Is there a need for special preventive medical check-ups in employees exposed to experimental animal dust?

OBJECTIVE: Due to new legal requirements in Germany, the employer must request preventive medical check-ups for activities involving exposure to dust from experimental animals in the rooms in which the animals are kept. The objective is to report our first experiences with these medical check-ups in the context of academic research. METHODS: The check-ups were carried out since November 2005 and comprised a questionnaire and a medical examination, including a pulmonary function test with whole-body plethysmography. Respiratory, nasal and ocular symptoms related to occupational exposure to animals were documented. Participation in skin prick tests (ubiquitous inhalation allergens and laboratory animal allergens), a bronchial provocation test with methacholine, and serological examinations for total IgE and specific IgE antibodies was voluntary. RESULTS: Data on 132 persons are presented. One hundred and six of these had already been exposed for at least 1 year. Main complaints at the workplace were sneezing and runny nose. Ocular symptoms and bronchial asthma were reported infrequently. The development of at least one of these symptoms occurred in 34% of employees with an exposure of at least 1 year. If the weekly exposure duration was at least 5 h, the proportion of employees with complaints rose to 44.9%. In employees occupationally exposed to mice and rats, work-related complaints occurred in 33.7 and 37.8%, respectively, and sensitisation rates were 12.7 and 16.3%, respectively. Employees with and without complaints differed in history of allergic symptoms, and workplace safety measures. CONCLUSIONS: In employees with occupational contact with laboratory animal dust, the frequency of complaints was high. The results confirm the necessity of regular medical check-ups for employees with contact with laboratory animal dust. Nevertheless, the medical check-ups must be part of a prevention strategy including education, engineering controls, administrative controls, use of personal protective equipment and vocational integration.

Elimination kinetics of metals after an accidental exposure to welding fumes.

OBJECTIVE: We had the opportunity to study the kinetics of metals in blood and urine samples of a flame-sprayer exposed to high accident-prone workplace exposure. We measured over 1 year, the nickel, aluminium, and chromium concentrations in blood and urine specimens after exposure. On this basis, we evaluated the corresponding half-lives. METHODS: Blood and urine sampling were carried out five times after accidental exposure over a period of 1 year. The metals were analysed by graphite furnace atomic absorption spectrometry and Zeeman compensation with reliable methods. Either a mono-exponential or a bi-exponential function was fitted to the concentration-time courses of selected metals using weighted least squares non-linear regression analysis. The amount excreted in urine was calculated integrating the urinary decay curve and multiplying with the daily creatinine excretion. RESULTS: The first examination was carried out 15 days after exposure. The mean aluminium concentration in plasma was 8.2 microg/l and in urine, 58.4 microg/g creatinine. The mean nickel concentration in blood was 59.6 microg/l and the excretion in urine 700 microg/g creatinine. The mean chromium level in blood was 1.4 microg/l in urine, 7.4 microg/g creatinine. For the three elements, the metal concentrations in blood and urine exceeded the reference values at least in the initial phase. For nickel, the German biological threshold limit values (EKA) were exceeded. CONCLUSIONS: Aluminium showed a mono-exponential decay, whereas the elimination of chromium and nickel was biphasic in biological fluids of the accidentally exposed welder. The half-lives were as follows: for aluminium 140 days (urine) and 160 days (plasma); for chromium 40 and 730 days (urine); for nickel 25 and 610 days (urine) as well as 30 and 240 days (blood). The renal clearance of aluminium and nickel was about 2 l/h estimated for the last monitoring day.

Weekly high-dose 5-fluorouracil as 24-h infusion and folinic acid (AIO) plus irinotecan as second- and third-line treatment in patients with colorectal cancer pre-treated with AIO plus oxaliplatin.

Our objective was to evaluate the efficacy and safety of high-dose 5-fluorouracil (5-FU) as a 24-h infusion and folinic acid (FA) (AIO regimen) plus irinotecan (CPT-11) after pre-treatment with AIO plus oxaliplatin (L-OHP) in colorectal carcinoma (CRC). Twenty-six patients with non-resectable distant CRC metastases were analyzed for second- or third-line treatment with AIO plus CPT-11 after pre-treatment with AIO plus L-OHP. On an outpatient basis, the patients received a treatment regimen comprising weekly 80 mg/m2 CPT-11 in the form of a 1-h i.v. infusion and 500 mg/m2 FA as a 1- to 2-h i.v. infusion, followed by 2000 mg/m2 5-FU i.v. administered as a 24-h infusion once weekly. A single treatment cycle comprised six weekly infusions followed by 2 weeks of rest. A total of 26 patients received 344 chemotherapy applications with AIO plus CPT-11. The main symptom of toxicity was diarrhea (NCI-CTC toxicity grade 3+4) occurring in five patients (19%; 95% CI 7-39%). Nausea and vomiting presented in two patients (8%; 95% CI 1-25%). The response rate of 26 patients can be summarized as follows: partial remission: n=7 (27%; 95% CI 12-48%); stable disease: n=9 (35%; 95% CI 17-56%) and progressive disease: n=10 (38%; 95% CI 20-59%). The median progression-free survival (n=26) was 5.8 months (range 3-13), the median survival time counted from the treatment start with the AIO plus CPT-11 regimen was 10 months (range 2-24) and counted from the start of first-line treatment (n=26) was 23 months (range 10-66). We conclude that the AIO regimen plus CPT-11 is practicable in an outpatient setting and well tolerated by the patients. Tumor control was achieved in 62% of the patients. The median survival time was 10 months and the median survival time from the start of first-line treatment (n=26) was 23 months.

Palliative chemotherapy with gemcitabine and weekly high-dose 5-fluorouracil as 24-h infusion in metastatic biliary tract and gall bladder adenocarcinomas.

At present, systemic treatment is not generally recommended for advanced biliary tract and gall bladder carcinomas. In particular cases, however, it may be justified to consider systemic chemotherapy treatment. In four cases we investigated the efficacy of palliative systemic treatment in metastatic biliary tract and gall bladder adenocarcinomas. Similar to the proceedings in a phase II study for metastatic pancreas adenocarcinomas, four patients with advanced biliary tract and gall bladder adenocarcinomas received a combination treatment of gemcitabine (GEM) and weekly high-dose 5-fluorouracil (5-FU) as a 24-h infusion. Altogether, the four patients received 96 chemotherapy applications. The palliative chemotherapy was tolerated well. In one patient, leukocytopenia (toxicity grade III) and thrombocytopenia (toxicity grade III) occurred. In three patients, the palliative systemic treatment led to stable disease, partly with a significant decrease of the CA 19-9 tumor marker, and in one patient to partial remission (PR). The survival times in these four patients were 6, 10, 17 and 26 months. Even in the case of PR, a curative hemihepatectomy right could be achieved after 'downsizing'. We conclude that in the four case studies, the applied palliative combination treatment based on GEM and 5-FU proved to be effective. However, future multicenter studies will be necessary to determine the significance of palliative chemotherapy in biliary tract and gall bladder carcinomas.