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Vs. Controls (vs + control)
Selected AbstractsNo effect of venoconstrictive thigh cuffs on orthostatic hypotension induced by head-down bed restACTA PHYSIOLOGICA, Issue 2 2000M.-A. Custaud Orthostatic intolerance (OI) is the most serious symptom of cardiovascular deconditioning induced by head-down bed rest or weightlessness. Wearing venoconstrictive thigh cuffs is an empirical countermeasure used by Russian cosmonauts to limit the shift of fluid from the lower part of the body to the cardio-cephalic region. Our aim was to determine whether or not thigh cuffs help to prevent orthostatic hypotension induced by head-down bed rest. We studied the effect of thigh cuffs on eight healthy men. The cuffs were worn during the day for 7 days of head-down bed rest. We measured: orthostatic tolerance (stand tests and lower body negative pressure tests), plasma volume (Evans blue dilution), autonomic influences (plasma noradrenaline) and baroreflex sensitivity (spontaneous baroreflex slope). Thigh cuffs limited the loss of plasma volume (thigh cuffs: ,201 ± 37 mL vs. control: ,345 ± 42 mL, P < 0.05), the degree of tachycardia and reduction in the spontaneous baroreflex sensitivity induced by head-down bed rest. However, the impact of thigh cuffs was not sufficient to prevent OI (thigh cuffs: 7.0 min of standing time vs. control: 7.1 min). Decrease in absolute plasma volume and in baroreflex sensitivity are known to be important factors in the aetiology of OI induced by head-down bed rest. However, dealing with these factors, using thigh cuffs for example, is not sufficient to prevent OI. Other factors such as venous compliance, microcirculatory changes, peripheral arterial vasoconstriction and vestibular afferents must also be considered. [source] Effects of a yoga breath intervention alone and in combination with an exposure therapy for post-traumatic stress disorder and depression in survivors of the 2004 South-East Asia tsunamiACTA PSYCHIATRICA SCANDINAVICA, Issue 4 2010T. Descilo Descilo T, Vedamurtachar A, Gerbarg PL, Nagaraja D, Gangadhar BN, Damodaran B, Adelson B, Braslow LH, Marcus S, Brown RP. Effects of a yoga breath intervention alone and in combination with an exposure therapy for PTSD and depression in survivors of the 2004 South-East Asia tsunami. Objective:, This study evaluated the effect of a yoga breath program alone and followed by a trauma reduction exposure technique on post-traumatic stress disorder and depression in survivors of the 2004 Asian tsunami. Method:, In this non-randomized study, 183 tsunami survivors who scored 50 or above on the Post-traumatic Checklist-17 (PCL-17) were assigned by camps to one of three groups: yoga breath intervention, yoga breath intervention followed by 3,8 h of trauma reduction exposure technique or 6-week wait list. Measures for post-traumatic stress disorder (PCL-17) and depression (BDI-21) were performed at baseline and at 6, 12 and 24 weeks. Data were analyzed using anova and mixed effects regression. Results:, The effect of treatment vs. control was significant at 6 weeks (F2,178 = 279.616, P < 0.001): mean PCL-17 declined by 42.5 ± 10.0 SD with yoga breath, 39.2 ± 17.2 with Yoga breath + exposure and 4.6 ± 13.2 in the control. Conclusion:, Yoga breath-based interventions may help relieve psychological distress following mass disasters. [source] Plasma urocortin in acute myocardial infarction patientsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 10 2010Arintaya Phrommintikul Eur J Clin Invest 2010; 40 (10): 874,882 Abstract Background, Despite its proposed cardioprotective effect, the role of plasma urocortin in acute myocardial infarction (AMI) remains unknown. We investigated plasma profile of urocortin in AMI patients and evaluated its long-term prognostic performance. Material and methods, Sixty-six AMI patients and 21 healthy subjects were included in this study. Blood samples for urocortin were collected on days 0 (onset), 1, 3 and 5 and at 3 and 6 months. Primary endpoint was mortality within 1 year of follow-up. Secondary endpoint was combined death and nonfatal adverse cardiac events (i.e. myocardial reinfarction, urgent revascularization or hospitalization due to heart failure) within 1 year. Results, During follow-up at 1 year, 38 (57·6%) patients were alive without cardiac events, nine (13·6%) had nonfatal cardiac events and 17 (25·8%) died. Plasma urocortin in AMI patients were increased on days 0, 1, 3 and 5 (P < 0·05 vs. control). The receiver-operating characteristic curve showed an area under curve (AUC) of day 0 urocortin to be 0·750 with 95% confidence interval (CI) of 0·619,0·881 (P = 0·004), whereas AUC of NT-proBNP was 0·857 (95% CI, 0·722,0·992; P = 0·003). Sensitivity values for predicting the mortality of urocortin NT-proBNP and a combined urocortin and NT-proBNP were 0·81 (95% CI, 0·54,0·95), 0·86 (95% CI, 0·42,0·99) and 1·0 (95% CI, 0·56,1·0), respectively. Conclusions, Plasma urocortin level is elevated in AMI patients for 5 days from onset. High plasma urocortin within 24 h after the onset is associated with increased mortality. Combined urocortin and NT-proBNP enhance prognostic performance in AMI patients. [source] Evaluation of effects of rofecoxib on platelet function in an in vitro model of thrombosis with circulating human bloodEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 4 2004M. R. Hernandez Abstract Background, Cyclooxygenase (COX)-2-selective non-steroidal anti-inflammatory drugs have been used for anti-inflammatory therapy. However, it has also been described that they may increase risk of cardiovascular events. Objectives, To study the effects of COX2 inhibitor rofecoxib on platelet function using in vitro tests. Results were compared with those obtained in a parallel experiment with acetyl salicylic acid (ASA). Methods, Studies of platelet aggregation, using different agonists, were performed by a turbidimetric method. Adhesive and cohesive function of platelets were analyzed by perfusion techniques, treated blood was exposed to thrombogenic surfaces and platelet interaction was morphometrically evaluated. Results, Twenty-five µM of rofecoxib induced a prolonged lag time and a reduction in the percentage of aggregation when arachidonic acid, ADP or collagen were used as agonists. In perfusion studies with parallel chamber rofecoxib 50 µM and ASA 500 µM reduced overall platelet interaction with the collagen surface (17·4 ± 3·7, P < 0·05; vs. 32·1 ± 2·6%P < 0·05 and 17·9 ± 2·4, vs. 31·9 ± 3·24, P < 0·05, respectively). In studies performed on annular chambers, 25 µM of rofecoxib reduced platelet interaction; values of the thrombus and covered surface were 17·4 ± 4·5%; P < 0·05 and 21·1 ± 4·1%; P < 0·05, respectively, vs. 30·4 ± 7·5% and 33·5 ± 6·5 in the control. ASA did also impair thrombus formation but differences did not reach the levels of statistical significance. Moreover, rofecoxib but not ASA reduced significantly thrombus height and thrombus area (7·4 ± 0·5 µM; P < 0·005 and 96·0 ± 21·2 µM2; P < 0·05 vs. control 11·2 ± 0·9 µM and 220·0 ± 47·7µM2, respectively). Conclusion, We conclude that under our experimental conditions, rofecoxib diminished platelet aggregation induced by different agonists and inhibited platelet-mediated thrombogenesis in an in vitro model of thrombosis. [source] Cholestasis enhances