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Biomedical subjects

C L Morin

Publications and source records attributed to C L Morin.

At least 37 records · Page 2Linked to original sources

Nutritional therapy of Crohn's disease in childhood.

Crohn's disease is a chronic, incurable inflammatory bowel disease commonly diagnosed in childhood and adolescence. Growth failure represents a common, serious complication unique to the pediatric age group. Although the etiology of growth failure is multifactorial, malnutrition due to inadequate nutrient intake is the primary cause. Recent studies have demonstrated that nutritional supplementation through an enteral or parenteral route restores body composition and reverses linear and ponderal growth failure. The development of elemental diets that can be administered nasogastrically at home has afforded a more practical, less expensive, and less hazardous method of providing Crohn's disease patients with nutritional supplementation and bowel rest. Elemental-diet therapy has also been shown to be a safe, effective method of inducing a remission in acute Crohn's disease. Further studies are required to develop optimal nutritional therapy which may sustain long-term remission in this disease.

Child↗

Malabsorption, hypocholesterolemia, and fat-filled enterocytes with increased intestinal apoprotein B. Chylomicron retention disease.

Eight infants presented with a malabsorption syndrome, normal fasting triglycerides, hypocholesterolemia (64.3 +/- 10.0 mg/dl), and deficiency of vitamins A and E. Plasma low-density lipoprotein, apolipoprotein B, and apolipoprotein A-I were decreased. After a fatty meal, plasma triglycerides did not increase and chylomicrons could not be identified. Lipoprotein composition was characterized by normal apoproteins, high phospholipids, and low cholesterol. Increased triglycerides were present in low-density lipoproteins. Immunoperoxidase localization of apolipoprotein B on fasting biopsy specimens showed increased staining of the lipid-laden intestinal epithelial cells compared to normals. On electron microscopy after a fat load, the enterocytes contained large numbers of fat particles vesiculating the endoplasmic reticulum. These particles, morphologically similar to chylomicrons, were also present as aggregates of well-individualized lipid droplets within dilated vesicles in the Golgi zone, but were not seen in the intercellular spaces and lacteals. This recessively transmitted condition differs from abetalipoproteinemia and from the homozygous form of hypobetalipoproteinemia and may be caused by a defect in the final assembly of chylomicrons or in the mechanism of their exocytosis.

Apolipoproteins B↗

Growth stimulating activity associated with an altered cell renewal pattern in the small intestine.

A growth stimulating activity has been recently identified in the rat proximal intestine during the transient stages of adaptation after small bowel resection. This study shows that the growth stimulating activity is associated with all the cells of the crypt-villus axis. At the same time the thymidine kinase activity is detectable in all the cells implying a more extensive proliferative zone during the transient stages of adaptation. The presence of the growth stimulating activity along with the more extensive proliferative zone suggests that the activity modulates the proliferation capacity of intestinal epithelial cells.

Adaptation, Physiological↗

Primary sclerosing cholangitis in children: study of five cases and review of the literature.

Primary sclerosing cholangitis in five children is described and 78 cases in the pediatric age group are reviewed. In 24% of the cases, primary sclerosing cholangitis is not associated with an underlying disease and may appear to be prolonged cholestasis of infancy. When an associated condition is present, chronic inflammatory bowel disease, in particular ulcerative colitis, is most common (47%). Histiocytosis X and a variety of immune disorders account for 15% and 10% of cases, respectively. Primary sclerosing cholangitis should be considered in the differential diagnosis of chronic liver disease in the pediatric age group, even in young infants. Results of this survey demonstrate that neither clinical features nor liver function tests are reliable diagnostic predictors, that histologic changes are often nonspecific, and that cholangiography is essential to establish the correct diagnosis.

Adolescent↗

Effect of dietary fat and residues on fecal loss of sterols and on their microbial degradation in cystic fibrosis.

