Shwachman-diamond syndrome: A case report.

RATIONALE: The aim of this study was to analyze the genetic abnormalities and clinical manifestations of Shwachman-Diamond syndrome (SDS). PATIENT CONCERNS: A Chinese infant with elevated transaminase and a novel mutation at of sbdsc.258 +2T>C and c.184a>Tc.292G>A. DIAGNOSES: The female patient was 5 months' old at onset, with elevated transaminase as the first manifestation accompanied by restricted growth and development and oily stool. After sequencing the blood samples from patients and their parents, the heterozygous mutations of sbdsc.258 +2T>C and c.184a>T were detected. INTERVENTIONS: After admission, the patient was provided compound glycyrrhizin, Newtide formula milk supplemented with probiotics, fat-soluble vitamins, oral medication to adjust the spleen and stomach, and other symptomatic treatments. OUTCOMES: The stool traits improved, and the levels of liver function transaminases decreased compared with before. LESSONS: SDS is a rare disease with a variety of clinical manifestations. Pancreatic exocrine dysfunction, blood system manifestations, and bone abnormalities are common clinical manifestations, and genetic testing is helpful for diagnosis.

[Pancreatic infringement exocrine and endocrine in cystic fibrosis]. / Atteinte pancréatique exocrine et endocrine dans la mucoviscidose.

The exocrine pancreatic insufficiency affects more than 80% of cystic fibrosis (CF) infants. Pancreatic insufficiency is diagnosed by low levels of fecal elastase. An optimal caloric intake, a pancreatic enzyme treatment are the keys to maintain a good nutritional status. The fat soluble vitamins supplementation will be associated with pancreatic enzymes treatment and will be adapted to plasma levels. Iron and oligo-element deficiency such as zinc is common. The pancreatic enzymes function is not optimal in the proximal bowel: the intraluminal intestinal pH is low because of the absence of bicarbonate release by the pancreas. The use of proton pump inhibitors may improve the functionality of pancreatic enzymes treatment. New therapies such as ivacaftor in patients with a G551D mutation allows a weight gain in particular by restoring intestinal pH similar to controls. Lengthening of the life expectancy of patients with CF is accompanied by the emergence new aspects of the disease, especially diabetes, favored by pancreatic cystic fibrosis resulting in an anatomical destruction of pancreatic islets. Currently, diabetes affects a third of the patients after 20 years, and half after 30 years. Cystic fibrosis-related diabetes is a major factor of morbidity-mortality in all stages of the disease and is characterized by a preclinical phase of glucose intolerance particularly long reaching up to 10 years. Its pathophysiology combines a lack of insulin secretion, an insulin resistance secondary to chronic infection, and a decrease in the production of the GIP and GLP-1. The insulin secretion depending on the channel chlorine (Cystic Fibrosis Transmembrane conductance Regulator [CFTR]) activity at the membrane surface of insulin cell is reduced prior to the occurrence of pancreatic histological lesions. At the stage of diabetes, obtaining a normoglycemia by insulin treatment began very early allows to slow the decline of lung function and nutritional status. Given the silent phase of diabetes, screening it is recommended by the realization of an annual OGTT from 10 years of age, or before in severe forms of CF. New treatments of CF able to target CFTR showed their efficacy in slowing the decline of lung function, and could also contribute to slow or prevent the onset of diabetes.

Individualized vitamin A supplementation for patients with cystic fibrosis.

