Influence of industrial sources on children's health--hot spot studies in North Rhine Westphalia, Germany

The aim of this study was to evaluate exposure and health outcome of children living close to industrial sources. Exposure and health outcome was assessed in nearly 1000 children at school beginner age living in the vicinity of industrial sources of three different hot spots (Duisburg North, Duisburg South and Dortmund H?rde) and in a rural area of North Rhine Westphalia (NRW), Germany. The cross-sectional study was undertaken between March and May 2000. Exposure assessment comprised modelling of ambient air quality data and human biomonitoring (HBM). Depending on the site-specific contaminants, HBM included the measurement of PAH (polycyclic aromatic hydrocarbons) and benzene metabolites in urine as well as heavy metals in blood and urine. Markers of early effects were DNA strand breaks as measured by the comet assay in lymphocytes and excretion of alpha-1-microglobuline and N-acetyl-beta-D-glucosamidase in urine. Health outcome was assessed by questionnaire, lung function test, dermatological examination as well as by RAST (radioallergosorbent test), patch tests and prick tests. The influence of exposure variables on biomarkers and health outcome was measured by means of multiple linear and logistic regression analysis. The most striking results were as follows. Children living close to a coke oven plant (Duisburg North) had increased levels of PAH metabolites in urine, and DNA exposure was increased. Children living at the Dortmund H?rde hot spot (increased chromium and nickel ambient air levels from a steel mill) revealed a high prevalence of allergic sensitizations. Sensitization, especially against nickel, was associated with the current internal nickel exposure, and nickel in ambient air was positively associated with the frequency of allergic symptoms. Children from the hot spot areas had increased specific airway resistance and total lung capacity as compared to those of the reference area. In Duisburg North particularly, specific airway resistance and total lung capacity significantly increased with increasing TSP (total suspended particulate). The only positive associations between external and internal exposure were found between benzo[a]pyrene in ambient air and 1-hydroxypyrene in urine, and between lead in ambient air and in the blood of the children. It is concluded that despite improvements of the general air quality during the last decades, living in the vicinity of industrial sources results to some extent in increased internal contaminant exposure and in effects on health outcome. Still ongoing studies are aimed to find out whether the increased PAH and DNA exposure of children from Duisburg North had decreased after the coke oven plant had been shut down in 2003, and if the striking results on the high prevalence of allergic sensitization can be confirmed by introducing an expanded cross-sectional study at four hot spots with increased chromium and nickel ambient air levels.     

Current management of secondary hyperparathyroidism: a multicenter observational study (COSMOS)

STUDY AIMS: To survey bone mineral disturbances in the hemodialysis (HD) population in Europe and current clinical practice in Europe for the prevention, diagnosis and treatment of secondary hyperparathyroidism (SHPT) in HD patients. PRIMARY OBJECTIVES: First, to estimate the prevalence of Kidney Disease Outcomes Quality Initiative (K/DOQI) guideline achievement in a representative sample of European hemodialysis subjects. As part of this objective, we will investigate the prevalence of achievement by type of dialysis, type of center and time on dialysis (less than or greater than 1 year). Among new dialysis subjects (less than 1 year), we will evaluate prevalence of K/DOQI target achievement until the end of the study. The study will run for 3 years. Second, to estimate the association of bone mineral markers (parathyroid hormone [PTH], calcium [Ca], serum phosphorus [P] and calcium phosphate product [CaxP]) classified by achievement of K/DOQI targets with mortality and overall cardiovascular hospitalization. Third, to characterize the longitudinal changes in bone mineral markers. As part of this objective, we will describe the patterns and predictors of bone mineral markers and achievement, with K/DOQI targets, using repeated measurements on individuals over time. SECONDARY OBJECTIVES: First, To estimate the association of bone mineral markers (PTH, Ca, P and CaxP) classified by achievement of K/DOQI targets with specific cardiovascular outcomes, parathyroidectomy, manifest bone disease (including incidence of symptomatic bone fractures), hospitalizations and vascular access. Second, to evaluate the additional value of albumin and hemoglobin levels in conjunction with bone mineral markers in the prediction of mortality and clinical events.     