Although various etiologic factors have been implicated, the mechanism responsible for bile acid malabsorption in CF remains unknown. Eight CF children studied twice on a normal diet supplemented with pancreatic enzymes and once during a one-month period of Vivonex administered by continuous nasogastric infusion were compared to age-matched controls. On the fat and residue-free elemental diet, there was a modest decrease in steatorrhea and no change in the daily excretion of nitrogen and neutral sterols. However, normalization of bile acid output (485.6 +/- 65.0 to 160.6 +/- 29.2 mg/24 hr) to control levels (150.2 +/- 60.7) was noted. Diminished microbial degradation of both neutral and acidic sterols and a smaller amount of bile acids adsorbed to decreased residues were also found. The data do not support the possibility of a bile acid ileal transport defect and suggest that the most important single factor responsible for the intraluminal sequestration of bile acids in CF is dietary residues. Because of significant ongoing losses of nitrogen and lipids, pancreatic enzymes should be given to CF patients on elemental diets.

Bile Acids and Salts↗

Secretory diarrhea with protein-losing enteropathy, enterocolitis cystica superficialis, intestinal lymphangiectasia, and congenital hepatic fibrosis: a new syndrome.

Four infants had noninfectious intractable diarrhea, vomiting, anasarca, hepatomegaly, hypoglycemia, and malnutrition within the first 3 months of life. Their parents originated from the same Northeastern part of Quebec, and consanguinity was found in two kindreds. Diarrhea was secretory in three infants (mean stool volume 87 ml/kg/day, Na+ 108 mEq/L, Cl- 85 mEq/L). Hypoalbuminemia (mean 2.0 gm/dl), present in all infants, appeared to be secondary to a protein-losing enteropathy, which was documented in two infants. Histologic examination of the upper small intestine showed only mild to moderate villous atrophy. The remarkable findings were those of cystic dilation of the crypts and acute inflammation of crypts and lamina propria, all of which were most prominent in the colon and terminal ileum; the changes were progressive over time. Mild lymphangiectasia was found in all of the patients. Congenital hepatic fibrosis, present in all, was associated in one patient with a nonfunctional multicystic kidney. Prolonged total parenteral nutrition, intravenously administered albumin, antisecretory agents, and antibiotics were unsuccessful in controlling the disease. Although a total colectomy was followed by a temporary decrease in stool output and normalization of serum albumin concentration in one infant, the patients died between 4 and 21 months of age.

Anti-Bacterial Agents↗

Establishment of an animal model of ovalbumin sensitised mouse to study protein induced enteropathy.

The protein induced modifications of the small bowel mucosa from ovalbumin-sensitised mouse have been studied in organ culture. A decrease in gamma-glutamyl transpeptidase, alkaline phosphatase, lactase, sucrase, and glucoamylase activities was observed in the explants cultured in the presence of ovalbumin. In contrast, a large increase of those enzymatic activities was noted in the culture media, the overall effect observed being a net stimulation of the total enzymatic activities of the culture system. The enzymes accumulated in the particulate fraction of the medium (brush border membrane fraction) suggesting an increased turnover of membrane components by a process of shedding or microvesiculation. This model serves as a useful tool in evaluating the local response of the small bowel mucosa induced by a specific protein.

Animals↗

Evidence for a growth-stimulating fraction in the rat proximal intestine after small bowel resection.

Small bowel resection results in a compensatory hyperplasia in the small intestine, but the molecular events that lead to the increased cell production are not known. In this study, a heat-stable acidic extract of the mucosa of the proximal intestine of Sprague-Dawley rats taken 96 h after a 50% small bowel resection was capable of stimulating DNA synthesis of mouse jejunal explants in organ culture. This stimulatory activity was present in the extracts obtained from resected animals after 48 h, 72 h, and 96 h, but was not detectable by 8 days, when presumably a new steady state was established. A significant enhancement of DNA synthesis was observed 96 h after resection when compared with groups of normal and transected animals that were pair-fed with the resected group. This activity was destroyed by protease treatment. Gel filtration experiments showed that the growth-stimulating activity present in the mucosal extract of the 96-h resected animals was due to the presence of two distinct molecules with approximate molecular weights of 4500 and 1500. The extract did not stimulate DNA synthesis in rat peripheral blood lymphocytes, mouse skin fibroblasts, and the colon adenocarcinoma cell line, HCT-8R. Similar extracts taken 96 h after resection from the distal intestine, colon, pancreas, liver, and muscle did not stimulate DNA synthesis of the mouse jejunal explants. These data suggest that the two molecules in the proximal intestine in response to resection could play a role in promoting the observed hyperplasia.

