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Biomedical subjects

D G Gall

Publications and source records attributed to D G Gall.

At least 91 records · Page 5Linked to original sources

Effect of epidermal growth factor on growth and postnatal development of the rabbit liver.

The effect of epidermal growth factor (EGF) on the postnatal development of the liver was examined. New Zealand White rabbits received 40 micrograms.kg-1.day-1 EGF from days 3 to 17 of age either intraperitoneally or orogastrically, whereas controls received saline. At days 18-20, animals underwent cannulation of the common duct using halothane anesthetic. Biliary output was measured directly for three 1-h periods: under basal conditions and in response to intravenous infusion of exogenous glycodeoxycholic acid at 0.75 and 1.5 mumol.min-1.kg-1, respectively. The bile salt pool size was measured by isotope dilution. Final mean body weight of intraperitoneal and orogastric groups did not differ from controls. Liver we weight, DNA, and protein content were significantly increased in intraperitoneally treated animals without morphological or biochemical evidence of fat deposition. Both intraperitoneal and orogastric EGF significantly increased bile salt secretion in the basal period and as a response to exogenous bile acid infusion. Bile flow was significantly increased in response to 1.5 mumol.min-1.kg-1 infusion of glycodeoxycholic acid. The bile salt pool was increased by both intraperitoneal and orogastric EGF. Administration of EGF resulted in a precocious development of glucokinase (EC 2.7.1.2) activity in the liver. EGF had no effect on serum cortisol, corticosterone, triiodothyronine, thyroxine, or free thyroxine levels. These findings suggest that in the neonatal period EGF can promote hepatic growth and maturation.

Animals↗

Effects of parenteral and enteral nutrition on postnatal development of the small intestine and pancreas in the rabbit.

Although TPN is used frequently in young infants, little information is available regarding its effect on postnatal development of the gut. The effect of total parenteral nutrition (TPN) and intragastric (IG) alimentation on ontogeny of the small intestine was examined in infant rabbits starting at 10-12 days. Animals were killed at 17-19 days. Body weight, organ weight and weight of segments of proximal, mid and distal small intestine were measured. Intestinal mucosa was scraped, weighed and homogenized for estimation of protein, DNA and disaccharidases. Na+ transport was examined in short-circuited jejunum. Weight gain was similar in controls, sham-treated and TPN animals, but was significantly reduced in IG animals. TPN induced precocious development of sucrase and maltase activity and glucose-stimulated Na+ transport, despite causing a significant decrease in mucosal weight and DNA and pancreatic amylase. IG alimentation also induced precocious development of sucrase, maltase and glucose-stimulated Na+ transport. Thus TPN, despite producing mucosal atrophy and decreased pancreatic exocrine development, stimulates accelerated postnatal maturation of the small intestine.

Animals↗

Chronic pancreatitis associated with ulcerative colitis.

A twelve-year-old girl without apparent predisposing factors developed chronic pancreatitis, and 10 months later had fulminant onset of ulcerative colitis requiring a colectomy. This report strengthens the evidence for a relationship between pancreatitis and inflammatory bowel disease.

Child↗

Rat jejunal mucosal response to histamine and anti-histamines in vitro. Comparison with antigen-induced changes during intestinal anaphylaxis.

We previously showed that rats sensitized to egg albumin (EA) respond in vivo intraluminal antigen-challenge with decreased net absorption of water and electrolytes and depletion of mucosal histamine. However, administration of anti-histamines did not prevent the transport abnormalities. The present in vitro studies examined the effect of histamine to alter net ion transport and the ability of diphenhydramine (DPH) and cimetidine (CIM) to block the responses to both histamine and antigen. Control rat jejunum was mounted in Ussing chambers and histamine was added to the serosal side either in the absence or presence of DPH or CIM. In control tissues histamine caused a transient increase in short-circuit current (Isc) in a dose-dependent manner between 10(-5) and 10(-4) M which was blocked by 10(-5) M DPH but was unaffected by CIM in concentrations up to 10(-4) M. There was no response to EA. Jejunum from sensitized rats exposed to EA demonstrated a biphasic Isc response: a rapid transient rise followed by a somewhat less elevated but sustained component. In tissues pre-treated with DPH the initial peak was unaffected but the sustained component was reduced. Our results indicate that H1-receptors mediated the effects of histamine in rat jejunal mucosa but that during intestinal anaphylaxis histamine is responsible for only a portion of the antigen-induced transport abnormalities. Our data also suggest that IgE-mediated reactions in the intestine may involve an interaction between mast cell mediators and enteric nerves.

