ceruletide and Celiac-Disease

To determine the relationship between pancreatic secretory capacity and nutritional status in celiac patients, we studied 52 patients with celiac disease (24 males, 28 females; age range 6-36 months) and 30 healthy control subjects (14 males, 16 females; age range 6-42 months). A secretin-cerulein test was performed on all patients, and levels of serum albumin and plasma fibronectin were assayed. In addition, weight/height ratios were calculated in the celiacs, who were then divided into three groups on this basis, as follows: celiacs with weight/height ratio < or = 3rd percentile; those with weight/height ratio between the 4th and 10th percentiles; and those with weight/height ratio > 10th percentile. There was no significant difference in the duodenal output of chymotrypsin, phospholipase and lipase between these groups. When the total celiac group was compared to control subjects, only lipase levels were significantly lower (P < 0.009). However, subnormal values in one or more pancreatic enzymes were observed in 15/52 celiacs (29%). A residual enzyme activity < 10% of normal secretory capacity, was also found in 4/52 patients. There was no correlation between the output of the various pancreatic enzymes and levels of albumin, fibronectin, and weight/height ratios in the patients. Furthermore, there was no difference in weight/height ratios and levels of albumin and fibronectin between the celiac subjects with pancreatic deficiency and those with normal pancreatic function. We conclude that a mild/moderate pancreatic insufficiency is quite frequent in celiacs, but that it may be completely independent of nutritional status; further studies are therefore required to shed light on its pathogenesis.

Topics: Biopsy; Celiac Disease; Ceruletide; Chi-Square Distribution; Child, Preschool; Exocrine Pancreatic Insufficiency; Female; Humans; Infant; Intestine, Small; Male; Nutritional Status; Pancreatic Function Tests; Prospective Studies; Secretin; Statistics, Nonparametric

The present study was undertaken to determine whether alterations in the gallbladder sensitivity to cholecystokinin (CCK), apart from a reduced endogenous CCK secretion, contribute to the abnormally decreased postprandial gallbladder contraction in patients with coeliac disease. Gallbladder emptying, measured by cholescintigraphy, and plasma CCK levels, measured by radioimmunoassay, were studied during infusion of graded doses of the CCK analog cerulein in six coeliac patients with subtotal villous atrophy, six coeliac patients on a gluten-free diet with normal villous architecture, and nine control subjects. Both in the patients and in the controls infusion of stepwise increasing doses of cerulein, in the range of 1-16 ng.kg-1.h-1, induced dose-related changes in plasma CCK-like immunoreactivity (CCK-LI) (r = 0.99; p less than 0.001) and gallbladder emptying (r greater than 0.97; p less than 0.01-p less than 0.001). Plasma CCK-LI and gallbladder responses were not significantly different among untreated coeliac patients, treated coeliac patients, and controls. Gallbladder sensitivity to cerulein in untreated and treated coeliac patients was not significantly different from that in controls. It is concluded that the abnormally decreased gallbladder contraction in coeliac patients is the result of a reduced endogenous CCK secretion and not of a lack of end-organ responsiveness to CCK.

Topics: Celiac Disease; Ceruletide; Cholecystokinin; Female; Gallbladder; Humans; Male; Middle Aged; Muscle Contraction; Muscle, Smooth; Radioimmunoassay; Radionuclide Imaging

This study was designed to determine the extent of pancreatic insufficiency in untreated coeliac disease and whether pancreatic secretion is impaired after a prolonged gluten free period. Three groups of patients were studied: group A comprised 44 patients, mean (SD) age 4.0 (3.1) years, with coeliac disease and total or subtotal atrophy of the intestinal mucosa; group B comprised 67 patients, mean age 4.4 (3.0) years, with coeliac disease but with normal morphology of the intestinal villi (after 12.9 months of a gluten free diet); group C comprised 49 control subjects, mean age 3.2 (3.0) years, with normal jejunal histology. In all subjects exocrine pancreatic function was determined by the secretin-caerulein test; bicarbonate concentration and lipase, phospholipase, and chymotrypsin activity were measured after an intravenous injection of secretin 1 clinical unit (CU) + caerulein 75 ng/kg body weight. Faecal chymotrypsin concentration was also assayed. No significant difference was found between values of the duodenal output of pancreatic enzymes and bicarbonate obtained in the three groups; however, 10 of 44 untreated coeliac patients showed tryptic or lipolytic activity, or both, below the normal limit for our laboratory. The mean value of the faecal chymotrypsin concentration was significantly lower in untreated than in treated coeliac patients (p less than 0.0001) or in control subjects (p less than 0.0001). It is concluded that untreated coeliac patients may have pancreatic deficiency independent of a decrease in enterohormone release. No primary or secondary pancreatic insufficiency was found in coeliac patients where the intestinal mucosa had returned to normal.

