Effects of antimicrobial agents on spontaneous and endotoxin-induced cytokine release of human peripheral blood mononuclear cells

 Because the immunomodulatory effects of antibiotics could possibly influence the degree of the systemic and local response to infection, knowledge of their intrinsic influence on the host's inflammatory response appears to be essential. Therefore, this study investigated the effects of frequently used antimicrobial agents (β-lactams, quinolones gentamicin, vancomycin and metronidazole) on the in-vitro tumor necrosis factor (TNF)-α and interleukin (IL)-6 production of isolated human peripheral blood mononuclear cells (PBMNC), cultured with or without endotoxin, in comparison with those effects obtained in a whole-blood assay system. In the presence of ciprofloxacin, ofloxacin, gentamicin, vancomycin, and metronidazole, a significant inhibition of the endotoxin-stimulated TNF-α production of human peripheral blood mononuclear cells (PBMNC) was found at therapeutic levels. Only ofloxacin showed a significant inhibitory influence on the endotoxin-induced IL-6 production of PBMNC. In the whole-blood assay, significant effects were not detectable. None of the antibiotics showed cytotoxicity. It is concluded that, at present, the direct immunological effects of antibiotics should be interpreted carefully with regard to the experimental conditions, and regardless of the therapeutic implications. To assess the potential direct immunomodulatory effect of antimicrobial agents, different cell culture procedures should be used. Received: October 19, 2001 / Accepted: February 15, 2002     

Finite element analysis of a bone-implant system with the proximal femur nail.

Static analysis with finite element of a realistic femur nail bone-implant system in a typical proximal femoral fracture under physiological load bearing situations provides results for stress, displacement and strain. The question to be answered is, if simulation with the finite element analysis is able to explain biomechanically clinical observed patterns of failure. Surface-Reconstruction with CT database of a proximal femur and reconstruction with CT based density data was done. Next steps were to unite the bone structure with the Proximal Femoral Nail and to model two relevant fractures (31-A2.2 and A2.3 according AO). After modelling of geometry, isotropic material behaviour and load application numeric calculation of the femur-nail system with FE-software was performed. FE simulation mainly shows an axial dislocation of the femoral head screw with nearly no dislocation of the antirotation screw. This so-called z-effect therefore means: (1) Tilting of the proximal main fragment around the sagittal axis between the screws and (2) relative movement of both screws in the frontal plane. Relative movement of the two screws against each other could be the reason for implant failure, the so called cut out. Furthermore simulation shows different gliding of the screws explaining the so called z-telescoping. The analyzed stress patterns have to be relativized, because isotropic material behaviour of cancellous bone was assumed. Further examinations for this issue are necessary.     

Medizinische Beurteilungskriterien zu bandscheibenbedingten Berufskrankheiten der Lendenwirbelsäule (I)

Occupational diseases Nos. 2108 and 2110 correspond to intervertebral disc-related diseases of the lumbar spine from many years of carrying or lifting heavy loads, occupations in extreme postures of full flexion or oscillation of the whole body when seated, and which compel the cessation of all activities which are or could be the cause for the origin, exacerbation or recurrence of the disease. These occupational diseases came into force at the start of 1993, but there have been considerable problems in their implementation. The present Part I of the contribution is the result of the work of an interdisciplinary study group and contains medical criteria for the assessment of possibly strain-related clinical characteristics and the evaluation of other possible causes. Part II is to be published in Volume 4/2005 and will deal with questions related to forced cessation and to the assessment of the loss of earning ability. Agreement was reached in many areas related to the assessment of occupational claims. This should allow for evidence-based decision making in the future for the occupational diseases Nos. 2108 and 2110.     

European view toward incorporating adverse events into package inserts.

The information contained in package inserts varies from country to country in Europe, although other regulatory aspects of data presentation are quite similar. West Germany's Drug Law of 1976 requires 11 items to be included in the package insert for both patient and health professional: name/address of manufacturer; drug name; active constituents; indications; contraindications; side effects; drug interactions; dosage instructions; method and duration of application; statement that drug should not be used after expiration date; and statement that drug should be kept out of reach of children. All information must be submitted to the Health Office at the time of application or the applicant is liable for criminal prosecution. Documentation of side effects must be complete, although no special form is required. Similarly, causality assessment needs to be made even though specific algorithms are not required. Proposed amendments to the Drug Law will include additional information to physicians concerning the overdose instructions, pharmacological properties, and bioavailability of the drug. Registration procedures are the same throughout Europe and are called Summary of Products Characteristics. Assessment reports are also required for each new chemical entity in the European Community.     

Repeated measurements of mite and pet allergen levels in house dust over a time period of 8 years

BACKGROUND: Studies of the association between indoor allergen exposure and the development of allergic diseases have often measured allergen exposure at one point in time. OBJECTIVE: We investigated the variability of house dust mite (Der p 1, Der f 1) and cat (Fel d 1) allergen in Dutch homes over a period of 8 years. METHODS: Data were obtained in the Dutch PIAMA birth cohort study. Dust from the child's mattress, the parents' mattress and the living room floor was collected at four points in time, when the child was 3 months, 4, 6 and 8 years old. Dust samples were analysed for Der p 1, Der f 1 and Fel d 1 by sandwich enzyme immuno assay. RESULTS: Mite allergen concentrations for the child's mattress, the parents' mattress and the living room floor were moderately correlated between time-points. Agreement was better for cat allergen. For Der p 1 and Der f 1 on the child's mattress, the within-home variance was close to or smaller than the between-home variance in most cases. For Fel d 1, the within-home variance was almost always smaller than the between-home variance. Results were similar for allergen levels expressed per gram of dust and allergen levels expressed per square metre of the sampled surface. Variance ratios were smaller when samples were taken at shorter time intervals than at longer time intervals. CONCLUSION: Over a period of 4 years, mite and cat allergens measured in house dust are sufficiently stable to use single measurements with confidence in epidemiological studies. The within-home variance was larger when samples were taken 8 years apart so that over such long periods, repetition of sampling is recommended.