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Selenium depletion in hemodialysis patients treated with polysulfone membranes.

BACKGROUND/AIMS: Epidemiological, animal and human studies have indicated that selenium deficiency is a risk factor for death from malignant diseases. The mechanisms that could modify selenium status may, therefore, be of particular interest in hemodialysis patients, considering their high cancer mortality rates. We aimed at evaluating the effect of hemodialysis with polysulfone membranes on selenium status. METHODS: Twenty- eight chronically dialyzed patients and 32 age-matched healthy controls were enrolled in the study. Serum and dialysis fluid selenium concentrations, serum total protein, and hemoglobin concentrations and serum glutathione peroxidase activity were determined before and after the hemodialysis procedure. RESULTS: The (mean +/- SD) serum selenium and total protein concentrations and glutathione peroxidase activities were significantly (p < 0.05) higher in healthy controls (75.9 +/- 8.3 microg/l, 78 +/- 6 g/l, and 23.8 +/- 4.8 mU/20 microl, respectively) than in the patients. There was no significant difference between serum selenium concentration before (63.6 +/- 11. 6 microg/l) and after (64.4 +/- 11.4 microg/l) hemodialysis sessions, although hemoglobin and total serum protein concentrations and serum glutathione peroxidase activities increased (from 98.5 +/- 1.3 to 114.8 +/- 1.5 g/l, from 64 +/- 8 to 71 +/- 9 g/l, and from 16.8 +/- 1.8 to 18.9 +/- 1.9 mU/20 microl, respectively) significantly (p < 0.05) during hemodialysis, indicating hemoconcentration. The selenium concentration doubled, and protein appeared in the dialysates during dialysis session. The correlation of the selenium concentrations with the protein concentrations in the dialysate is significant (p < 0.01) with a Spearman R value of 0.97. CONCLUSION: The results of the present study suggest that selenium is lost through the pores of polysulfone membranes during hemodialysis which is associated with their protein permeability.

Adult↗

Metabolic polymorphisms as susceptibility markers for lung and oral cavity cancer.

Lung and oral cavity cancers are causally associated with tobacco use. Alcohol is an independent risk factor for oral cavity cancer. Major classes of carcinogens present in tobacco and tobacco smoke are converted into DNA-reactive metabolites by cytochrome P450 (CYP)-related enzymes, several of which display genetic polymorphism. Individual susceptibility to cancer is likely to be modified by the genotype for enzymes involved in the activation or detoxification of carcinogens in tobacco and repair of DNA damage. Molecular epidemiological studies to assess the risk associated with metabolic polymorphisms for cancers of the lung and head and neck have shown that the overall effect of common polymorphisms is moderate in terms of penetrance and relative risk. However, some gene combinations like mutated CYP1A1/GSTM1-null genotype seem to predispose the lung and oral cavity of smokers to an even higher risk for cancer or DNA damage, although these results require confirmation in larger well defined studies that take into account the existence of ethnic variations even within the commonly defined groups. Retinoids, isothiocyanates and tea polyphenols have been identified as possible chemopreventive agents for cancers of the lung and oral cavity. While a number of trials have been conducted with retinoids or beta-carotene, the results were ambiguous and the causes are still being debated. The possible interaction of chemopreventive agents with metabolic polymorphisms as biomarkers in chemoprevention trials is discussed.

Anticarcinogenic Agents↗

[The role of antioxidants in the prevention of tumors].

The potential role of antioxidant vitamins (ascorbic acid, beta-carotene, alpha-tocopherol), minerals (selenium) and non-vitamin natural antioxidants (e.g. glutathione) in the prevention of cancer diseases is reviewed. Free oxygen radicals, especially the hydroxyl radical .OH modify nitrogen bases, split DNA, stimulate oncogene activators and probably in many other ways participate in carcinogenesis. In a great number of experimental and epidemiological studies a significant increase of cancer risk in laboratory animals and in humans with low antioxidant status was found. Significant protective effects of ascorbic acid, beta-carotene, alpha-tocopherol and selenium against the incidence of gastrointestinal and lung cancer were achieved in most, but not in all prospective and intervention studies. It is probable that extremely high premature cancer mortality in postcommunist countries of Central and East Europe is caused by high consumption of cigarettes, spirits and saturated fats, by pollution, and by very low consumption of the chief sources of natural antioxidants (fruits, vegetables). (Fig. 13, Ref. 29).

