Urothelial carcinoma associated with Balkan endemic nephropathy. A worldwide disease

Balkan endemic nephropathy (BEN), a familial chronic tubulo-interstitial disease with a slow progression to terminal renal failure, affects people living in the alluvial plains along the tributaries of the Danube River. One of its most peculiar characteristics is a strong association with upper urothelial cancer. An increased incidence of upper urinary tract (UUT) transitional cell cancer (TCC) was discovered among the inhabitants of endemic settlements and in families affected by BEN. In areas where BEN is endemic, the incidence of upper tract TCC is significantly higher, even 100 times, than in non-endemic regions. A high incidence of urothelial cancer in end-stage BEN patients strongly suggests preventive nephro-ureterectomy in all end-stage patients with BEN treated with either transplantation or dialysis. Better understanding of the molecular mechanisms involved in carcinogenesis and tumor progression, has provided a large number of molecular markers of TCC, with a potential diagnostic and prognostic value. Markers that distinguish among TCC, normal urothelium, and benign urothelial conditions are potentially diagnostic, prognostic, and therapeutic targets. The geographic correlation and presence of AA-DNA adducts in both BEN and associated urothelial cancer, support the speculation that these diseases share a common etiology. Dietary exposure to AA is a significant risk factor for BEN and its attendant transitional cell cancer. These are cases of well-known AA induced urothelial carcinoma, and could be detected worldwide. The presence of more than one risk factors is possible and it is important to test etiological hypotheses in different endemic foci, preferably as a multicentric research.     

Functional micro-ultrasound imaging of rodent cerebral hemodynamics

Healthy cerebral microcirculation is crucial to neuronal functioning. We present a new method to investigate microvascular hemodynamics in living rodent brain through a focal cranial window based on high-frequency ultrasound imaging. The method has a temporal resolution of 40ms, and a 100μm in-plane and 600μm through-plane spatial resolution. We use a commercially available high-frequency ultrasound imaging system to quantify changes in the relative cerebral blood volume (CBV) by measuring the scattered signal intensity from an ultrasound contrast agent circulating in the vasculature. Generalized linear model analysis is then used to produce effect size and significance maps of changes in cerebral blood volume upon electrical stimulation of the forepaw. We observe larger CBV increases in the forelimb representation of the primary somatosensory cortex than in the deep gray matter with stimuli as short as 2s (5.1 ± 1.3% vs. 3.3 ± 0.6%). We also investigate the temporal evolution of the blood volume changes in cortical and subcortical gray matter, pial vessels and subcortical major vessels, and show shorter response onset times in the parenchymal regions than in the neighboring large vessels (1.6 ± 1.0s vs. 2.6 ± 1.3s in the cortex for a 10 second stimulus protocol). This method, which we termed functional micro-ultrasound imaging or fMUS, is a novel, highly accessible, and cost-effective way of imaging rodent brain microvascular topology and hemodynamics in vivo at 100micron resolution over a 1-by-1cm field of view with 10s-100s frames per second that opens up a new set of questions regarding brain function in preclinical models of health and disease.     

Somatostatine analogue in nonoperative treatment of posttraumatic pancreatic pseudocyst in a child: a case report

Pancreatic pseudocyst is a complication of pancreatic trauma. We describe improved nonoperative treatment of patient with posttraumatic pancreatic pseudocyst with somatostatin analogue. A 9-year-old girl was admitted to our hospital after blunt abdominal trauma with handlebar. Three weeks after abdominal trauma, pancreatic pseudocyst developed. Nonoperative treatment of posttraumatic pancreatic pseudocyst (the largest dimensions 70 × 55 × 65 mm) with somatostatin analogue, octreotide acetate, was applied for the next 52 days. The patient was followed up for 24 months after the discontinuation of octreotide and there were no recurrence of pancreatic pseudocyst. Somatostatin analogue could be usefull in the nonoperative treatment of posttraumatic pancreatic pseudocysts in children.     

Knowledge of the pharmacological profile of a patient improves the quality of prescribing,the outcomes of treatment,and the utilization of health services in primary health care

Purpose  

To evaluate the influence of the pharmacological profile of a patient (PPP) on quality of drug prescribing, treatment effectiveness, safety, and health services utilization in a group of outpatients.     

Tubular marker excretion in children from families with Balkan nephropathy

Balkan nephropathy (BN) has not been described in children; however, some previous studies in children from families with BN have revealed abnormalities of the urinary tract. In this study, urinary excretion of β2-microglobulin, N-acetyl-β-D-glucosaminidase (NAG) and gamma-glutamyl transpeptidase (GGT) was studied three times a year: spring, autumn, and winter, during a 3-year period, in 703 healthy children, initial age 9–13, from endemic and nonendemic settlements around the South Morava River. Beta-2-microglobulin excretion in urine, in all three seasons, was highest in children from families with BN compared with the excretion in children from the city, nonendemic villages, and those from nonendemic families. Increased urinary GGT excretion in children from endemic villages in October was higher than in children from the city and control villages, being the same in both endemic and nonendemic families. However, in February, it was similar in children from the city, endemic, and control villages. In conclusion, children from families with BN excreted significantly more β2-microglobulin in all three seasons (spring, autumn, winter) of the study, in multivariate analysis significant for family status, gender, and the season (p < 0.001). NAG emerged as a potentially useful marker for seasonal exposure to an environmental nephrotoxin.     

