The proteolytic erosion of the temporal bone is the key event in the pathognomonic course of cholesteatoma progression. The molecular mechanisms of bone resorption, endangering the ossicles, the inner ear, the facial nerve, large vessels or the brain, are not understood. Recently, a new family of proteolytic enzymes, the matrix-metalloproteinases (MMP's) has been described and identified, which seems to play a pivotal role in matrix- and bone homeostasis and inflammatory osteolytic diseases, e.g. osteoarthritis and periodontitis. These enzymes are sophisticatedly controlled by specific inhibitors and activation cascades. We investigated whether human cholesteatoma tissue expresses MMP's and MMP-inhibitors. By immunocytochemistry of cholesteatoma-cryosections, the expression of MMP-2 (72 kD collagenase), MMP-9 (92 kD collagenase), and MMP-3 (stromelysin-1) could be seen to be strictly confined to the basal and suprabasal cell layer of the cholesteatoma epithelium. The neutrophil collagenase (MMP-8) showed a more disseminated expression in the epithelium and the granulation tissue as well. The tissue inhibitor of metalloproteases, TIMP-1, could be detected only in very limited areas of the granulation tissue in a quite randomized manner. Therefore, a derailment in favor of proteolysis of the normally tightly controlled MMP-system might be postulated. The results indicate that members of the MMP-family could play an active role in the molecular mechanisms of cholesteatoma invasion into the temporal bone. This offers new insights into the pathophysiology of the disease and of potential therapeutic approaches.

AimsTo analyze the relationship between exposure to chlorinated and aromatic organic solvents and malignant lymphoma in a multi-centre, population-based case-control study.MethodsMale and female patients with malignant lymphoma (n = 710) between 18 and 80 years of age were prospectively recruited in six study regions in Germany (Ludwigshafen/Upper Palatinate, Heidelberg/Rhine-Neckar-County, Würzburg/Lower Frankonia, Hamburg, Bielefeld/Gütersloh, and Munich). For each newly recruited lymphoma case, a gender, region and age-matched (± 1 year of birth) population control was drawn from the population registers. In a structured personal interview, we elicited a complete occupational history, including every occupational period that lasted at least one year. On the basis of job task-specific supplementary questionnaires, a trained occupational physician assessed the exposure to chlorinated hydrocarbons (trichloroethylene, tetrachloroethylene, dichloromethane, carbon tetrachloride) and aromatic hydrocarbons (benzene, toluene, xylene, styrene). Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression analysis, adjusted for smoking (in pack years) and alcohol consumption. To increase the statistical power, patients with specific lymphoma subentities were additionally compared with the entire control group using unconditional logistic regression analysis.ResultsWe observed a statistically significant association between high exposure to chlorinated hydrocarbons and malignant lymphoma (Odds ratio = 2.1; 95% confidence interval 1.1–4.3). In the analysis of lymphoma subentities, a pronounced risk elevation was found for follicular lymphoma and marginal zone lymphoma. When specific substances were considered, the association between trichloroethylene and malignant lymphoma was of borderline statistical significance. Aromatic hydrocarbons were not significantly associated with the lymphoma diagnosis.ConclusionIn accordance with the literature, this data point to a potential etiologic role of chlorinated hydrocarbons (particularly trichloroethylene) and malignant lymphoma. Chlorinated hydrocarbons might affect specific lymphoma subentities differentially. Our study does not support a strong association between aromatic hydrocarbons (benzene, toluene, xylene, or styrene) and the diagnosis of a malignant lymphoma.

Aims: To identify occupations suspected to be associated with malignant lymphoma and to generate new hypotheses about occupational risks in a multicentre, population based case control study. Methods: Male and female patients with malignant lymphoma (n = 710) aged 18-80 years of age were prospectively recruited in six study regions in Germany. For each newly recruited lymphoma case, a sex, region, and age matched control was drawn from the population registers. Odds ratios and 95% confidence intervals for major occupations and industries were calculated using conditional logistic regression analysis, adjusted for smoking (in pack-years) and alcohol consumption. Patients with specific lymphoma subentities were additionally compared with the entire control group using unconditional logistic regression analysis. Results: The following economic/industrial sectors were positively associated with lymphoma: food products, beverages, tobacco; paper products, publishing and printing; and metals. Chemicals; real estate, renting, and business activities were negatively associated with lymphoma diagnosis. The authors observed an increased overall lymphoma risk among architects; maids; farmers; glass formers; and construction workers. Shoemaking and leather goods making was negatively associated with the lymphoma diagnosis (although based on small numbers). In the occupational group analysis of lymphoma subentities, Hodgkin's lymphoma was significantly associated only with rubber and plastic products making; diffuse large B cell lymphoma risk was considerably increased among metal processors; follicular lymphoma showed highly significant risk increases for several occupational groups (medical, dental, and veterinary workers; sales workers; machinery fitters; and electrical fitters); and multiple myeloma showed a particularly pronounced risk increase for farmers as well as for agriculture and animal husbandry workers. Conclusions:The results partly confirm previously defined occupational risks. Occupational risk factors for follicular lymphomas might differ from the overall risk factors for malignant lymphoma. During the past few decades, the incidence of nonHodgkin's lymphoma (NHL) increased in most Western countries. [1][2][3][4] Only recent data indicate a leveling off of this trend. In Germany, NHL made up an estimated 3% of the male and 3.4% of the female incident cancer cases in 2000. 5The aetiology of malignant lymphoma is still largely unknown. Strong evidence exists for the association between NHL and congenital or acquired immunosuppression, especially AIDS.6-10 Immune factors also seem to play a role in the aetiology of Hodgkin's lymphoma:7 an excess has been found after transplantations 11 12 as well as among HIV infected patients. 14The known risk factors explain only a small proportion of malignant lymphoma. Several studies point to a potential aetiological role of occupational factors to malignant lymphoma. Hodgkin The aim of the present multicentre, population based case control study is to identify occupati...

Although some causes for malignant lymphoma are known their etiology is not well understood so far. We analyze the relationship between sun exposure and malignant lymphoma in a multicenter, population-based case-control study. Patients with malignant lymphoma (n 5 710, 18-80 years) were prospectively recruited in 6 study regions in Germany. For each case, a gender, region and age-matched control was drawn from population-registers. In personal interviews, lifetime holidays spent in sunny climate, outdoor leisure activities and sunbed or sunlamp use were recorded. On basis of job task-specific supplementary questionnaires, an occupational physician assessed the cumulative working time outside. Odds ratios (OR) and 95%-confidence-intervals (CI) were calculated using conditional logistic regression analysis, adjusted for smoking and alcohol consumption. To increase statistical power, patients with specific lymphoma subentities were additionally compared with the entire control group using unconditional logistic regression. We observed a reduced overall lymphoma risk among subjects having spent vacations at sunny climates or frequently used sunbeds or sunlamps. The analysis of lymphoma subentities revealed similar results with the exception of T-NHL and follicular lymphoma which were positively associated with outdoor leisure activities. While cumulative working time outside appeared unrelated to NHL overall and most subentities, it was negatively associated with follicular lymphoma and weakly positively to HL. This data suggest that exposure to natural and artificial ultraviolet radiation may reduce the OR for lymphoma in this study population. ' 2007 Wiley-Liss, Inc.