Animals↗

Renal and immunologic markers for chloralkali workers with low exposure to mercury vapor.

OBJECTIVES: The aim of this study was to investigate renal function and immunologic markers among chloralkali workers with long-term low exposure to mercury vapor. METHODS: Forty-seven currently exposed workers were compared with reference workers matched for age in a cross-sectional design. RESULTS: The mean urinary mercury concentration was 5.9 (range 1.1-16.8) nmol/mmol creatinine (Cr) for the exposed workers and 1.3 (range 0.2-5.0) nmol/mmol Cr for the referents. The chloralkali workers had been exposed for an average of 13.3 (range 2.8-34.5) years. The activity of N-acetyl-beta-D-glucosaminidase in urine (U-NAG) was higher in the exposed workers (mean 0.18 U/mmol Cr versus 0.14 U/mmol Cr, P=0.02). Associations between current urinary mercury, cumulative urinary mercury, and cumulative urinary mercury per year (intensity) and U-NAG, autoantibodies to myeloperoxidase (anti-MPO) and proteinase 3 in serum, respectively, were observed. The activity of U-NAG and anti-MPO was increased in the workers with the highest exposure, as assessed by their mean intensity of exposure. The highest activity of U-NAG was observed in the exposed workers with the lower concentrations of selenium in whole blood. CONCLUSIONS: The study indicates an effect of exposure on the kidney proximale tubule cells, possibly modified by individual selenium status, and an effect mediated by neutrophil granulocytes.

Acetylglucosaminidase↗

A mutation in the human apolipoprotein A-I gene. Dominant effect on the level and characteristics of plasma high density lipoproteins.

Epidemiologic and genetic data suggest an inverse relationship between plasma high density lipoprotein (HDL) cholesterol and the incidence of premature coronary artery disease. Some of the defects leading to low levels of HDL may be a consequence of mutations in the genes coding for HDL apolipoproteins A-I and A-II or for enzymes that modify these particles. A proband with plasma apoA-I and HDL cholesterol that are below 15% of normal levels and with marked bilateral arcus senilis was shown to be heterozygous for a 45-base pair deletion in exon four of the apoA-I gene. This most likely represents a de novo mutation since neither parent carries the mutant allele. The protein product of this allele is predicted to be missing 15 (Glu146-Arg160) of the 22 amino acids comprising the third amphipathic helical domain. The HDL of the proband and his family were studied. Using anti-A-I and anti-A-II immunosorbents we found three populations of HDL particles in the proband. One contained both apoA-I and A-II, Lp(A-I w A-II); one contained apoA-I but no A-II, Lp(A-I w/o A-II); and the third (an unusual one) contained apoA-II but no A-I. Only Lp(A-I w A-II) and (A-I w/o A-II) were present in the plasma of the proband's parents and brother. Analysis of the HDL particles of the proband by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed two protein bands with a molecular mass differing by 6% in the vicinity of 28 kDa whereas the HDL particles of the family members exhibited only a single apoA-I band. The largely dominant effect of this mutant allele (designated apoA-ISeattle) on HDL levels suggests that HDL particles containing any number of mutant apoA-I polypeptides are catabolized rapidly.

Amino Acid Sequence↗

Comparative risk assessment of the burden of disease from climate change.

