Renalase Gene Polymorphisms in Patients With Type 2 Diabetes, Hypertension and Stroke

Renalase is a novel, recently identified, flavin adenine dinucleotide-dependent amine oxidase. It is secreted by the kidney and metabolizes circulating catecholamines. Renalase has significant hemodynamic effects, therefore it is likely to participate in the regulation of cardiovascular function.The aim of our study was to investigate the involvement of renalase gene polymorphisms in hypertension in type 2 diabetes patients. A total of 892 patients and 400 controls were genotyped with three SNPs in the renalase gene. The C allele of rs2296545 SNP was associated with hypertension (P < 0.01). For rs2576178 SNP, frequencies in hypertensive patients differed from controls, but not from normotensive patients. For rs10887800 SNP, the differences in the G allele frequencies were observed in hypertensive patients with stroke, with 66% of patients being GG homozygotes. To confirm observed association we later genotyped 130 stroke patients without diabetes. The OR for risk allele was 1.79 (95% CI 1.33–2.41). In conclusion, the renalase gene polymorphism was associated with hypertension in type 2 diabetes patients. The most interesting result is a strong association of the rs10887800 polymorphism with stroke in patients with and without diabetes. The G allele of this polymorphism might thus be useful in identifying diabetes patients at increased risk of stroke

Exploring haemodynamics of haemodialysis using extrema points analysis model

Background: Haemodialysis is a form of renal replacement therapy used to treat patients with end stage renal failure. It is becoming more appreciated that haemodialysis patients exhibit higher rates of multiple end organ damage compared to the general population. There is also a strong emerging evidence that haemodialysis itself causes circulatory stress. We aimed at examining haemodynamic patterns during haemodialysis using a new model and test that model against a normal control. Methods: We hypothesised that blood pressures generated by each heart beat constantly vary between local peaks and troughs (local extrema), the frequency and amplitude of which is regulated to maintain optimal organ perfusion. We also hypothesised that such model could reveal multiple haemodynamic aberrations during HD. Using a non-invasive cardiac output monitoring device (Finometer®) we compared various haemodynamic parameters using the above model between a haemodialysis patient during a dialysis session and an exercised normal control after comparison at rest. Results: Measurements yielded 29,751 data points for each haemodynamic parameter. Extrema points frequency of mean arterial blood pressure was higher in the HD subject compared to the normal control (0.761Hz IQR 0.5-0.818 vs 0.468Hz IQR 0.223-0.872, P < 0.0001). Similarly, extrema points frequency of systolic blood pressure was significantly higher in haemodialysis compared to normal. In contrary, the frequency of extrema points for TPR was higher in the normal control compared to HD (0.947 IQR 0.520-1.512 vs 0.845 IQR 0.730-1.569, P < 0.0001) with significantly higher amplitudes. Conclusion: Haemodialysis patients potentially exhibit an aberrant haemodynamic behaviour characterised by higher extrema frequencies of mean arterial blood pressure and lower extrema frequencies of total peripheral resistance. This, in theory, could lead to higher variation in organ perfusion and may be detrimental to vulnerable vascular beds

Mitochondrial polymorphisms in rat genetic models of hypertension

Hypertension is a complex trait that has been studied extensively for genetic contributions of the nuclear genome. We examined mitochondrial genomes of the hypertensive strains: the Dahl Salt-Sensitive (S) rat, the Spontaneously Hypertensive Rat (SHR), and the Albino Surgery (AS) rat, and the relatively normotensive strains: the Dahl Salt-Resistant (R) rat, the Milan Normotensive Strain (MNS), and the Lewis rat (LEW). These strains were used previously for linkage analysis for blood pressure (BP) in our laboratory. The results provide evidence to suggest that variations in the mitochondrial genome do not account for observed differences in blood pressure between the S and R rats. However, variants were detected among the mitochondrial genomes of the various hypertensive strains, S, SHR, and AS, and also among the normotensive strains R, MNS, and LEW. A total of 115, 114, 106, 106, and 16 variations in mtDNA were observed between the comparisons S versus LEW, S versus MNS, S versus SHR, S versus AS, and SHR versus AS, respectively. Among the 13 genes coding for proteins of the electron transport chain, 8 genes had nonsynonymous variations between S, LEW, MNS, SHR, and AS. The lack of any sequence variants between the mitochondrial genomes of S and R rats provides conclusive evidence that divergence in blood pressure between these two inbred strains is exclusively programmed through their nuclear genomes. The variations detected among the various hypertensive strains provides the basis to construct conplastic strains and further evaluate the effects of these variants on hypertension and associated phenotypes

