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. myocardial infarction, percutaneous transluminal coronary angioplasty (including stenting), aortocoronary bypass, stroke and angiographically verified stenosis of peripheral arteries and cardiovascular (CV) death, in 191 patients with chronic kidney disease Stage V receiving hemodialysis therapy.At baseline, CD14+/TLR-4+ monocytes correlated significantly with age (r = 0.2; P = 0.007), high-sensitivity C-reactive protein (r = 0.2; P = 0.008) and mean arterial pressure (r = -0.2; P = 0.02 (...) TLR-4+ peripheral blood monocytes and cardiovascular events in patients with chronic kidney disease--a prospective follow-up study. Atherosclerosis is an inflammatory process mediated by circulating immune cells, including monocytes. There is accumulating evidence for the involvement of Toll-like receptor 4 (TLR-4) as a mediator of atherogenesis.We evaluated the association between CD14+/TLR-4+ monocytes in peripheral blood (flow cytometry) and future cardiovascular events (CVE), e.g
-Friday batch were coming off the long interdialytic interval, with possible medical problems (i.e. high increase in weight gain, bloodpressure, etc.). In spite of manifold difficulties (including road interruption and shortage of means of transportation, problems in establishing contact between patients and care personnel due to failure of phone and electronic communication and the limited number of available dialysis posts), no patient missed any scheduled HD session. This was obtained thanks (...) emergency in the aftermath of the earthquake that struck the Italian town of L'Aquila and a surrounding district, on Monday 6 April 2009, causing 308 deaths, some 1500 injured and 66,000 people to be displaced.The Dialysis Centre in the town did not collapse but was seriously damaged and out of action, making it necessary to move 88 patients on regular dialysis treatment to the closest available facilities to continue treatment. This was all the more urgent in that 45 patients of the Monday-Wednesday
Extrahepatic portal vein thrombosis after umbilical catheterization: is it a good choice for Rex shunt? Extrahepatic portal vein thrombosis (EHPVT) is an important cause of portal hypertension in children. Rex shunt has been used successfully to treat these patients.We report our experience in 19 infants and children (5 months to 14 years) with HPVT eligible for a mesenteric-portal surgical shunt with left internal jugular vein autograft. Eight children had idiopathic EHPVT, nine had post (...) -umbilical catheterization EHPVT, one had portal vein agenesis, and one had posttransplant EHPVT.It was possible to perform the Rex shunt in all patients except for 8 of 9 cases in the post-umbilical catheterization EHPVT group. A Warren procedure was performed in 4 of those patients and a proximal splenorenal shunt in 1. Current follow-up ranges from 3 to 26 months. Shunt thrombosis occurred in one patient with portal vein agenesis and associated cardiac anomaly. Portal hypertension has significantly
Vasorelaxation by extracts of Casimiroa spp. in rat resistance vessels and pharmacological study of cellular mechanisms. Casimiroa spp. are Mexican plants traditionally used for treatment of hypertension. To study their antihypertensive action, we determined the arterial dilatation induced by extracts from leaves and seeds of Casimiroa calderoniae F. Chiang & Medrano, Casimiroa edulis Llave et Lex, and Casimiroa pubescens Ramirez.The vascular effects of Casimiroa spp. extracts were investigated (...) caused a greater relaxation in comparison to those from leaves. The most active were the methanolic seed extracts of Casimiroa edulis (Ce8) and Casimiroa pubescens (Cp12). To study the pharmacological mechanisms of vasodilatation we used various inhibitors selective to different receptor subtypes or intracellular enzymes. The vasorelaxant effect of Ce8 (20 μg/ml) remained unaffected by the pretreatment with pyrilamine (10 μM), an antagonist of histamine H(1) receptors, but was inhibited by atropine