The World Health Organization has developed standardized comparative risk assessment methods for estimating aggregate disease burdens attributable to different risk factors. These have been applied to existing and new models for a range of climate-sensitive diseases in order to estimate the effect of global climate change on current disease burdens and likely proportional changes in the future. The comparative risk assessment approach has been used to assess the health consequences of climate change worldwide, to inform decisions on mitigating greenhouse gas emissions, and in a regional assessment of the Oceania region in the Pacific Ocean to provide more location-specific information relevant to local mitigation and adaptation decisions. The approach places climate change within the same criteria for epidemiologic assessment as other health risks and accounts for the size of the burden of climate-sensitive diseases rather than just proportional change, which highlights the importance of small proportional changes in diseases such as diarrhea and malnutrition that cause a large burden. These exercises help clarify important knowledge gaps such as a relatively poor understanding of the role of nonclimatic factors (socioeconomic and other) that may modify future climatic influences and a lack of empiric evidence and methods for quantifying more complex climate-health relationships, which consequently are often excluded from consideration. These exercises highlight the need for risk assessment frameworks that make the best use of traditional epidemiologic methods and that also fully consider the specific characteristics of climate change. These include the longterm and uncertain nature of the exposure and the effects on multiple physical and biotic systems that have the potential for diverse and widespread effects, including high-impact events.

Climate↗

Combined effects of complex mixtures of potentially anti-carcinogenic compounds on antioxidant enzymes and carcinogen metabolizing enzymes in the rat.

The anti-carcinogenic activity of dietary fruit and vegetables observed in several epidemiological and experimental animal studies is likely to be an effect of the combined exposure to a large number of substances acting together. This is plausible, as these compounds are present simultaneously in a diet containing vegetables and fruit. Further, some compounds have been experimentally demonstrated to modify several mechanisms involved in carcinogenesis. The effect of combined exposure is demonstrated in the present article, summarizing the effects of a complex mixture of anti-carcinogenic substances (from broccoli) on different antioxidative defense enzymes and on cytochrome P-450 activities in rat liver, kidney and colon. The responses were related to the levels of different specific glucosinolates.

Animals↗

Quantitative risk assessment of Cryptosporidium species infection in dairy calves.

Cryptosporidium parvum is a zoonotic protozoan that infects many different mammals including cattle and humans. Cryptosporidiosis has become a concern for dairy producers because of the direct losses due to calves not performing well and the potential for environmental contamination with C. parvum. Identifying modifiable control points in the dynamics of infection in dairy herds will help identify management strategies that mitigate its risk. The quantitative risk assessment approach provides estimates of the risk associated with these factors so that cost-effective strategies can be implemented. Using published data from epidemiologic studies and a stochastic approach, we modeled the risk that C. parvum presents to dairy calves in 2 geographic areas: 1) the New York City Watershed (NYCW) in southeastern New York, and 2) the entire United States. The approach focused on 2 possible areas of exposure--the rearing environment and the maternity environment. In addition, we evaluated the contribution of many risk factors (e.g., age, housing, flies) to the end-state (i.e., total) risk to identify areas of intervention to decrease the risk to dairy calves. Expected risks from C. parvum in US dairy herds in rearing and maternity environments were 41.7 and 33.9%, respectively. In the NYCW, the expected risks from C. parvum in the rearing and maternity environments were 0.36 and 0.33%, respectively. In the US scenarios, the immediate environment contributed most of the risk to calves, whereas in the NYCW scenario, it was new calf infection. Therefore, within the NYCW, risk management activities may be focused on preventing new calf infections, whereas in the general US population, cleaning of calf housing would be a good choice for resource allocation. Despite the many assumptions inherent with modeling techniques, its usefulness to quantify the likelihood of risk and identify risk management areas is illustrated.

Aging↗

[Epidemiological research in autism: an integrative view].

