Access to intracellular calcium during development in the feline gastric antrum.

Circular smooth muscle cells from the feline newborn antrum, unlike the adult, are unable to respond to myogenic agonists in the absence of extracellular calcium or to exogenous inositol 1,4,5-trisphosphate (IP3). This study examined the reasons behind the relative inaccessibility of intracellular calcium stores in the newborn period. IP3 binding was determined in antral smooth muscle homogenates from adult cats and newborns by evaluating the competitive binding of D-myo-[3H]IP3 and unlabeled IP3. Receptor density (Bmax) (fmol/mg of protein) and binding affinity (Kd) were determined. The Kd was similar in adults (31 +/- 4 nM) and newborns (28 +/- 7 nM); however, the Bmax was markedly decreased in the newborn (647 +/- 181.0 fmol/mg) compared with the adult (1755 +/- 275 fmol/mg). In adult and newborn antral cells, thapsigargin, which causes a net release of Ca2+ from intracellular stores by inhibiting Ca(2+)-ATPase-dependent reuptake activity, caused an early contraction at 30 s that was maintained for at least 20 min. We conclude that, in the newborn, dynamic intracellular calcium stores are present in the smooth muscle of the feline antrum and that differences in accessibility of intracellular calcium stores may be related to changes in the release of calcium from IP3-sensitive stores.

Signal transduction pathways associated with contraction during development of the feline gastric antrum.

BACKGROUND & AIMS: Unlike adult antral cells, feline newborn antral cells are unable to contract in response to agonists in the absence of extracellular calcium or in response to exogenous inositol 1,4,5-triphosphate (IP3) after permeabilization. Changes in intracellular pathways that are associated with these differences were examined. METHODS: In adult and kitten antrum isolated smooth muscle cell contraction, levels of 1,2-diacylglycerol (DAG) and IP3 were assessed in response to cholecystokinin (CCK). RESULTS: CCK-induced contraction was transient in the adult and sustained in the kitten. U73122 blocked contraction in adult antral cells but not kitten antral cells. In adult antral tissue, CCK (10(-7) mol/L) caused an early transient increase in the level of DAG, whereas in the newborn antrum, CCK (10(-7) mol/L) caused a sustained increase in the DAG level for up to 4 minutes. IP3 showed an early increase in both age groups. Newborn contraction is associated with an initial increase in IP3 and sustained elevation of DAG levels, whereas in adult antral cells, there is a transient increase in both IP3 and DAG. CONCLUSIONS: The relative inaccessibility of intracellular calcium stores in the newborn is associated with age-related differences in signal transduction pathways.

Lack of evidence for seasonal variation in extrahepatic biliary atresia during infancy.

Biliary atresia has been reported anecdotally to occur with temporal and geographic clustering suggestive of an infectious etiology. We examined the birth dates of infants with extrahepatic biliary atresia (EHBA) during an 18-year period for evidence of a monthly or seasonal distribution. Sixty-five patients referred for biliary atresia to the University of Michigan over this period were used as index cases. The monthly and seasonal distributions of birth dates of patients with EHBA were compared by chi 2 analysis to the monthly and seasonal birth rates of infants born in Michigan (p < 0.77 and p < 0.91, respectively). No significant difference was identified. A power analysis showed that our study had an 80% probability of recognizing a 30% variation in birth rates grouped over a 3-month period. The monthly and seasonal distributions of conception dates of patients with EHBA were also compared and found not to be significantly different from the conception dates of infants born in Michigan. We conclude that there is no monthly or seasonal variation in the date of birth or the date of conception of infants with biliary atresia.

Gastroesophageal reflux. Diagnostic and therapeutic approaches.

The clinical challenge of determining the medical conditions that are associated with obvious symptoms of gastroesophageal reflux and what diagnostic tests are appropriate to define this relationship is substantial. To determine which infants may be suffering from pathologic conditions associated with subtle signs of gastroesophageal reflux is even more challenging. This determination is essential to avoid subjecting many healthy infants to costly and potentially invasive testing. This article focuses on the physiology, clinical presentations, diagnosis and evaluation, and therapy of gastroesophageal reflux.

Update of the Adult and Pediatric Liver Transplant Program at the University of Michigan.

Significant technical innovations and improvements in immunosuppression have been introduced into our liver transplant program since its inception in 1985. The indications for transplantation have been extended to younger and older patients, and simultaneously more patients with comorbidities have been accepted for transplant. The net impact of these changes has been a continuing trend toward improved survival. Overall, patients with hepatitis B or malignancy have had poor survival rates. The introduction of prophylactic anti-hepatitis B immunoglobulin and lamivudine, and better selection of patients with malignancy may improve results for these patients in the future. As in other programs, our most vexing problem is the continuing scarcity of donor organs which has led to an ever-expanding waiting list, more deaths while awaiting transplant, and more suffering before transplantation. The introduction of living donor hepatic transplantation will be of some help in alleviating this shortage. We are confident that the evolution of our program into a joint multidisciplinary structure will provide more efficient, convenient and cost-effective care to our patients.

