Assessment of atherosclerosis risk due to the homocysteine–asymmetric dimethylarginine–nitric oxide cascade in children taking antiepileptic drugs

PurposeThe aim of this study was to assess the atherogenicity risk of antiepileptics in children by investigating the cascade, “hyperhomocysteinemia (HHcy) → asymmetric dimethylarginine (ADMA) increase → nitric oxide (NO) decrease”, which is thought to contribute to the developmental process of atherosclerosis.MethodsThe participants included 53 epilepsy patients who received either valproic acid (VPA, n = 26) or oxcarbazepine (OXC, n = 27). Twenty-four healthy sex- and age-matched children served as controls. Fasting plasma total homocysteine (tHcy), ADMA and NO levels were measured.ResultsThe differences in Hcy, ADMA, NO, vitamin B₁₂ and folate levels between VPA, OXC and control groups were all insignificant (p > 0.05 for all). In the patient group (VPA and OXC groups), 22.6% of the children (12/53) had tHcy levels above the normal cutoff (13.1 μmol/l) for children and 17% of the children (9/53) had tHcy levels of greater than 15 μmol/l which is accepted as the critical value for an increased atherosclerosis risk (p < 0.05 for both). The difference in rate of HHcy between VPA and OXC groups was statistically insignificant (p > 0.05, for both cut off levels of HHCy). There was a positive correlation of tHcy levels and antiepileptic drug treatment duration in the patient group (r = +0.276, p < 0.05).ConclusionHHcy may develop in patients using OXC. Contrary to some previous publications, our data do not suggest that OXC is safer than VPA in terms of HHcy risk. Further prospective, large scale and longer term studies investigating all suggested pathways responsible for development of atherosclerosis due to HHcy should be conducted to define the exact mechanism responsible for AEDs related atherosclerosis.     

Risk factors for high fall risk in elderly patients with chronic kidney disease

International Urology and Nephrology - Patients with chronic kidney disease (CKD) usually represent an aging population, and both older age and CKD are associated with a higher risk of falling....     

High concentrations of soluble P-selectin are associated with risk of venous thromboembolism and the P-selectin Thr715 variant

BACKGROUND: The cell adhesion molecule P-selectin has an important role in the pathophysiology of thrombosis. The effect on venous thromboembolism (VTE) of increased circulating concentrations of soluble P-selectin (sP-selectin) and their association with the P-selectin variant Thr715Pro is still uncertain. METHODS: This study was a case-control study of 116 patients with confirmed recurrent VTE and at least 1 event of unprovoked deep venous thrombosis or pulmonary embolism, and 129 age- and sex-matched healthy individuals. We measured sP-selectin by ELISA and P-selectin gene (SELP) variation by genotyping and sampled blood after a mean interval of 2.55 years after the most recent VTE event. RESULTS: The mean (SD) sP-selectin concentration was higher in patients than in controls: 47.3 (15.0) microg/L vs 36.8 (11.0) microg/L, P <0.001. The unadjusted odds ratio (OR) for sP-selectin >55.1 microg/L, representing the 95th percentile for controls, was 8.5 (95% CI, 3.7-23.3; P <0.001) and increased after adjustment for factor V Leiden, the prothrombin G20210A variant, increased factor VIII, and hyperhomocysteinemia (OR, 10.6; 95% CI, 4.1-31.2; P <0.001). Pro715 carriers were more prevalent among controls than patients (21.7% vs 14.7%). sP-selectin concentrations were lower in this subgroup than in noncarriers: 31.3 (7.9) microg/L vs 44.1 (14.1) microg/L; P <0.001). CONCLUSIONS: Increased sP-selectin concentrations are associated with VTE and genotype status. sP-selectin concentrations are lower in individuals carrying the P-selectin Pro715 variant than in those without this variant.     

An evaluation of the role of tumor load in cytoreductive nephrectomy

IntroductionNew radiological tools can accurately provide preoperative three-dimensional spatial assessment of metastatic renal cell carcinoma (RCC). We aimed to determine whether the distribution, volume, shape, and fraction of RCC resected in a cytoreductive nephrectomy associates with survival.MethodsWe retrospectively reviewed 560 patients undergoing cytoreductive nephrectomy, performing a comprehensive volumetric analysis in eligible patients of all detectable primary and metastatic RCC prior to surgery. We used Cox regression analysis to determine the association between the volume, shape, fraction resected, and distribution of RCC and overall survival (OS).ResultsThere were 62 patients eligible for volumetric analysis, with similar baseline characteristics to the entire cohort, and median survivor followup was 34 months. Larger primary tumors were less spherical, but not associated with different metastatic patterns. Increased primary tumor volume and tumor size, but not the fraction of tumor resected, were associated with inferior survival. The rank of tumors based on unidimensional size did not completely correspond to the rank by primary tumor volume, however, both measurements yielded similar concordance for predicted OS. Larger tumor volume was not associated with a longer postoperative time off treatment.ConclusionsPrimary tumor volume was significant for predicting OS, while the fraction of disease resected did not appear to impact patient outcomes. Although rich in detail, our study is potentially limited by selection bias. Future temporal studies may help elucidate whether the primary tumor shape is associated with tumor growth kinetics.     

