tbuckley/cabot-search huggingface dataset:
Dialysis Treatment Is an Independent Risk Factor for Foot Ulceration in Patients With Diabetes and Stage 4 or 5 Chronic Kidney Disease
Authors: Agbor Ndip, Martin K. Rutter, Loretta Vileikyte, Anand Vardhan, Ashwinbhai Asari, Mehreen Jameel, Hassan A. Tahir, Lawrence A. Lavery, Andrew J.M. Boulton
Journal: Diabetes Care (2010)

OBJECTIVE To determine whether dialysis treatment is an independent risk factor for foot ulceration in patients with diabetes and renal impairment. RESEARCH DESIGN AND METHODS We performed a cross-sectional study of consecutive patients with diabetes and stage 4 or 5 chronic kidney disease (CKD) attending clinics in Manchester (U.K.). Patients were classified as either receiving dialysis therapy (dialysis) or not (no dialysis). Foot assessment included diabetic peripheral neuropathy (DPN), peripheral arterial disease (PAD), prior foot ulceration and amputation, and foot self-care. Risk factors for prevalent foot ulceration were assessed by logistic regression. RESULTS We studied 326 patients with diabetes and CKD (mean age 64 years; 61% male; 78% type 2 diabetes; 11% prevalent foot ulceration). Compared with no dialysis patients, dialysis patients had a higher prevalence of DPN (79 vs. 65%), PAD (64 vs. 43%), prior amputations (15 vs. 6.4%), prior foot ulceration (32 vs. 20%), and prevalent foot ulceration (21 vs. 5%, all P &amp;lt; 0.05). In univariate analyses, foot ulceration was related to wearing bespoke footwear (odds ratio 5.6 [95% CI 2.5–13]) dialysis treatment (5.1 [2.3–11]), prior foot ulceration (4.8 [2.3–9.8], PAD (2.8 [1.3–6.0], and years of diabetes (1.0 [1.0–1.1], all P &amp;lt; 0.01). In multivariate logistic regression, only dialysis treatment (4.2 [1.7–10], P = 0.002) and prior foot ulceration (3.1 [1.3–7.1], P = 0.008) were associated with prevalent foot ulceration. CONCLUSIONS Dialysis treatment was independently associated with foot ulceration. Guidelines should highlight dialysis as an important risk factor for foot ulceration requiring intensive foot care.
Titrating Steroids on Exhaled Nitric Oxide in Children with Asthma
Authors: Mariëlle W. Pijnenburg, E. Marije Bakker, Wim C. Hop, Johan C. De Jongste
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Corticosteroids are the antiinflammatory treatment of choice in asthma. Treatment guidelines are mainly symptom-driven but symptoms are not closely related to airway inflammation. The fraction of nitric oxide in exhaled air (FENO) is a marker of airway inflammation in asthma.We evaluated whether titrating steroids on FENO improved asthma management in children.Eighty-five children with atopic asthma, using inhaled steroids, were allocated to a FENO group (n=39) in which treatment decisions were made on both FENO and symptoms, or to a symptom group (n=46) treated on symptoms only. Children were seen every 3 months over a 1-year period.Symptoms were scored during 2 weeks before visits and 4 weeks before the final visit. FeNO was measured at all visits, and airway hyperresponsiveness and FEV1 were measured at the start and end of the study. Primary endpoint was cumulative steroid dose.Changes in steroid dose from baseline did not differ between groups. In the FENO group, hyperresponsiveness improved more than in the symptom group (2.5 vs. 1.1 doubling dose, p=0.04). FEV1 in the FENO group improved, and the change in FEV1 was not significantly different between groups. The FENO group had 8 severe exacerbations versus 18 in the symptom group. The change in symptom scores did not differ between groups. FENO increased in the symptom group; the change in FENO from baseline differed between groups (p=0.02).In children with asthma, 1 year of steroid titration on FENO did not result in higher steroid doses and did improve airway hyperresponsiveness and inflammation.
Clostridium difficile toxin-induced intestinal secretion in rabbit ileum in vitro.
Authors: S Hughes, G Warhurst, L A Turnberg, N B Higgs, L G Giugliano, B S Drasar
Journal: Gut (1983)

