Disease relevance of Exocrine Pancreatic Insufficiency

• We have measured the level of lingual lipase activity in gastric and duodenal aspirates of five patients with cystic fibrosis (CF) and pancreatic insufficiency [1].
• Gastric lipase secretion could be increased in several clinical conditions and particularly in patients with pancreatic insufficiency caused by alcoholic chronic pancreatitis who have been abstinent for a long time [2].
• Cftr (-/-) mice have mild pancreatic insufficiency, which partially explains the blunted increase of pancreatic and serum digestive enzymes during acute pancreatitis [3].
• Fifteen patients with cystic fibrosis and pancreatic insufficiency were studied during four randomised seven day treatment periods in which they received only pancreatic supplement (Pancrelipase, 27 capsules per day) or supplement plus cimetidine (20 mg/kg body weight/24 h) or sodium bicarbonate (15 g/m2/24 h) alone or in combination [4].
• Here we report a 9 year old Thai male patient, who was diagnosed to have CF based on recurrent pneumonia, a slow weight gain, pancreatic insufficiency and repeatedly elevated sweat chloride levels by two different methods [5].

High impact information on Exocrine Pancreatic Insufficiency

• No effects of cimetidine on the therapeutic response to oral enzymes in severe pancreatic insufficiency [6].
• Here we show that mutants reported to be associated with CF with pancreatic insufficiency do not support HCO3- transport, and those associated with pancreatic sufficiency show reduced HCO3- transport [7].
• Cholesterol malabsorption in pancreatic insufficiency: effects of enzyme substitution [8].
• In fact, the present data suggest that sterol absorption may be disturbed more sensitively than fat absorption in pancreatic insufficiency [8].
• Lipid metabolism in pancreatic insufficiency was studied by measuring serum lipoproteins, cholesterol absorption with double labels and serum plant sterols, and bile acid and cholesterol synthesis with fecal and dietary steroid analysis and cholesterol precursor sterols before and during exogenous pancreatic enzyme substitution [8].

Chemical compound and disease context of Exocrine Pancreatic Insufficiency

• These findings suggest that proximal duct epithelial cells play a key role in the early events leading to pancreatic insufficiency in CF, and imply that apical chloride transport by these cells is essential for normal pancreatic secretory function [9].
• The bentiromide test using plasma p-aminobenzoic acid for diagnosing pancreatic insufficiency in young children. The effect of two different doses and a liquid meal [10].
• In conclusion, the bentiromide test is a simple, clinically useful means of detecting pancreatic insufficiency in young children, but a higher dose administered with a liquid meal is recommended [10].
• Our results indicate that in adult patients with pancreatic insufficiency, the fecal triglyceride content does not differ from the controls [11].
• Bile acid malabsorption in cystic fibrosis and acquired pancreatic insufficiency is minimal and probably not clinically important [12].

Biological context of Exocrine Pancreatic Insufficiency

• In contrast, pancreata from pdx-1(-/-) mice expressing the mutant PDX-1 transgene were hypoplastic, and these mice died within 3 weeks of birth from pancreatic insufficiency [13].
• This loss of 97% of normal CFTR mRNA must be responsible for the pancreatic insufficiency and for the severe CF phenotype in these patients [14].
• The second major CF mutation is associated with pancreatic insufficiency and occurred in the same haplotype in which the delta F508 arose [15].
• In these patients with severe pancreatic insufficiency, we suggest that the lingual lipase is responsible for a considerable proportion of triglyceride hydrolysis [16].
• CF heterozygote serum or sera form children with diarrhoeal disorders not associated with exocrine pancreatic insufficiency had no effect of transport [17].

Anatomical context of Exocrine Pancreatic Insufficiency

• Shwachman-Diamond syndrome (SDS) is an autosomal recessively inherited disorder characterized by exocrine pancreatic insufficiency and bone marrow failure [18].
• We utilized a readily accessible source of mouse pancreatic islets [CBA/J mice lacking exocrine pancreas (exocrine pancreatic insufficiency syndrome)] to experimentally induce ICAs inbred mice [19].
• Both patients had sufficient lipase and colipase secretion to maintain normal digestion of fat, confirming that meconium disease in CF does not necessarily imply pancreatic insufficiency and the need for enzyme supplementation in infancy [20].
• In six patients with pancreatic insufficiency, cimetidine produced a pronounced decrease in the output of gastric acid and secretory volume, resulting in reduction of postprandial acidity and intragastric volume [21].
• Rats with chronically elevated plasma CCK levels induced by experimental exocrine pancreatic insufficiency did not show any change in tissue concentrations of SLI or in D-cell number, both in the antrum and corpus [22].

Gene context of Exocrine Pancreatic Insufficiency

• UBR1(-/-) mice are viable but have defects that include pancreatic insufficiency, similarly to UBR1(-/-) human patients with Johanson-Blizzard syndrome [23].
• Patients with chronic pancreatitis with mild to moderate impairment of exocrine function and abdominal pain, had significantly higher plasma CCK concentrations, whereas patients with pancreatic insufficiency had a significantly lower plasma CCK response to a test meal than the healthy subjects [24].
• Shwachman-Diamond syndrome (SDS) is an autosomal-recessive disorder characterized by short stature, exocrine pancreatic insufficiency, and hematologic defects [25].
• CONCLUSIONS: After total gastrectomy, patients develop severe primary exocrine pancreatic insufficiency with decreased gastrin, decreased late postprandial pancreatic polypeptide, and increased cholecystokinin levels [26].
• Pancreatic insufficiency led to elevated NT-concentrations, in response to a standard meal, which could be reduced by enzyme replacement therapy [27].

Analytical, diagnostic and therapeutic context of Exocrine Pancreatic Insufficiency

• During a combined intravenous infusion of secretin (1 CU/kg X h) and pancreozymin (1 Ivy dog unit/kg X h), amino acid concentrations decreased maximally by 31% +/- 19% (mean +/- SD) in controls, but only by 6.3% +/- 4.7% in patients with exocrine pancreatic insufficiency (p less than 0.001 vs. controls) [28].
• BACKGROUND AND AIMS: The 13C-Hiolein breath test (98% [U-13C] labelled long chain triglyceride mixture (highly labelled triolein) was evaluated as a non-invasive, non-radioactive test for exocrine pancreatic insufficiency [29].
• Diagnosis of pancreatic insufficiency was established for a fecal E1 <200 microg/g. RESULTS: The DM and control groups were comparable regarding age (62 +/- 10 yr vs 56 +/- 10 yr), sex (18 men and 24 women vs 15 men and 23 women), and proportion of patients with excess weight (50% vs 42%) [30].
• The results of the current study suggest that, for assessment of pancreatic insufficiency in CF, the radioimmunoassay for cationic trypsin(ogen) is more useful than the presently available radioimmunoassay for the anionic form [31].
• The 18 CF patients with this complication had varied clinical features including mild pulmonary involvement, early onset severe pancreatic insufficiency, and profound electrocardiogram (ECG) changes [32].

References