Tobacco smoking, body mass index, hypertension, and kidney cancer risk in central and eastern Europe

In a case–control study of kidney cancer in four central European countries, with 1097 incident cases and 1476 controls, we found an increased risk for self-reported hypertension and for obesity. Additional unknown risk factors are likely to be responsible for the high rates of kidney cancer in this region

Carotid Baroreflex Activation: Past, Present, and Future

Electrical activation of the carotid baroreceptor system is an attractive therapy for the treatment of resistant hypertension. In the past, several attempts were made to directly activate the baroreceptor system in humans, but the method had to be restricted to a few selected patients. Adverse effects, the need for better electrical devices and better surgical techniques, and the lack of knowledge about long-term effects has greatly hampered developments in this area for many years. Recently, a new and promising device was evaluated in a multicenter feasibility trial, which showed a clinically and statistically significant reduction in office systolic blood pressure (>20 mm Hg). This reduction could be sustained for at least 2 years with an acceptable safety profile. In the future, this new device may stimulate further application of electrical activation of the carotid baroreflex in treatment-resistant hypertension

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Patterns of Interspecific Variation in the Heart Rates of Embryonic Reptiles

New non-invasive technologies allow direct measurement of heart rates (and thus, developmental rates) of embryos. We applied these methods to a diverse array of oviparous reptiles (24 species of lizards, 18 snakes, 11 turtles, 1 crocodilian), to identify general influences on cardiac rates during embryogenesis. Heart rates increased with ambient temperature in all lineages, but (at the same temperature) were faster in lizards and turtles than in snakes and crocodilians. We analysed these data within a phylogenetic framework. Embryonic heart rates were faster in species with smaller adult sizes, smaller egg sizes, and shorter incubation periods. Phylogenetic changes in heart rates were negatively correlated with concurrent changes in adult body mass and residual incubation period among the lizards, snakes (especially within pythons) and crocodilians. The total number of embryonic heart beats between oviposition and hatching was lower in squamates than in turtles or the crocodilian. Within squamates, embryonic iguanians and gekkonids required more heartbeats to complete development than did embryos of the other squamate families that we tested. These differences plausibly reflect phylogenetic divergence in the proportion of embryogenesis completed before versus after laying

Reporting bias in medical research - a narrative review

Reporting bias represents a major problem in the assessment of health care interventions. Several prominent cases have been described in the literature, for example, in the reporting of trials of antidepressants, Class I anti-arrhythmic drugs, and selective COX-2 inhibitors. The aim of this narrative review is to gain an overview of reporting bias in the medical literature, focussing on publication bias and selective outcome reporting. We explore whether these types of bias have been shown in areas beyond the well-known cases noted above, in order to gain an impression of how widespread the problem is. For this purpose, we screened relevant articles on reporting bias that had previously been obtained by the German Institute for Quality and Efficiency in Health Care in the context of its health technology assessment reports and other research work, together with the reference lists of these articles

Serum Levels of Soluble Adhesion Molecules as Prognostic Factors for Acute Liver Failure

Background/Aims: In patients with septic shock, the degree of liver dysfunction is correlated with serum levels of soluble intercellular adhesion molecule (sICAM)-1. We aimed to assess the usefulness of serum levels of soluble adhesion molecules as prognostic factors for acute liver failure (ALF). Methods: Serum levels of soluble platelet endothelial cell adhesion molecule (sPECAM)-1, sICAM-3, soluble endothelial (sE) selectin, sICAM-1, soluble platelet selectin, and soluble vascular cell adhesion molecule-1 on admission were measured in 37 ALF patients and 34 healthy controls. Results: Twenty-two ALF patients (59%) reached to fatal outcomes. Serum levels of sPECAM-1, sICAM-3, sE-selectin and sICAM-1 were higher in ALF patients than healthy controls. In 37 ALF patients, by the multivariate logistic regression analysis, ratio of direct to total bilirubin (per 0.1 increase; OR 0.11, 95% CI 0.01-0.99), serum sPECAM-1 level (per 100 ng/ml increase; OR 4.37, 95% CI 1.23-15.5) and serum sICAM-1 level (per 100 ng/ml increase; OR 0.49, 95% CI 0.27-0.89) were associated with fatal outcomes. Using receiver operating characteristics curve, each area under the curve of serum sPECAM-1 and sICMA-1 levels as prognostic factors was 0.71 and 0.74, respectively. Conclusion: Serum sPECAM-1 and sICAM-1 levels may be useful for predicting the prognosis of ALF