared with docetaxel alone when given to an unselected HER2/neu-negative cohort as first-line treatment for ABC. Sunitinib combination therapy may also have resulted in AEs that yield an unfavorable risk-benefit ratio. The sunitinib-docetaxel regimen evaluated in this study is not recommended for further use in ABC.
P99 30-Day COPD readmissions relate to disease severity and demographic factors rather than simply organisation and delivery of hospital care
Authors: J. Hare, E. Thompson, K. Bodger, P. Walker, M. Pearson
Journal: Thorax (2011)

30-Day readmission rates after hospitalisation have risen and the UK Department of Health plans to introduce financial penalties for early readmissions. The surgical argument is reasonably clear but for chronic conditions such as COPD the presumption that early readmission is either avoidable or due to poor hospital care is far from clear. We used Hospital Episode Statistics data to examine the characteristics of patients readmitted within 30 days of an index COPD hospitalisation during 2006–2007. Mortality data were obtained from ONS death registration. There were 124 834 COPD admissions in 2006–2007 with 78 693 different patients discharged from hospital and we followed the first admission of each. 28 533 (36%) patients were readmitted within 1-year and 8439 (11%) within 30 days. Patients readmitted within 30 days were more likely to be male (53% vs 50%; p&lt;0.001), older (72.7 vs 71.6 yrs; p&lt;0.001), live in a more deprived area (55% vs 51% highest quintile; p&lt;0.001) and much more likely to die (30-day mortality 11% vs 3%; p&lt;0.001; and 1-year mortality 40% vs 20%; p&lt;0.001). For the index admission, patients readmitted within 30 days were more likely to have been admitted via A&amp;E rather than via their GP (74% vs 70%; p&lt;0.001), more likely to have had a LRTI (88% vs 83%; p&lt;0.001), had a longer median length of stay (6 vs 5 days; p&lt;0.001) and were more likely to have been discharged from the care of a chest physician (44% vs 40%; p&lt;0.001). Hospitals with the lowest inpatient mortality during the first admission had the highest 30-day readmission rate (r=0.22; p&lt;0.01). Early readmission would appear to be driven by demographics, severity of the index admission and disease severity which cannot be influenced by care delivery or organisation of care. It9s possible that better care—keeping more patients alive during their index admission—may lead to those hospitals being penalised for a higher 30-day readmission rate.
Crosstalk between the canonical NF-κB and Notch signaling pathways inhibits Pparγ expression and promotes pancreatic cancer progression in mice
Authors: Eleni Maniati, Maud Bossard, Natalie Cook, Juliana B. Candido, Nia Emami-Shahri, Sergei A. Nedospasov, Frances R. Balkwill, David A. Tuveson, Thorsten Hagemann
Journal: Journal of Clinical Investigation (2011)

The majority of human pancreatic cancers have activating mutations in the KRAS proto-oncogene. These mutations result in increased activity of the NF-κB pathway and the subsequent constitutive production of proinflammatory cytokines. Here, we show that inhibitor of κB kinase 2 (Ikk2), a component of the canonical NF-κB signaling pathway, synergizes with basal Notch signaling to upregulate transcription of primary Notch target genes, resulting in suppression of antiinflammatory protein expression and promotion of pancreatic carcinogenesis in mice. We found that in the Kras(G12D)Pdx1-cre mouse model of pancreatic cancer, genetic deletion of Ikk2 in initiated pre-malignant epithelial cells substantially delayed pancreatic oncogenesis and resulted in downregulation of the classical Notch target genes Hes1 and Hey1. Tnf-α stimulated canonical NF-κB signaling and, in collaboration with basal Notch signals, induced optimal expression of Notch targets. Mechanistically, Tnf-α stimulation resulted in phosphorylation of histone H3 at the Hes1 promoter, and this signal was lost with Ikk2 deletion. Hes1 suppresses expression of Pparg, which encodes the antiinflammatory nuclear receptor Pparγ. Thus, crosstalk between Tnf-α/Ikk2 and Notch sustains the intrinsic inflammatory profile of transformed cells. These findings reveal what we believe to be a novel interaction between oncogenic inflammation and a major cell fate pathway and show how these pathways can cooperate to promote cancer progression.
New 2010 British Society of Gastroenterology colitis surveillance guidelines: costs and surveillance intervals
Authors: N. N. Elsadani, J. E. East, J. R. F. Walters
Journal: Gut (2010)

We report a case of a 38-year-old man with a background of a neglected neurogenic bladder, who presented with a recent onset history of stress urinary incontinence. He was diagnosed as having large prostatic stones along with a low-compliance, small capacity bladder and bilateral hydronephrosis with deranged renal functions. As self-catheterisation was not possible due to obstructing prostatic stones, holmium-YAG laser lithotripsy of prostatic stones was performed as initial procedure that resulted in complete resolution of stress incontinence as well. Successful gastrocystoplasty was performed as a second step to deal with the underlying condition of neurogenic poorly compliant bladder. The present case describes the successful endoscopic management of prostatic calculi using holmium-laser lithotripsy and draws attention to other important issues that need to be addressed in certain special situations like neurogenic bladder.