Plasma concentrations of cholecystokinin and neurotensin in patients with cystic fibrosis.

BACKGROUND: Regulation of pancreatic exocrine secretion is controlled by vagovagal reflexes and hormones. A negative feedback control mechanism exists between the intraduodenal protease concentration and pancreatic enzyme secretion. In man cholecystokinin (CCK) is the major regulator of postprandial pancreatic enzyme secretion. There is a 50% reduction of meal-stimulated secretion by the specific CCK receptor antagonist loxiglumide, whereas atropine completely blocks postprandial secretion. Neurotensin is released postprandially by nerval reflexes and fat. It has been claimed that both hormones are increased in patients with pancreatic insufficiency. METHODS: We investigated CCK and neurotensin levels in patients with cystic fibrosis and pancreatic insufficiency. In 35 patients (2-24 years old) with cystic fibrosis with steatorrhea and in 15 patients (1.5-24 years old) with cystic fibrosis without pancreatic insufficiency pre- and post-prandial CCK and neurotensin plasma levels were measured 3 days after pancreatic enzyme therapy had been withdrawn. Nine patients (3-14 years old) who had no complaint of abdominal disease served as controls. RESULTS: Basal and postprandial CCK plasma levels did not differ statistically in the three groups, whereas basal and postprandial neurotensin levels were significantly increased in the cystic fibrosis groups. The severity of the disease had no effect on the neurotensin levels. CONCLUSIONS: Cystic fibrosis patients with severe pancreatic insufficiency did not have increased CCK plasma levels, suggesting that a CCK-mediated feedback mechanism of pancreatic enzyme secretion does not operate in our patients. In contrast, basal and postprandial neurotensin plasma levels were significantly increased in patients with cystic fibrosis but were independent of the severity of the pancreatic insufficiency.

Genotype-phenotype correlations in cystic fibrosis patients.

Genetic and biomedical data from 346 cystic fibrosis patients of German origin have been evaluated. We demonstrated an age dependent distribution of CFTR genotypes, and confirmed the previously reported association between the dF508 mutation in the CFTR gene and pancreatic insufficiency. However 3 out of 22 pancreatic sufficient patients were dF508 homozygous. When patients were grouped with respect to height development, significant differences were seen in the distribution of J3.11-MspI alleles. We conclude that genetic determinants in and around the CFTR gene contribute to the variability in the clinical course of the disease.

Linkage relationships and allelic associations of the cystic fibrosis locus and four marker loci.

The linkage relationships between the cystic fibrosis (CF) locus and four marker loci (MET-H, MET-D, D7S8 and D7S16), allelic associations between these loci and the extent of informativity at these marker loci were investigated in a sample of 206 families with at least one child affected by CF. The data were contributed by 11 laboratories from Europe and Israel. The maximum lod scores and recombination frequency estimates (luminal diameter) (and confidence limits of luminal diameter) were: 18.3 at luminal diameter = 0.007 (0.001-0.038) for CF vs. MET, 11.0 at luminal diameter = 0.016 (0.001-0.068) for CF vs. D7S8, and 5.7 at luminal diameter = 0.0 (0.0-0.064) for CF vs. D7S16. A gene order of CF-MET-D7S8 was best supported by the data, but its preference to the order D7S8-CF-MET is mainly based on one single family. There are significant allelic associations between CF, MET, D7S8 and D7S16; these allelic associations affect the risk of random individuals to be carriers of CF.