Internal and external quality control in the toxicological analysis of blood and urine samples in the Federal Republic of Germany

Summary Due to a technical rule for dangerous agents (TRGS 410), issued by the Ministry of Labor in the Federal Republic of Germany in 1979, toxicological analyses in biological materials must be carried out under conditions of statistical quality control. This quality-control scheme provides internal and external control programmes. For internal quality control, the results of many years of experience with five commercially available control specimens and one home-made control have been evaluated. The control samples showed good, comparable results over a long period. Except in a few cases, there was good agreement between our results and the assigned values. Since 1982, the German Society of Occupational Medicine has offered eight intercomparison programmes for external quality. In samples from 80–90 laboratories, 6 metals in blood and around 20 inorganic and organic parameters in urine in 2 concentration adjustments have been analysed. Successful participation was certified if both results obtained for one parameter were within the tolerance range (assigned] value ± 3 SD). The average success rate was around 60%.     

Determination of tetrahydrophtalimide and 2-thiothiazolidine-4-carboxylic acid,urinary metabolites of the fungicide captan,in rats and humans

Summary Capillary gas chromatographic (GC) methods using sulphur and mass selective detection for the qualitative and quantitative determination of tetrahydrophtalimide (THPI) and 2-thiothiazolidine-4-carboxylic acid (TTCA), urinary metabolites of the fungicide captan in rat and humans, were developed. Urinary detection limits were 2.7 g/l for THPI and 110 g/l for TTCA. Intraperitoneal and oral administration of captan to rats resulted in a 48-h cumulative urinary excretion of THPI of 1%–2% and 3%–9% of the dose, respectively. Cumulative urinary excretion of TTCA over 48 h ranged from 2% to 5% of the captan dose for the respective routes of administration. In urine of non-exposed human subjects, neither THPI nor TTCA could be detected. In urine of fruit-growers who were occupationally exposed to captan, both THPI and TTCA could be detected. Based on these results, THPI and TTCA are proposed as promising parameters for the biological monitoring of occupational exposure to captan.     

Serum fluoride as an indicator of occupational hydrofluoric acid exposure

Summary To define the relationship between ionic fluoride concentration in the serum of workers and the amount of hydrofluoric acid (HF) in the work environment, pre-and postshift serum and urine samples of 142 HF workers and 270 unexposed workers were examined. The maximum and minimum concentrations of HF in the air in each workshop varied from the mean by less than 30%. The pre-exposure levels of serum and urinary fluoride in HF workers were higher (P < 0.001) than the control values. This suggests that fluoride excretion from the body continues for at least 12 h. The postshift serum and urinary fluoride concentrations of these workers were significantly higher (P < 0.001) than the preshift concentrations. A good correlation (r = 0.64) was obtained between postshift serum fluoride and postshift urine fluoride. There was a linear relationship between mean serum fluoride concentration and HF concentration in the workshop. A mean fluoride concentration of 82.3 g/l with a lower fiducial limit (95%, P = 0.05) of 57.9 g/l was estimated to correspond to an atmospheric HF concentration of 3 ppm. This is the maximum allowable environmental concentration recommended by the Japanese Association of Industrial Health, and it is also the threshold limit value suggested by the American Conference of Governmental Industrial Hygienists. The results demonstrate that exposure to HF can be monitored by determining the serum fluoride concentration.     

Exposure to soluble barium compounds: an interventional study in arc welders

Summary Soluble barium (Ba) compounds are well-known toxicants. Intoxications are mainly known in an acute form from casual or suicidal oral ingestion. No scientifically based data are available on possible health effects of inhalative exposure to soluble Ba salts at the workplace. Therefore, we investigated 18 welders in an interventional study over 1 week. They performed welding of Ba-containing stick electrodes and self-shielded flux cored wires under conditions similar to real working conditions. The welding fumes contained 31%–37% Ba, more than 90% of which was soluble in acids. Without appropriate preventive measures, a high rate of measurements exceeded the TLV values for total welding fumes of 5 mg/m³ and for soluble Ba of 0.5 mg/m³. The median fume concentrations were 13.2 mg/m³ in stick electrode welding and 12.3 mg/m³ in flux cored wire welding. The median Ba concentrations were 4.4 and 2.0 mg/m³ respectively. An integrated exhaust system built into the gun proved to be efficient in flux cored wire welding. The internal exposure to Ba reached median urine levels up to 101.7 g/l (normal: below 20 g/l) and median plasma concentrations of up to 24.7 g/l (normal: below 8 g/l). No health impact on the welders could be proven, but hypokalemia may have occurred as a result of the Ba exposure.     

Effect of administration of diethylcarbamazine on experimental bacterial and fungal infections in mice

Other researchers have found that diethylcarbamazine (DEC) is effective treatment for filariasis despite a lack of demonstrated in vitro antifilarial activity. The results of our previous investigations using feline and murine leukemia virus models encouraged us to investigate the use of DEC with other infections. In the current experiments, DEC treatmentS was associated with (a) increased survival and decreased brain Streptococcus pneumoniae levels following S. pneumoniae challenge in previously immunized mice; (b) increased serum antibody levels to S. pneumoniae, Escherichia coli, and Haemophilus influenzae following inoculation of live bacteria; and (c) lower brain fungal levels following intravenous injection of Aspergillus fumigatus or increasing numbers of Cryptococcus neoformans organisms, and lower brain and kidney levels of Candida albicans following intravenous injection of increasing numbers of C. albicans.     