liver ischemia/reperfusion-induced coagulation activation in ratsHEPATOLOGY RESEARCH, Issue 2 2010Jaap J. Kloek Aim:, Cholestasis is associated with increased morbidity and mortality in patients undergoing major liver surgery. An additional risk is induced when vascular inflow occlusion is applied giving rise to liver ischemia/reperfusion (I/R) injury. The role of the coagulation system in this type of injury is elusive. The aim of the current study was to assess activation of coagulation following hepatic I/R injury in cholestatic rats. Methods:, Male Wistar rats were randomized into two groups and subjected to bile duct ligation (BDL) or sham laparotomy. After 7 days, both groups underwent 30 min partial liver ischemia. Animals were sacrificed before ischemia or after 6 h, 24 h, and 48 h reperfusion. Results:, Plasma AST and ALT levels were higher after I/R in cholestatic rats (P < 0.05). Hepatic necrosis, liver wet/dry ratio and neutrophil influx were increased in the BDL group up to 48 h reperfusion (P < 0.05). Liver synthetic function was decreased in the BDL group as reflected by prolonged prothrombin time after 6 h and 24 h reperfusion (P < 0.05). I/R in cholestatic rats resulted in a 12-fold vs. 7-fold (P < 0.01) increase in markers for thrombin generation and a 6-fold vs. 2-fold (P < 0.01) increase in fibrin degradation products (BDL vs. control, respectively). In addition, the cholestatic rats exhibited significantly decreased levels of antithrombin (AT) III and increased levels of the fibrinolytic inhibitor plasminogen activator inhibitor (PAI-1) during reperfusion. Conclusions:, Cholestasis significantly enhances I/R-induced hepatic damage and inflammation that concurs with an increased activation of coagulation and fibrinolysis. [source] , -Carotene is incorporated or mobilized along with triglycerides in bovine adipose tissue in response to insulin or epinephrineJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 1 2009E. Arias Summary Pasture fed cattle ingest substantial amounts of , -carotene (, -C). Not all of the carotenoid compound is transformed into vitamin A, but the surplus is deposited in adipose tissue (AT). The mechanisms of , -C incorporation and mobilization are unknown. Two experiments were conducted using explants from bovine AT cultured in vitro. First, , -C incorporation by explants from three animals was examined with different , -C concentrations (0, 1, 5 and 20 ,m) and different times of incubation (every 5 h up to 25 h). The data showed a significant increase of , -C concentration in explants only for 20 ,m, -C. Secondly, effects of insulin and epinephrine on , -C and triglyceride (TG) contents of explants were studied. Explants from six animals were incubated with either hormone and 0 or 20 ,m, -C for 20 h. Both TG and , -C contents were affected positively by insulin and negatively by epinephrine. Interestingly, changes in ratios of , -C/TG (hormone vs. control) were similar (1.7 × 10,3 and 1.8 × 10,3), respectively, for insulin and epinephrine, indicating that , -C level is directly related to TG content. We also report the presence of mRNA for , -C 15, 15, oxygenase in bovine AT. The in vitro culture system using explants from bovine AT is a promising model to investigate factors that might affect the accumulation and metabolism of , -C. [source] The Theory of Planned Behavior and Ecstasy Use: Roles for Habit and Perceived Control Over Taking Versus Obtaining SubstancesJOURNAL OF APPLIED SOCIAL PSYCHOLOGY, Issue 1 2001Sheina Orbell Despite increasing use of the illicit substance known as ecstasy, there is a paucity of research concerning psychosocial correlates of its use. A prospective study examined the ability of variables specified by the theory of planned behavior (TPB) to predict ecstasyuse intentions and behavior. Regression analyses showed that theory of reasoned action and TPB variables provided good prediction of intentions to use the substance. Moreover, support was obtained for a distinction between perceptions of behavioral control over taking ecstasy vs. control over obtaining the substance in the prediction of intentions. Habit contributed additional variance to the prediction of intentions, and reduced the effects of perceived behavioral control over taking ecstasy to nonsignificance. Ecstasy use over 2 months was directly predicted from intentions to use the substance. [source] Induction of Angiogenesis and Inhibition of Apoptosis by Hepatocyte Growth Factor Effectively Treats Postischemic Heart FailureJOURNAL OF CARDIAC SURGERY, Issue 1 2005Vasant Jayasankar M.D. Hepatocyte growth factor (HGF) is a potent angiogenic and anti-apoptotic protein whose receptor is upregulated following MI. This study was designed to investigate the ability of HGF to prevent heart failure in a rat model of experimental MI. Methods: The rats underwent direct intramyocardial injection with replication-deficient adenovirus encoding HGF (n = 7) or null virus as control (n = 7) 3 weeks following ligation of the left anterior descending coronary artery. Analysis of the following was performed 3 weeks after injection: cardiac function by pressure,volume conductance catheter measurements; LV wall thickness; angiogenesis by Von Willebrand's factor staining; and apoptosis by the TUNEL assay. The expression levels of HGF and the anti-apoptotic factor Bcl-2 were analyzed by Western blot. Results: Adeno-HGF-treated animals had greater preservation of maximum LV pressure (HGF 77 ± 3 vs. control 64 ± 5 mmHg, p < 0.05), maximum dP/dt (3024 ± 266 vs. 1907 ± 360 mmHg/sec, p < 0.05), maximum dV/dt (133 ± 20 vs. 84 ± 6 ,L/sec, p < 0.05), and LV border zone wall thickness (1.98 ± 0.06 vs. 1.53 ± 0.07 mm, p < 0.005). Angiogenesis was enhanced (151 ± 10.0 vs. 90 ± 4.5 endothelial cells/hpf, p < 0.005) and apoptosis was reduced (3.9 ± 0.3 vs. 8.2 ± 0.5%, p < 0.005). Increased expression of HGF and Bcl-2 protein was observed in the Adeno-HGF-treated group. Conclusions: Overexpression of HGF 3 weeks post-MI resulted in enhanced angiogenesis, reduced apoptosis, greater preservation of ventricular geometry, and preservation of cardiac contractile function. This technique may be useful to treat or prevent postinfarction heart failure. [source] Therapeutic effect of statin on aortic stenosis: a review with meta-analysisJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 4 2010H. Ge MD Background:, Aortic stenosis (AS) is a common progressive disease. Statins have been hypothesized to delay its progression via pleiotropic mechanisms. However, results of clinical trials focusing on statin therapy in AS patients have been controversial. Objective:, To analyse and summarize the findings in recent statin trials and to discuss the rationale of statin usage in AS populations. Methods:, A comprehensive database search was conducted by two independent reviewers. Controlled trials that compared progression of AS between statin and non-statin therapy published before 31 December 2008 were included. Data were extracted for meta-analysis, to estimate overall effects, if available. Factors that contributed to heterogeneities among the trials were analysed. Results:, The meta-analysis included nine trials with a total of 2947 patients. Statin therapy displayed an overall statistically significant effect on delaying AS progression. The weighted mean difference (statin vs. control) of