A rise in the incidence of bullous pemphigoid (BP) was documented recently in Europe, and the main risk factors for BP remain unknown. We conducted a multicenter case-control study to evaluate risk factors for BP. We identified 201 incident BP cases and 345 controls individually matched for age, gender, center, and place of residence (home, nursing home, or extended-care facility). We used univariate and multivariate logistic regression analyses to compare drugs used for over 3 months, comorbidities, and physical and cognitive impairments between cases and controls. Mean age of BP patients was 84.2 (±8.7) years. Factors independently associated with BP by multivariate analysis were major cognitive impairment (odds ratio (OR), 2.19; 95% confidence interval (95% CI), 1.24-3.87), bedridden condition (OR, 2.19; 95% CI, 1.23-3.89), Parkinson's disease (OR, 2.16; 95% CI, 1.09-4.27), unipolar or bipolar disorder (OR, 5.25; 95% CI, 1.21-22.86), and chronic use of spironolactone (OR, 2.30; 95% CI, 1.20-4.46) or phenothiazines with aliphatic side chains (OR, 3.70; 95% CI, 1.21-11.34). Chronic analgesic use was associated with a lower risk of BP (OR, 0.49; 95% CI, 0.30-0.81). Thus, risk factors for BP include neurological disorders, particularly dementia and Parkinson's disease, psychiatric disorders (unipolar and bipolar disorders), bedridden condition, and chronic use of several drugs.

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Summary Rats bearing a transplanted nickel-induced rhabdomyosarcoma (RMS 9-4/0), treated with chlorozotocin (CZT), an alkylating agent, showed an amplified metastatic invasion of the lung (median of 165 lung tumour nodules, compared to 3 for untreated controls). A higher level of metastatic invasion (200 nodules) was reached spontaneously after the grafting of the S4T line, which was obtained by successive in vivo passages of RMS 9-4/0 cells in CZT treated rats. S4T tumour cells also invaded the liver and a considerable proportion of the lymph nodes. The NT4T line, obtained by successive in vivo passages in untreated rats, showed a lesser degree of enhancement of metastatic capacity (57 nodules). Both derived lines proved to be more aggressive than the parental, proliferated more rapidly, and were resistant to CZT toxicity. Only the non-treated lineage became more resistant to NK lysis. The S4T line lost its myogenic differentiation and was best described as a fibrohistiosarcoma, whereas NT4T did not. Chromosome analysis demonstrated a reduced range of chromosome number per cell in both lines. We conclude that both S4T and NT4T tumours became more metastatic than RMS 9-4/0 as the result of tumour progression through in vivo passages, and that in addition S4T acquired a spontaneously higher metastatic potential, similar to that which occurred in rats grafted with RMS 9-4/0 or NT4T tumours and treated by CZT. This suggests an inheritable mutation in the S4T line.A major problem of cancer therapy is the emergence of tumour subpopulations resistant to the treatment. The probability that a tumour will generate resistant variants could be related to genetic instability (Goldie & Coldman, 1984;Stephens et al., 1986 Davies, 1982). Repair mechanisms may allow mutated cells to survive, and increase both tumour drug resistance and phenotypic heterogeneity.We have described the enhancing effect of a nitrosourea, chlorozotocin 2-(3-(2-chloroethyl)-3-nitrosoureido)-D-glucopyranose (CZT), on the metastatic ability of RMS 9-4/0, a rat rhabdomyosarcoma (Poupon et al., 1984). We hypothesized that this action was due to the emergence of a subpopulation of the RMS 9-4/0 tumour, that was both resistant to CZT and highly metastatic. We failed to obtain a selection for CZT resistance in the primary tumour because the treated rats were rapidly killed by the growth of lung metastases. To overcome this, the treated primary tumour cells were injected into new recipients that were also treated and this cycle was repeated until a fully resistant population was obtained. The metastatic ability of these cells was then studied. A group of the tumour-bearing rats were not drug-treated and gave rise to the NT(x)T tumour lineage, where (x) designates the number of cycles performed. When rats were moribund the tumour was excised, finely minced with a scalpel, and then allowed to grow in the complete medium described above. At confluence, cells were injected s.c. into new animals. Part of the cells were frozen for further analyses. Materials and me...

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