Animals↗

Intestinal anaphylaxis in the rat: jejunal response to in vitro antigen exposure.

In previous studies we showed that rats sensitized to egg albumin respond to in vivo intraluminal antigen with decreased net absorption of Na+, Cl-, and water. These abnormalities are associated with high serum levels of immunoglobulin E (IgE) antibodies and mucosal mast cell degranulation. In the present in vitro study electrical parameters, unidirectional fluxes of Na+ and Cl-, and levels of cAMP were determined in jejunum from sensitized and control rats during a basal period and after antigen addition. In Ussing chambers potential difference and short-circuit current increased significantly in tissue from sensitized rats after addition of 100 micrograms/ml of egg albumin to both mucosal and serosal surfaces. These changes were accompanied by a reversal of net Cl- absorption to net Cl- secretion. The presence of doxantrazole, a mast cell-stabilizing agent, in the buffer prevented these abnormalities. No changes occurred in response to antigen challenge in tissue from controls. In a further series of experiments the antigen was added only to the mucosal side of the tissue in Ussing chambers. In these studies short-circuit current increased after a lag period of approximately 25 min and was significantly increased (P less than 0.025) at 35 min. cAMP levels increased significantly in jejunal slices from sensitized rats exposed to antigen for 2 min. Our findings suggest that the in vivo transport abnormalities induced by IgE-mediated mucosal reactions to a food protein are related to antigen stimulation of a Cl- secretory process.

Anaphylaxis↗

Clinical, morphological, and biochemical alterations in acute intestinal Yersiniosis.

The aim of this study was to examine the intestinal response to Yersinia enterocolitica (YE) infection. Growing New Zealand white rabbits (450-800 g) were infected with 10(10) organisms of a human pathogenic strain (n = 43) or NaHCO3 for controls (n = 30) and studied 3, 6, 10, and 14 days after infection. In a separate experiment infected (n = 6) and pair-fed controls (n = 6) were studied 6 days after infection. Weight gain, excretion of YE, and diarrhea were examined daily. At sacrifice segments of proximal and mid- and distal small intestine, cecum, and colon were obtained for histologic examination and mucosa of small intestine and colon for enzyme determinations. Infection with YE resulted in weight loss and diarrhea within 48-72 h. Microabscesses were present in all sections of small and large intestine by day 3 but became more severe in the ileocecal region by day 6. In infected animals at day 6 there was crypt hyperplasia throughout the small intestine and villus atrophy in the ileum. Disaccharidases were decreased in all regions by day 3 but returned to normal by day 14 in proximal and mid-, but not distal, small intestine. The pair-fed controls experienced a similar weight loss to infected animals, but showed only minor morphologic changes and no mucosal enzyme abnormalities. Our findings demonstrate that infection of weanling rabbits with YE causes diarrhea and weight loss and that, while the weight loss is largely due to reduced food intake, the morphologic and mucosal enzyme alterations are due to intestinal injury by the organism.

Acute Disease↗

Postnatal development of hepatic bile formation in the rabbit.

To investigate postnatal maturation of hepatic bile formation, bile output was measured in four groups of rabbits: suckling infants at ages 10-14, 18-22, and 26-30 days, and adults. Bile output was collected directly from the common duct during three 1-hr periods: a basal period followed by intravenous infusion of 1 and then 2 mumol/min/kg of glycodeoxycholic acid. [14C]Erythritol and [3H]inulin clearances measured canalicular bile flow and biliary permeability. Under basal conditions and with the exogenous bile acid, bile flow and bile salt secretion were lowest in 10- to 14-day-old infants and showed a gradual increase with increasing age. Bile salt-dependent flow, the linear increase in flow relative to bile salt secretion, was higher in the 10- to 14- and 17- to 22-day-old compared to the adult and 25- to 30-day-old groups. The ratio of chloride to bile salt secreted was also higher in the two younger groups. Bile salt-independent flow at theoretical zero bile salt secretion was absent in the younger groups, but evident in the adult and 25- to 30-day-old rabbits. Canalicular flow estimated by erythritol clearance was linearly related to bile salt secretion. Inulin clearance relative to erythritol clearance was higher in the 10- to 14-day-old infants than the adults. Thus, bile flow and bile salt secretion are reduced in the young infant but rise to near adult levels at the time of weaning, 25-30 days in the rabbit. The increase in flow results from increased bile salt secretion and the appearance of bile salt-independent flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Transport abnormalities during intestinal anaphylaxis in the rat: effect of antiallergic agents.