Protective effect of rutin on mercuric chloride-induced reproductive damage in male rats

This study investigated the effects of rutin against reproductive damage caused by toxic mercury in male rats. Thirty-five Sprague Dawley rats were used. Control group was injected with saline for 7 days. The rutin-100 group received 100 mg/kg/b.w. rutin for 7 days. Mercuric chloride (HgCl₂) group received 1.23 mg/kg/b.w. of HgCl₂ for 7 days. Mercury chloride + rutin-50 group received 50 mg/kg/b.w. rutin and HgCl₂ 1.23 mg/kg/b.w. for 7 days. HgCl₂ + rutin-100 group received 100 mg/kg/b.w. rutin and HgCl₂ 1.23 mg/kg/b.w. for 7 days. It was detected that HgCl₂ treatment increased malondialdehyde (MDA) levels, tumour necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2) expressions, necrosis and degeneration of spermatogonium, dead and abnormal sperm percentages; tubular walls thinning; and decreased antioxidant enzyme activities and sperm motility. It was determined that rutin application reduced testicular damage caused by HgCl₂. In conclusion, rutin administration may treat HgCl₂ toxicity in testes.     

Fournier's gangrene after hemorrhoidectomy: Association with drug-induced agranulocytosis

An unusual case of Fournier's gangrene after hemorrhoidectomy and drug-induced agranulocytosis, as the predisposing condition, is described. The patient had severe granulocytopenia that was attributed to the recent use of dipyrone. Together with hemodynamic resuscitation, broad-spectrum antibiotic and recombinant human granulocyte colony-stimulating factor were started. Wide surgical excision of all the gangrenous tissues, in addition to laparoscopic formation of a defunctioning sigmoid loop colostomy, was performed. The white blood cell count rose steadily and the patient experienced a rapid recovery. We emphasize that radical surgery must be accompanied by pharmacologic interventions for a successful outcome in such cases.     

Aortic pulse wave velocity in subjects with aortic valve sclerosis

Background: Aortic stiffness is an independent risk factor for cardiovascular events and mortality. The measurement of pulse‐wave velocity (PWV) is the most simple, noninvasive, and robust method to determine aortic stiffness. Whether aortic stiffness contributes to aortic valve sclerosis (AVS) remains unknown. The aim of the present study was to examine the relationship between PWV and AVS in subjects free of clinically evident atherosclerotic disease. Methods: We enrolled 62 patients (48 men; age 65 ± 8 years) diagnosed with AVS and an additional 62 age‐, hypertension‐, diabetes mellitus‐, and history of smoking‐matched subjects without AVS. Applanation tonometry was applied to assess the augmentation index and aortic PWV. The subjects with symptomatic vascular disease were excluded from the study. AVS was defined by echocardiography as thickening and calcification of the normal trileaflet aortic valve without obstruction to the left ventricular outflow. Results: There was no significant difference between the two groups regarding the aortic PWV and augmentation index (11.7±3.3 vs 11.8±3.7, P=0.85; 28.0±9.4 vs 25.0±8.6, P=0. 17, respectively). The presence of AVS was significantly correlated with ejection fraction (r=0.211, P=0.011), male gender (r=0.362, P=0.0001), and age (r=0.200, P=0.026). Conclusions: The lack of an association between the aortic PWV and AVS suggests that AVS is a complex phenomenon consisting of several distinct processes, related to both atherosclerotic and nonatherosclerotic processes.     

Relationship between exercise-induced heart rate increase and the formation of microbubbles and high-intensity transient signals in mechanical heart valve implanted patients

Introduction

The formation and collapse of vapor-filled bubbles near a mechanical heart valve is called cavitation. Microbubbles can be detected in vivo by doppler ultrasonography (USG) as HITS (high intensity transient signals) in cranial circulation. We investigated the relationship between exercise induced heart rate increase and HITS formation in cranial circulation.

Material and methods

Thirty-nine mechanical heart valve implanted (8 aortic valve replacement (AVR) + mitral valve replacement (MVR), 9 AVR, 22 MVR) patients aged 18-80 years old were included in our study. Microbubbles were counted in the left ventricular cavity via transthoracic echocardiography at rest per cardiac cycle. Afterwards transcranial Doppler USG was performed and HITS were counted in each patient''s middle cerebral artery at 5 min duration. Subsequently an exercise test according to the Bruce protocol was performed. After achieving maximal heart rate, microbubbles in the left ventricle and HITS were counted again.

Results

Microbubbles in the left ventricle and transcranial HITS increased after exercise significantly compared to resting values (15.79 ±10.91 microbubbles/beat vs. 26.51 ±18.00 microbubbles/beat, p < 0.001; 6.13 ±8.07 HITS/5 min vs. 13.15 ±15.87 HITS/5 min, p = 0.001). There was a significant correlation between microbubbles and HITS counts after peak exercise (r = 0.55, p < 0.001).

Conclusions

In our study, we found that the microbubbles were increasing as the heart rate increased and more HITS were propelled to the cerebral circulation. As previously shown, HITS can alter cognitive functions. Therefore heart rate control is essential in mechanical heart valve patients to protect neurocognitive functions.