Biomarkers of nucleic acid oxidation, polymorphism in, and expression of, hOGG1 gene in styrene-exposed workers

This study investigated nucleic acid oxidation associated with styrene exposure, mRNA expression levels of hOGG1 gene and the role of the genetic polymorphism Ser326Cys of human 8-oxoguanine DNA N-glycosylase 1 (hOGG1) in 60 styrene-exposed workers and 50 unexposed clerks. Biomarkers of exposure (styrene in blood, mandelic and phenylglyoxylic acids and 4-vinylphenol in urine) and urinary biomarkers of nucleic acid oxidation, namely 8-oxo-7,8-dihydro-2′-deoxyguanosine (U-8-oxodGuo), 8-oxo-7,8-dihydroguanosine (U-8-oxoGuo) and 8-oxo-7,8-dihydroguanine (U-8-oxoGua) were determined by liquid chromatography–tandem mass spectrometry. The levels of 8-oxodGuo adduct and 2′-deoxyguanosine (dGuo) were measured by HPLC in DNA from white blood cells (WBC). Genomic DNA and RNA from blood samples were used to characterize the Ser326Cys polymorphism and the mRNA expression levels of the hOGG1 gene, respectively, by PCR-based methods. Exposed workers showed lower values of 8-oxodGuo/10⁵ dGuo ratio in WBC-DNA but higher concentrations of U-8-oxoGuo compared to controls (p = 0.002 and p = 0.008, respectively, t-test for independent samples). In the whole group, all urinary biomarkers of nucleic acid oxidation correlated with both the sum of mandelic and phenylglyoxylic acids (rho > 0.33, p < 0.0001) and 4-vinylphenol (rho > 0.29, p < 0.001), whereas 8-oxodGuo/10⁵ dGuo in WBC showed a negative correlation with exposure parameters (rho < −0.24, p < 0.02). Subjects bearing the hOGG1 Ser/Ser genotype showed lower values of 8-oxodGuo/10⁵ dGuo in WBC than those with at least one variant Cys allele (0.34 ± 0.16 vs 0.45 ± 0.21, p = 0.008). In the subgroup of hOGG1 Ser/Ser subjects, laminators showed lower levels of WBC 8-oxodGuo/10⁵ dGuo ratio and significantly higher concentrations of U-8-oxoGua than controls (p = 0.07 and p = 0.01, respectively, t-test for independent samples). Interestingly, workers showed higher levels of hOGG1 expression compared to controls (p < 0.0005). Styrene exposure seems to be associated with oxidation damage to nucleic acids, particularly to RNA and with an induction of the BER system.     

Miliary tuberculomas of the brain: case report

Tuberculosis (TB) of the central nervous system (CNS) is still prevalent in many developing countries. Tuberculoma is always considered in the differential diagnosis of enhancing intra-axial lesions of the brain. Brain tuberculomas can present in many different clinical and radiological patterns, disseminated or miliary brain tuberculomas are very rare. We describe the case of a 25-year-old immunocompetent female with miliary brain tuberculomas. She presented with a history of progressive headache and unsteady gait. Serial Magnetic resonance imaging (MRI) studies revealed growing, multiple small enhancing lesions in the brain, most lesions measured approximately 2mm in diameter, in both the supratentorial and infratentorial compartments. Her investigation failed to reveal any evidence of TB outside the CNS. Open biopsy revealed multiple caseating granulomas and mycobacterin tuberculosis was cultured. She improved clinically and radiologically after starting anti-tuberculous pharmacotherapy. The clinical course, radiological images and pathological studies of this patient are presented. In conclusion miliary brain tuberculomas are rare and unique clinical and radiological entity. It may affect immunocompetent individuals with no other signs of other systemic involvement.     