Our previous studies demonstrated that rats sensitized to egg albumin had reduced intestinal absorption of water and electrolytes in response to intraluminal antigen. The rapid onset of this effect and reduction in mucosal histamine and numbers of granulated mast cells in the lamina propria suggested a reaginic (IgE) mechanism involving mast cell mediators. In this study we examined the effect of antiallergic agents on the intestinal transport abnormalities in our model. Sensitized rats, 14 days after intraperitoneal injection of 10 micrograms of egg albumin plus alum had specific IgE serum titers greater than or equal to 1:64; control rats had no measurable IgE antibodies. Net fluxes of Na+, Cl-, and H2O were determined by in vivo perfusion during a 1-hour antigen-free period and then a 1-hour antigen period. Sodium cromoglycate, administered intravenously (20 mg/kg) or in the perfusate (5 X 10(-4) mol/L) failed to prevent mucosal mast cell degranulation as evidenced by histamine release or the decrease in absorption of H2O, Na+, and Cl- induced by antigen exposure. In contrast, 10(-3) mol/L of doxantrazole in the perfusate completely inhibited these changes. Histamine receptor antagonists, H1, diphenhydramine, or H2, cimetidine, in perfusates had no effect on the transport abnormalities. Our findings support a role for intestinal mucosal mast cells, but not connective tissue mast cells, in the pathogenesis of the intestinal dysfunction associated with mucosal IgE-mediated reactions to food proteins and suggest that mast cell mediators other than histamine are involved.

Animals↗

Gastroesophageal reflux in patients with cystic fibrosis.

Children with cystic fibrosis (CF) and their asymptomatic siblings were surveyed to determine the incidence of symptomatic gastroesophageal reflux. A subgroup of patients with CF with poor nutritional status were studied with esophageal manometry, 24-hour esophageal pH recording, and pulmonary function testing before and after initiation of supplemental continuous nighttime nasogastric feeds. Of 68 patients with CF greater than or equal to 5 years of age, 20.6% experienced regurgitation and 26.5% had heartburn. In the control group of 23 asymptomatic siblings greater than or equal to 5 years of age, none experienced regurgitation and 5.6% had heartburn. Among the patients there was no significant association between symptoms of gastroesophageal reflux and bronchodilator therapy. Eight patients had normal lower esophageal sphincter pressure of 24.8 +/- 8.8 mm Hg and thoracoabdominal pressure gradient of 11.4 +/- 4.6 mm Hg; peristalsis and upper esophageal sphincter pressure were normal. There was a significant increase in reflux episodes, episodes greater than 5 minutes, duration of the longest episode, and percent time esophageal pH was less than 4 in patients, compared with published control data, for the entire 24-hour period and during sleep. During sleep, continuous nasogastric feeding significantly increased episodes of reflux, but did not result in an increase in percent time esophageal pH was less than 4, and was not associated with evidence of aspiration or deterioration in pulmonary function. Our findings indicate that symptoms of gastroesophageal reflux, heartburn, and regurgitation are more frequent in patients with CF than in asymptomatic siblings and that gastroesophageal reflux is significantly more common in patients with CF than in controls. Nighttime nasogastric feedings can safely be used as a means of nutritional rehabilitation in patients with CF.

Adolescent↗

Membranous glomerulonephritis in a patient with Crohn's disease of the small bowel.