annual increase of peak aortic-jet velocity was ,0·12 m/s (95% confidence interval ,0·22 to ,0·03); the increase of mean transaortic pressure gradient was ,1·64 mmHg per year (,3·27 to ,0·01); Heterogeneity-analysis suggested that the baseline risk factors and characteristics of the patients, the use of different statins, and the time point to initiate statin therapy, may be important considerations when interpreting the result of individual studies. Conclusion:, Although the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial reported negative results in delaying AS progression in low-risk patients, the potential benefits of statins in those with multiple risk factors and their value in preventing future coronary events call for further investigation of different categories of AS patients. [source] Altered knee kinematics in ACL-deficient non-copers: A comparison using dynamic MRIJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 2 2006Peter J. Barrance Abstract Kinematics measured during a short arc quadriceps knee extension exercise were compared in the knees of functionally unstable ACL-deficient patients, these patients' uninjured knees, and uninjured control subjects' knees. Cine phase contrast dynamic magnetic resonance imaging, in combination with a model-based tracking algorithm developed by the authors, was used to measure tibiofemoral kinematics as the subjects performed the active, supine posture knee extension exercise in the terminal 30 degrees of motion. Two determinants of tibiofemoral motion were measured: anterior/posterior location of the tibia relative to the femur, and axial rotation of the tibia relative to the femur. We hypothesized that more anterior tibial positioning, as well as differences in axial tibial rotation patterns, would be observed in ACL-deficient (ACL-D) knees when compared to uninjured knees. Multifactor ANOVA analyses were used to determine the dependence of the kinematic variables on (i) side (injured vs. uninjured, matched by subject in the control group), (ii) flexion angle measured at five-degree increments, and (iii) subject group (ACL-injured vs. control). Statistically significant anterior translation and external tibial rotation (screw home motion) accompanying knee extension were found. The ACL-D knees of the injured group exhibited significantly more anterior tibial positioning than the uninjured knees of these subjects (average difference over extension range,=,3.4,±,2.8 mm, p,<,0.01 at all angles compared), as well as the matched knees of the control subjects. There was a significant effect of interaction between side and subject group on A/P tibial position. We did not find significant differences in external tibial rotation associated with ACL deficiency. The changes to active joint kinematics documented in this entirely noninvasive study may contribute to cartilage degradation in ACL-D knees, and encourage more extensive investigations using similar methodology in the future. © 2005 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res [source] Differential apoptotic response of J774 macrophages to alumina and ultra-high-molecular-weight polyethylene particlesJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 1 2002Alain Petit We recently identified apoptosis in in vitro wear particle-stimulated macrophages. The recent explosion of interest in apoptosis lies in the fact that it is under positive and negative regulation through evolutionary conserved biochemical pathways. It may also be possible to modulate macrophage apoptosis in the treatment of periprosthetic osteolysis. The purpose of this study was to compare the macrophage response to identically sized particles of alumina ceramic (Al2O3) and ultra-high-molecular-weight polyethylene (UHMWPE) in terms of TNF-, release and induction of apoptosis. J774 mouse macrophages were incubated for 0,24 h in the presence of Al2O3 and UHMWPE particles. TNF-, release was measured by ELISA; Poly(ADP-ribose)polymerase (PARP) and caspase-3 expression was analyzed by Western blot; DNA fragmentation (DNA laddering) was visualized on agarose gel containing ethidium bromide. Al2O3 particles induced TNF-, release after 4 h incubation with concentrations reaching 483 and 800 pg/ml after 24 h with 125 and 250 particles/macrophage, respectively (control = 161 pg/ml) (P < 0.05 vs. control). The same concentrations of UHMWPE particles induced a much larger and significant TNF-, release after only 1 h incubation, increasing up to 6250 pg/ml after 24 h (P < 0.05 vs. control). Western blot analysis demonstrated that the active caspase-3 fragment (17 kDa) and the proteolytic PARP fragment (85 kDa) were expressed after 2 h incubation with 125 and 250 Al2O3 particles/macrophage. The active caspase-3 and the PARP fragment had lower expression and appeared after a longer incubation time (8 h) with 125 and 250 UHMWPE particles/macrophage. Finally, DNA fragmentation (DNA laddering) was observed after 16 h with 125 and 250 particles of Al2O3 per macrophage whereas no laddering was induced by UHMWPE particles even after 24 h incubation. This study shows that although both Al2O3 and UHMWPE particles induce TNF-, release, this stimulation was much greater (8,10 times higher) with UHMWPE than A12O3 (P < 0.05 vs. control). As well, the induction of apoptosis, as measured by activation of caspase-3, PARP cleavage and DNA laddering, is different for these two particles, being faster and more important with Al2O3 than UHMWPE. We hypothesize that the ability of Al2O3 to induce macrophage apoptosis may explain the lower TNF-, release observed with these particles and explain the differences seen in osteolysis patterns of ceramic,ceramic (CC) vs. metal,polyethylene (Mpe) articulations. In conclusion, apoptosis may be a major internal mechanism to decrease macrophage activity and may be a desired therapeutic endpoint. The identification of an apoptosis-related pathway in the macrophage response to ceramic particles provides crucial data for a rational approach in the treatment and/or prevention of periprosthetic osteolysis. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source] Inhibition of Alcohol-Associated Colonic Hyperregeneration by ,-Tocopherol in the RatALCOHOLISM, Issue 1 2003P. Vincon Background: Chronic alcohol consumption results in colorectal mucosal hyperregeneration, a condition associated with an increased risk for colorectal cancer. Possible mechanisms may involve the effects of acetaldehyde and/or free radicals generated during alcohol metabolism. Vitamin E is part of the antioxidative defense system, and its concentration is decreased or its metabolic utilization increased in various tissues after chronic alcohol consumption. We wondered whether ,-tocopherol supplementation may prevent ethanol-induced colorectal cell cycle behavior and whether these changes were related to alterations in protein synthesis. Methods: Five groups of male Wistar rats, each consisting of 14 animals, received liquid diets as follows: group 1, alcohol; group 2, alcohol +,-tocopherol; group 3, control (i.e., isocaloric glucose); group 4; control (i.e., isocaloric glucose) +,-tocopherol. Group 5 was fed a solid chow diet ad libitum. After 4 weeks of feeding, immunohistology was performed with anti-proliferating cell nuclear antigen (PCNA) or anti-BCL2 antibodies. Fractional (ks) and absolute (Vs) rates