[Diabetes screening and prevention in a large chemical company]. / Diabetes-Screening und Prävention in einem Großunternehmen der chemischen Industrie.

INTRODUCTION: Diabetes is with 6 million cases in Germany one of the most common and most expensive chronic diseases. Studies presume a high number of unreported cases. Early detection of diabetes with a specific screening method is very important. In Germany family physicians offer a preventive check-up starting at the age of 35 years but only 19% males participate. From this background the BASF department for Occupational Medicine and Health Protection introduced for all 35.000 employees at the headquarter, in Ludwigshafen a general health check focused on the early detection of lifestyle diseases. METHODS: From April 2011 to June 2013 12.114 employees participated in the general health check offered by the medical department (2.530 women, 9.584 men). All participants filled out a questionnaire named "Findrisk" a scientifically validated questionnaire which focuses on risk factors for diabetes. Furthermore, the blood glucose and the HbA1c of the participants have also been checked in a laboratory test RESULTS: Following the Findrisk criteria the results are: 1.368 employees had an elevated risk of 17%, 854 employees a risk factor of 33% and 131 employees a risk factor of 33%. In 1.533 employees (13,2% of all participants) we diagnosed a prediabetes with an elevated HbA1c-parameter between 5.7 to 6,4%. In 243 employees a manifest diabetes disease with HbA1c of > than 6,5% was diagnosed. DISCUSSION: We found out that diabetes prevention within the workplace setting is helpful to detect prediabetes and diabetes earlier than family doctors outside the company are able to do.Occupational physicians have the opportunity to inform the employees on risks for lifestyle diseases at an early stage when they are still healthy (primary prevention).For secondary prevention surveillance and clearance examination can be easily combined with screening tests for diabetes. For further diagnostics and therapy the family doctors will be addressed. This system helps individuals to prevent negative health effects, it helps the employer to reduce incapacity time and it also helps the state health system to safe money for therapy and rehabilitation.

One- vs 4-week stent placement after laparoscopic and robot-assisted pyeloplasty: results of a prospective randomised single-centre study.

OBJECTIVES: To determine whether 1-week stenting of the pelvi-ureteric anastomosis of laparoscopic or robot-assisted pyeloplasty is as effective as 4-week stenting, based on their respective success rates. PATIENTS AND METHODS: A total of 100 patients with pelvi-ureteric junction obstruction were treated by Anderson-Hynes pyeloplasty and the anastomosis was stented using a 6-F JJ catheter for either 1 week (1W series) or 4 weeks (4W series), based on a randomisation protocol. Postoperative follow-up was performed at 3 months using intravenous urography (IVU), at 6 months using diuretic renography and at 1, 3 and 5 years using ultrasonography. Statistical analysis was performed using a one-sided Z-test, Pearsons's chi-squared test and a Wilcoxon rank sum test. RESULTS: The primary outcome measure, success rate, which was defined as no obstruction on IVU and diuretic renography, was 100% in the 1W series and not inferior to the success rate of 98% in the 4W series (P = 0.006). The following secondary outcome measures were not significantly different between the 1W and the 4W series with regard to residual symptoms (10 vs 6%; P = 0.48), rate of complications (4 vs 6%; P = 0.65), need for synchronous robot-assisted pyelolithotomy (4 vs 8%; P = 0.47), improvement in split renal function (1 vs 0%; P = 0.59) and duration of surgery (200 vs 192 min; P = 0.87). Only length of hospital stay was significantly different; this was shorter in the 1W series (5 vs 6 days; P = 0.01). CONCLUSIONS: Stenting of the pelvi-ureteric anastomosis after laparoscopic or robot-assisted pyeloplasty for 1 week is as effective as stenting for 4 weeks. Both procedures, laparoscopic or robot-assisted pyeloplasty have an excellent success rate.

Tissue-specific gene expression in medullary thyroid carcinoma cells employing calcitonin regulatory elements and AAV vectors.

