Refractory coeliac disease in a country with a high prevalence of clinically-diagnosed coeliac disease.

BACKGROUND: Refractory coeliac disease (RCD) is thought to be a rare disorder, but the accurate prevalence is unknown. AIM: We aimed to identify the prevalence of and the risk factors for developing RCD in a Finnish population where the clinical detection rate of coeliac disease is high. METHODS: The study involved 11 hospital districts in Finland where the number of treated RCD patients (n = 44), clinically diagnosed coeliac disease patients (n = 12 243) and adult inhabitants (n = 1.7 million) was known. Clinical characteristics at diagnosis of coeliac disease between the RCD patients and patients with uncomplicated disease were compared. RESULTS: The prevalence of RCD was 0.31% among diagnosed coeliac disease patients and 0.002% in the general population. Of the enrolled 44 RCD patients, 68% had type I and 23% type II; in 9% the type was undetermined. Comparing 886 patients with uncomplicated coeliac disease with these 44 patients that developed RCD later in life, the latter were significantly older (median 56 vs 44 years, P < 0.001), more often males (41% vs. 24%, P = 0.012) and seronegative (30% vs. 5%, P < 0.001) at the diagnosis of coeliac disease. Patients with evolving RCD had more severe symptoms at the diagnosis of coeliac disease, including weight loss in 36% (vs. 16%, P = 0.001) and diarrhoea in 54% (vs. 38%, P = 0.050). CONCLUSIONS: Refractory coeliac disease is very rare in the general population. Patients of male gender, older age, severe symptoms or seronegativity at the diagnosis of coeliac disease are at risk of future refractory coeliac disease and should be followed up carefully.

Asbestos-related malignant mesothelioma: growth, cytology, tumorigenicity and consistent chromosome findings in cell lines from five patients.

Seven mesothelioma cell lines were established from clinical specimens from five patients with asbestos-related malignant pleural mesothelioma. The cells in culture show either epithelial or mixed epithelial/fibrosarcomatous growth with an average doubling time of 30 h. Giant multinucleated cells are common in all the cell lines, as well as long thin microvilli on the cell surfaces. All cell lines were cytokeratin positive and they stained negatively for monocyte-macrophage markers. All seven cell lines and one long-term tissue culture from a sixth mesothelioma patient were characterized cytogenetically. Karyotype analyses revealed complex structural and numerical abnormalities, primarily involving chromosome 1, 4, 5, 6, 7, 8, 9, 11, 12, 13 and 22. An excess of chromosome material of the short arm of chromosome 5 was seen consistently in six cell lines and in the long-term culture. In cell lines from four patients, changes in chromosome 13, mainly monosomy 13, were observed. The marker chromosomes observed in the early passages were conserved and few additional changes appeared in later passages. Six of the cell lines tested for tumorigenicity in athymic nude mice were weakly positive.

Induction of chromosome aberrations by styrene and vinylacetate in cultured human lymphocytes: dependence on erythrocytes.

Two vinyl monomers, styrene and vinylacetate, were tested for their ability to induce chromosome aberrations in cultured human lymphocytes. The effects of a 24-h treatment (48 h after culture initiation) were studied both in whole-blood cultures (with 2 X 10(8) erythrocytes/ml) and in isolated lymphocytes (with 4000 erythrocytes/ml). Styrene produced a clear dose-dependent increase in chromatid-type aberrations in whole-blood cultures (0.5-6 mM) and a weaker effect in cultures of isolated lymphocytes (1-4 mM). A statistically significant elevation in aberrations was observed at 2 mM in the former culture type and at 1 mM in the latter. These results support earlier studies on the importance of erythrocytes in the metabolic activation of styrene, but also suggest that a part of this activation occurs in the lymphocytes themselves. Vinylacetate (0.125-2 mM), the more potent clastogen of the two monomers tested, induced a distinct dose-dependent increase in chromatid-type aberrations and a slight elevation in chromosome-type breaks in both culture types. The lowest concentration giving a positive result was 0.25 mM. The clastogenic effects of vinylacetate were somewhat more pronounced in isolated lymphocytes than in whole blood. Vinylacetate is known to be rapidly hydrolyzed in vitro to acetaldehyde, which probably explains the positive result.