INTRODUCTION: Sixty years after the first descriptions of Autism, the same diagnostic criteria based on clinical observation used then are still valid today. Two years ago, the Instituto de Salud Carlos III set up the Grupo de Estudio en los Trastornos del Espectro Autista (Autism Spectrum Disorders Study Group) with the aim of evaluating the current state of research in autism spectrum disorders (ASD) in Spain. This group established collaborative links with different associations and set up a way of working that was more coordinated and closer to the real day-to-day situation experienced by the families involved. AIMS AND DEVELOPMENT: The aim of this review is to update certain areas of knowledge concerning the distribution of the factors that determine ASD, that is to say, about the epidemiology of these disorders. At the same time, it intends to arouse a greater degree of interest among professionals who are more directly involved in the study of pervasive developmental disorders. The latest diagnostic tools offer a higher degree of certainty in the complicated process of evaluating a case with symptoms of autism. Nevertheless, given the effectiveness of early attention and how it affects the prognosis, population-based ASD screening programmes must be implemented. These would have to include the use of Modified Check List for Autism in Toddlers (M-CHAT)-type questionnaires, followed by several levels of diagnosis, in order to reduce the number of false positives while at the same time increasing the true positives.

Autistic Disorder↗

The social science contribution to pharmacoepidemiology.

An understanding of the inappropriate use of pharmaceuticals (the prescribing of unnecessary or ineffective medications, and non-compliance by consumers) can be furthered by considering the psychological, social and cultural contexts in which medicines are used. The consumers are influenced by their beliefs about benefits, safety and cost; opinions of their social group; and emotions associated with taking the medication itself. Similar considerations apply to the prescribers or dispensers of the drugs, who are also influenced by the marketing and regulatory practices of their countries. A model of drug use which takes these factors into account can suggest various strategies to increase optimal pharmaceutical utilization. To date, these efforts have focused almost exclusively on the prescriber or manufacturer, and have had limited success. However, other, more effective techniques exist, which can modify the behavior of both of these groups, and of the consumers. A strategy of research in this area is outlined.

Attitude to Health↗

Controlling for time-varying population distributions in disease clustering studies.

Both the Knox test and the Mantel test for the presence of disease clustering have previously been shown to be sensitive to changes that occur in the relative geographic population distribution during the time period of study. Although these procedures do not require knowledge of the underlying population density, they implicitly assume it is constant with time. If this is not the case, one may detect clustering which is completely independent of the disease process and simply reflects time-space clustering of the population. Modified procedures are presented which incorporate information from appropriately selected controls to adjust for the effect of a shifting population. Results of a computer simulation study demonstrating the stability of the modified tests in the face of an expanding population are reported.

Cluster Analysis↗

Lumbar spinal stenosis: assessment of long-term outcome 12 years after operative and conservative treatment.

The present study focuses on the long-term prognosis of radiographically verified stenosis of the lower lumbar spine. The purpose here was to describe the outcome 12 years after radiographic diagnosis of spinal stenosis and to identify factors predicting disability after operative or conservative treatment. Data were compiled on 75 patients (43 men and 32 women) with changes in functional myelography diagnostic for spinal stenosis. Their mean age at the interview 12 years later was 61 years. The sagittal diameter of the dural sac was measured from baseline myelographs at all intervertebral levels and was corrected for magnification. In the interview, subjective outcome assessment was obtained with a structured questionnaire, and the low-back disorder was scored using the Oswestry disability index. The sagittal diameter of the dural sac was severely stenotic (<7.0 mm) in 32 patients (26 operated), and moderately stenotic (7.0-10.5 mm) in 43 patients (31 operated). The severity of the stenosis significantly predicted disability, even when the effects of age, sex, therapy regimen, and body mass index were adjusted for. For moderate and severe stenosis, the adjusted mean Oswestry indices were 28.4 and 39.1, respectively (p = 0.01). Therapy as such (operative versus nonoperative) did not significantly correlate with later disability. The radiographic severity of lumbar spinal stenosis predicts disability independently of therapy regimen. Randomized clinical trials are needed to establish the indications for surgical and conservative treatment. Radiographic severity of the stenosis should be considered as an effect-modifying or confounding factor in clinical trials and other studies focusing on the outcome of lumbar spinal stenosis.