Calcitonin (CT), the major secretory product of the C cell, is also expressed in C-cell-derived neoplasia. To investigate the role of the CT gene regulatory sequence in tissue-specific gene expression, the genes coding for the herpes simplex virus thymidine kinase (HSVtk) and for the enhanced green fluorescent protein (EGFP) regulated by the CT promoter (rAAV/CT266tkneo), the CT promoter/enhancer element (rAAV/CTenhtkneo), or the cytomegalovirus (CMV) promoter (rAAV/CMVtkneo) were transduced by recombinant adenoassociated viral (AAV) vectors into the medullary thyroid carcinoma (MTC) cell lines TT and hMTC and into HeLa cells as controls. In TT cell lines and hMTC cell lines transiently infected by the rAAV/CT266tkneo viruses, a significant increase in (3)H ganciclovir uptake was observed. Upon ganciclovir treatment, TT cells infected by rAAV/CT266tkneo revealed a significant growth inhibition, which was less tissue-specific because HeLa cells were also affected by these particles (74.5%). In contrast, a minor but more tissue-specific growth inhibition (33.6%) was observed for TT cells after transient infection with the rAAV/CTenhtkneo particles. Employing EGFP controlled by CMV promoter and the individual CT regulatory sequences for transduction by rAAV particles, similar results were obtained indicating that both the CT promoter and enhancer element are required for tissue-specific gene expression in MTC.

5-Fluoro-1-(2'-deoxy-2'-fluoro-beta-D-ribofuranosyl) uracil trapping in Morris hepatoma cells expressing the herpes simplex virus thymidine kinase gene.

UNLABELLED: The planning and individualization of gene therapy with suicide genes such as herpes simplex virus thymidine kinase (HSV-tk) necessitates the assessment of the enzyme activity expressed in the tumor. This can be done by uptake measurements of specific substrates for HSV-tk. Due to the molecular structure of 5-fluoro-1-(2'-deoxy-fluoro-beta-D-ribofuranosyl)uracil (FFUdR), it may be a substrate for both the mammalian thymidine kinase and HSV-tk. METHODS: Using a HSV-tk-expressing rat hepatoma cell line and a control cell line (bearing the empty vector) the uptake of 3H-FFUdR was determined with increasing incubation periods. Furthermore, measurements with graded mixtures of HSV-tk-expressing cells and control cells were made. To elucidate the mechanism of FFUdR transport into cells, a series of inhibition/competition experiments was performed with challenge inhibitors of the nucleoside and the nucleobase transport systems. RESULTS: The uptake studies with tritiated FFUdR revealed a 14- to 19-fold higher accumulation in the HSV-tk-expressing cell line compared to the control cell line. While the 3H-FFUdR uptake was 3- to 4-fold higher than the 3H-ganciclovir uptake in the HSV-tk-expressing cells, it was also higher in control cells (5-fold). Furthermore, FFUdR accumulation was linearly correlated with the amount of HSV-tk-expressing cells. FFUdR uptake and growth inhibition by therapeutic doses of ganciclovir were highly correlated, with r = 0.96. Inhibition/competition experiments showed that FFUdR is transported mainly by the equilibrative and the concentrative nucleoside transporter but not by the nucleobase transport systems. CONCLUSION: The FFUdR uptake is an indicator of the HSV-tk activity in tumor cells and can be used as a prognostic marker during gene therapy with HSV-tk. The relative merits of ganciclovir and FFUdR as specific substrates for HSV-tk will need to be further explored in vivo.

Multitracer studies during gene therapy of hepatoma cells with herpes simplex virus thymidine kinase and ganciclovir.

