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101.
Lack of availability of reference standards for drug metabolites, newly released drugs, and illicit drugs hinders the analysis of these substances in biologic samples. To counter this problem, an approach is presented here for quantitative drug analysis in plasma without primary reference standards by liquid chromatography-chemiluminescence nitrogen detection (LC-CLND). To demonstrate the feasibility of the method, metabolic ratios of the opioid drug tramadol were determined in the setting of a pharmacogenetic study. Four volunteers were given a single 100-mg oral dose of tramadol, and a blood sample was collected from each subject 1 hour later. Tramadol, O-desmethyltramadol, and nortramadol were determined in plasma by LC-CLND without reference standards and by a gas chromatography-mass spectrometry reference method. In contrast to previous CLND studies lacking an extraction step, a liquid-liquid extraction system was created for 5-mL plasma samples using n-butyl chloride-isopropyl alcohol (98 + 2) at pH 10. Extraction recovery estimation was based on model compounds chosen according to their similar physicochemical characteristics (retention time, pKa, logD). Instrument calibration was performed with a single secondary standard (caffeine) using the equimolar response of the detector to nitrogen. The mean differences between the results of the LC-CLND and gas chromatography-mass spectrometry methods for tramadol, O-desmethyltramadol, and nortramadol were 8%, 32%, and 19%, respectively. The sensitivity of LC-CLND was sufficient for therapeutic concentrations of tramadol and metabolites. A good correlation was obtained between genotype, expressed by the number of functional genes, and the plasma metabolite ratios. This experiment suggests that a recovery-corrected LC-CLND analysis produces sufficiently accurate results to be useful in a clinical context, particularly in instances in which reference standards are not readily accessible.  相似文献   
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PURPOSE: Multiple factors contribute to mortality in the elderly, but the extent to which traditional factors contribute independently to mortality in different countries is not known. Our objective is to determine the differential impact of socio-demographic variables, selected diseases, health habits and disability on all-cause mortality, among older people living in five European countries and Israel. METHODS: From six longitudinal studies on aging (TamELSA-Tampere (Finland), CALAS-Israel, ILSA-Italy, LASA-Netherlands, AL-Leganés (Spain), SATSA-Sweden), a harmonized common database was created in the context of the CLESA Project (Cross-national determinants of quality of life and health services for the elderly). A common five-year follow-up was used. RESULTS: The highest mortality rate was found in Tampere among females (98.7%) and in Israel among males (108.3%), whereas the lowest was observed in Leganés for males (72.3%) and in The Netherlands for females (44.6%). In multivariate models, some predictors were homogeneously, significantly distributed across the six countries, including older age (HR = 1.57) and male sex (HR = 1.60) among the socio-demographic variables; smoking status (HR = 1.15) and alcohol consumption (HR = 0.81) among the health habits variables; presence of heart disease (HR = 1.34), diabetes (HR = 1.46), cancer (HR = 1.93), respiratory disease (HR = 1.19), and disability (HR = 2.92) among the health status variables. Marital status, education, and drug use did not have homogeneous effects in the six countries. DISCUSSION: This large international study shows that multiple factors contribute to increased risk of all cause mortality among older people and that most risk factors are similar across countries. Disability, age greater than 80 years, cancer and male sex were identified as the strongest common risk factors of mortality.  相似文献   
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Aim: This prospective study investigated the role of viral infections in the pathogenesis of intussusception, including human herpesvirus 6 (HHV‐6), a known lymphotropic virus. Methods: Fifty‐three children with intussusception treated in hospital were enroled, and children of comparable age and gender served as controls. Blood, stool and throat swab specimens, as well as mesenteric lymph nodes and pieces of intestine from patients requiring surgery were tested for various viruses by PCR methods. Results: Altogether, 85% of intussusception cases showed evidence of a recent or ongoing viral infection. Among the 53 intussusception cases, adenovirus was detected in 25 (47%), HHV‐6 in 24 (45%), rhinovirus in 12 (23%), cytomegalovirus in 7 (13%), enterovirus in 4 (8%) and rotavirus in 3 (6%) patients. Of the 50 whole blood samples, 44% were positive for HHV‐6 and of the 16 resected mesenteric lymph nodes, 50% were positive for HHV‐6. Simultaneous presence of HHV‐6 and adenovirus infection correlated significantly with intussusception (OR 12.1, 95% CI 2.2 to 66.5). Conclusions: A statistically significant association was observed between adenovirus and childhood intussusception. HHV‐6 was a common finding and occurred concomitantly with other viruses. A simultaneous infection with HHV‐6 and adenovirus carried the highest risk for intussusception.  相似文献   