Neurotransmitter markers in the cerebrospinal fluid of normal subjects effects of aging and other confounding factors

Summary We have investigated neurotransmitter-related markers of the cerebrospinal fluid (CSF) in a carefully screened series of normally aging subjects in standardized conditions in order to find out the influence of age and other confounding factors on CSF measures. The levels of 3-methoxy-4-hydroxyglycol (MHPG) and the activity of acetylcholinesterase (AChE) also increased with age, while homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5 HIAA) and immunoreactivities of somatostatin (SLI), beta-endorphin (BLI) and adrenocorticotropic hormone (ACTH) were unrelated to age. The gender of subjects had no significant effect on the levels of neurotransmitter markers, while seasonal changes, as well as height and weight of the subjects seemed to cause some variations in the levels of HVA, dopamine--hydroxylase (DBH) and ACTH. The study underscores the importance of standardized conditions and matched patient groups in the CSF studies.     

Characterization of rat hyperplastic bile ductular epithelial cells in culture andin vivo

A novel intrahepatic biliary cell culture/in vivo transplantation system has been developed with an essentially pure population of bile ductular epithelial cells isolated from rat liver 6–12 weeks after bile duct ligation. In primary culture, these cells retain staining strongly for -glutamyltranspeptidase and glutathione S-transferase P. The cytoplasm of cultured bile ductular cells reacts with an anti-laminin antibody, but loses immunoreactivity with a monoclonal anti-cytokeratin 19 antibody. Semiconservative DNA synthesis in the cultured cells was dependent upon the continued presence of 10% fetal calf serum in the medium. Replicating bile ductular cells could be subcultured for a finite number of passages. In addition, freshly isolated bile ductular epithelial cells gave rise to well differentiated bile ductular structures when transplanted into the interscapular fat pads of syngeneic recipient rats.Presented at the Proceedings of the International Meeting on Normal and Neoplastic Growth in Hepatology, Bari, Italy, June 1989.This work was supported by USPHS Grant RO1 CA39225 to Dr. Sirica by the National Cancer Institute, Department of Health and Human Services.     

宫颈癌组织血管内皮生长因子测定的临床意义

目的 :探讨血管内皮生长因子 (vascularen dothelialgrowthfactor ,VEGF)在宫颈癌诊断、治疗以及转移中的临床意义。方法 :酶联免疫吸附分析法(enzyme linkedimmunosorbentassay ,ELISA)测定 2 0例宫颈上皮内瘤样变患者和 60例宫颈癌患者组织中的VEGF含量。结果 :VEGF含量在宫颈上皮内瘤样变、宫颈癌组织中分别为 5 5 6pg/mg、410 2pg/mg ,差异有统计学意义 ,P <0 0 1。肿 瘤≥ 4cm者为 960 0 pg/mg ,淋巴结转移者为 780 5 pg/mg ,而肿瘤 <4cm者 ,淋巴结未转移者分别为 180 5 pg/mg、2 3 0 0pg/mg。差异有统计学意义 ,P <0 0 5。而在临床分期、病理分型、病理分级间差异无统计学意义。结论 :组织VEGF含量检测对宫颈癌的诊断有一定的临床价值 ,其含量变化可监测宫颈癌的转移。     

乳腺癌骨髓微转移状况与ER PR VEGF 及Cath-D等因子的关系

目的:检测乳腺癌骨髓组织CK19 mRNA的表达,判断骨髓微转移状况,探讨其与各因子的关系.方法:采用RT-PCR法(一步法)检测骨髓组织中CK19 mRNA表达;用免疫组化SP法检测乳腺癌组织中ER、PR、Cath-D、C-erbB-2及VEGF的表达.结果:102例乳腺癌患者骨髓组织CK19 mRNA表达阳性率56.9%.骨髓CK19 mRNA表达随乳腺癌组织中ER及PR蛋白表达增强而降低(P＜0.05,P＜0.01);随Cath-D、VEGF蛋白表达增强而呈增高趋势(P＜0.005,P＜0.05);但与C-erbB-2表达状况无关.结论:乳腺癌骨髓微转移与癌组织中某些生物学因子表达有关;这些因子决定癌细胞的生物学行为.     

多种肿瘤标志物蛋白芯片检测系统对恶性肿瘤的临床应用价值

 目的　研究多种肿瘤标志物蛋白芯片检测系统对恶性肿瘤诊断的临床意义。方法　用该检测系统测定分析 4 6 9例恶性肿瘤患者 ,130例良性疾病患者和 14 4 8例健康查体者血清中 12种常见肿瘤标志物 (CA199,NSE ,CEA ,CA2 4 2 ,CA12 5 ,CA15 3,AFP ,Ferrtin ,free PSA ,PSA ,β HCG及HGH)的水平。结果　恶性肿瘤组的阳性率为 81.4 5 % ,显著高于良性疾病组 (5 0 .0 0 % )和健康查体组 (2 9.77% ) (P <0 .0 5 )。除胰腺癌之外 ,联合检测对其余 14种恶性肿瘤的敏感性均显著高于单一标志物检测 (P <0 .0 5 )。结论　运用蛋白芯片技术联合检测多种肿瘤标志物可以明显提高恶性肿瘤诊断的敏感性 ,同时也可以作为无症状人群的早期肿瘤普查手段之一 ,尤其对肿瘤高危人群的防癌普查具有一定意义。