Estimated risk for altered fetal growth resulting from exposure to fine particles during pregnancy: an epidemiologic prospective cohort study in Poland

The purpose of this study was to estimate exposure of pregnant women in Poland to fine particulate matter [less than or equal to 2.5 microm in diameter (PM 2.5)] and to assess its effect on the birth outcomes. The cohort consisted of 362 pregnant women who gave birth between 34 and 43 weeks of gestation. The enrollment included only nonsmoking women with singleton pregnancies, 18-35 years of age, who were free from chronic diseases such as diabetes and hypertension. PM 2.5 was measured by personal air monitoring over 48 hr during the second trimester of pregnancy. All assessed birth effects were adjusted in multiple linear regression models for potential confounding factors such as the size of mother (maternal height, prepregnancy weight), parity, sex of child, gestational age, season of birth, and self-reported environmental tobacco smoke (ETS). The regression model explained 35% of the variability in birth weight (beta = -200.8, p = 0.03), and both regression coefficients for PM 2.5 and birth length (beta = -1.44, p = 0.01) and head circumference (HC; beta = -0.73, p = 0.02) were significant as well. In all regression models, the effect of ETS was insignificant. Predicted reduction in birth weight at an increase of exposure from 10 to 50 microg/m3 was 140.3 g. The corresponding predicted reduction of birth length would be 1.0 cm, and of HC, 0.5 cm. The study provides new and convincing epidemiologic evidence that high personal exposure to fine particles is associated with adverse effects on the developing fetus. These results indicate the need to reduce ambient fine particulate concentrations. However, further research should establish possible biologic mechanisms explaining the observed relationship.     

A novel highly pathogenic Alzheimer presenilin-1 mutation in codon 117 (Pro117Ser): Comparison of clinical, neuropathological and cell culture phenotypes of Pro117Leu and Pro117Ser mutations

A novel presenilin-1 (PS1) mutation (P117S) in an American pedigree is described. We compare clinical, neuropathological and cell culture phenotypes produced by this mutation with another codon 117 mutation that was earlier discovered by our group in a Polish kindred. Both mutations are associated with an unusually severe Alzheimer disease (AD) phenotype, with the onset starting before the third decade of life, rapid disease progression and acute presentation of clinical symptoms. The severity of clinical phenotype was closely correlated with the abundance of pathology: massive deposition of Abeta42 in plaques, severe neurofibrillary degeneration and neuronal loss. When overexpressed in mouse neuroblastoma N2a cells, both mutations caused loss of an ability to promote neurite outgrowth and produced an increase in the ratio of secreted Abeta42/40 amyloid peptides. In stably transfected N2a cell lines only mutant proteins were endoproteolytically cleaved indicating some dependability of this process on the presence of mutation. Taken together, our results show that clinical and cell culture phenotypes produced by these 2 codon 117 mutations are closely related suggesting that the pathogenic action of PS1 may involve effect on neurite outgrowth and endoproteolytic cleavage of the full-length protein. Given the high potency in vivo and in vitro of both codon 117 mutations, this site of PS1 must be particularly important for its normal/pathogenic function.     

A probabilistic functional atlas of the human subthalamic nucleus

This paper introduces a method for generation and validation of a probabilistic functional brain atlas of subcortical structures from electrophysiological and neuroimaging data. The method contains three major steps: (1) acquisition of pre, intra, and postoperative multimodal data; (2) selection of an accurate data set for atlas generation; and (3) generation of the atlas from the selected data set. The method is applied to construct the probabilistic functional atlas of the human subthalamic nucleus (STN). The STN atlas has been built from data collected during surgical treatment of 184 patients with Parkinson’s disease. It is based on preoperative X-ray ventriculography imaging, intraoperative electrophysiological measurements and X-ray imaging, and postoperative neurological assessment. The atlas features a high resolution of 0.25 mm³ and a high accuracy of 0.25 mm. It is dynamic and can be rapidly recalculated for arbitrary resolution and extended by adding new patient data. The atlas can easily be reformatted and warped to match patient-specific data. Its applications include planning of subthalamic stimulations and neuroscience research to study functional properties of the STN. The presented method is general and can be applied for constructing human and animal probabilistic brain atlases.     

Mental changes in course of pituitary gland tumour--a case study

The aim of this paper is to present a case of a 59-year old patient diagnosed with a pituitary gland tumour. The psychiatric examination at the day of admission to the clinic suggested the manic episode was based upon the disseminated organic brain lesion. The patient presented mood elevation, carefree joviality, excitement, loss of social inhibition, inability to sustain attention. In course of the clinical observation and diagnostic progress the pituitary gland tumour was revealed and neurosurgical treatment was applied. The psychopathological course of the disorder was not typical for the established location. The psychopathological syndrome that was presented by the patient gave the global clinical impression of frontal and temporal lobes' dysfunction. This case report supports the present neurobiological opinions criticizing the direct relation of the location to the function within the central nervous system.     