BACKGROUND & AIMS: To determine the vitamin A status and appropriate supplementation dosage of cystic fibrosis (CF) patients who received vitamin A supplementation based on annual serum retinol measurements. METHODS: Vitamin A food intake, supplementation dosage, and serum retinol levels were obtained for 32 CF patients >4 years of age (4.3-27.3 years old) who had pancreatic insufficiency and mild-to-moderate lung disease (percent predicted of forced expiratory volume in 1 s > 40%). These measurements were compared with the dietary reference intake for healthy children and adults (D-A-CH dietary recommendations), US and German CF recommendations, and serum retinol concentrations from National Health and Nutrition Examination Survey (NHANES) data. RESULTS: Total vitamin A intake from food and supplementation was 315% ± 182% of D-A-CH recommendations, with 65% from supplements. The range of the prescribed vitamin A supplementation dosage was 0-20,000 IU/day (median 5500 IU), and it was consistent with CF recommendations in 28% of participants. A quarter of all patients did not need any vitamin A supplementation. The total vitamin A intake exceeded the recommended upper limit of intake in 69% of subjects. The mean (range) serum retinol was 38.6 µg/dl (22.1-59.1 µg/dl). All subjects had serum retinol levels above 20 µg/dl and below 72 µg/dl (95th percentile of NHANES reference range). CONCLUSION: Individualized vitamin A supplementation of 0-20,000 IU/day based on annual serum retinol measurements may prevent deficiency and high serum retinol levels, but it may lead to vitamin A intake above the tolerable upper intake level.

[Effects of Chaiqinchengqi decoction on exocrine function of pancreatic acinar cells of acute pancreatitis rats].

OBJECTIVE: To investigate the effects of Chaiqinchengqi decoction(CQCQ-D) on exocrine function of pancreatic acinar cells and the changes of intracellular calcium concentration ([Ca2+]i) of acute pancreatitis (AP) rats, so as to explore the mechanism of CQCQ-D. METHODS: Acute pancreatitis model was induced in Sprague-Dawley rat by ligation of bile-pancreatic duct, pancreatic acinar cells were isolated by collagenase digestion and in vitro co-incubated with the drug serum containing Chaiqingchengqi decoction(CQCQ-S) which was collected from normal rats intragastrically fed on CQCQ-D, then the amylase activity secreted into the buffer was assayed and intracellular fluorescent intensity were observed and analyzed to investigate the changes of intracellular calcium concentration ([Ca2+]i). RESULTS: Amylase secretion in AP group was lower than that in sham-operation(SO) group (P < 0.01), while CQCQ-S treatment led to more significant decrease (P < 0.05); [Ca2+]i elevated in AP rats (P < 0.05), while the level of [Ca2+]i elevation was reduced after CQCQ-S treatment (P < 0.05). CONCLUSION: CQCQ-D has inhibitive effects on exocrine function of pancreatic acinar cells and the calcium overload of AP rats.

Physiological evaluation of the severity of pancreatic exocrine dysfunction during endoscopy.

OBJECTIVES: Despite the advances in pancreatic imaging, there continues to be a need to measure exocrine function to determine which patient requires enzyme supplementation. To evaluate the potential use of a rapid endoscopic test that can be conducted by nonacademic centers, we investigated whether concentration of trypsin in food-stimulated secretion is related to trypsin synthesis and secretion. METHODS: Subjects include 22 chronic pancreatitis patients (10 mild, 5 moderate, and 7 severe radiological disease) and 11 healthy controls. During upper gastrointestinal endoscopy, pancreatic secretion was stimulated by a single 30-mL duodenal injection of an enteral diet, followed 5 minutes later by periampullary juice aspiration (endoscopic pancreatic function test [ePFT]). This was followed by a conventional 2-hour marker-perfusion diet-stimulated pancreatic trypsin secretion and synthesis study (2-hour PFT [2hPFT]). RESULTS: Severity of radiological disease was associated with a progressive loss of enzyme secretion measured by the 2hPFT. The endoscopic PFT correlated positively with 2hPFT (r2 = 0.48; P < 0.0001) and an activity of less than 5% of the average normal had a 96% specificity and 75% sensitivity for the detection of pancreatic insufficiency as defined by a loss of greater than 90% of pancreatic secretion. CONCLUSIONS: The diagnostic power of endoscopy may be enhanced by the collection of a pancreatic juice sample after enteral feed stimulation because measurement of the trypsin content will identify chronic pancreatitis patients who will be benefited by enzyme supplementation.