Plasma levels of annexins IV and V in relation to antiphospholipid antibody status in women with a history of recurrent miscarriage

INTRODUCTION: The presence of antiphospholipid (aPL) antibodies increases the risk for recurrent miscarriage (RM). Annexins are a family of structurally related proteins which all bind to anionic phospholipids (PLs) preventing clotting on vascular phospholipid surfaces. The aim of our study was to define plasma concentrations of circulating annexins IV and V at the beginning of pregnancy among women with a history of RM, and in connection to their aPL antibody status. MATERIALS AND METHODS: Sixty-eight women with RM and 25 controls without history of adverse pregnancy outcome were included in the study. Concentrations of annexins IV and V in plasma were determined by using a sandwich ELISA technique. RESULTS: Hereditary or acquired thrombophilic disorders were found in 53% (36/68) of the patients with RM. Plasma levels of annexin V were significantly higher at the beginning of pregnancy (P=0.03), at the 6th (P=0.01) and 8th week of pregnancy in women with aPL antibodies compared with those without aPL antibodies. A tendency towards higher plasma levels of annexin V was observed in those whose pregnancies ended in miscarriage compared with those with successful pregnancy, although the results did not reach statistical significance (P=0.10). Plasma levels of annexin IV at the first visit in women with aPL antibodies were similar to those at 6 and 8 weeks of gestation. There were no significant differences in plasma annexin IV levels between women with and without aPL antibodies. CONCLUSIONS: Patients with RM show elevated plasma levels of annexin V in presence of aPL antibodies. These antibodies could displace annexin from anionic phospholipid surfaces of syncytiotrophoblasts (STBs) and hereby promote coagulation activation.     

Balkan endemic nephropathy and associated urothelial cancer

Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial disease described only in some rural parts of southeastern Europe. One of its most peculiar characteristics is a strong association with upper urothelial cancer (UUC). BEN-related UUC has the same histological features as other forms of UUC in general, but is more frequently bilateral, less frequently affects the bladder and has a sex ratio close to 1. BEN and BEN-associated UUC share the same etiology. Over time, incidence of these conditions has been declining. Since BEN was first described, around half a century ago, socioeconomic changes (in housing, farming, living standards, etc.) have been profound and have obscured the factors responsible for the observed reduction in incidence. Whatever the causes of BEN, the disease might not be restricted only to southeastern Europe. Rather, the intensity of exposure to risk factors for BEN and, consequently, clustering of cases has more likely determined our knowledge of topographical distribution of an etiological entity that is much more widespread, or that might even be ubiquitous in its sporadic form.     

Effects of aerobic exercise on microalbuminuria and enzymuria in type 2 diabetic patients

Increased urinary albumin excretion is a strong predictor for the development of overt diabetic nephropathy and overall cardiovascular morbidity and mortality in patients with type 2 diabetes. In a previous study, regular aerobic physical activity in overweight/obese patients with type 2 diabetes mellitus was found to have significant beneficial effects on glycemic control, insulin resistance, cardiovascular risk factors, and oxidative stress. The aim of the present study was to investigate the effects of aerobic exercise in the same cohort of type 2 diabetic patients on urinary albumin excretion, serum levels and urinary excretion of enzymes, tubular damage, and metabolic control markers in type 2 diabetic patients. Changes from baseline to 3 and 6 months of aerobic exercise were assessed for urinary albumin excretion, serum activities, and urinary excretion of N-acetyl-beta-D-glucosaminidase (NAGA), plasma cell glycoprotein 1 (PC-1) and aminopeptidase N (APN), as well as their association with insulin resistance, cardiovascular risk factors, and oxidative stress parameters in 30 male type 2 diabetic patients (aged 54.8 +/- 7.3 years, with a mean BMI of 30.8 +/- 3.0 kg/m2). Microalbuminuria was found in six (20%) diabetic patients at baseline, three of them (10%) after three months, and only one patient (3.33%) at the end of the study period. A significant correlation was found for urinary albumin excretion at baseline both with sulfhydryl-groups and catalase, but not for urinary albumin excretion with MDA and glutathione. The prevalence of microalbuminuria tended to decrease after six months of aerobic exercise in type 2 diabetic patients, independently of any improvement in insulin resistance and oxidative stress parameters. Neither between-group nor within-group changes were found for urinary PC-1, APN, and NAGA activity. Serum NAGA was significantly increased (p < 0.05) over the control level in diabetic patients at baseline, but it decreased to the normal level after six months of exercise. This study has shown that a six-month aerobic exercise, without any change in the medication, tended to decrease microalbuminuria without changing enzymuria. However, further studies are needed not only to confirm those findings, but to elucidate potential mechanisms that would clarify the beneficial effects of exercise.