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The 2.4 billion working people in the developing countries often have to endure employment conditions, which do not meet even basic occupational safety and health (OSH) standards. The lack of work safety, excessive work loads, and occupational physical, chemical and biological exposures result in occupational diseases, injuries and as many as 1.2 million fatalities each year. Furthermore, as little as 15% of workers in the developing countries have access to occupational health and safety services. Some collaboration between the industrialized and developing countries in the field of OSH has been practiced for 30 years but its volume has been modest compared to other sectors of development assistance. The lessons learned from 30 years of experience are that the most important OSH improving factors in developing countries include legal and policy instruments, national OSH programs, infrastructure for OSH implementation, and OSH services. The establishment of OSH expert human resources, centers serving as engines for research, training, as well as information and registration systems can also be considered as key factors in any such collaboration. A convincing government OSH policy, and close cooperation between social partners and the government are also critical factors that guarantee sustainable OSH programs in a developing country over a long-term basis.  相似文献   
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Multicolor fluorescent in situ hybridization (FISH) was used to identify acquired chromosomal aberrations in 12 patients with mycosis fungoides or Sézary syndrome, the most common forms of primary cutaneous T-cell lymphoma (CTCL). The most frequently affected chromosome was 12, which showed clonal deletions or translocations with a break point in 12q21 or 12q22 in five of seven consecutive Sézary syndrome patients and a clonal monosomy in the sixth patient. The break point of a balanced translocation t(12;18)(q21;q21.2), mapped in the minimal common region of two deletions, fine mapped to 12q2. By locus-specific FISH, the translocation disrupted one gene, NAV3 (POMFIL1), a human homologue of unc-53 in Caenorhabditis elegans. A missense mutation in the remaining NAV3 allele was found in one of six cases with a deletion or translocation. With locus-specific FISH, NAV3 deletions were found in the skin lesions of four of eight (50%) patients with early mycosis fungoides (stages IA-IIA) and in the skin or lymph node of 11 of 13 (85%) patients with advanced mycosis fungoides or Sézary syndrome. Preliminary functional studies with lentiviral small interfering RNA-based NAV3 silencing in Jurkat cells and in primary lymphocytes showed enhanced interleukin 2 expression (but not CD25 expression). Thus, NAV3 may contribute to the growth, differentiation, and apoptosis of CTCL cells as well as to the skewing from Th1-type to Th2-type phenotype during disease progression. NAV3, a novel putative haploinsufficient tumor suppressor gene, is disrupted in most cases of the commonest types of CTCL and may thus provide a new diagnostic tool.  相似文献   
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BACKGROUND: The prognostic value of morphometric nuclear features in Dukes' Stages B/C and D colorectal cancer (CRC) was assessed. PATIENTS AND METHODS: Primary tumours from 86 CRC patients were analysed, using an image overlay drawing system (Prodit Morphometry Program), for the following nuclear features: area, perimeter, diameter, form factor, roundness. RESULTS: The median nuclear area (NA) was 104.6 microm2 (range 57.2 - 237.2 microm2). The NA was larger in patients with lymph node metastasis (p < 0.02). Altogether, 43% of the patients showed clinical response to irinotecan-based chemotherapy. All six patients with complete response (CR) had a NA above the median (p < 0.03). The disease-specific survival of the patients with a NA above the median was significantly better than in patients with smaller NA (p < 0.02). CONCLUSION: Using the median NA as the cut-off value seems to effectively discriminate patients who are likely to respond to irinotecan-based chemotherapy (with improved prognosis) from those who are non-responsive and develop progressive disease.  相似文献   
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