Topics: Adolescent; Celiac Disease; Ceruletide; Child; Child, Preschool; Chymotrypsin; Duodenum; Exocrine Pancreatic Insufficiency; Feces; Female; Glutens; Humans; Infant; Intestinal Mucosa; Male; Pancreas; Secretin

We have investigated the possibility that the abnormally decreased gall bladder contraction after meals in patients with coeliac disease might result in part from an abnormality in the gall bladder response to endogenous cholecystokinetic hormones--for example, cholecystokinin and motilin--rather than solely from decreased secretion of such hormones. Eight patients with untreated coeliac disease and nine controls received intravenous infusions of the pure synthetic cholecystokinin analogue caerulein, 2-16 ng/kg/hour. Gall bladder emptying was measured on a minute-by-minute basis using 99mTc-HIDA scans. In the patients with coeliac disease, gall bladder emptying was greatly decreased (34.6 +/- 9.9 v 61.5 +/- 7.5% at 60 minutes, p less than 0.02), and a much greater dose of caerulein was needed to initiate gall bladder contraction (3.80 +/- 1.08 v 1.49 +/- 0.56 ng/kg, p less than 0.02). These results suggest that the abnormal gall bladder contraction in coeliac disease is not simply because of impaired release of cholecystokinin. Although mechanical factors secondary to the increased gall bladder size in patients with coeliac disease might to some extent account for the findings, the alternative explanation is that the gall bladder muscle is for some reason resistant to the action of cholecystokinetic agents. A similar phenomenon affecting the pancreas might contribute to the abnormally decreased pancreatic secretion found in coeliac disease.

Topics: Adult; Celiac Disease; Ceruletide; Gallbladder; Humans; Imino Acids; Muscle Contraction; Organometallic Compounds; Radionuclide Imaging; Technetium Tc 99m Lidofenin; Time Factors

To test the discriminatory potential of certain indices of pancreatic function we performed duodenal perfusion studies and measured trypsin, bicarbonate, and lactoferrin outputs, and plasma concentrations of pancreatic polypeptide and motilin in the basal state and during continuous intravenous stimulation with 100 ng kg-1h-1 Ceruletide and 1 CU kg-1h-1 secretin. The following groups were studied: 12 normal volunteers (NV), seven patients with chronic pancreatitis with steatorrhea (CPS), and seven without steatorrhea (CP). Stimulated trypsin outputs, after 45 min of stimulation, were the best discriminant among the groups (NV versus CPS, p less than 0.0005; NV versus CP, p less than 0.005; CP versus CPS, p less than 0.05). Basal trypsin outputs showed similar patterns but failed to discriminate between NV and CP. Bicarbonate outputs were less discriminatory than trypsin outputs. Lactoferrin outputs failed to discriminate, but transient high peak outputs occurred in the initial stimulation period in all four patients with calcific chronic pancreatitis, suggesting a washout phenomenon. Basal motilin levels were elevated in both groups of pancreatitis (p less than 0.05). Stimulated pancreatic polypeptide levels were lower in CPS (NV versus CPS, p less than 0.05) but higher in CP (NV versus CP, p less than 0.005). These differences were also apparent in the basal state. We conclude that the best discrimination among the three groups was achieved by measurement of trypsin outputs, after 45 min of stimulation. In addition, the pancreatic polypeptide response may be used as a marker of residual pancreatic function in chronic pancreatitis.

Topics: Adult; Aged; Bicarbonates; Celiac Disease; Ceruletide; Chronic Disease; Female; Humans; Islets of Langerhans; Lactoferrin; Male; Middle Aged; Motilin; Pancreas; Pancreatic Polypeptide; Pancreatitis; Secretin; Trypsin