of protein synthesis and rates of protein synthesis relative to RNA (kRNA) and DNA (kDNA) were measured with a flooding dose of L-[4- 3H] phenylalanine with complementary analysis of protein and nucleic acid composition. Results: The PCNA index was increased significantly in the colon after ethanol administration compared with controls (ethanol, 10.3 ± 2.3 vs. control, 6.51 ± 1.6% PCNA positive cells, p < 0.05), although neither the protein, RNA, and DNA concentrations nor ks, kRNA, kDNA, and Vs were affected. This increase in PCNA index was significantly diminished by coadministration of ,-tocopherol (ethanol +, - tocopherol, 7.86 ± 1.71% PCNA positive cells, p < 0.05) without significant alterations in protein synthetic parameters. A similar result was obtained for the PCNA index in the rectal mucosa (ethanol, 14.6 ± 4.4 vs. control, 12.1 ± 4.2% PCNA positive cell), although this did not reach statistical significance. Neither ethanol nor , - tocopherol feeding had any significant effect on BCL-2 expression in the colorectal mucosa. As with the colon, protein synthetic parameters in the mucosa were not affected by alcohol feeding at 4 weeks. These effects on colonic cell turnover without corresponding changes in protein synthesis thus represent a specific localized phenomenon rather than a general increase in anabolic processes in the tissue and reaffirm the hyperregenerative properties of chronic alcohol consumption. Conclusions: Alcohol-associated hyperproliferation could be prevented, at least in part, by supplementation with ,-tocopherol. This may support the hypothesis that free radicals are involved in the pathogenesis of alcohol-associated colorectal hyperproliferation. [source] Generalized and neurotransmitter-selective noradrenergic denervation in Parkinson's disease with orthostatic hypotension,MOVEMENT DISORDERS, Issue 12 2008Yehonatan Sharabi MD Abstract Patients with Parkinson's disease (PD) often have manifestations of autonomic failure. About 40% have neurogenic orthostatic hypotension (NOH), and among PD+NOH patients virtually all have evidence of cardiac sympathetic denervation; however, whether PD+NOH entails extra-cardiac noradrenergic denervation has been less clear. Microdialysate concentrations of the main neuronal metabolite of norepinephrine (NE) and dihydroxyphenylglycol (DHPG) were measured in skeletal muscle, and plasma concentrations of NE and DHPG were measured in response to i.v. tyramine, yohimbine, and isoproterenol, in patients with PD+NOH, patients with pure autonomic failure (PAF), which is characterized by generalized catecholaminergic denervation, and control subjects. Microdialysate DHPG concentrations were similarly low in PD+NOH and PAF compared to control subjects (163 ± 25, 153 ± 27, and 304 ± 27 pg/mL, P < 0.01 each vs. control). The two groups also had similarly small plasma DHPG responses to tyramine (71 ± 58 and 82 ± 105 vs. 313 ± 94 pg/mL; P < 0.01 each vs. control) and NE responses to yohimbine (223 ± 37 and 61 ± 15 vs. 672 ± 130 pg/mL, P < 0.01 each vs. control), and virtually absent NE responses to isoproterenol (20 ± 34 and 14 ± 15 vs. 336 ± 78 pg/mL, P < 0.01 each vs. control). Patients with PD+NOH had normal bradycardia responses to edrophonium and normal epinephrine responses to glucagon. The results support the concept of generalized noradrenergic denervation in PD+NOH, with similar severity to that seen in PAF. In contrast, the parasympathetic cholinergic and adrenomedullary hormonal components of the autonomic nervous system seem intact in PD+NOH. © 2008 Movement Disorder Society [source] Fiber-knob modifications enhance adenoviral tropism and gene transfer in malignant gliomaTHE JOURNAL OF GENE MEDICINE, Issue 3 2007Sophy Zheng Abstract Background Malignant gliomas remain refractory to Ad5-mediated gene therapy due to deficiency of the coxsackie adenovirus receptor on tumor cells. The purpose of this study was to evaluate whether changes in adenoviral tropism can enhance gene transfer in the context of malignant glioma. Methods We have identified several receptors that are over-expressed on tumor cells and created a series of pseudotyped Ad5 vectors that recognize these receptors: Ad5-RGD which binds ,v,3/,v,5 integrins; Ad5/3 which contains adenovirus serotype 3 knob and binds to CD46; Ad5-Sigma which incorporates the reovirus sigma knob and binds to junctional adhesion molecule-1; and Ad5-pk7 which contains the polylysine motif and binds heparan sulfate proteoglycans. We also investigated the Ad5-CAV1 vector, which contains the knob of canine adenovirus type 1, a virus previously shown to infect glioma via an unknown mechanism. In this study, we compared these modified vectors for their ability to promote the expression of luciferase transgene both in vitro and in vivo. Results Our results indicate that all five modified vectors attained higher mean luciferase activity vs. control. Among them, Ad5-CAV1 and Ad5-pk7 attained the highest transduction efficiency independent of different tumor lines or infection time. Ad5-Sigma and Ad5-pk7 also demonstrated the least nonspecific infection in normal human astrocytes. Most importantly, Ad5-pk7 achieved 1000-fold increased transgene expression in human glioma xenografts in vivo. Conclusions These results indicate that modifications of adenoviral tropism can enhance gene transfer in tumors that are poorly susceptible to adenoviral vectors and warrant further development of Ad5-pk7 for glioma gene therapy. Copyright © 2007 John Wiley & Sons, Ltd. [source] ORIGINAL RESEARCH,BASIC SCIENCE: A Nitric Oxide-Releasing PDE5 Inhibitor Relaxes Human Corpus Cavernosum in the Absence of Endogenous Nitric OxideTHE JOURNAL OF SEXUAL MEDICINE, Issue 1 2005Jasjit S. Kalsi BSc, MRCS ABSTRACT Introduction., In conditions with severe deficiency of endogenous nitric oxide (NO), such as long-term diabetes and cavernosal nerve injury, phosphodiesterase type 5 (PDE5) inhibitors have reduced efficacy in the treatment of erectile dysfunction. NO-releasing PDE5 inhibitors could be an alternative therapeutic approach in such cases. Aim., We therefore aimed to compare sildenafil and NO-releasing sildenafil (NCX-911) in relaxing human corpus cavernosum in the absence or presence of endogenous NO. Methods., The two compounds were compared in reducing the phenylephrine-induced tone of human corpus cavernosum in the presence or absence of an inhibitor of NO synthase (L-NAME; 500 µM) or an inhibitor of soluble guanylate cyclase (ODQ, 10 µM). Results., NCX-911 was as potent as sildenafil in control conditions (EC50 = 733.1 ± 94.4 nM and 800.7 ± 155.8 nM, respectively). The potency of NCX-911 was not altered but that of sildenafil decreased significantly in the presence of L-NAME (EC50 = 980.4 ± 106.7 nM and 2446.7 ± 256.8 nM, respectively; P < 0.001 for sildenafil vs. control). Both compounds below 1 µM failed to induce relaxation in the presence of ODQ (EC50 = 6578 ± 1150 nM and 6488 ± 938 nM for NCX-911 and sildenafil, respectively). Conclusion., These results show that the potency of NCX-911 was maintained unlike sildenafil in the absence of endogenous NO confirming the potential use of NO-releasing PDE5 inhibitors in NO-deficient conditions. [source] 44-55-66-PM, a Mnemonic That Improves Retention of the Ottawa Ankle and Foot Rules: A Randomized Controlled TrialACADEMIC EMERGENCY MEDICINE, Issue 8 