Adaptation, Physiological↗

[Crohn's disease in children and adolescents].

93 children and adolescents with Crohn's disease have been studied. Terminal ileum (25.8%) and ileum and colon (61.3%) were the most common sites of involvement as determined by X-ray examination. The mean age at the time of diagnosis was 13.2 years. A familial incidence of chronic inflammatory bowel disease was found in 12 patients (12.9%). The most common symptoms were: abdominal pain, anorexia, lassitude, diarrhea, loss of weight. Weight below the third percentile, pain on abdominal palpation, anal lesions, mouth ulcers and clubbing of the fingers were the most common clinical signs at the time of diagnosis. Growth retardation (below the third percentile) was present in 22 of 79 children (27.8%) with a mean follow-up of 40 months. 16 patients out of 75 had initial rectal biopsies with histologic changes characteristic of Crohn's disease. 27 patients had surgical treatment; six of them experienced a relapse within a mean period of 26.7 months. Lastly, the authors show that continuous elemental enteral alimentation (CEEA) during 3 weeks induces a remission. CEEA on a longer period is specially targetted to the treatment of growth retardation.

Adolescent↗

Short-term clinical, nutritional, and functional effects of continuous elemental enteral alimentation in children with cystic fibrosis.

Ten children with cystic fibrosis, aged 3.5 to 12 years, whose weights were lower than 90% of the expected weight for height, received high-calorie elemental enteral alimentation for four weeks. Clinical, anthropometric, and biochemical evaluations as well as blood gas analyses and chest radiograph scoring were performed in all. Pulmonary function tests were performed in the five older children, and progressive exercise tests in three. These evaluations were done before, immediately after, and two months after termination of therapy. Nutritional therapy resulted in an increase of caloric intake and in dramatic weight gain, which persisted only for a short time and was mainly related to adipose tissue accretion. No functional improvement accompanied the amelioration in nutritional status. This short-term nutritional therapy in malnourished children with cystic fibrosis was effective in increasing relative weight and energy stores, but there was no evidence of any long-term functional benefit.

Blood Chemical Analysis↗

The adaptation of the small intestine after resection in response to free fatty acids.

The effects of long-chain triglycerides and a mixture of free fatty acid on the adaptive response to small bowel resection were examined. Rats with a 50% small bowel resection were divided into four groups. Two received 10% of their calories intragastrically either as corn oil or as free fatty acid and the remaining calories intravenously while the two control groups were given all their calories either intravenously or orally. The results of DNA and protein determination show that free fatty acids were more effective than long-chain triglyceride in promoting adaptation (p less than 0.01) in both small intestine and in the colon. Furthermore the intragastric infusion of free fatty acids was as effective as the orally fed group. Of the plasma hormones measured (gastrin, gastric inhibitory polypeptide, enteroglucagon, and insulin) gastric inhibitory polypeptide was significantly higher (p less than 0.05) in the orally fed group and insulin levels in the free fatty acid group (p less than 0.05) than in other groups. There was no significant difference obtained in enteroglucagon and gastrin levels for the four groups. This study shows that a small amount of free fatty acids (10% of the total calories) given by continuous gastric infusion is effective in promoting intestinal adaptation after resection.

Adaptation, Physiological↗

Relapsing pancreatitis in association with Crohn's disease.