A 12-year-old girl presented with concurrent onset of membranous glomerulonephritis and Crohn's disease of the small intestine. Subsequent investigations failed to implicate any other systemic disease as a cause of the glomerulonephritis. Membranous glomerulonephritis is an immune complex--mediated glomerulopathy frequently associated with underlying systemic disease. The association of immune complex phenomenon with Crohn's disease and the variation of renal abnormalities in parallel with activity of bowel disease in this patient suggest that the glomerulonephritis may be due to the underlying Crohn's disease.

Child↗

Reduced bile output with chronic enteral and parenteral infusion of amino acids, glucose, and fat emulsion in rabbits.

To assess the effect of chronic administration of amino acids, glucose, and fat on hepatic excretory function, bile flow and bile salt secretion were directly measured in adult rabbits alimented either intravenously or intragastrically. Five groups of animals were studied after 9-11 days on different nutritional regimes: the first, controls, received 154 mM NaCl intravenously and rabbit chow ad libitum; the second, 2.5% amino acid-10% glucose-10% fat emulsion intravenously; the third, the same nutrients intragastrically; the fourth, reduced intake of rabbit chow to match the weight change in the intragastrically fed animals; the fifth was allowed rabbit chow ad libitum and then received the nutrient solutions intragastrically only during bile collection. Bile was collected directly at laparotomy from the common bile duct during three 1-h periods: a basal period when no exogenous bile salt was infused, then with the addition of 1, and finally 2 mumol/min/kg of glycodeoxycholic acid, the main bile acid of rabbits. During the 3-h experiment either saline (control) or the nutrient solution was administered by the respective route. Chronic administration of the nutrient solutions, whether intravenously or intragastrically, significantly (p less than 0.05) reduced bile flow and bile salt secretion compared with controls and the rabbits on a reduced chow intake. The chronic intravenous route had a more pronounced cholestatic effect than the intragastric route. Acute intragastric nutrient infusion had no effect. The decreased bile output in the chronic groups resulted from a reduction in both bile salt secretion and bile salt-independent flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

Laxative abuse and secretory diarrhoea.

Three children with chronic diarrhoea secondary to laxative abuse are reported. Growth disturbance, a previously unrecognised feature of this form of abuse, is recorded.

Adolescent↗

Effect of epidermal growth factor on ontogeny of the gastrointestinal tract.

The effect of epidermal growth factor (EGF) on the ontogeny of the gastrointestinal tract was examined in New Zealand White rabbits. EGF, 40 micrograms X kg-1 X day-1, was administered to suckling animals from 3-18 days of age either intraperitoneally or orogastrically. Controls received saline. Animals were killed at 17-18 days of age. Body weight and wet weight of stomach, pancreas, and 10-cm segments of proximal, mid, and distal small intestine were measured. The total pancreas was homogenized for determination of protein, DNA, and amylase, and the intestinal mucosa was scraped, weighed, and homogenized for estimation of protein, DNA, sucrase, and lactase. While body weights were similar wet weight of stomach and pancreas were increased by intraperitoneal and orogastric EGF. Small intestinal wet weights were increased in all segments by intraperitoneal but not orogastric EGF, and both routes significantly increased mucosal DNA in the distal segment. EGF administered orogastrically induced precocious maturation of intestinal brush-border disaccharidase activities but had no effect on pancreatic amylase, whereas EGF administered intraperitoneally induced precocious maturation of pancreatic amylase but had no effect on brush-border disaccharidase activities. These findings suggest that both systemic and oral EGF play a role in regulating growth and postnatal maturation of the gastrointestinal tract.

Amylases↗

Total parenteral nutrition-associated cholestasis: acute studies in infant and adult rabbits.

To assess the basis of cholestasis associated with total parenteral nutrition (TPN), we studied the short-term effect of the component solutions on bile flow and bile salt secretion in infant and adult rabbits. Groups of four to six adult and infant rabbits received intravenously 154 mM NaCl (control), 2.5% amino acid, 10% glucose, or 10% fat emulsion alone or in combination. Bile was collected directly from the common bile duct for 3 h. Solutions containing both amino acids and glucose significantly (p less than 0.05) reduced bile flow and bile salt secretion in both age groups. Glucose alone also decreased bile flow and bile salt secretion, whereas amino acids as the sole infusate significantly (p less than 0.05) decreased bile flow only. The suppressive effect of the amino acid-glucose solutions on bile flow was more pronounced in infants than in adults. Fat emulsion alone had no effect on bile formation. Our findings demonstrate that short-term intravenous administration of nutrient solutions containing amino acids and glucose reduces bile flow and bile salt secretion, suggesting that these components are responsible for TPN-associated cholestasis.