) and hypertensive ADPKD patients with eGFR < 60 mL/min/1.73 m(2) (P > 0.05). According to multiple regression analysis, predictors of AIx in ADPKD included age, height, heart rate and mean arterial pressure (P < 0.05). Vascular inflammatory markers were not predictors of AIx in ADPKD.Systemic vascular dysfunction, manifesting as an increase in AIx and vascular inflammation is evident in young normotensive ADPKD patients with preserved renal function. Vascular inflammation is not associated with elevated AIx (...) Peripheral augmentation index and vascular inflammation in autosomal dominant polycystic kidney disease. Cardiovascular disease is the leading cause of premature mortality in autosomal dominant polycystic kidney disease (ADPKD). We examined peripheral augmentation index (AIx) as a measure of systemic vascular function and circulating markers of vascular inflammation in patients with ADPKD.Fifty-two ADPKD patients with hypertension and estimated glomerular filtration rate (eGFR) <60 mL/min/1.73
of inappropriate drug use was 13.3% (contraindication, 0.8%): it was 52.5% (4.5%) in those with an eGFR of 30-59 and 96% (48%) in those <30 mL/min/1.73 m(2). Antihypertensive agents, fibrates and psycholeptics accounted for most of the drugs with dosing recommendations and antidiabetic agents and antihistamines for those contraindicated. Individuals at risk were more likely to be men, older, and under treatment for hypertension or hypercholesterolemia. Exposure to either risk was independently related (...) to higher all-cause mortality (hazard ratio 1.4, 95% confidence interval 1.0-1.9) in participants with eGFR <60 mL/min/1.73 m(2).Contraindicated drug prescription was uncommon but >10% of the population took drugs requiring renal dosing adjustments. Regular monitoring of eGFR may prevent excess mortality associated with inappropriate drug prescription in the elderly.
. Among the congenital left-sided obstructive lesions, four levels of obstruction coexisted in 3 cases (7.9%), three levels in 10 cases (26.3%), and two levels in 25 cases (65.8%). Supra-annular mitral stenosis caused by a supravalvular mitral ring was diagnosed in 1 case. Mitral valvular stenosis was diagnosed in 24 cases including a parachute mitral valve (4 cases), a double-orifice mitral valve (1 case), and partly fused thickened mitral valvular leaflets (19 cases). Subaortic stenosis (...) type (2 cases). Coarctation of the aorta was diagnosed in 26 cases. Of these, focal coarctation was described in 15 cases, long segment coarctation in 7 cases, and dysplastic isthmus and/or descending aorta in 4 cases. Secondary changes in Shone's complex manifested as left atrial dilation (26 cases), left ventricular hypertrophy (26 cases), and pulmonary hypertension (19 cases). Echocardiography plays an important role in the diagnosis of atypical Shone's complex, in comprehensive evaluation
bloodpressure, anaerobic cerebral metabolism, excessive brain tissue oxygenation, elevated brain temperature). Finally, extracellular fluid neurofilament heavy chain levels were of prognostic value, predicting mortality with an odds ratio of 7.68 (confidence interval 2.15-27.46, P = 0.001). In conclusion, this study describes the discovery of Pavlov's enterokinase in the human brain, a novel neuronal proteolytic pathway that gives rise to specific protein biomarkers (NfH(476-986) and Nf(H476-1026 (...) In vivo monitoring of neuronal loss in traumatic brain injury: a microdialysis study. Traumatic brain injury causes diffuse axonal injury and loss of cortical neurons. These features are well recognized histologically, but their in vivo monitoring remains challenging. In vivo cortical microdialysis samples the extracellular fluid adjacent to neurons and axons. Here, we describe a novel neuronal proteolytic pathway and demonstrate the exclusive neuro-axonal expression of Pavlov's enterokinase