UNLABELLED: Using different tracers of tumor metabolism, the application of PET for monitoring gene therapy with the suicide gene herpes simplex virus thymidine kinase (HSVtk) is investigated in this in vitro study. METHODS: Morris hepatoma cells were transfected with a retroviral vector bearing the HSVtk gene, and different clones were established by selection with the neomycin analog G418. Thereafter, uptake measurements using fluorodeoxyglucose (FDG), 3-O-methylglucose, aminoisobutyric acid and methionine were performed in a thymidine kinase (TK)-expressing cell line and in control cells bearing the empty vector in the presence of different concentrations of ganciclovir (GCV). These experiments were done up to 48 hr after the onset of therapy. The values were expressed as Bq/well or as Bq/10(5) cells. RESULTS: During GCV treatment therapy, a decrease of the uptake/well was measured for all tracers in the TK-expressing cell line. After normalization to the viable cell number, the uptake for FDG and 3-O-methylglucose increases up to 195% after 24 hr incubation with GCV. A high-pressure liquid chromatography analysis revealed a decline of the FDG-6-phosphate fraction after 48 hr incubation with GCV. Consequently, a normalization of FDG uptake was observed after this incubation period, whereas the 3-O-methylglucose uptake was still increased. Experiments performed with different amounts of TK-expressing cells and control cells showed that these effects are dependent on the percentage of TK-expressing cells. The aminoisobutyric acid uptake decreases to 47%, while the methionine uptake decreases in the acid-insoluble fraction (to 17%) and increases in the acid-soluble fraction (to 150%). CONCLUSION: These data indicate that combinations of the PET tracers used in these experiments may be applied for monitoring gene therapy with HSVtk. The increase in FDG and 3-O-methylglucose uptake in vitro is interpreted as stress reaction of the tumor cells. However, an uncoupling of transport and phosphorylation was observed after 48 hr incubation. The amino acid uptake experiments point to an inhibition of protein synthesis as well as of the neutral amino acid transport.

Monitoring gene therapy with herpes simplex virus thymidine kinase in hepatoma cells: uptake of specific substrates.

UNLABELLED: This study investigates the application of PET with specific substrates for the assessment of enzyme activity after transfer of the herpes simplex virus thymidine kinase (HSV-tk) gene. METHODS: After transfection of a rat hepatoma cell line with a retroviral vector containing the HSV-tk gene, different clones were established by G418 selection. Uptake measurements were performed up to 48 hr in a TK-expressing cell line and in a control cell line using thymidine (TdR; measured under therapy conditions), fluorodeoxycytidine (FdCyt) and ganciclovir (GCV). Additionally, bystander experiments and inhibition/competition studies were done. RESULTS: In TK-expressing cells GCV treatment caused an increased (up to 250%) TdR uptake in the acid-soluble fraction and a decrease to 5.5% in the acid-insoluble fraction. The FdCyt uptake was higher in the TK-expressing cells than in controls with a maximum after 4 hr (12-fold and 3-fold higher in the acid-insoluble and acid-soluble fraction). GCV accumulated up to 180-fold more in the acid-insoluble and 26-fold more in the acid-soluble fraction. GCV uptake occurred mainly by the nucleoside transport systems. Bystander experiments revealed a relation between growth inhibition or GCV uptake and the amount of TK-expressing cells. GCV uptake and growth inhibition were correlated with r = 0.96. CONCLUSION: Assessment of GCV accumulation may serve as an indicator of the enzyme activity and of therapy outcome. TdR may be useful to measure therapy effects on DNA synthesis, whereas the potential of FdCyt has to be investigated in further studies.

Study of morbidity of personnel with potential exposure to vinclozolin.