Age Factors↗

Epithelial response to intestinal anaphylaxis in rats: goblet cell secretion and enterocyte damage.

The effects of immunoglobulin E (IgE)-mediated reactions on the intestinal epithelium were examined during intestinal anaphylaxis in the rat. Rats sensitized by intraperitoneal injection of egg albumin (EA) plus alum developed high serum titers of IgE anti-EA antibodies after 14 days; sham-treated littermate controls had no anti-EA antibodies. Two isolated loops of jejunum were prepared in vivo in anesthetized rats. The loops were injected with EA in saline or saline alone, and intraluminal contents of each loop were examined after 4 h. Mucosal histamine decreased in sensitized rat intestine exposed to EA. Luminal mucin, measured by radioimmunoassay, was not increased by antigen challenge. In contrast, DNA, protein, and sucrase activities were elevated in contents from the isolated segments exposed to EA in sensitized rats. Histology revealed that periodic acid-Schiff-stained material was contained in goblet cells in sections prepared from these segments after antigen exposure. Cellular debris was present over the tips of the villi. These findings suggest that IgE-mediated reactions in the intestine cause epithelial damage and loss of material from cells other than goblet cells. The results indicate that release of goblet cell mucus is not a feature of intestinal anaphylaxis.

Albumins↗

Role of gastrin and cholecystokinin in the ontogenic development of the gastrointestinal tract.

The role of gastrin and cholecystokinin (CCK) in postnatal development of the small intestine was examined in infant rabbits. Experimental animals received daily intraperitoneal injections of pentagastrin, 500 micrograms/kg, or CCK-octapeptide, 40 micrograms/kg, starting on day 3 of life. The animals were sacrificed at age 17-18 days. Weight and histologic sections of pancreas, stomach, duodenum, proximal jejunum, and ileum were obtained and mucosal lactase and sucrase activities determined in the intestinal segments. No differences were seen in any of the parameters assessed in pentagastrin-treated animals compared to saline-injected littermate controls. Body weight, weight and morphology of pancreas, stomach and intestinal segments, and enzyme activities did not differ significantly. Na+ transport in proximal jejunum under short-circuited conditions was not altered by pentagastrin. CCK-octapeptide also had no effect on weight or morphology of pancreas, stomach, and duodenum, but did lead to a significant increase in weight of proximal jejunum and ileum. Mucosal enzyme activities and morphometric measurements of villus height and mucosal thickness, however, did not differ significantly between CCK-octapeptide-treated animals and saline-injected littermate controls. The increase in weight of jejunal and ileal segments was reflected by an increase in thickness of the muscle layer. The findings indicate that neither gastrin nor CCK plays a role in the ontogenic development of the small intestine.

Animals↗

Localized rigidity and narrowing of the antrum: a cause of gastric outlet obstruction in infancy.

In infants with persistent vomiting without bile staining, in whom congenital hypertrophic pyloric stenosis has been excluded, an upper gastrointestinal roentgenogram may show antral obstruction. Of four infants with partial gastric outlet obstruction described by the authors, an antral membrane was demonstrated radiologically in two. Other causes of antral obstruction, such as granulomatous disease, hour-glass deformity of the antrum, cholecystogastrocolic band and antral dysmotility, were considered and excluded as the cause of the vomiting. After medical management failed, gastroscopy revealed a rigid stenotic circumferential area in the antrum in all four infants. An antral membrane was not found. Laparotomy confirmed this finding and a pyloroplasty successfully resolved the symptoms. Localized rigidity and narrowing of the pyloric antrum, masquerading as an antral membrane radiologically, should be considered among the causes of gastric outlet obstruction in infancy. Treatment is determined by the severity of the symptoms. Pyloroplasty is successful when medical management fails.

Body Weight↗