In rabbit ileum in vitro Clostridium difficile toxin (200 microliter crude extract) almost abolished net Na absorption, by decreasing mucosa to serosa flux, and induced net Cl secretion by increasing the serosa to mucosa flux. These flux changes were induced when there was no visible histological damage to the mucosa. The toxin did not influence adenylate or guanylate cyclase activity in a plasma membrane fraction of isolated rabbit enterocytes nor did it affect cAMP concentrations in intact rabbit ileum pre-incubated with toxin. The flux responses to the toxin were prevented by removing calcium from the serosal medium, suggesting that the secretory process may be calcium dependent. These results indicate a possible mechanism by which this toxin could induce diarrhoea.
Thrombotic Microangiopathy Associated with Parvovirus B 19 Infection after Renal Transplantation
Authors: LUISA MURER, GRAZIELLA ZACCHELLO, DANIELA BIANCHI, ROBERTO DALL'AMICO, GIOVANNI MONTINI, BARBARA ANDREETTA, MARINO PERINI, ELISABETTA CURRO[Combining Grave Accent] DOSSI, GIANFRANCO ZANON, FRANCO ZACCHELLO
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Human parvovirus B19 is considered an etiologic agent of aplastic anemia in immunosuppressed patients. Microscopic vasculitis, with or without renal involvement, has recently been attributed to this viral infection in immunocompetent patients. This study describes four cases of thrombotic renal graft microangiopathy presumably secondary to B19 infection. Twelve to 50 days after transplantation, four patients presented a renal graft dysfunction with creatinine rising to 360 to 1088 μmol/L and requiring hemodialysis in three cases. Renal involvement appeared after a systemic illness characterized by fever, fatigue and arthralgia, aplastic anemia (hemoglobin ranged from 5.3 to 7.8 g/dl), and thrombocytopenia. A thrombotic microangiopathy was observed in the renal biopsies, and the parvovirus B19 genome was isolated by PCR from the specimens. All four patients also became IgM-positive for parvovirus. Three of the four renal biopsies taken at the time of transplantation (T0) from the same patients were found positive for the B19 genome. Graft function recovered, with resolution of the aplastic anemia, within 22 to 110 d. Twenty biopsies performed as routine controls or for suspected acute rejection and nine T0 biopsies of patients with no signs of B19 infection were used. The B19 genome was found in two of 20 posttransplant biopsies and in one of nine T0 biopsies. The temporal association between aplastic anemia and the onset of thrombotic graft microangiopathy, isolation of the viral genome in renal specimens, seroconversion, and endothelial tropism of the virus suggests that B19 could be the etiologic agent of thrombotic microangiopathy in these cases. The development of the disease after infection could depend on other detrimental cofactors, which make the patient more susceptible to microthrombi formation in the renal microvasculature. The renal graft could represent the route of B19 transmission.
Canonical Wnt signaling is antagonized by noncanonical Wnt5a in hepatocellular carcinoma cells
Authors: Haluk Yuzugullu, Khemais Benhaj, Nuri Ozturk, Serif Senturk, Emine Celik, Asli Toylu, Nilgun Tasdemir, Mustafa Yilmaz, Esra Erdal, Kamil Can Akcali, Nese Atabey, Mehmet Ozturk
Journal: Molecular Cancer (2009)

beta-catenin mutations that constitutively activate the canonical Wnt signaling have been observed in a subset of hepatocellular carcinomas (HCCs). These mutations are associated with chromosomal stability, low histological grade, low tumor invasion and better patient survival. We hypothesized that canonical Wnt signaling is selectively activated in well-differentiated, but repressed in poorly differentiated HCCs. To this aim, we characterized differentiation status of HCC cell lines and compared their expression status of Wnt pathway genes, and explored their activity of canonical Wnt signaling.We classified human HCC cell lines into "well-differentiated" and "poorly differentiated" subtypes, based on the expression of hepatocyte lineage, epithelial and mesenchymal markers. Poorly differentiated cell lines lost epithelial and hepatocyte lineage markers, and overexpressed mesenchymal markers. Also, they were highly motile and invasive. We compared the expression of 45 Wnt pathway genes between two subtypes. TCF1 and TCF4 factors, and LRP5 and LRP6 co-receptors were ubiquitously expressed. Likewise, six Frizzled receptors, and canonical Wnt3 ligand were expressed in both subtypes. In contrast, canonical ligand Wnt8b and noncanonical ligands Wnt4, Wnt5a, Wnt5b and Wnt7b were expressed selectively in well- and poorly differentiated cell lines, respectively. Canonical Wnt signaling activity, as tested by a TCF reporter assay was detected in 80% of well-differentiated, contrary to 14% of poorly differentiated cell lines. TCF activity generated by ectopic mutant beta-catenin was weak in poorly differentiated SNU449 cell line, suggesting a repressive mechanism. We tested Wnt5a as a candidate antagonist. It strongly inhibited canonical Wnt signaling that is activated by mutant beta-catenin in HCC cell lines.Differential expression of Wnt ligands in HCC cells is associated with selective activation of canonical Wnt signaling in well-differentiated, and its repression in poorly differentiated cell lines. One potential mechanism of repression involved Wnt5a, acting as an antagonist of canonical Wnt signaling. Our observations support the hypothesis that Wnt pathway is selectively activated or repressed depending on differentiation status of HCC cells. We propose that canonical and noncanonical Wnt pathways have complementary roles in HCC, where the canonical signaling contributes to tumor initiation, and noncanonical signaling to tumor progression.
<i>N</i> -Terminal Pro–Brain Natriuretic Peptide and Other Risk Markers for the Separate Prediction of Mortality and Subsequent Myocardial Infarction in Patients With Unstable Coronary Artery Disease
Authors: Stefan K. James, Bertil Lindahl, Agneta Siegbahn, Mats Stridsberg, Per Venge, Paul Armstrong, Elliot S. Barnathan, Robert Califf, Eric J. Topol, Maarten L. Simoons, Lars Wallentin
Journal: Circulation (2003)