clinically relevant inhibitory effects on amine oxidases, aminotransferases, and decarboxylases, and it lowers pyridoxal phosphate levels. It commonly causes pyridoxal deficiency, weight gain, sedation, and sexual dysfunction, but only rarely causes hepatic damage and failure, or neurotoxicity. The adverse effects and difficulties with monoamine oxidase inhibitors are less than previously believed or estimated, including a lower risk of hypertension, because the tyramine content in foods is now lower (...) . Potent norepinephrine reuptake inhibitors have a strong protective effect against tyramine-induced hypertension. The newly discovered trace amine-associated receptors probably mediate the pressor response. The therapeutic potential of tranylcypromine and L-dopa in depression and Parkinson disease is worthy of reassessment. Monoamine oxidase inhibitors are not used to an extent proportionate with their benefits; medical texts and doctors' knowledge require a major update to reflect the evidence
scale.A novel analysis technique is proposed for detecting the signature of somatic gene conversion from SNP microarray data. The Wellcome Trust Case Control Consortium has gathered SNP microarray data for two control populations and cohorts for bipolar disorder (BD), cardiovascular disease (CAD), Crohn's disease (CD), hypertension (HT), rheumatoid arthritis (RA), type-1 diabetes (T1D) and type-2 diabetes (T2D). Using the new analysis technique, the seven disease cohorts are analyzed to identify (...) Evidence for somatic gene conversion and deletion in bipo- lar disorder, Crohn's disease, coronary artery disease, hyper- tension, rheumatoid arthritis, type-1 diabetes, and type-2 diabetes. During gene conversion, genetic information is transferred unidirectionally between highly homologous but non-allelic regions of DNA. While germ-line gene conversion has been implicated in the pathogenesis of some diseases, somatic gene conversion has remained technically difficult to investigate on a large
, smoking, history of cardiovascular disease, obesity, hypertension, hemoglobin A(1c), diabetes duration, total cholesterol, use of statins, abnormal ankle-brachial index, estimated glomerular filtration rate (eGFR), and proteinuria. The adjusted HRs for logarithmically transformed serum VAP-1 were 5.83 (95% CI 1.17-28.97) for cardiovascular mortality, 6.32 (95% CI 1.25-32.00) for mortality from cardiovascular and diabetic causes, and 17.24 (95% CI 4.57-65.07) for cancer mortality. There were four (...) 2003, we enrolled 661 type 2 diabetic subjects at National Taiwan University Hospital. Serum VAP-1 in the samples obtained at enrollment was measured by time-resolved immunofluorometric assay. The vital status of all subjects was ascertained by linking their data with computerized death certificates in Taiwan.The medium follow-up period was 10.4 years. Subjects with serum VAP-1 in the highest tertile had a hazard ratio (HR) of 2.19 (95% CI 1.17-4.11) for all-cause mortality adjusted for age, sex
Microsomal Prostaglandin E2 Synthase-1 Modulates the Response to Vascular Injury. Microsomal (m) prostaglandin (PG) E₂ synthase (S)-1 catalyzes the formation of PGE₂ from PGH₂, a cyclooxygenase product that is derived from arachidonic acid. Previous studies in mice suggest that targeting mPGES-1 may be less likely to causehypertension or thrombosis than cyclooxygenase-2-selective inhibition or deletion in vivo. Indeed, deletion of mPGES-1 retards atherogenesis and angiotensin II-induced aortic (...) . This raises for consideration the therapeutic potential of mPGES-1 inhibitors as adjuvant therapy for percutaneous coronary intervention.
Distortion of Axonal Cytoskeleton: an Early Sign of Glaucomatous Damage. Glaucoma damages the retinal nerve fiber layer (RNFL). The purpose of this study was to investigate the distribution of major cytoskeleton components, F-actin, microtubules (MTs), and neurofilaments (NFs), in the RNFL during the development of glaucoma. methods: Intraocular hypertension was induced in a rat model by laser photocoagulation of the trabecular meshwork. Retinas were obtained after 2 to 3.5 weeks of treatment (...) RNFL. Glaucoma causes alteration of the cytoskeleton in the RNFL. F-actin is the most sensitive component in its response to stress on the retina. An increase in the number of nuclei in the RNFL may be an early sign of glaucomatous damage.