2010FRCPC, Jocelyn Gravel MD ACADEMIC EMERGENCY MEDICINE 2010; 17:859,864 © 2010 by the Society for Academic Emergency Medicine Abstract Objectives:, Studies have suggested that poor knowledge of the Ottawa Ankle Rules (OAR) limits its clinical impact. This study evaluated the ability of a mnemonic to improve knowledge of the OAR. Methods:, This was a single-blind randomized controlled trial performed among residents and medical students doing a pediatric emergency medicine rotation. At baseline, all participants were tested for their baseline knowledge of the OAR. The intervention was a standardized information sheet providing a mnemonic of the OAR (44-55-66-PM), while control subjects received its classic description. Block randomization (medical student vs. type of resident) was used. Each participant answered the same questionnaire at the end of rotation (3 weeks later) and via a Web-based survey 5 to 9 months postrandomization. Main outcome measures were knowledge of the components of the ankle rule based on a 13-item criterion grid and the foot rule based on a 10-item criterion grid. All questionnaires were marked at the end of the study by two reviewers blinded to the randomization. Discrepancies in final scores were resolved by consensus. Student's t-test was performed to compare mean scores on the evaluation between groups using an intention-to-treat approach. Results:, Among the 206 eligible participants, 96 medical students and 94 residents were recruited and agreed to participate. Primary outcomes were measured in 95% of the participants at 3 weeks postrandomization and in 72% on the long-term follow-up. Participants in both groups were similar with regard to baseline characteristics and prior knowledge of the OAR. Both groups showed improvement in their knowledge of the rule during the study period. At mid-term, knowledge of the OAR was similar for the ankle components (score for mnemonic 10.9; control 10.2; 95% confidence interval [CI] for difference = ,0.3 to 1.7) and for the foot (mnemonic 7.6 vs. control 7.5; 95% CI for difference = ,0.7 to 0.9). On the long term, randomization to the mnemonic was associated with a better knowledge of the OAR as demonstrated by a higher score for the ankle component (mnemonic 10.1 vs. control 8.9; 95% CI for difference = 0.6 to 1.8) and for the foot (mnemonic 7.8 vs. control 6.5; 95% CI for difference = 0.8 to 1.9). Conclusions:, Mid-term knowledge of the OAR drastically improved for all participants of the study. The use of the mnemonic 44-55-66-PM was associated with a better long-term knowledge of the OAR among medical students and residents. The improvement in knowledge of the OAR among the control group highlights the importance of using controlled trials for studies evaluating knowledge transfer. [source] Furosemide in preterm infants treated with indomethacin for patent ductus arteriosusACTA PAEDIATRICA, Issue 5 2009Peter Andriessen Abstract Objective: To evaluate the effect of furosemide on renal function and water balance in preterm infants treated with indomethacin (3 × 0.2 mg/kg at 12-h intervals) for symptomatic patent ductus arteriosus. Patients and Methods: We performed a retrospective multi-centre double cohort study in preterm infants <32 weeks of gestational age. Thirty-two infants treated with furosemide (1 mg/kg i.v.) before each indomethacin dose (furosemide group) were matched with 32 infants with indomethacin treatment alone (control-group). Renal effects (urine output, weight gain, serum creatinine, sodium concentration) were registered. Results: The study groups were comparable for gestational age, birth weight and day of therapy. Pretreatment differences were observed for urine output, weight and serum sodium. However, no differences were noticed in day-to-day urine output change or weight gain between the groups. A significant increase in serum creatinine concentration (50% vs. control, 18%; p < 0.05) and a concomitant significant decrease in serum sodium (,9 vs. control, ,3 mmoL/L; p < 0.05) in the furosemide group was observed 72,96 h after starting therapy. Conclusion: Furosemide before each indomethacin dose resulted in a significant increase in serum creatinine and hyponatremia, without increasing urine output. [source] A national evaluation of school breakfast clubs: evidence from a cluster randomized controlled trial and an observational analysisCHILD: CARE, HEALTH AND DEVELOPMENT, Issue 5 2004I. Shemilt Abstract Study objective To measure the health, educational and social impacts of breakfast club provision in schools serving deprived areas across England. Design A cluster randomized controlled trial and an observational analysis. Setting England, the UK. Intervention: funding to establish a school-based breakfast club vs. control (no funding). Main results Intention to treat analysis showed improved concentration (Trail Making Test Part A) amongst the intervention group at 3 months. Fewer pupils within the intervention group reported having skipped classes within the last month and fewer pupils within the intervention group reported having skipped 1 or more days of school within the last month at 1 year. Observational analysis at 1 year showed a higher proportion of primary-aged breakfast club attendees reported eating fruit for breakfast in comparison to non-attendees. A higher proportion of breakfast club attendees had borderline or abnormal conduct and total difficulties scores (primary-aged pupils) and prosocial score (secondary-aged pupils). Conclusions Analyses revealed a mixed picture of benefit and apparent disbenefit. This study illustrated the challenges of evaluating a complex intervention in which the evaluators had less control than is usual in randomized trials over recruitment, eligibility checking and implementation. If the impact of new policy initiatives is to be assessed using the most robust forms of evaluation, social policy needs to be organized so that evaluations can be constructed as experiments. This is likely to prove most difficult where the perceived value of implementing an intervention rapidly is high. [source] Airway smooth muscle chemokine receptor expression and function in asthmaCLINICAL & EXPERIMENTAL ALLERGY, Issue 11 2009R. Saunders Summary Background Chemokine receptors play an important role in cell migration and wound repair. In asthma, CCR3 and 7 are expressed by airway smooth muscle (ASM) and CCR7 has been implicated in the development of ASM hyperplasia. The expression profile of other chemokine receptors by ASM and their function needs to be further explored. Objective We sought to investigate ASM chemokine receptor expression and function in asthma. Methods ASM cells were derived from 17 subjects with asthma and 36 non-asthmatic controls. ASM chemokine receptor expression was assessed by flow cytometry and immunofluorescence. The function of chemokine receptors expressed by more than 10% of ASM cells was investigated by intracellular calcium measurements, chemotaxis, wound healing, proliferation and survival assays. Results In addition to CCR3 and 7, CXCR1, 3 and 4 were highly expressed by ASM. These CXC chemokine receptors were functional with an increase in intracellular calcium following ligand activation and promotion of wound healing [CXCL10 (100 ng/mL) 34 ± 2 cells/high-powered field (hpf) vs. control 29 ± 1; P=0.03; n=8]. Spontaneous wound