Biochemical markers are useful for prediction of cardiac events in patients with non-ST-segment-elevation acute coronary syndrome (ACS). The associations between N-terminal pro-brain natriuretic peptide (NT-proBNP) and other biochemical and clinical risk indicators, as well as their prognostic value concerning the individual end points of death and myocardial infarction (MI), were elucidated in a large cohort of ACS patients.NT-proBNP, troponin T, and C-reactive protein (CRP) were analyzed in blood samples obtained at a median of 9.5 hours from symptom onset in 6809 of 7800 ACS patients in the Global Utilization of Strategies To Open occluded arteries-IV (GUSTO-IV) trial. Levels of NT-proBNP were correlated independently with age, female gender, low body weight, diabetes, renal dysfunction, history of MI, heart failure, heart rate, ongoing myocardial damage, and time since onset of ischemia. Increasing quartiles of NT-proBNP were related to short- and long-term mortality that reached 1.8%, 3.9%, 7.7%, and 19.2%, (P<0.001), respectively, at 1 year. Levels of troponin T, CRP, heart rate, and creatinine clearance, in addition to ST-segment depression, were also correlated independently with 1-year mortality, but NT-proBNP was the marker with the strongest relation. In contrast, only troponin T, creatinine clearance, and ST-segment depression were independently related to future MI. The combination of NT-proBNP and creatinine clearance provided the best prediction, with a 1-year mortality of 25.7% with both markers in the top quartile vs 0.3% with both markers in the bottom quartile.The use of NT-proBNP appears to add critical prognostic insight to the assessment of patients with ACS.
The value of phenol red and chromic chloride as nonabsorbable gastric indicators
Authors: R. J. Clarke, J. A. Williams
Journal: Gut (1971)

A comparison is made of gastric loss of phenol red and chromic chloride other than by emptying. Chromic chloride appears to be lost by adsorption on to mucus to a considerably greater extent than does phenol red, suggesting that chromic chloride is less satisfactory as a nonabsorbable gastric indicator.
PTU-125 Joint Hypermobility is a Risk Factor for Oesophageal Hypersensitivity: Abstract PTU-125 Table 1
Authors: A Fikree, D Annan, E Woo, P Balendran, J Choy, J Jafari, E Yazaki, Q Aziz, D Sifrim
Journal: Gut (2013)

