First Spanish Trauma Registry: analysis of 1500 cases.

OBJECTIVES: To develop the first Spanish Pediatric Trauma Registry to collect and evaluate infomation concerning aspects of injuries in our pediatric population. METHODS: From January 1995 to August 1998, 35,946 children younger than 16 years were treated in our hospital for acute injury: 1500 were admitted and included in our database. Our file registry consists of 108 data points including: patient identification, type, place and mechanism of injury, pre-hospital care, transport, assessment on admission, severity scores, diagnostic studies, injuries, treatment morbidity and mortality. RESULTS: Accidents were more frequent in males (68%) than in females. The predominant age group was 12-15 years of age (34%). Accidents were more frequent in the street (35.1%) than at home (18.9%) or school (13%). Falls and traffic-related accidents were the leading cause of injury (39% and 21.2%, respectively). Two hundred and thirty-five (15.7%) had a Pediatric Trauma Score < or = 8. Fifty of these sustained multiple trauma (33%) (Injury Severity Score > or = 15). Musculoskeletal and head trauma were the most frequent injuries (48.5% and 42.0%, respectively). Surgical or orthopedic procedures were performed in 906 patients (56.5%). The average length of stay was 4.5 days (range 1-93 days). Functional impairment in children older than 4 years of age was found in 413 children (33.3%). We encountered 7 deaths in the 1500 patients, or an overall mortality of 0.5%. These 7 deaths were only seen in the I.S.S. > or = 15 group (50 patients) with 14% mortality. CONCLUSIONS: The goals of this Registry are to establish the epidemiology of our injured pediatric population, to review patient care, to develop prevention programs and to compare results with other centers so that potential deficiencies can be corrected.     

Genetic and Non-genetic Predictors of LINE-1 Methylation in Leukocyte DNA

Background: Altered DNA methylation has been associated with various diseases.Objective: We evaluated the association between levels of methylation in leukocyte DNA at long interspersed nuclear element 1 (LINE-1) and genetic and non-genetic characteristics of 892 control participants from the Spanish Bladder Cancer/EPICURO study.Methods: We determined LINE-1 methylation levels by pyrosequencing. Individual data included demographics, smoking status, nutrient intake, toenail concentrations of 12 trace elements, xenobiotic metabolism gene variants, and 515 polymorphisms among 24 genes in the one-carbon metabolism pathway. To assess the association between LINE-1 methylation levels (percentage of methylated cytosines) and potential determinants, we estimated beta coefficients (βs) by robust linear regression.Results: Women had lower levels of LINE-1 methylation than men (β = –0.7, p = 0.02). Persons who smoked blond tobacco showed lower methylation than nonsmokers (β = –0.7, p = 0.03). Arsenic toenail concentration was inversely associated with LINE-1 methylation (β = –3.6, p = 0.003). By contrast, iron (β = 0.002, p = 0.009) and nickel (β = 0.02, p = 0.004) were positively associated with LINE-1 methylation. Single nucleotide polymorphisms (SNPs) in DNMT3A (rs7581217-per allele, β = 0.3, p = 0.002), TCN2 (rs9606756-GG, β = 1.9, p = 0.008; rs4820887-AA, β = 4.0, p = 4.8 × 10^–7; rs9621049-TT, β = 4.2, p = 4.7 × 10^–9), AS3MT (rs7085104-GG, β = 0.7, p = 0.001), SLC19A1 (rs914238, TC vs. TT: β = 0.5 and CC vs. TT: β = –0.3, global p = 0.0007) and MTHFS (rs1380642, CT vs. CC: β = 0.3 and TT vs. CC; β = –0.8, global p = 0.05) were associated with LINE-1 methylation.Conclusions: We identified several characteristics, environmental factors, and common genetic variants that predicted DNA methylation among study participants.     