The p53/p21 DNA damage-signaling pathway is defective in most meningioma cells

Although meningiomas represent the most common class of tumors of the central nervous system, the molecular events underlying their genesis and development are still not well defined. In the present study we have used the immuno-blotting technique to study the expression level of the tumor suppressor proteins p53, p21 and PTEN in primary meningioma cells. We have also studied the induction of p21 and p53 in response to both UV light and gamma-rays. We present evidence that the p53/p21-dependent gamma-ray signaling pathway is defective in 5 out of 8 (62%) of these cells. Furthermore, we have shown that the tumor suppressor p21, p53 and PTEN proteins are differently expressed in these cells, with up to 40-folds difference between the lowest and the highest levels of each protein. These results suggest that the tumor suppressors p53/p21 signaling pathway and PTEN play important roles in the development of benign meningiomas.     

Nodular lesions of choroid plexus in Hurler disease

Neuropathologic examination of six brains from children with Hurler disease revealed nodular lesions in the glomus of choroid plexus caused by proliferation of vacuolated pericytes, fibroblasts, and arachnoid cells on the background of collagenized and myxoid stroma. This localization of lesions can be explained by the presence of a rich vascular network, as well as cellular heterogeneity greater in the glomus than in other parts of the choroid plexus or in the brain parenchyma. The development of nodules did not correlate with the age, severity of hydrocephalus, or the degree of expansion of the perivascular spaces in the brain.     

Interrelationship between uremic toxicity and oxidative stress.

Uremic syndrome is associated with several metabolic disturbances. Oxidative stress is an important factor involved in the pathologic mechanism of these changes. The goal of this study was to understand the relationship between oxidative stress markers and two compounds included among uremic toxins. Two independent studies were performed, one with 29 peritoneal dialysis patients and the other with 43 predialysis subjects. In both groups of patients, known oxidative stress markers, malonyldialdehyde (MDA) and carbonyl groups (CG) formation were measured. Additionally, in the predialysis group, glutathione in erythrocytes (GSH) was estimated. In peritoneal dialysis patients, the concentration of advanced glycation end products (AGEs) was found to be significantly increased and correlated with both markers of oxidative stress. In predialysis patients, the increment of newly described uremic toxin purine nucleotide end products (Me2PY and Me4PY) were found and significant correlation was observed between both compounds versus MDA (positive) and GSH (negative). This relationship was visible especially in patients with more advanced renal failure. CG concentration was within the normal values and did not show any correlation with estimated toxin concentrations. In summary, results of both studies suggest that the interrelationship between uremic toxicity and oxidative stress is an important component of uremic syndrome. Nevertheless, further complex studies are needed to elucidate closer pathogenic links.     

PRE-dialysis survey on anaemia management.

BACKGROUND: The PRE-dialysis survey on anaemia management (PRESAM) was designed to assess the care given to pre-dialysis patients in the 12 months before haemodialysis or peritoneal dialysis, with emphasis on anaemia management. METHODS: For this epidemiological study, a retrospective chart review was conducted for patients who started haemodialysis or peritoneal dialysis between 1 August, 1999 and 6 April, 2000. All adult patients who entered one of the 779 participating centres in 21 European countries, Israel or South Africa were included, except for patients who underwent dialysis only during an acute episode. In addition to demographic characteristics, the study examined the prevalence of anaemia, anaemia management including the use of iron supplementation and epoetin, source of referral to the dialysis centre, comorbidities and major clinical events. RESULTS: A total of 4333 new dialysis patients were included in the survey. At the first visit to the dialysis centre, 68% of the patients had a haemoglobin (Hb) concentration < or = 11.0 g/dl; Hb concentration was positively correlated with creatinine clearance rate (r = 0.43, P < 0.01). Patients who received epoetin had a mean Hb concentration of 8.8 g/dl at the start of epoetin treatment, and 96% of these patients had an Hb concentration < or = 11.0 g/dl. Only 26.5% of the patients received epoetin before dialysis. The length of time under the care of a nephrologist was associated with meeting the European Best Practice Guidelines (EBPG) target Hb concentration, as well as receiving epoetin. CONCLUSIONS: Few pre-dialysis patients met the EBPG target for Hb concentration, despite regular nephrology care.