healing was inhibited by CXCR3 neutralizing antibody (mean difference 7 ± 3 cells/hpf; P=0.03; n=3). CXC chemokine receptor activation did not modulate ASM chemotaxis, proliferation or survival. No differences in chemokine receptor expression or function were observed between ASM cells derived from asthmatic or non-asthmatic donors. Conclusions Our findings suggest that the chemokine receptors CXCR1, 3 and 4 modulate some aspects of ASM function but their importance in asthma is uncertain. [source] Relationship of peak growth hormone to cardiovascular parameters, waist circumference, lipids and glucose in HIV-infected patients and healthy adultsCLINICAL ENDOCRINOLOGY, Issue 6 2009Janet Lo Summary Objective, Relative growth hormone (GH) deficiency is highly prevalent in patients with HIV. The purpose of this study was to investigate relationships of GH to metabolic and anthropometric parameters in HIV patients and non-HIV controls. Design, Peak GH and metabolic parameters were assessed in a cross-sectional study of 191 HIV patients and 62 age and BMI-matched healthy controls. Methods, Peak GH was assessed by GHRH/arginine stimulation testing. Results, HIV patients demonstrated similar BMI, but increased waist circumference (WC) and reduced peak GH to GHRH/arginine compared with control subjects [median = 12·4 (interquartile range: 6·3,24·8) vs. 21·3 (8·8, 34·5) ,g/l, P = 0·006, HIV vs. control]. Among HIV and non-HIV groups, peak GH was inversely associated with WC (rho = ,0·44, P < 0·0001; rho = ,0·63, P < 0·0001; HIV patients and controls, respectively), blood pressure (rho = ,0·17, P = 0·02; rho = ,0·36, P = 0·004), triglycerides (rho = ,0·37, P < 0·0001; rho = ,0·43, P = 0·001), glucose (rho = ,0·34, P < 0·0001; rho = ,0·30, P = 0·02), insulin (rho = ,0·43, P < 0·0001; rho = ,0·60, P < 0·0001) and CRP (rho = ,0·29, P < 0·0001; rho = ,0·59, P < 0·0001). Among HIV patients, the inverse association between peak GH and fasting glucose remained significant (, = ,0·006 mmol/l change in glucose per ,g/l change in GH, P = 0·004) controlling for age, gender, race, BMI, WC, protease inhibitor (PI) and nucleoside reverse transcriptase inhibitors. Similarly, the inverse association between peak GH and triglycerides remained significant (, = ,0·01 mmol/l change in triglycerides per ,g/l change in GH, P = 0·02) controlling for age, gender, race, BMI, WC, PI and lipid-lowering medications. HIV men with peak GH < 7·5 ,g/l demonstrated higher BMI, WC, SBP, triglycerides, glucose and CRP. Conclusions, Reduced GH secretion is independently associated with dyslipidaemia and higher glucose, among HIV patients with abdominal fat accumulation. [source] Childhood life events and childhood trauma in adult patients with depressive, anxiety and comorbid disorders vs. controlsACTA PSYCHIATRICA SCANDINAVICA, Issue 1 2010J. G. F. M. Hovens Hovens JGFM, Wiersma JE, Giltay EJ, van Oppen P, Spinhoven P, Penninx BWJH, Zitman FG. Childhood life events and childhood trauma in adult patients with depressive, anxiety and comorbid disorders vs. controls. Objective:, To investigate the association between childhood life events, childhood trauma and the presence of anxiety, depressive or comorbid anxiety and depressive disorders in adulthood. Method:, Data are from 1931 adult participants in the Netherlands Study of Depression and Anxiety (NESDA). Childhood life events included divorce of parents, early parental loss and ,placed in care', whereas childhood trauma was assessed as experienced emotional neglect, psychological, physical and sexual abuse prior to age 16. Results:, Childhood life events were not associated with psychopathology, except for ,placed in care' in the comorbid group. All types of childhood trauma were increasingly prevalent in the following order: controls, anxiety, depression, and comorbid group (P < 0.001). The higher the score was on the childhood trauma index, the stronger the association with psychopathology (P < 0.001). Conclusion:, Childhood trauma rather than childhood life events are related to anxiety and depressive disorders. The strong associations with the comorbid group suggest that childhood trauma contributes to the severity of psychopathology. Our study underscores the importance of heightened awareness of the possible presence of childhood trauma, especially in adult patients with comorbid anxiety and depressive disorders. [source] Association of aldose reductase gene Z+2 polymorphism with reduced susceptibility to diabetic nephropathy in Caucasian Type 1 diabetic patientsDIABETIC MEDICINE, Issue 8 2004M. Lajer Abstract Aims The Z,2 allele of the (AC)n polymorphism in the aldose reductase gene (ALR2) confers increased risk of microvascular diabetic complications, whereas the Z+2 allele has been proposed to be a marker of protection. However data are conflicting. Therefore, we investigated whether this polymorphism is associated with diabetic nephropathy and retinopathy in Type 1 diabetes mellitus in a large case,control study and a family-based analysis. Methods A total of 431 Type 1 diabetic patients with diabetic nephropathy and 468 patients with longstanding Type 1 diabetes and persistent normoalbuminuria were genotyped for the case,control study. In addition, 102 case trios and 98 control trios were genotyped for a family-based study. Results Thirteen different alleles were identified. In the case,control study, the Z+2 allele frequency was significantly higher in the normoalbuminuric diabetic than in patients with diabetic nephropathy (0.17 vs. 0.11, P = 0.008), suggesting a protective function of the Z+2 allele. No significant increase in the frequency of the putative risk allele Z,2 was found in patients with diabetic nephropathy vs. controls (0.39 vs. 0.36). No association with diabetic retinopathy was found. Although the results of the transmission of the Z,2 and Z+2 alleles in the independent family-based study were consistent with the association study, the number of informative families was limited and thus differences were not statistically significant. Conclusions The Z+2 allele of the ALR2 promoter polymorphism is associated with a reduced susceptibility to diabetic nephropathy in Danish Type 1 diabetic patients, suggesting a minor role for the polyol pathway in the pathogenesis of diabetic kidney disease. No association of the ALR2 polymorphism with diabetic retinopathy was found. [source] Changes of gallbladder and gastric dynamics in patients with acute hepatitis AEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 7 2001P. Portincasa Transient alterations of gallbladder morphology and dynamics have been reported in patients with during acute hepatitis A. The presence of dyspepsia also suggests involvement of gastric motility. During a 60-day follow-up, we investigated gallbladder and gastric motility in relation to dyspepsia in acute viral hepatitis A patients. Twenty patients were assessed at referral (day 0) and at days 7, 21, 42 and 60 and compared with 20 healthy volunteers. Gallbladder morphology and motility and gastric motility were assessed in the fasting and postprandial period by functional ultrasonography using a liquid test meal. Dyspeptic symptoms were scored. At day 0, fasting gallbladder volume was 5·9 ± 1·3 mL, 32·6 ± 4·6 mL, and 21·5 ± 1·9 mL (mean ±,SE) in patients with gallbladder sludge (n = 7), without sludge (n = 13) and controls, respectively (P < 0·05 in sludge vs. no sludge and controls; P < 0·05 in no sludge vs. controls, anova). Small fasting gallbladder volume in patients with sludge increased and sludge disappeared within 7 days. At day 0, patients with sludge also had increased thickness of fasting gallbladder wall and increased serum transaminase levels compared with patients without sludge and controls. Gallbladder contraction was similar in patients and controls. However, patients had delayed gastric emptying, which positively correlated with dyspepsia score. Gallbladder morphological changes observed in the acute phase of hepatitis A are transient and are associated with hepatocellular damage. Gastric emptying is delayed during the first week of disease and is associated with dyspeptic symptoms. [source] Helicobacter pylori Infection and Gastric Autoimmune Diseases: Is There a Link?HELICOBACTER, Issue 6 2003Fabio Presotto ABSTRACT Background.,Helicobacter pylori is thought to be involved in atrophic body gastritis. We explored the prevalence of H. pylori infection in asymptomatic subjects with gastric parietal cell antibodies, as well as in patients with pernicious anemia, to evaluate a possible role of H. pylori gastric infection in gastric autoimmunity. Patients and Methods., We studied 79 consecutive asymptomatic subjects with parietal cell antibodies, 24 patients with pernicious anemia, and 66 parietal cell antibody-negative controls. All patients underwent gastric biopsies for histology and detection of H. pylori. Red blood cell count and volume, serum levels of gastrin, pepsinogen I, iron, folic acid, vitamin B12, and circulating antibodies to H. pylori and to intrinsic factor were also determined. Results., We found an atrophic body gastritis in 14 of the 79 asymptomatic subjects with parietal cell antibodies (18%) and in 2 of the 66 controls (3%) (p = .01). Mean levels of gastrin were increased (p < .0001), while those of pepsinogen were reduced (p < .001) compared with controls. H. pylori was identified at the gastric level and/or circulating anti- H. pylori antibodies were detected in 46 parietal cell antibody-positive subjects (58%) compared with 26 controls (39%) (p = .03). In patients with pernicious anemia we found an atrophic body gastritis in 18 of 24 cases (75%) (p < .001 vs. controls). Mean levels of gastrin were markedly increased (p < .0001) and those of pepsinogen I decreased (p < .0001) relative to controls. Only five of these patients (21%) had evidence of H. pylori infection compared with 46 of the parietal cell antibody-positive subjects (58%) (p = .003) and 26 of the controls (39%). Considering all patients with gastric autoimmunity (i.e. with parietal cell antibodies and/or with pernicious anemia), H. pylori was found in 44 of 72 of those without atrophy (61%) but in 6 of 31 with gastric body atrophy (19%) (p < .001), indicating that H. pylori infection is greatly reduced when gastric acid secretion decreases. Conclusions., The frequent detection of H. pylori infection in subjects with early gastric autoimmunity, indicated by the presence of parietal cell antibodies, suggests that H. pylori could have a crucial role in the induction and/or the maintenance of autoimmunity at the gastric level. [source] Revisiting Autonomic Dysfunction in End-Stage Renal Disease PatientsHEMODIALYSIS INTERNATIONAL, Issue 3 2003Jocemir R. Lugon Background:,Autonomic dysfunction is frequent in end-stage renal disease (ESRD) patients, but both the relative involvement of the parasympathetic and sympathetic branches and the role of antihypertensive drugs in this setting are still controversial. The present study addressed these issues employing a battery of standard noninvasive cardiovascular autonomic tests. Methods:,Sympathetic (S) function was evaluated by responses of both systolic blood pressure (BP) to passive tilting and diastolic BP to handgrip; parasympathetic (P) function, through the respiratory sinus arrhythmia test and the heart rate response to the 4-s unloaded exercise test. Additional tests influenced by both branches of the autonomic system (P + S) were accomplished by the assessment of heart rate response to the Valsalva maneuver, handgrip, and tilting. Results:,Studied subjects belonged to one of the three groups: ESRD patients not requiring BP medications (n = 11; 8 men, 3 women); ESRD patients receiving antihypertensive therapy (n = 36; 21 men, 15 women); and apparently healthy controls (n = 15; 10 men, 5 women). When the variables grouped according to the branch of the autonomic nervous system predominantly probed were analyzed, only the frequency of impaired sympathetic autonomic responses was higher in ESRD patients not receiving BP drugs compared to controls (55 vs. 23%, P = 0.040). In contrast, when ESRD patients receiving BP drugs were compared to controls, the differences became significant in S, P, and P + S tests (46 vs. 23%, P = 0.045; 22 vs. 3%, P = 0.020; and 34 vs. 13%, P = 0.010, respectively). With the criterion of more than one positive finding in any of the variables examined for diagnosing autonomic dysfunction, the prevalence of autonomic dysfunction was 20% in controls, 64% in ESRD patients not receiving BP drugs (P = 0.005 vs. controls), and 67% in ESRD patients receiving BP drugs (P = 0.043 vs. controls). Conclusions:,ESRD continues to be associated with a high prevalence of autonomic dysfunction. ESRD patients receiving BP drugs were found to have detectable impairment in the entire autonomic system in contrast to those not receiving BP drugs in whom inadequate responses were restricted to the sympathetic branch. [source] Endogenous ursodeoxycholic acid and cholic acid in liver disease due to cystic fibrosisHEPATOLOGY, Issue 6 2004Jeffery L. Smith Focal biliary cirrhosis causes significant morbidity and mortality in cystic fibrosis (CF). Although the mechanisms of pathogenesis remain unclear, bile acids have been proposed as potential mediators of liver injury. This study examined bile acid composition in CF and assessed altered bile acid profiles to determine if they are associated with incidence and progression of liver injury in CF-associated liver disease (CFLD). Bile acid composition was determined by gas,liquid chromatography/mass spectrometry in bile, urine, and serum samples from 30 children with CFLD, 15 children with CF but without liver disease (CFnoLD), and 43 controls. Liver biopsies from 29 CFLD subjects were assessed histologically by grading for fibrosis stage, inflammation, and disruption of the limiting plate. A significantly greater proportion of endogenous biliary ursodeoxycholic acid (UDCA) was demonstrated in CFnoLD subjects vs. both CFLD subjects and controls (2.4- and 2.2-fold, respectively; ANOVA, P = .04), and a 3-4 fold elevation in endogenous serum UDCA concentration was observed in both CFLD subjects and CFnoLD subjects vs. controls (ANOVA, P < .05). In CFLD, there were significant correlations between serum cholic acid and hepatic fibrosis, inflammation, and limiting plate disruption as well as the ratio of serum cholic acid/chenodeoxycholic acid to hepatic fibrosis, inflammation, and limiting plate disruption. In conclusion, elevated endogenous UDCA in CFnoLD suggests a possible protective role against liver injury in these patients. The correlation between both cholic acid and cholic acid/chenodeoxycholic acid levels