Mechanism of exocrine pancreatic insufficiency in streptozotocin-induced type 1 diabetes mellitus.

Diabetes mellitus (DM) is a major health problem at present affecting about 180 million people worldwide. DM is associated with many metabolic abnormalities in the body including the indigestion of carbohydrates leading to malnutrition and weight loss. In this article we investigate the cellular and molecular mechanisms of exocrine pancreatic insufficiency in streptozotocin (STZ, 60 mg kg(-1), i.p.)-induced DM in male rats compared to healthy age-matched controls. Either electrical field stimulation (EFS) or cholecystokinin octapeptide (CCK-8, 10(-8) M) can elicit large and significant (P < 0.05) increases in amylase output from pancreatic segments compared to basal secretion. Insulin (10(-6) M) alone has no significant effect on amylase output compared to basal but it enhanced the secretory responses to either EFS or CCK-8. When rats were rendered diabetic with STZ, either EFS or CCK-8-evoked amylase output was significantly (P < 0.01) decreased compared to the responses obtained with either EFS or CCK-8 alone in healthy age-matched control pancreas. In addition, CCK-8 can elicit large dose-dependent release of amylase in age-matched control and diabetic acinar cells with significantly (P < 0.05) reduced responses in diabetic acinar cells. CCK-8 evoked a large rapid increase in peak cytosolic free calcium concentration ([Ca2+]c) followed by a decrease to a plateau phase in age-matched control fura-2-loaded pancreatic acinar cells. These responses were significantly (P < 0.05) decreased in STZ-induced diabetic acinar cells. In the presence of 10(-6) M insulin, CCK-8 evoked a much larger increase in the Ca2+ transient compared to the response obtained with CCK-8 alone. These effects were significantly (P < 0.01) inhibited in STZ-induced diabetic acinar cells. Similarly, in zero extracellular Ca2+ [Ca2+]c, the CCK-8-evoked [Ca2+]c was significantly (P < 0.05) reduced in both diabetic and age-matched control acinar cells, but with more pronounced reduction in diabetic acinar cells. CCK(A) receptor mRNA levels remained unchanged in diabetic rat acinar cells compared to age-matched healthy control. In contrast, amylase mRNA was significantly (P < 0.05) reduced in diabetic acinar cells compared to control. The results indicate that reduced amylase secretion in response to either EFS or CCK-8 in the diabetic pancreas may be due to reduced [Ca2+]c and gene expression for amylase and not to the gene expression of CCK(A) receptor in pancreatic acinar cells.

Gastric electrical stimulation is associated with improvement in pancreatic exocrine function in humans.

OBJECTIVE: To define the possible effects of gastric electrical stimulation (GES) for gastroparesis on pancreatic function, we performed 2 related human studies. METHODS: Fecal elastase values were compared in 2 patient groups: (1) GES devices ON and (2) GES devices OFF and (2) in 3 control groups: (1) no response (NR) to prokinetic medications, (2) positive response (RES) to medications, and (3) normal controls. Polypeptide levels in 7 of 9 GES patients with device ON and OFF, elastase results, GI symptoms (TSS), and heart rate variability (HRV) were compared by paired t tests and/or ANOVA and reported as mean +/- SE. RESULTS: Elastase was different for GES-ON and OFF (508.0 +/- 92.2 vs. GES-OFF 378.6 +/- 87.4, P < 0.05). Elastase was lower in medication NR and RES than in normal controls. Postprandial pancreatic polypeptide was greater with GES ON than OFF (P = 0.07). HRV revealed a lower percentage of change with device ON versus OFF (44.2 +/- 5.5 vs. 48.5 +/- 5.2, P = 0.08) and lower TSS with ON versus OFF (15.9 +/- 4.5 vs. 25.7 +/- 5.3, P < 0.05). CONCLUSIONS: GES improves exocrine pancreatic release, effects autonomic control, and improves GI symptoms, suggesting a possible role for GES in the treatment of pancreatic insufficiency associated with gastroparesis.