Hypothalamic expression of anorexigenic and orexigenic hormone receptors in obese females Neotomodon alstoni: Effect of fasting

Obesity is a world problem that requires a better understanding of its physiological and genetic basis, as well as the mechanisms by which the hypothalamus controls feeding behavior. The volcano mouse Neotomodon alstoni develops obesity in captivity when fed with regular chow diet, providing a novel model for the study of obesity. Females develop obesity more often than males; therefore, in this study, we analysed in females, in proestrous lean and obese, the differences in hypothalamus expression of receptors for leptin, ghrelin (growth hormone secretagogue receptor GHS-R), and VPAC, and correlates for plasma levels of total ghrelin. The main comparisons are between mice fed ad libitum and mice after 24 hours of fasting. Mice above 65 g body weight were considered obese, based on behavioral and physiological parameters such as food intake, plasma free fatty acids, and glucose tolerance. Hypothalamic tissue from obese and lean mice was analysed by western blot. Our results indicate that after ad libitum food access, obese mice show no significant differences in hypothalamic leptin receptors, but a significant increase of 60% in the GHS-R, and a nearly 62% decrease in VPAC2 was noted. After a 24-hour fast, plasma ghrelin increased nearly two fold in both lean and obese mice; increases of hypothalamic leptin receptors and GHS-R were also noted, while VPAC2 did not change significantly; levels of plasma free fatty acids were 50% less after fasting in obese than in lean animals. Our results indicate that in obese N. alstoni mice, the levels of orexigenic receptors in the hypothalamus correlate with overfeeding, and the fact that lean and obese females respond in different ways to a metabolic demand such as a 24-hour fast.     

Anthropometric cutoff points for predicting chronic diseases in the Mexican National Health Survey 2000

OBJECTIVE: To determine optimum anthropometric cutoffs for predicting the likelihood ratios of type 2 diabetes mellitus (DM) and hypertension (HT) in Mexicans. RESEARCH METHODS AND PROCEDURES: Data from a randomly selected, nationally representative health survey (2000) with 11,730 men [37.4 (+/- 12.9) years] and 26,647 women [37.3(+/- 12.9) years] were assessed for values of body mass index (BMI) and waist circumference (WC) for predicting DM or HT by receiver operating characteristic curve analyses. Likelihood ratios for DM and HT were calculated, and BMIs or WCs for public-health screening were developed. Subanalyses included regional data. RESULTS: Likelihood ratios of DM and HT increased from BMI values of 22 to 24 kg/m(2) in both sexes and with WC values of 75 to 80 cm in men and 70 to 80 cm in women. The best BMI cutoffs for predicting DM were 26.3 to 27.4 kg/m(2) in men and 27.7 to 28.9 kg/m(2) in women, with similar values for HT, i.e., 26.2 to 27.0 kg/m(2) and 27.7 to 28.5 kg/m(2), for men and women, respectively; WC cutoffs for DM were 93 to 98 cm in men and 94 to 99 cm in women, and cutoffs for HT were 92 to 96 cm and 93 to 96 cm for men and women, respectively. The WC cutoffs had higher sensitivity and specificity than those of BMI. DISCUSSION: The risk for DM and HT starts at lower levels of BMI and WC than those suggested by WHO. WC is a better discriminator than BMI measures for use in public health.     

Spontaneous reporting of hepatotoxicity associated with antiandrogens: data from the Spanish pharmacovigilance system

PURPOSE: To analyse the type and main features of the hepatotoxicity induced by steroidal and non-steroidal antiandrogens spontaneously reported by physicians, pharmacists and nurses. This analysis could increase the information related to these adverse reactions mainly available from the published isolated cases. METHODS: Using the Spanish Pharmacovigilance database we searched for spontaneous reports recorded since the date of approval of each antiandrogen up to the present time. We analysed the frequency of liver disorders, the preferred terms coded, the presence of other hepatotoxic drugs, and the characteristics of cases of hepatitis. RESULTS: Liver disorders were the most common adverse reactions associated with flutamide and bicalutamide, but not with cyproterone acetate. 'Hepatitis' and 'cholestatic hepatitis' were the most frequent terms coded. In 38% of the reports related to cyproterone acetate, 18% of those related to flutamide and 33% of those related to bicalutamide the patient had simultaneously received other hepatotoxic drugs. The disproportionality analysis of hepatitis showed a strong association with flutamide and a weak association with bicalutamide and cyproterone acetate. Mean doses of flutamide and bicalutamide were very close to their defined daily dose (DDD) to treat prostate cancer, although in the case of cyproterone acetate it was slightly higher. The latency period of hepatitis was between 3 and 10 months for the three antiandrogens, and the recovery period was shorter (0.5-3 months). The majority of the reported cases of hepatitis evolved favourably. CONCLUSION: Our results highlight the hepatotoxic potential of flutamide compared to cyproterone acetate. The data related to bicalutamide should be cautiously considered due to the smaller number of reports.     