with histological liver injury and fibrosis progression suggests a potential monitoring role for these bile acids in CFLD. (HEPATOLOGY 2004;39:1673,1682.) [source] Sensorimotor network rewiring in mild cognitive impairment and Alzheimer's diseaseHUMAN BRAIN MAPPING, Issue 4 2010Federica Agosta Abstract This study aimed at elucidating whether (a) brain areas associated with motor function show a change in functional magnetic resonance imaging (fMRI) signal in amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD), (b) such change is linear over the course of the disease, and (c) fMRI changes in aMCI and AD are driven by hippocampal atrophy, or, conversely, reflect a nonspecific neuronal network rewiring generically associated to brain tissue damage. FMRI during the performance of a simple motor task with the dominant right-hand, and structural MRI (i.e., dual-echo, 3D T1-weighted, and diffusion tensor [DT] MRI sequences) were acquired from 10 AD patients, 15 aMCI patients, and 11 healthy controls. During the simple-motor task, aMCI patients had decreased recruitment of the left (L) inferior frontal gyrus compared to controls, while they showed increased recruitment of L postcentral gyrus and head of L caudate nucleus, and decreased activation of the cingulum compared with AD patients. Effective connectivity was altered between primary sensorimotor cortices (SMC) in aMCI patients vs. controls, and between L SMC, head of L caudate nucleus, and cingulum in AD vs. aMCI patients. Altered fMRI activations and connections were correlated with the hippocampal atrophy in aMCI and with the overall GM microstructural damage in AD. Motor-associated functional cortical changes in aMCI and AD mirror fMRI changes of the cognitive network, suggesting the occurrence of a widespread brain rewiring with increasing structural damage rather than a specific response of cognitive network. Hum Brain Mapp, 2010. © 2009 Wiley-Liss, Inc. [source] Elevated lipoprotein (a) and apolipoprotein B to AI ratio in South Asian patients with ischaemic stroke,INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 11 2007K. M. Sharobeem Summary Background:, Stroke is a continuing cause of excess cardiovascular disease (CVD) mortality amongst migrants from the Indian subcontinent (South Asians) living in Britain. However, little is known about the dyslipidaemia associated with stroke in South Asians. In particular, the highly atherogenic lipoprotein (a) [Lp(a)] and high apolipoprotein (Apo) B to AI ratio are emerging risk factors for CVD. Methods:, Using a case,control study, we investigated features of the dyslipidaemia in South Asian patients with stroke compared with South Asian subjects with no history of clinically detectable stroke. We studied 55 consecutive South Asian patients with ischaemic stroke (confirmed on computerised scan of the brain) and 85 controls. Results:, The stroke patients were significantly older than controls (65.2 vs. 59.8 years, p = 0.001), but were similarly matched for male gender (63.6 vs. 61.2%), smoking habit (20.7 vs. 18.1%) and presence of type 2 diabetes (25.5 vs. 19.3%). There were no differences between serum total cholesterol (p = 0.07) and high-density lipoprotein cholesterol (p = 0.08) between the groups, but stroke patients had higher serum triglycerides (p = 0.005). Mean [95% confidence interval (CI)] Apo B to AI ratio was higher amongst stroke patients [1.0 (0.9,1.0) vs. 0.7 (0.7,0.75), p < 0.001]. Similarly, geometric mean serum Lp(a) was significantly higher (p = 0.037) in stroke patients [19.9 mg/dl (14.0,28.5)] vs. controls [15.1 mg/dl (11.4,20.1)]. On logistic regression, stroke was independently associated with age and Apo B to AI ratio (p < 0.01). Conclusion:, The present study suggests that Lp(a) and the Apo B to AI ratio are associated with ischaemic stroke in South Asians. A prospective analysis is needed to elucidate the role of Lp(a), Apo B and AI as risk factors for ischaemic stroke in this population, as well as the effects of intervention. [source] Report: Cutaneous disorders in uremic patients on hemodialysis: an Egyptian case-controlled studyINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 9 2010Enas A. S. Attia MD Summary Background, We studied the prevalence of mucocutaneous disorders in uremic adults and children on hemodialysis (HD) vs. controls, in Egypt. Methods, A total of 206 Egyptians with uremia (163 adults and 43 children) undergoing HD, and 199 healthy controls (161 adults and 38 children), were examined for mucocutaneous abnormalities. Results, Specific cutaneous diseases associated with renal insufficiency were found in five adults, including acquired perforating dermatosis and pseudo-porphyria. Non-specific abnormalities included xerosis (54%), pallor (42.2%), nail changes (34.9%), hair changes (34%), pruritus (32%), hyper-pigmentation (22.2%), coated tongue (14.1%), ecchymosis (1.5%), and gingival hypertrophy (1.5%). Disorders found significantly more often in uremics than controls included pallor, nail changes, hair changes, pruritus, hyper-pigmentation and coated tongue in adults (P < 0.05), and nail changes, hair changes, and hyper-pigmentation in children (P < 0.05). The prevalence of each mucocutaneous abnormality was similar in uremic adults and children except for pallor [more common in adults (P = 0.001)], and hyper-pigmentation [more common in children (P = 0.003)]. A greater number of hepatitis C virus-positive than -negative adult uremics had hyper-pigmentation (P < 0.05), and more diabetic uremics had pruritus than did non-diabetics (P < 0.05). Conclusion, Mucocutaneous disorders occur in adults and children with uremia, some of which are specific associations with the underlying renal disease. Occurrence of some of the non-specific abnormalities, such as xerosis, ecchymosis, and gingival hypertrophy, may be coincidental or associated with factors other than renal insufficiency. [source] Aberrant expression of TRAIL in B chronic lymphocytic leukemia (B-CLL) cellsJOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2005Paola Secchiero Analysis of peripheral blood (>85% CD19+/CD5+ B) lymphocytes, obtained from 44 patients affected by B chronic lymphoid leukemia (B-CLL), showed that surface TNF-related apoptosis inducing ligand (TRAIL) was expressed in all samples and at higher levels with respect to unfractionated lymphocytes and purified CD19+ B cells, obtained from 15 normal blood donors. Of note, in a subset of B-CLL samples, the addition to B-CLL cultures of a TRAIL-R1-Fc chimera, which binds at high affinity to surface TRAIL, significantly decreased the percentage of viable cells with respect to untreated control B-CLL cells, suggesting that surface TRAIL may play an unexpected role in promoting B-CLL cell survival. In spite of the majority of B-CLL lymphocytes expressed variable surface levels of "death receptors" TRAIL-R1 and TRAIL-R2, the addition in culture of recombinant TRAIL increased (>20% vs. controls) the degree of spontaneous apoptosis in only 11/44 of the B-CLL samples, had no effect in 19/44, while it significantly increased leukemic cell survival in 14/44. Taken together, these findings suggest that an aberrant expression of TRAIL might contribute to the pathogenesis of B-CLL by promoting the survival in a subset of B-CLL cells. © 2005 Wiley-Liss, Inc. [source] | ||||||||||||||||||||||||||||||||||