<h3>Introduction</h3> Generalised joint hypermobility (HM) refers to an increased flexibility of the joints which is present in 5–17% of the population, and is assessed by clinical examination or validated hypermobility questionnaire. HM is associated with increased incidence of somatic pain and hypersensitivity, but its relationship with visceral hypersensitivity is unknown. Gastro-oesophageal reflux symptoms occur in over 50% of hypermobile patients (1). We hypothesised that we would observe a higher prevalence of HM in patients with hypersensitive oesophagus compared to patients with either erosive (GERD) or non erosive (NERD) reflux disease, functional heartburn, or a healthy control group. <h3>Methods</h3> A cross sectional study of patients attending our GI physiology unit for investigation of reflux symptoms between Jan 2010 and March 2012 was undertaken. Patients completed the validated joint hypermobility questionnaire; scores ≥2 out of 5 represented HM (Hakim 2003). Information from gastrosocopy and physiology testing was used to determine whether patients had GERD, NERD, hypersensitive oesophagus, or functional heartburn. Patients who were on PPI were excluded. Hypermobility questionnaire data from a group of 250 healthy volunteers was obtained from another study. <h3>Results</h3> 457 (59% female, age range: 15–79) patients with complete data were included. HM was present in 79 (17%) patients. The prevalence of HM was highest in patients diagnosed with hypersensitive oesophagus (31%) and lowest in NERD (15%)-see table 1. The prevalence of HM was significantly higher in hypersensitive oesophagus (31%) compared to the combined prevalence in other reflux diagnoses (16%), p = 0.009, and to the healthy control group (18%), p = 0.04. <h3>Conclusion</h3> 17% of patients with reflux symptoms severe enough to warrant physiology investigation have HM, which is similar to the prevalence in healthy controls. The prevalence of HM in patients with hypersensitive oesophagus (31%) was almost twice as high as in healthy controls, whereas, the prevalence in other subgroups (GERD, NERD) is similar to that of controls. This suggests that the link between HM and gastro-oesopheageal reflux disease is related to visceral hypersensitivity, rather than to increased reflux. HM appears to be a risk factor for oesophageal hypersensitivity, and may contribute to the pathogenesis of this reflux entity. <h3>Disclosure of Interest</h3> None Declared <h3>Reference</h3> Castori, M., <i>et al.</i>, <i>Natural history and manifestations of the hypermobility type Ehlers-Danlos syndrome: a pilot study on 21 patients.</i> Am J Med Genet A. <b>152A</b>(3): p. 556–64.
Lectures on the Diagnosis of Epilepsy
Authors: J. H. Jackson
Journal: BMJ (1879)

It is significant that the rule is that all sorts of epileptic and epileptiform convulsions begin in small muscles, or in muscles whose ordinary movements require little energy for the displacements they have to effect.I have advanced the hypothesis that small muscles are represented in the cerebrum by small cells, or rather that movements of parts which require little energy for the displacements they have to effect are represented by small cells.As the researches of Bevan Lewis show, this is not altogether an hypothesis in so far as "centres" in Ferrier's region are concerned; "centres", chiefly representing" small movements", are those which have fewest large cells.This matter has wide bearings.
Adoptive transfer of suppression of arthritis in the mouse model of collagen-induced arthritis. Evidence for a type II collagen-specific suppressor T cell.
Authors: T F Kresina, R W Moskowitz
Journal: Journal of Clinical Investigation (1985)

This study details the suppressive mechanism involved in the antigen-specific suppression of collagen-induced arthritis. Intravenous injection of 500 micrograms of soluble native type II collagen 3 d before immunization with native type II collagen emulsified in complete Freund's adjuvant resulted in animals with decreased in vitro cellular and humoral immune response to native and denatured type II collagen compared with control groups. Control groups were composed of animals preinoculated with saline and type I collagen and established the antigen-specific nature of the observed suppression. Mice with reduced immune responses to type II collagen also were observed to portray little or no erythema and edema associated with collagen-induced arthritis. Adoptive transfer experiments established the requirement of T cells for the suppression of collagen-induced arthritis. Analysis of the phenotype of responding splenic cells in chronic immunotherapeutically suppressed mice in vitro revealed that responding cells were Ly1-2+ (suppressor/cytotoxic) T cells. On the other hand, the cellular phenotype of T cells responding to type II collagen in nonsuppressed collagen-induced arthritic mice was Ly1+2- (helper/inducer T cells). The data indicate that type II collagen-specific T cells are generated on intravenous inoculation of soluble native type II collagen. These cells are observed in type II collagen-immune animals, which are nonarthritic and portray reduced humoral and in vitro cellular immune response to type II collagen. This study suggests that specific suppression of immune responses to type II collagen by T-suppressor cells can be immunotherapeutic in certain forms of arthritis.
CELLULAR MECHANISMS OF NEURONAL POPULATION OSCILLATIONS IN THE HIPPOCAMPUS IN VITRO
Authors: Roger D. Traub, Andrea Bibbig, Fiona E.N. LeBeau, Eberhard H. Buhl, Miles A. Whittington
Journal: Annual Review of Neuroscience (2004)

