In a German company polychlorinated biphenyls (PCB)-containing transformers and capacitors were recycled on a large scale. Human biomonitoring revealed a high PCB body burden in workers of the recycling company, in surrounding locations of this plant, in companies in the neighborhood of this plant, and in family members of these employees. In order to clarify whether possible adverse health effects occurred or may occur in the future, a prospective surveillance program was initiated. After an extensive literature search, an interdisciplinary group of experts developed a surveillance program based on current knowledge with respect to possible adverse health effects that might occur in the recycling process of transformers and capacitors. Exposure to various hazardous substances (PCB, polychlorinated dibenzo-p-dioxins and dibenzo-furans [PCDD/F], metals, solvents) was considered. Criteria derived from human biomonitoring results of PCB were used for admission to the program. Participants in the surveillance program are first informed about risks and aims of the program. Subsequently, physicians started a detailed documentation of participants' general and occupational history, with their complaints, diseases, and nutritional habits, as well as information regarding their living areas, by means of a standardized questionnaire. In addition, separate examinations were performed to detect possible neurological, immunological, (neuro)psychological, hormonal, and skin effects. Moreover, DNA exposure as assessed by the comet assay and antioxidative status were determined. The program will be offered at yearly intervals for 3 years, and then at 5 and 10 years after program onset. Until now the program has proved to be feasible, and acceptance among workers and their families has been high. Based on the results, criteria will be developed to define adverse health effects that might be attributable to a hazardous substance exposure.
Summary
The Symphony study showed superior 1‐year kidney graft outcome in patients on immunosuppression with tacrolimus/mycophenolate mofetil (Tacr/MMF). To analyze whether differences in clinical outcome between maintenance regimens may be explained by their impact on clinically relevant immune parameters, we assessed CD4 helper activity, immunoglobulin‐secreting cell (ISC) formation, neopterin, sCD30, and intracellular cytokine production in a prospective study in 77 renal transplant recipients treated with cyclosporine A/azathioprine (CsA/Aza), CsA/MMF, Tacr/Aza or Tacr/MMF at 2 years post‐transplant. Tacr‐ compared with CsA‐based immunosuppression was independently associated with increased IL‐2 (P < 0.0001, CD4 cells; P = 0.014, CD8 cells) and CD4 cell IL‐4 responses (P = 0.046; stepwise logistic regression) resulting in physiological responses in Tacr/Aza patients as compared with 25 healthy controls. MMF versus Aza treatment was proven to be an independent variable associated with suppression of CD4 cell IL‐10 responses (P = 0.008), B‐cell IL‐6R expression (P < 0.0001) and ISC formation [P = 0.020, staphylococcus cowan strain I (SAC I); P = 0.021, pokeweed mitogen (PWM)]. Our data suggest that Tacr/MMF had the most effective impact on graft protective Th2 responses (enhanced CD4 cell IL‐4 by Tacr, decreased CD4 cell IL‐10 responses by MMF) and suppression of B‐cell functions (MMF), whereas Tacr/Aza was associated with physiological IL‐2 and IL‐4 and stronger humoral responses which may reduce the risk of infectious disease complications.
(ClinicalTrials.gov number: NCT00150891).
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