The Glu298Asp polymorphism in the endothelial nitric oxide synthase gene is strongly associated with coronary spasm

BACKGROUND: Coronary spasm seems to be associated with coronary nitric oxide deficiency. OBJECTIVES: We investigated whether the Glu298Asp polymorphism in the endothelial nitric oxide synthase (eNOS) gene is a definite risk factor for coronary spasm and whether diffuse spasm involving normal-looking coronary artery correlates significantly with the Glu298Asp polymorphism, in contrast with focal spasm superimposed on an atherosclerotic plaque. METHODS: A polymerase chain reaction followed by restriction fragment length polymorphism analysis was performed in 118 control participants and in 102 patients with variant angina and a similar degree of atherosclerotic burden. Patients with coronary spasm were divided into diffuse spasm and focal spasm subgroups according to morphological criteria. RESULTS: There was a significantly higher incidence of the Glu298Asp polymorphism in the coronary spasm group than in the control group (21.5% compared with 8.5%, P=0.006). Multiple logistic regression analysis using risk factors and the Glu298Asp polymorphism showed that the most important predictive factor for coronary spasm was the Glu298Asp polymorphism (odds ratio 2.83, 95% confidence interval 1.25-6.41, P=0.009). The diffuse spasm subgroup had a significantly higher frequency of the Glu298Asp polymorphism than the control group (25.9% compared with 8.5%, P=0.002). However, the focal spasm subgroup did not differ from the control group in the frequency of Glu298Asp polymorphism. CONCLUSION: The Glu298Asp polymorphism in the eNOS gene is a definite risk factor for coronary spasm, especially for diffuse coronary spasm. This result supports the notion that diffuse coronary spasm is significantly associated with endothelial dysfunction, in contrast to focal spasm.     

Fluoroscopically guided peritoneal dialysis catheter placement: long-term results from a single center.

OBJECTIVE: Despite percutaneous fluoroscopy ensuring appropriate placement of peritoneal dialysis (PD) catheters, the efficacy of this method is not well known. Therefore, we evaluated our long-term experience with fluoroscopy-assisted placement of PD catheters. Patients and METHODS: We retrospectively reviewed 134 PD catheters in 114 PD patients that were treated in the PD center of a university-based hospital. We evaluated complications related to PD catheters, causes for catheter removal, and catheter survival. We used the multivariate Cox proportional hazard model to identify independent factors related to PD catheter survival. RESULTS: Early complications related to insertion included 1 case of pericatheter bleeding; there were no placement failures. Early complications occurred in 8.5% of patients. Most late complications were migration and leakage, which occurred in 10.4% and 9.7% of patients respectively. The most common cause for catheter removal was intractable and recurrent peritonitis. The 12- and 24-month survival rates of the catheters were 80.0% and 74.9%. The most significant prognostic factor of percutaneous fluoroscopy-assisted PD catheter survival was late leakage (p < 0.01). CONCLUSIONS: In addition to the advantages of simplicity, minimal invasiveness, and relative safety, the survival rate of PD catheters placed using the percutaneous fluoroscopy-assisted method was comparable to that of more invasive methods. Percutaneous fluoroscopy-assisted placement of PD catheters should be considered when available, and may be preferred to other placement methods.     

Change in kidney function after unilateral adrenalectomy in patients with primary aldosteronism: identification of risk factors for decreased kidney function

Purpose

Glomerular filtration rate (GFR) has been reported to decrease after unilateral adrenalectomy in patients with primary aldosteronism (PA). The aim of this study was to identify clinical predictors for decreased GFR after adrenalectomy in patients with PA.

Methods

The records of 187 patients (98 patients with PA and 89 with non-PA adrenal disease) who were followed up for at least 6 months after unilateral adrenalectomy were retrospectively analyzed. Estimated GFR (eGFR) was investigated at 1, 3, and 6 months postoperatively. Preoperative risk factors for eGFR% decline at 1 month ([preoperative eGFR?eGFR at 1 month]/preoperative eGFR?×?100) and postoperative CKD development were investigated.

Results

The eGFR decreased significantly at 1 month and remained stable in the PA group. However, there were no significant changes in eGFR in the non-PA group over the 6-month period. In the PA group, a high preoperative eGFR and high aldosterone to renin ratio (ARR) were independently associated with eGFR% decline at 1 month. In patients with PA but without preoperative CKD (n?=?68), a low preoperative eGFR and high ARR were independent risk factors for developing postoperative CKD. The best preoperative cut-off values of eGFR and ARR for predicting the development of postoperative CKD were ≤?102 ml/min/1.73 m² and ≥?448 ng/dl:ng/ml/h, respectively.

Conclusions

Renal function deteriorated significantly after unilateral adrenalectomy in patients with PA. Clinicians must pay attention to postoperative renal function in PA patients at elevated risk of developing decreased kidney function.

     

Association between N-terminal pro-brain natriuretic peptide and acute ischemic stroke in patients on chronic hemodialysis

Background

Plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) has been reported as a predictor for ischemic stroke in general population. However, predictive value of plasma NT-proBNP for acute ischemic stroke in patients on chronic hemodialysis has not been well established. The aim of this study was to determine whether NT-proBNP could predict acute ischemic stroke in patients on chronic hemodialysis.

Methods

This study was designed prospectively. Clinical, laboratory, and echocardiographic variables were assessed in 72 patients on chronic hemodialysis. The plasma levels of NT-proBNP were measured by immunoassay.

Results

During the follow-up period of 45 months, 11 patients had an acute ischemic stroke. The Kaplan–Meier plot showed an increased frequency of acute ischemic stroke in patients with plasma levels of NT-proBNP above the median values compared to patients with lower concentrations (P = 0.028). The multivariate Cox proportional hazard models showed that the NT-proBNP was a significant independent predictor of acute ischemic stroke after adjustment for age, sex, mean blood pressure, diabetes, serum cholesterol levels, left ventricular mass index, and left ventricular fractional shortening (HR 6.66, 95% CI, 1.22–36.48, P = 0.029).

Conclusions

Our data suggest that plasma NT-proBNP levels predict the risk of acute ischemic stroke in patients on chronic hemodialysis.     

Effect of short-term culture on functional and stress-related parameters in isolated human islets

The Edmonton protocol for islet transplantation utilizes fresh islet grafts but other protocols increasingly transplant short-term cultured grafts mainly for practical reasons. To improve our understanding of the impact of culture pretreatment of human islets, we assessed post-transplant function by nude mouse bioassay, islet ATP, activity of stress-activated MAP kinases, and expression of stress-related genes by focused cDNA array in freshly isolated and cultured islets. Mean blood glucose levels over 4 weeks after transplantation (2000 IE) of (i) freshly isolated, (ii) cultured and preculture counted (recovery rate; 78 ± 6%), and (iii) cultured and postculture counted islets in diabetic mice were 330 ± 40, 277 ± 65, and 256 ± 52 mg/dl (i versus ii, P  = 0.004; i versus iii, P  = 0.002). During culture, islet ATP/DNA and ATP/ADP increased; JNK and p38 MAPK activities decreased. Among 96 genes studied, mRNA expression of heat shock protein 70 genes decreased >twofold during culture in all four pairs; expression of cyclooxygenase-2, superoxide dismutase-2, interleukin-6 and cytochromes P450 1A1 genes increased. Our results show that culturing human islets before transplantation is not disadvantageous in regard of functional recovery from changes induced by nonphysiologic stimuli during islet isolation. The increase in expression of several stress-related genes during culture also shows that improving culture conditions may further enhance post-transplant islet function.