Developmental characteristics of the kitten antrum.

The changes in dietary constituents during growth and development from predominantly liquid to mixed solid liquid meals places an increasing burden on the antrum, which is required to triturate solids. The authors hypothesize that concomitant with these changing dietary constituents different pathways are used to mediate contraction in response to acetylcholine. Smooth muscle cells were isolated by collagenase digestion from the fundus and circular muscle layer of the antrum in the adult cat and 1-week-old kitten. The unstimulated cells from the fundus and antrum were larger in the adult than in the kitten. In normal physiological salt solution, all cells contracted in a similar dose dependent manner in response to acetylcholine in both age groups. Fundic muscle cell contraction in response to acetylcholine was unchanged in calcium-free physiological salt solution or in the presence of the calcium channel blocker, methoxyverapamil. In the adult, antral cells contracted 50% less in the absence of extracellular calcium. In the kitten, antral cells did not contract under the same conditions. After permeabilization with saponin, fundic muscle cells from the adult and kitten contracted fully in response to 1,4,5-inositol trisphosphate, whereas contraction of adult antral cells was reduced by 50% and contraction of kitten antral cells was completely blocked. These data suggest that isolated muscle cells from the fundus of both the adult cat and newborn kitten use intracellular calcium stores to contract in response to acetylcholine and 1,4,5-inositol triphosphate. In adult antral cells, acetylcholine-induced contraction requires both influx of extracellular calcium and release of intracellular calcium. In kitten antral cells, intracellular calcium stores are not used or available to mediate contraction in response to acetylcholine.

Pseudoascites: unusual presentation of omental cyst.

An unusual case of omental cyst is described. The child initially presented with a unilocular intraperitoneal fluid collection on CT. After paracentesis, CT showed freely layering peritoneal fluid, with eventual complete resolution of fluid. CT eight months later demonstrated re-appearance of a multi-septated cystic mass. At surgery, an omental cyst was found.

Bismuth subsalicylate in the treatment of chronic diarrhea of childhood.

Twenty-nine infants and children, age 2-70 months with chronic diarrhea, were admitted to a double-blind, parallel clinical trial. The subjects were randomly assigned to receive either a bismuth subsalicylate liquid or a placebo liquid formulation. Treatment was given for 7 days with dosage varied according to age. Analysis of the results showed that the subjects in the bismuth subsalicylate-treated group gained significantly more weight (p less than 0.05), had significantly fewer (p less than 0.01) and firmer (p less than 0.01) stools with less water content (p less than 0.01) during the course of the study than did the placebo-treated group. Response to treatment, as graded by nursing staff, family, and physicians was moderate to excellent in 86% of the treated group while none of the placebo group received such a rating (p less than 0.01). No differences were noted between stool weights or bile acid excretion.

Delayed gastric emptying in children with Crohn's disease.

To evaluate the role of delayed gastric emptying in the decreased nutritional intake and growth retardation of some patients with Crohn's disease, we looked at four groups: 1) Crohn's disease with growth retardation; 2) Crohn's disease with malnutrition or acute weight loss; 3) Crohn's disease without growth retardation or malnutrition; and 4) normal controls. Gastric emptying was measured by a test meal incorporating 99mTc sulfur colloid-labeled chicken liver as the solid phase marker and 111In-labeled water as the liquid phase marker. The percent of each isotope retained in the stomach over 120 minutes was compared among the groups and correlated with established nutritional parameters, caloric intake, and disease activity. Gastric emptying of the liquid component was the same in all groups, and emptying of solids in patients with Crohn's disease and growth retardation was not significantly different from controls. However, gastric emptying of solids was delayed in five of seven patients in the malnourished group; the mean emptying rate of all seven patients was significantly slower compared both to the normals (p less than 0.01) and the Crohn's patients without growth disturbances (p less than 0.05). This delay was correlated with caloric intake, but not with disease activity or any individual nutritional parameter except arm muscle area (p less than 0.01). Multiple regression analysis revealed that 54% of the variation in the emptying of solids could be accounted for by nutritional factors. Fifty-seven percent of patients with delayed gastric emptying had radiologic and/or endoscopic evidence of nonconstrictive involvement of the duodenum with Crohn's disease, while 80% of patients with such involvement had delayed gastric emptying. These results help explain the decreased caloric intake observed in Crohn's disease patients and support the role of liquid caloric supplements.

Effect of non-nutritive and nutritive suck on gastric emptying in premature infants.

Ten healthy preterm infants were studied to determine if non-nutritive and nutritive suck significantly altered gastric emptying patterns when compared with gavage feeding alone. We used a 10% dextrose meal with phenol red marker and a double sampling technique to determine gastric emptying at 10-min intervals over a 30-min test period. A crossover study design compared the effects of the three feeding methods in each infant. The gastric residual volumes expressed in milliliters per kilogram did not differ significantly when comparisons were made among groups at 10, 20, and 30 min following the test meal. Non-nutritive suck and nutritive suck and swallow of a liquid dextrose meal do not significantly improve gastric emptying in healthy preterm infants. The beneficial effects of non-nutritive and nutritive sucking on the nutritional status of preterm infants, demonstrated by others, are not related to improved gastric evacuation of feeds. Alternative explanations for these beneficial effects require further investigation.