Two adolescent girls, aged 15 and 18, in whom the diagnosis of Crohn's ileocolitis had been made 6 months and 3 years previously, developed acute pancreatitis with relapses of varying duration and severity. The younger patient's condition progressed to chronic relapsing pancreatitis with intractable pain despite partial pancreatectomy. The other has had recurrent acute attacks but has been well between bouts. No duodenal involvement could be found in the two cases and there was no evidence to implicate drugs as a factor responsible for this rare association between pancreatitis and Crohn's disease.

Acute Disease↗

Hepatobiliary disease in cystic fibrosis: a survey of current issues and concepts.

The incidence of hepatobiliary complications of cystic fibrosis (CF) has been increasing in parallel with the rate of survival. Detection of hepatic involvement remains a problem, as liver function tests, serum bile acid determinations, and ultrasonography do not permit an early diagnosis. The pathogenesis of cholelithiasis has been elucidated in the past few years. However, the mechanism leading to the pathognomonic CF lesion, focal biliary cirrhosis, is still unknown. There are indications that mucus plugging may be the ancestral lesion and the triggering factor. The possibility that correction of the abnormalities of bile acid metabolism could slow the progress or prevent CF cirrhosis is discussed in light of recent experimental data.

Adolescent↗

Exocrine pancreatic function following proximal small bowel resection in rats.

1. In order to assess if proximal enterectomy induces changes in the function of the exocrine pancreas, the exocrine pancreas was studied 1 week, 4 weeks, and 6 months after 50 or 75% proximal small bowel resection. 2. One week after 50 and 75% proximal small bowel resections, basal pancreatic bicarbonate outputs, studied by means of an external pancreatic fistula in conscious rats, were increased significantly over control values by 43 and 78% respectively. Four weeks after a 75% resection, the bicarbonate output was still significantly higher in resected animals than in sham operated animals. 3. The increase of volume and bicarbonate of the basal pancreatic secretion coincided with a 4-fold increase in plasma secretin concentration 1 week after resection. Both increased pancreatic secretion and plasma secretin concentration were transient. 4. The pancreatic hypersecretion was specifically reversed to control values with an I.P. injection of jejunoileal mucosa homogenate. 5. Serum gastrin and somatostatin values in intestinal mucosa and pancreas were not changed 1 and 4 weeks after enterectomy compared with sham operated animals. 6. The weight of the pancreas and its content of DNA were unaltered by resection. Amylase and chymotrypsinogen per gram pancreatic tissue and per microgram DNA were reduced 4 weeks following resections as compared with sham operated rats. After 6 months, chymotrypsinogen appeared further reduced in resected animals. 7. It is concluded that extensive proximal enterectomy in rats produced early, transient and marked increases in basal pancreatic water and bicarbonate secretion and in plasma secretin due to the loss of jejunoileal inhibitor(s), and a selective decrease in certain enzymes in pancreatic tissue.

Animals↗

Severe familial cholestasis in North American Indian children: a clinical model of microfilament dysfunction?

Studies of 14 North American Indian children with a familial type of severe neonatal cholestasis are described. Jaundice occurred during the neonatal period in 9 children, but disappeared before the end of the 1st yr. Progressive liver damage was documented by the persistence of high levels of alkaline phosphatase, moderate elevation of transaminases, and severe pruritus. Serum bile acids were constantly elevated (3.0-119.5 microgram/ml). Early portal hypertension and variceal bleeding necessitated portal-systemic shunts in 7 children. By light microscopy, the early stage was characterized by hepatitis with giant-cell transformation and biliary stasis. Later on, portal fibrosis became evident and was followed by cirrhosis. By electron microscopy bile canaliculi appeared slightly dilated with preservation or only partial loss of microvilli. They were surrounded by a prominent pericanalicular filamentous web. Immunofluorescence studies indicated the presence of action-containing microfilaments. This group of children might represent a human model of microfilament dysfunction-induced cholestasis.

Actins↗