Transcriptional profiling of medulloblastoma in children

OBJECT: Although medulloblastoma is the most common malignant brain tumor found in children, little is known about its molecular pathogenesis. The authors have attempted to compare patterns of gene expression in medulloblastoma samples with those in the healthy cerebellum. METHODS: The authors used complementary (c)DNA microarray analysis to compare the expression of genes in samples of medulloblastoma and normal cerebellum. The expression levels of a subset of genes were then verified by immunohistochemical analysis. Six genes were identified that were expressed at a much higher level in at least five of six medulloblastomas: ezrin, cyclin D2, high mobility group protein 2, MAPRE1, histone deacetylase 2, and ornithine decarboxylase 1. A number of potentially important genes whose expression was much lower in medulloblastomas than in control cerebellum were also identified: tenascin R, TRK-B, FGF receptor, and death receptor 3. The expression levels of a subset of the identified genes were confirmed by immunohistochemical analysis, which was performed on fetal cerebellum and medulloblastoma samples. CONCLUSIONS: The authors demonstrate that cDNA microarray analysis is an effective method of increasing understanding of the molecular biology of medulloblastomas found in children. A comparison between gene expression patterns in medulloblastoma and those observed in healthy cerebellum may provide clues as to the origin of these tumors and may lead to the identification of new genes or pathways to be targeted for future therapies.     

The cost effectiveness of tacrolimus versus microemulsified cyclosporin: a 10-year model of renal transplantation outcomes

INTRODUCTION AND OBJECTIVE: In 1983, the launch of cyclosporin was a significant clinical advance for organ transplant recipients. Subsequent drug research led to further advances with the introduction of cyclosporin microemulsion (cyclosporin ME) and tacrolimus. This paper presents the results from a long-term model comparing the clinical and economic outcomes associated with cyclosporin ME and tacrolimus immunosuppression for the prevention of graft rejection following renal transplantation. STUDY DESIGN: A model was developed to project the costs and outcomes over a 10-year period following transplantation. The model was based on the results of a prospective, randomised study of 179 renal transplantation recipients receiving either cyclosporin ME or tacrolimus, which was conducted by the Welsh Transplantation Research Group (median follow-up: 2.7 years). METHODS: The short-term costs and outcomes were the averages from the actual head-to-head trial data. From this, the long-term costs and outcomes were extrapolated based on the rate of change in patient and graft survival at 3, 5 and 10 years post transplant, as reported in the 1995 United Kingdom Transplant Support Service Authority Renal Transplant Audit. PERSPECTIVE AND YEAR OF COST DATA: The analysis was conducted from the perspective of a UK transplant unit. Costs were at 1999 prices (pounds sterling 1 = dollars US 1.42 = Euro 1.5) and costs and outcomes were discounted at 6% and 1.5%, respectively. RESULTS: The model estimated that 10 years after transplantation, the proportion of patients surviving was 56% of the cyclosporin ME cohort and 64% of the tacrolimus cohort. The cumulative cost of maintenance therapy at 10 years was pounds sterling 23204 per patient maintained on cyclosporin ME versus pounds sterling 23803 per patient on tacrolimus. The cost per survivor at 10 years was pounds sterling 37000 (tacrolimus) versus pounds sterling 41000 (cyclosporin ME) and the cost per patient with a functioning graft was pounds sterling 39000 versus pounds sterling 45000. A Monte Carlo simulation of the model (10000 simulations) gave an average cost at 10 years of pounds sterling 23279 (SD pounds sterling 3457) for cyclosporin ME and pounds sterling 22841 (SD pounds sterling 3590) for tacrolimus. A (second order) probabilistic sensitivity analysis was also performed. The average cost at 10 years from a simulated cohort of 1000 was pounds sterling 23473 (SD pounds sterling 2154) for cyclosporin ME and pounds sterling 24087 (SD pounds sterling 2025) for tacrolimus. CONCLUSION: Renal transplant recipients maintained on tacrolimus have better short- and long-term outcomes than patients maintained on cyclosporin ME. The long-term use of tacrolimus is a more cost-effective solution in terms of the number of survivors, patients with a functioning graft and rejection-free patients.     

Ototoxic effects of occupational exposure to styrene and co-exposure to styrene and noise

Ototoxicity of styrene and the synergistic action of styrene and noise have been shown in rats. The respective data in humans are scarce and equivocal. This study evaluated the effects of occupational exposure to styrene and combined exposures to styrene and noise on hearing. The study group, comprised of 290-yacht yard and plastic factory workers, was exposed to a mixture of organic solvents, having styrene as its main compound. The reference group, totaling 223 subjects, included (1) white-collar workers, exposed neither to solvents nor noise and (2) metal factory workers, exposed exclusively to noise. All subjects were assessed by means of a detailed questionnaire and underwent otorhinolaryngological and audiometric examinations. Multiple logistic regression analysis revealed almost a 4-fold (or 3.9; 95% CI = 2.4-6.2) increase in the odds of developing hearing loss related to styrene exposure. The factors adjusted for were: age, gender, current occupational exposure to noise, and exposure to noise in the past. In cases of the combined exposures to styrene and noise, the odds ratios were two to three times higher than the respective values for styrene-only and noise-only exposed subjects. The mean hearing thresholds--adjusted for age, gender, and exposure to noise--were significantly higher in the solvent-exposed group than in the unexposed reference group at all frequencies tested. A positive linear relationship existed between an averaged working life exposure to styrene concentration and a hearing threshold at the frequencies of 6 and 8 kHz. This study provides the epidemiological evidence that occupational exposure to styrene is related to an increased risk of hearing loss. Combined exposures to noise and styrene seem to be more ototoxic than exposure to noise alone.     

