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All-trans retinoic acid (ATRA) has been previously shown to inhibit the proliferation of some human ovarian carcinoma cell lines, and this inhibition was accompanied by cellular changes that were indicative of differentiation (Caliaro et al, 1994). In this work, a pretreatment of these adenocarcinoma cells with ATRA, for their respective doubling time, enhanced cisplatin (CDDP) cytotoxicity in the cell ines that were sensitive to its antiproliferative effect, but not in the ATRA-resistant ones. Results were assessed using median effect analysis in two ATRA-sensitive cell lines (OVCCR1 and NIHOVCAR3 cells) and in one ATRA-insensitive cell line (IGROV1 cells). Synergy between these two agents was observed only in cells sensitive to ATRA, regardless of their relative sensitivity to CDDP. Potential mechanisms for this synergy were investigated. ATRA did not increase the cellular platinum content, did not decrease the cellular glutathione and had no influence on the metallothionein IIA mRNA levels in NIHOVCAR3 cells. Moreover, the protein kinase C (PKC) activity was modulated by this differentiating agent in all cell lines tested, indicating that this activity was not directly involved in this potentiation. However, an ATRA inhibition of glutathione-S-transferase activity associated with an increase in the total DNA adducts formation could explain the potentiation of the CDDP cytotoxicity observed in NIHOVCAR3 cells. Finally, the ATRA modulation of the epidermal growth factor (EGF) receptor mRNA level could also be implicated in this synergy.

The Chernobyl accident, which occurred 32 years after the accidental exposure of Marshall islanders, resulted in the exposure of neighbouring populations to a mixture of iodine isotopes and in an increased incidence of thyroid cancer. The highest thyroid doses were received by the youngest age groups. This review describes the existing evidence, and examines factors that may have increased the risk. It also stresses problems with contemporary thyroid measurements, and the lack of information on the sensitivity of the thyroid to short-lived iodine isotopes and iodine-131. Practical considerations for nuclear physicians, epidemiologists and thyroidologists are discussed in the light of this major accident.

Combined treatment with cimetidine 1 g daily and cisapride 40 mg daily in patients with endoscopically diagnosed severe reflux oesophagitis was compared with single drug therapy (cimetidine and placebo). At the end of the six to 12 weeks treatment, 11 (46%) of the 24 patients under single drug therapy were endoscopically healed and three were improved. In contrast, 16 (70%) of the 23 patients under combined therapy were healed and all of the remainder were improved (p = 0.025). The severity of diurnal and nocturnal heartburn, decreased significantly more (p less than 0.05) on cimetidine + cisapride than on cimetidine + placebo. The combined treatment was well tolerated. These results suggest that combined therapy with cisapride and cimetidine may be useful in patients with severe reflux oesophagitis.

To the Editor: A case of bacterial endocarditis after endoscopy in a patient with mitral stenosis has recently been described. 1 It has been argued that this risk of endocarditis after endoscopy in patients with valvular heart disease justifies the use of prophylactic antibiotics. 2 , 3 In five years, we have performed upper endoscopy in 59 patients with valvular heart disease and biopsies in 21 patients, without antimicrobial prophylaxis. We have not encountered any case of bacterial endocarditis. At the beginning of the endoscopy list and between cases, we wash the endoscope and the biopsy channel with benzalkonium chloride and water. Our data . . . No extract is available for articles shorter than 400 words.

To the Editor: Cancer of the ampulla of Vater in Gardner's syndrome is well known. 1 Cancer is perhaps related to the degeneration of preexisting adenomas. What should be done when adenomas of the ampulla of Vater are found during the systematic examination of a digestive polyposis? We have observed three patients with Gardner's syndrome; in each of them, colectomy with ileoproctostomy had been performed previously. In each of the three patients, the ampulla of Vater when observed endoscopically was slightly enlarged in volume, and biopsies indicated adenomatous proliferation. What can we suggest to our three patients? A regular endoscopic examination . . . No extract is available for articles shorter than 400 words.