OBJECTIVES: To examine internal exposure and targeted health outcomes of employees exposed to 3-(3,5-dichlorophenyl)-5-methyl-5-vinyl-1,3-oxazolidine-2,4-dione; chemical abstracts service (CAS) number: 50471-44-8 (vinclozolin). METHODS: A cross sectional study of 67 men exposed to vinclozolin for one to 13 years during synthesis and formulation operations and 52 controls. Biomonitoring was based on determination of urinary metabolites that contained a 3,5-dichloroaniline (3,5-DCA) moiety. Targeted health endpoints were the same as in previous subchronic and chronic animal studies--namely, reversible changes in the concentrations of hormones of the adrenocorticotrophic and gonadotrophic feedback systems, signs of liver injury, haemolytic anaemia, cataract formation (uniquely in rats), and hormonally induced hyperplasia and tumours at high doses. The clinical investigation consisted of a medical and occupational history questionnaire, physical examination, laboratory determinations (including testosterone, LH, and FSH measurements), ultrasonography of the liver and prostate, a detailed eye examination, and routine spirometry. RESULTS: The mean 3,5-DCA concentration for two thirds of the study group exceeded an equivalent of the vinclozolin acceptable daily intake (ADI) used for consumer regulatory purposes. Even the highest concentrations were, however, at least 10 times below the no observable adverse effect level (NOAEL) based on animal studies. Analysis of physical examination and laboratory data provided no evidence of hormonal responses induced by vinclozolin. Furthermore, no evidence of liver injury, prostate changes, cataract formation, or haemolytic anaemia was found. CONCLUSION: There was no evidence of any health effects induced by vinclozolin among employees with potential long term exposure. In particular, no antiandrogenic effects were found.

Laboratory results for selected target organs in 138 individuals occupationally exposed to TCDD.

Blood specimens for dioxin congener analysis and clinical laboratory studies were recently obtained for 138 employees who had been potentially exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) following a 1953 trichlorophenol autoclave accident. Results for 34 clinical tests were regressed on three exposure measures (current TCDD concentration, log TCDD concentration back-calculated to the time of exposure, and chloracne status). Age, smoking status and body-mass-index were included as additional explanatory factors in the analyses. Positive associations were found between each of the exposure measures and both serum thyroxine (T4) and thyroxine binding globulin (TBG). Additional exposure-response associations were detected relative to several immune system parameters, erythrocyte sedimentation rate, platelet count and serum alkaline phosphatase. These data will be specifically helpful in interpreting the results of additional morbidity and mortality studies conducted within the same target population.

Morbidity study of extruder personnel with potential exposure to brominated dioxins and furans. I. Results of blood monitoring and immunological tests.

The potential for exposure of employees to polybrominated dibenzofurans (PBDFs) and dibenzo-p-dioxins (PBDDs) during extrusion blending of resins containing decabromodiphenyl ether was established through previous air monitoring (area samples) and biomonitoring studies. The findings presented herein are further biomonitoring results for 42 employees and immunological tests for exposed and referent employees. Among potentially exposed men, 2,3,7,8-TBDF and 2,3,7,8-TBDD concentrations in blood lipid ranged from non-detectable to 112 parts per trillion (ppt) and from non-detectable to 478 ppt respectively. Biomonitoring results correlated well with assignments in the extruder work area when adjusted for process changes and engineering improvements and provided biological half life estimates of between 1.1 and 1.9 years for 2,3,7,8-TBDF and between 2.9 and 10.8 years for 2,3,7,8-TBDD. Results for 16 measures of the immune system were examined in relation to exposure (exposed v referent group) and in relation to the biomonitoring data. Some individual trends in immunological parameters with exposure and covariates such as age and cigarette smoking were found (for example, an increase in complement C4 with increasing concentrations of PBDFs and PBDDs, increased lymphocyte subpopulation counts with cigarette smoking); however, the overall clinical assessment was that the immune system of exposed employees was not adversely impacted at these burdens of PBDFs and PBDDs.

[Late results following tibial fractures in childhood]. / Spätergebnisse nach Unterschenkelfrakturen im Kindesalter.

At the Department of Pediatric Surgery, University of Munich, 440 children between 2 months and 16 years old were treated for lower leg fractures between 1976 and 1985. In 93% of the cases, conservative therapy was administered. Between 2 and 12 years later, 110 patients (including all of those in whom the course was complicated) underwent a follow-up examination. Very good and good results were found in 76.4% of cases and satisfactory results in 18.2%. Unsatisfactory findings such as discrepancies in leg length and the consequences of compartment syndrome were found in 5.4%. Our results support the conservative treatment of such fractures; if there are special indications, the course of therapy can be supplemented effectively by osteosynthesis.