Aged↗

Major burns in Cape Town: a modified burns score for patient triage.

Major burns equal to, or greater than, 30 per cent total body surface area (TBSA) constitute 23 per cent of the admissions to the adult burns unit in Cape Town. A retrospective review over a 28-month period identified 87 cases of major burns. This paper summarizes the epidemiology and mortality amongst this patient group over this period. Demand for treatment can exceed bed availability in the unit. The difficult issue, this raises, of patient triage in relation to the relatively limited resources is addressed and a simple modified burns score proposed for this unit. The effect this score would have in optimizing the use of our resources is demonstrated.

Adolescent↗

The LNT model is the best we can do--today.

The form of the dose-response curve for radiation-induced cancers, particularly at low doses, is the subject of an ongoing and spirited debate. The present review describes the current database and basis for establishing a low dose, linear no threshold (LNT) model. The requirement for a dose-response model to be used for risk assessment purposes is that it fits the great majority of data derived from epidemiological and experimental tumour studies. Such is the case for the LNT model as opposed to other nonlinear models. This view is supported by data developed for radiation-induced mutations and chromosome aberrations. Potential modifiers of low dose cellular responses to radiation (such as adaptive response, bystander effects and genomic instability) have not been shown to be associated with tumour development. Such modifiers tend to influence the slope of the dose-response curve for cellular responses at low doses and not the shape--thereby resulting in a quantitative modification rather than a qualitative one. Additional data pertinent to addressing the shape of the tumour dose-response relationship at low doses are needed.

Chromosome Aberrations↗

The community epidemiology of trachoma.

Effective eradication of avoidable blindness due to trachoma requires an understanding of the epidemiologic determinants that promote the disease. These determinants include both host factors, such as age, sex, and race, and environmental determinants, including climate, water availability, and general socioeconomic conditions. All of these factors may drastically modify the incidence, prevalence, and severity of trachoma within a community. Longitudinal seroepidemiologic studies on the transmission of the infection have helped to elucidate the more important risk factors in trachomatous communities, and this information must be carefully considered in the assessment of proposed programs for trachoma control.

Age Factors↗

Hyperlipidemia and cardiovascular disease after organ transplantation.

Hyperlipidemia, a frequent and persistent complication after solid organ transplantation, contributes to cardiovascular morbidity and mortality and may influence the development of allograft vasculopathy. The pathogenesis of posttransplantation hyperlipidemia is not fully understood, although several epidemiological factors are strongly implicated including age, weight, pretransplantation lipid levels, and immunosuppressive therapy. Management strategies to reduce hyperlipidemia and modify cardiovascular risk include dietary restrictions and the use of lipid-lowering agents. The selective use of immunosuppressants, such as tacrolimus, that have neutral or fewer adverse effects on lipid metabolism may also provide a useful option. A combination of lipid-lowering therapies and optimization of immunosuppressive regimens compatible with prolonged allograft survival is probably necessary to significantly reduce posttransplantation hyperlipidemia and its potentially harmful consequences.

Graft Rejection↗

[Phytoestrogen and cancer prevention].

Phytoestrogens are defined to be plant chemicals that modify estrogenic effects in the body by binding to the estrogen receptors in mammals. Isoflavones, coumestane, lignan, and prenylflavones are examples of these, with isoflavones from soy foods and lignans from rye being a major dietary contribution. Mechanisms of cancer prevention by these phytoestrogens are reviewed, and human epidemiological studies, especially for breast and prostate cancers, are summarized and the results discussed.

Breast Neoplasms↗

Depression in Guatemalan adolescents.

A sample of 339 adolescents from the school population of three social classes in Guatemala City were administered a modified version of the Center for Epidemiological Studies Depression Scale for Children (CES-DC-M). Of the total sample, 35.1% were found to be depressed. A two-way analysis of variance (gender by social class) showed differences which approached statistical significance and reflected a significant main effect of gender but not social class. Implications of the findings are discussed.

Adolescent↗