A variety of population oscillations, at frequencies approximately 5 Hz up to 200 Hz and above, can be induced in hippocampal slices either by (a) manipulation of the ionic environment, or (b) by stimulation of metabotropic receptors; brief oscillations can even occur spontaneously. In this review, we consider in vitro theta (4-12 Hz), gamma/beta (15-70 Hz), and very fast oscillations (VFO) (>70 Hz). Many in vitro oscillations are gated by synaptic inhibition but are influenced by electrical coupling as well; one type depends solely on electrical coupling. For some oscillations dependent upon inhibition, the detailed firing patterns of interneurons can influence long-range synchronization. Two sorts of electrical coupling are important in modulating or generating various in vitro oscillations: (a) between interneurons, primarily between dendrites; and (b) between axons of pyramidal neurons. VFO can exist in isolation or can act as generators of gamma frequency oscillations. Oscillations at gamma frequencies and below probably create conditions under which synaptic plasticity can occur, between selected neurons-even those separated by significant axonal conduction delays.
ERNEST E. GLYNN, M.D., F.R.C.P
Authors: A. D. Bigland
Journal: BMJ (1929)

THE niews of tlhe death of Professor Ernest Glynn:1l on Sunday, September 22nd, did not come as a surprise to his frieends.For many years he had sufferted from diabetes mellitus, and latterly complications 'had supervelned so serious thlat two years ago he was
Mitochondrial damage: a possible mechanism of the “topical” phase of NSAID induced injury to the rat intestine
Authors: S Somasundaram, S Rafi, J Hayllar, G Sigthorsson, M Jacob, A B Price, A Macpherson, T Mahmod, D Scott, J M Wrigglesworth, I Bjarnason
Journal: Gut (1997)

Background —The “topical” effect of non-steroidal anti-inflammatory drugs (NSAIDs) seems to be an important cause of NSAID induced gastrointestinal damage. Aim —To examine the possible mechanism of the “topical” phase of damage in the small intestine. Methods —Electron microscopy and subcellular organelle marker enzyme studies were done in rat small intestine after oral administration of indomethacin (doses varied between 5 and 30 mg/kg). The effect of conventional and non-acidic NSAIDs on rat liver mitochondrial respiration was measured in vitro in a Clarke-type oxygen electrode. Results —The subcellular organelle marker enzymes showed mitochondrial and brush border involvement within an hour of indomethacin administration. Electron microscopy showed dose dependent mitochondrial changes following indomethacin administration consistent with uncoupling of oxidative phosphorylation (or inhibition of electron transport) which were indistinguishable from those seen with the uncoupler dinitrophenol. Parenteral indomethacin caused similar changes, but not in rats with ligated bile ducts. A range of NSAIDs, but not paracetamol or non-acidic NSAIDs which have a favourable gastrointestinal tolerability profile, uncoupled oxidative phosphorylation in vitro at micromolar concentrations and inhibited respiration at higher concentrations. In vivo studies with nabumetone and aspirin further suggested that uncoupling or inhibition of electron transport underlies the “topical” phase of NSAID induced damage. Conclusion —Collectively, these studies suggest that NSAID induced changes in mitochondrial energy production may be an important component of the “topical” phase of damage induction.
Echocardiographic Predictors of Survival and Response to Early Revascularization in Cardiogenic Shock
Authors: Michael H. Picard, Ravin Davidoff, Lynn A. Sleeper, Lisa A. Mendes, Christopher R. Thompson, Vladimir Dzavik, Richard Steingart, Ken Gin, Harvey D. White, Judith S. Hochman
Journal: Circulation (2003)

Background— Although echocardiography is used in diagnosis and management of myocardial infarction, it has not been established whether specific features of cardiac structure or function early in the course of cardiogenic shock provide prognostic value. The purposes of this substudy of the SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK (SHOCK) trial were to describe the echocardiographic features of cardiogenic shock, identify findings on early echocardiograms associated with outcome, examine the interaction of such features with treatment, and determine whether these features could provide insights into the survival benefit observed with early revascularization and guide selection of patients for this strategy. Methods and Results— One hundred seventy-five echocardiograms performed within 24 hours of randomization to the early revascularization (ERV) or initial medical stabilization (IMS) arms of the trial were submitted for quantitative assessment, and 169 were suitable for analysis. The 2 groups were similar in terms of clinical and early echocardiographic characteristics. Mean left ventricular ejection fraction (LVEF) was 31%, and moderate or greater mitral regurgitation (MR) was noted in 39.1%. On multivariate analysis, the only independent predictors of survival were MR severity and LVEF. A survival benefit for the ERV strategy was observed at all levels of LVEF and MR. Conclusions— A wide range of cardiac structural and functional abnormalities exists in patients presenting with acute cardiogenic shock. Both short- and long-term mortality appear to be associated with initial left ventricular systolic function and MR as assessed by echocardiography, and a benefit of ERV is noted regardless of baseline LVEF or MR.