Potential impact of steatosis on cytochrome P450 enzymes of human hepatocytes isolated from fatty liver grafts.

Liver grafts discarded for transplantation because of macrosteatosis can constitute a valuable source of human hepatocytes for in vitro metabolic and pharmacotoxicological studies or for therapeutic applications. A condition for using hepatocyte suspensions for these purposes is the preservation of their metabolic competence and, particularly, drug-metabolizing enzymes. A reduction in microsomal cytochrome P450 (P450) activities was observed in fatty livers (>40% steatosis) with respect to normal tissue. Similarly, decreased levels of 7-ethoxycoumarin O-deethylation and testosterone metabolism were observed in human hepatocyte cultures prepared from steatotic liver tissue. To clarify the potential impact of lipid accumulation on human hepatic P450 enzymes, we have used an in vitro model of "cellular steatosis" by incubation of cultured hepatocytes with increasing concentrations (0.25-3 mM) of long-chain free fatty acids (FFA). A dose-dependent accumulation of lipids in the cytosol is induced by FFA mixture. Hepatocytes exposed to 1 mM FFA for 14 h showed lower activity values of CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2D6, CYP2E1, and CYP3A4 enzymes than nontreated hepatocytes (about 45-65% reduction). This treatment also produced significant decreases in CYP1A2, CYP2A6, CYP2C9, CYP2D6, CYP2E1, and CYP3A4 mRNA to about 55 to 75% of mRNA levels in control cells. Our results suggest that although human hepatocytes isolated from steatotic liver show reduced P450 activities, they are metabolically competent and can be used for drug metabolism studies.     

Risks for abuse against pregnant Hispanic women: Morelos, Mexico and Los Angeles County, California

BACKGROUND: Although violence against women is gaining international attention as a prevention priority, little is known about how risks differ across countries. METHODS: A comparative study of violence against pregnant Mexican women in Morelos, Mexico, and Latina women in Los Angeles County, California, United States. In 1998 and 1999, women in prenatal clinics were interviewed about psychological abuse and sexual and physical violence by their partner, during and the 1 year prior to the index pregnancy. The overall response rate for Morelos was 99%, with a sample size of 914; Los Angeles County had a response rate of 96.9%, with a sample size of 219. RESULTS: Women in Morelos reported a higher prevalence of violence compared to women in the California (14.8% v 11.9%, respectively). A partner aged <20 years was associated with increased violence in both countries, but the association of violence with other socioeconomic factors differed by country. For example, employed women had higher odds of violence in California but lower odds in Morelos. Women who experienced violence during both the year prior to pregnancy and as a child were more than 25 times more likely to be abused during pregnancy than women not reporting this type of abuse. CONCLUSION: The identification of factors associated with violence against women, especially as they differ by culture and ethnicity, will help clinicians to better identify victims and to design and implement culturally appropriate prevention programs.     

Improvement in performance status after erythropoietin treatment in lung cancer patients undergoing concurrent chemoradiotherapy

PURPOSE: A prospective Phase II trial was carried out to evaluate the effectiveness of erythropoietin in improving or maintaining performance status as determined by the Karnofsky performance status (KPS) score and hemoglobin (Hb) levels in lung cancer patients treated with concurrent chemoradiation (CH-RT). METHODS AND MATERIALS: A total of 51 patients with lung cancer (11 with small-cell, limited stage and 40 with non-small-cell disease, 17 with Stage IIIA and 23 with Stage IIIB), who underwent three different concurrent CH-RT protocols were enrolled. Baseline Hb and KPS values were recorded, as were the nadir Hb and KPS values before concurrent CH-RT. The final Hb and KPS values were recorded the last week of concurrent CH-RT. An Hb level of 相似文献