Up-regulation of arginase II contributes to pulmonary vascular endothelial cell dysfunction during experimental pulmonary embolism. Pulmonary embolism (PE) causes pulmonary hypertension by mechanical obstruction and constriction of non-obstructed vasculature. We tested if experimental PE impairs pulmonary vascular endothelium-dependent dilation via activation of arginase II. Experimental PE was induced in male Sprague-Dawley rats by infusing 25 μm microspheres in the right jugular vein (...) , producing moderate pulmonary hypertension. Shams received vehicle injection. Pulmonary arterial rings were isolated after 18 h and isometric tensions were determined. Dilations were induced with acetylcholine, calcium ionophore A23187 or nitroglycerin (NTG) in pre-contracted rings (phenylephrine). Protein expression was assessed by Western blot and immunohistochemistry. Arginase activity was inhibited by intravenous infusion of N(w)-hydroxy-nor-l-arginine (nor-NOHA). l-Arginine supplementation was also
deformity correction and can be treated by elevating the mean arterial bloodpressure or by decreasing the amount of correction. However, other reversible etiologies of neurologic compromise theoretically exist as well. SK is associated with degenerative changes in the intervertebral disc, and an intraoperative neural compromise could be due to disc herniations during application of powerful deformity corrective forces.The patient's medical history, physical examination, and diagnostic studies were (...) retrospectively reviewed.We encountered a previously unreported complication of intraoperative disc herniation causing neural compromise during deformity correction of SK. A 17-year-old patient developed a T10-T11 herniated nucleus pulposus during posterior spinal fusion for SK. We postulate that abnormal intervertebral disc degeneration associated with SK and significant pressure on the middle spinal column during application of the cantilever correction maneuver contributed to the disc herniation, which
TRPC6 Enhances Angiotensin II-induced Albuminuria. Mutations in the canonical transient receptor potential cation channel 6 (TRPC6) are responsible for familial forms of adult onset focal segmental glomerulosclerosis (FSGS). The mechanisms by which TRPC6 mutations cause kidney disease are not well understood. We used TRPC6-deficient mice to examine the function of TRPC6 in the kidney. We found that adult TRPC6-deficient mice had BP and albumin excretion rates similar to wild-type animals (...) . Glomerular histomorphology revealed no abnormalities on both light and electron microscopy. To determine whether the absence of TRPC6 would alter susceptibility to hypertension and renal injury, we infused mice with angiotensin II continuously for 28 days. Although both groups developed similar levels of hypertension, TRPC6-deficient mice had significantly less albuminuria, especially during the early phase of the infusion; this suggested that TRPC6 adversely influences the glomerular filter. We used
hernia.Forty-two patients (mean age, 49.6 years) underwent incisional herniorrhaphy (mean area, 99.9 cm(2)) following renal transplantation (26 cadaveric donor renal, 12 combined renal-pancreas, and 4 living related donor renal) from January 1, 1995, to December 31, 2005. Using various techniques, hernia repairs were performed on average 36.4 months following transplantation. Diabetes mellitus was a frequent cause of end-stage renal disease (16 patients), followed by polycystic kidney disease (6 patients (...) ), focal segmental glomerular sclerosis (3 patients), hypertension (2 patients), Alport syndrome (2 patients), and IgA nephropathy (2 patients), with 11 patients having lupus or glomerulonephritis. Four patients developed cellulitis, 2 patients required mesh removal, and 1 patient was admitted for abscess drainage and intravenous antibiotics. Fourteen patients had recurrence of incisional hernias, with 3 patients experiencing 2 recurrences and 1 patient experiencing 4 recurrences.To our knowledge
Ten-year experience with renal artery in-stent stenosis. Atherosclerotic renal artery stenosis (RAS) is the most common cause of secondary hypertension. Renal stenting has become the treatment of choice for RAS in most centers. Primary patency of RAS is well defined, but limited data are available on outcomes of secondary interventions for treatment of in-stent restenosis.This was a retrospective analysis of a 10-year experience with renal artery stenting in patients presenting with recurrent (...) symptomatic stenosis. End points included freedom from tertiary procedures, change in baseline renal function by ≥20% measured by estimated glomerular filtration rate (eGFR), patency confirmed by duplex imaging, long-term hypertension response, freedom from hemodialysis, and survival.We reviewed 948 patients with 1150 treated renal arteries. Of these, 107 patients (122 renal stents) returned with symptomatic in-stent restenosis and required reintervention (target vessel revascularization [TVR] rate, 10.6
by age, sex, race, and BMI-Z with 100 controls. Patients with BBS and controls were compared for differences in body composition (dual-energy x-ray absorptiometry, abdominal magnetic resonance imaging), bloodpressure Z-score (BP-Z; standardized for age, sex, and height), and fasting concentrations of leptin, lipids, insulin, and glucose. Patients with BBS were also compared by genotype.Leptin, triglycerides, intraabdominal fat mass, and diastolic BP-Z were significantly greater in patients with BBS (...) with BBS may indicate a predisposition for metabolic complications, including hypertension and hypertriglyceridemia. The observation of disparate results in the BBS10 vs. BBS1 mutation groups is the first demonstration of physiological differences among patients with BBS caused by mutations in distinct genes. These results suggest that the obesity of BBS is distinct from nonsyndromic obesity.