The study of the quercetin action on human erythrocyte membranes

Quercetin is a naturally occurring flavonoid that exerts multiple pharmacological effects. In our previous study, we showed that quercetin greatly affects the lipid membrane. In this report, a study of quercetin on human erythrocyte membrane has been performed to determine the influence of this flavonoid on the fluidity and the conformational changes of membrane proteins. An additional aim of the study was to find how quercetin presence affects the resistance of membrane to haemolytic agents. The results showed that incorporation of quercetin into the erythrocyte membranes caused the changes of the partition coefficient of the Tempo spin label between the water and polar head group phases. In the studies, the W/S ratio has been used as a monitor of changes in protein conformation and in the environment within the membrane. It was observed that quercetin caused an increase in protein-protein interactions in human erythrocyte membranes. Haemolytic action of quercetin in the dark was also investigated. This compound showed protective effect against hypotonic haemolysis. However, in the heat-induced haemolysis quercetin caused acceleration of haemolysis. Dark reaction of erythrocyte with quercetin resulted in a shrinkage of the cells and alteration of their shapes. From the results we have concluded that modification of erythrocyte membrane by quercetin proceeds via reaction with membrane lipids and proteins.     

Increased burden of respiratory disease in the first six months of life due to prenatal environmental tobacco smoke: Krakow birth cohort study

The main purpose of our study was to assess the effects of prenatal tobacco smoke on respiratory symptoms and on doctor consultations in a birth cohort of 445 infants who had no smoking mothers and who had no postnatal exposure to environmental tobacco smoke (ETS). Before and after delivery, questionnaires and interviews with mothers were administered to solicit information on prenatal and postnatal ETS exposure. Newborns were followed-up over six months of life, and respiratory outcomes such as runny or stuffed nose, cough with or without cold, difficult (puffed) breathing, wheezing or whistling in the chest irrespective of respiratory infection were considered. In addition, medical visits related to the occurrence of respiratory symptoms were recorded for each child over a six-month study period. In the multivariate Poisson regression analysis, a set of potential confounders has been taken into account such as gender of child, season of birth, gestational age, maternal education, maternal atopy, presence of moulds in households and prenatal level of personal exposure to fine particles. The adjusted rate ratio (RR) estimated for the occurrence of episodes of running nose was significantly higher in infants exposed to prenatal ETS (1.40; 95% confidence interval [CI]: 1.11-1.68) and the corresponding RR estimates for cough, difficult breathing and wheezing were 1.49 (95% CI: 1.15-1.93), 1.96 (95% CI: 1.22-3.16) and 5.12 (95% CI: 2.86-9.16). The rate ratios of doctor consultations attributable to prenatal ETS because of cough was 1.94 (95% CI: 1.49-2.54). The risk estimate for consultations due to difficult breathing was 2.77 (95% CI: 1.76-4.36), and that for wheezing was 5.86 (95% CI: 3.56-9.64). The data strongly support the view about the impact of the in-utero effect of passive smoking on children's respiratory health. Higher utilization rates of doctor consultations in infants attributable to prenatal ETS exposure demand the revision of public health policy, which should be focused also on cessation of smoking practices by all household members during and after the pregnancy period.     

An algorithm for rapid calculation of a probabilistic functional atlas of subcortical structures from electrophysiological data collected during functional neurosurgery procedures

The paper introduces an optimal algorithm for rapid calculation of a probabilistic functional atlas (PFA) of subcortical structures from data collected during functional neurosurgery procedures. The PFA is calculated based on combined intraoperative electrophysiology, pre- and intraoperative neuroimaging, and postoperative neurological verification. The algorithm converts the coordinates of the neurologically most effective contacts into probabilistic functional maps taking into account the geometry of a stimulating electrode. The PFA calculation comprises the reconstruction of the contact coordinates from two orthogonal projections, normalizing (warping) the contacts modeled as cylinders, voxelizing the contact models, calculating the atlas, and computing probability. In addition, an analytical representation of the PFA is formulated based on Gaussian modeling. The initial PFA has been calculated from the data collected during the treatment of 274 Parkinson's disease patients, most of them operated bilaterally (487 operated hemispheres). It contains the most popular stereotactic targets, the subthalamic nucleus, globus pallidus internus, and ventral intermedius nucleus. The key application of the algorithm is targeting in stereotactic and functional neurosurgery, and it also can be employed in human and animal brain research.