The expression of several forms of cytochrome P450 including P450 1A2, 2D6, 2E1, and 3A was investigated in human hepatocytes maintained in primary culture for 96 h in the absence or presence of 50 microM of various imidazole derivatives. These included ketoconazole, clotrimazole, miconazole, fluconazole, secnidazole and metronidazole. In addition, the typical inducers rifampicin and beta-naphthoflavone were used for comparison. Western and Northern blot analysis of microsomes and RNA prepared from these cultures as well as de novo synthesis experiments revealed that, among the imidazole derivatives tested, only clotrimazole was a strong rifampicin-like inducer of P450 3A. The expression of the other forms of P450 tested was not affected by the treatments. Analysis of the inhibition of 13 monoxygenase activities, including ethoxyresorufin and phenacetin O-deethylases, coumarin 7 alpha-, lauric acid 11- and 12-, mephenytoin 4-, debrisoquin 4-, and aniline hydroxylases, benzphetamine, aminopyrine, mephenytoin and erythromycin demethylases, and cyclosporin oxidase (representative of 10 different forms of P450 in human liver microsomes) revealed that ketoconazole was a strong and selective in vitro inhibitor of P450 3A (cyclosporin oxidase) with a Ki less than 1 microM. Clotrimazole and miconazole were also strong inhibitors of P450 3A-mediated activities in contrast to the other imidazole derivatives.

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During an 18-year period, 2600 patients were treated for colorectal carcinoma in the Montpellier Cancer Institute. Of the 93 patients younger than 40 years of age (3.6%), 78 records were retrospectively studied. The overall 5-year survival rate was 30%. Their survival was not significantly affected by the site of the primary tumor, the degree of tumor differentiation, or sex. The only significant parameter was Dukes' staging at presentation (P less than 0.0001). An analysis of sites of recurrence revealed the frequency of liver metastasis, ovarian metastasis in women, and local recurrence of rectal cancer. Although the high failure rate in these areas clearly justifies aggressive combined therapy, the high frequency of inaugural Stage D patients (27%) and their short mean survival time (5 months), underline the crucial importance of early detection. However, it is unfortunate that colorectal cancer screening in young patients is difficult because of the low rates of precancerous states (4%).

Thirty-nine patients with short bowel syndrome after extensive small bowel resection, with or without associated partial or total colectomy, received continuous total parenteral nutrition followed by discontinuous parenteral nutrition. Home parenteral nutrition was introduced in 16 of these patients; in eight it was permanent. The assessment of nutritional status included body weight; standard urinary and blood studies; albumin, prealbumin, and transferrin serum levels; and both urinary and fecal nitrogen. A statistically significant correlation (P less than 0.001) was observed between the length of the remaining small bowel and the necessary duration of nutritional support. Multivariate analysis allowed us to classify patients into three groups as a function of remaining gut length and the duration of required nutritional support. This study should help to define the best nutritional support protocol for patients with various short bowel syndromes in order to ensure the best possible intestinal adaptation and to improve their quality of life.