Effects of domperidone therapy on symptoms and upper gastrointestinal motility in infants with gastroesophageal reflux.

We evaluated the effect of domperidone, a novel prokinetic agent, on symptoms and esophageal and gastric motility in 15 infants (six boys), mean age 7.9 months, with moderate to severe gastroesophageal reflux (GER) and upper gastrointestinal motility disturbances. Patients received domperidone orally for 6 weeks and underwent weekly assessment of five GER-associated symptoms, weight change, and side effects. Mean total symptom scores significantly improved after treatment (P less than 0.01). Vomiting, "spitting," and coughing each improved significantly. Postprandial reflux time (defined as esophageal pH less than 4.0) and percent peristaltic esophageal contractions improved significantly (p less than 0.05). Gastric fundic contractions, present in only four infants before treatment, occurred in nine after domperidone administration. Although mean gastric emptying of isotope-labeled formula was not improved, it improved greater than or equal to 10% over baseline in nine patients. Peristaltic amplitude, lower esophageal sphincter pressure, and esophageal acid clearance time were unchanged. Side effects were minimal. We conclude that domperidone is a useful and safe agent for treatment of gastroesophageal reflex in infants because it addresses the motility abnormalities inherent in the pathophysiology of the disorder.

Fecal alpha 1-antitrypsin clearance in patients with inflammatory bowel disease.

We evaluated fecal clearance of alpha 1-antitrypsin (alpha 1-AT) as a method of detecting and quantitating intestinal protein loss in patients with inflammatory bowel disease. We investigated alpha 1-AT clearance (C alpha 1-AT) in 14 patients (seven with Crohn's disease, seven with ulcerative colitis) and in 10 children with gastrointestinal disorders and normal serum albumin values who served as controls. The inflammatory bowel disease patients were analyzed for nutritional status, intestinal absorption, disease activity and distribution, and presence or absence of rectal bleeding. alpha 1-AT was measured in stool (72-h collections) and serum by radial immunodiffusion, and the clearance was calculated. The mean C alpha 1-AT in patients with inflammatory bowel disease was significantly (p less than 0.05) higher than that of the controls. C alpha 1-AT in the former patients was inversely related to the serum albumin level (p less than 0.001), but not to disease activity, medications, absorption, nutritional status, or moderate rectal bleeding. In the patients with Crohn's disease there was a trend to increased C alpha 1-AT from only ileal to diffuse small intestinal disease involvement. We conclude that in patients with inflammatory bowel disease, fecal clearance of alpha 1-AT is a useful method for quantitating intestinal protein loss, and that moderate rectal bleeding does not affect the C alpha 1-AT determination.

Esophageal and gastric motor abnormalities in gastroesophageal reflux during infancy.

Thirty-four infants with symptoms of gastroesophageal reflux were evaluated by esophageal manometry, pH probe, and gastric emptying studies. Infants with failure to thrive (group A) and recurrent pulmonary disease (group B) had more severe reflux by pH probe (41.6% and 36.3% reflux time postprandially, respectively) than the group of infants without serious sequellae of gastroesophageal reflux (group C), who had 19.0% reflux time postprandially, p less than 0.01. Lower esophageal sphincter pressure did not vary significantly between infants with severe reflux and milder disease. Groups A and B had significantly decreased peristaltic amplitude in the distal body of the esophagus (28.3 +/- 4.8 and 23.2 +/- 5.5 mmHg, respectively) when compared to group C (50.2 +/- 3.2 mm Hg, p less than 0.01); in addition to a significantly increased number of nonperistaltic sequences. Gastric emptying of isotope-labeled cow's milk formula after 1 h was 20.9% and 22.8% in groups A and B, respectively; significantly delayed compared to 40.6% of the meal emptied in group C infants. Gastric retention was significantly correlated with impaired distal esophageal peristaltic amplitude (r = 0.68) and increased postprandial pH documented reflux (r = 0.60). Our results provide evidence for the diffuse nature of the upper gastrointestinal motility disorder present in severe gastroesophageal reflux of infancy.

Volvulus of the ascending colon: an unusual complication of non-rotation of the midgut.

A case of non-rotation of the bowel is presented wherein volvulus of the colon occurred causing acute obstruction. Spontaneous reduction following a barium enema as well as the patient's history leads us to suspect that volvulus had occurred in the past and was responsible for the intermittent nature of the patient's symptoms. This type of volvulus is distinctly different from midgut volvulus and is a rare complication of the anomaly of intestinal rotation and fixation known as non-rotation of the bowel. Efforts should be made to study patients with malrotation anomalies at a time when they are acutely symptomatic so that intermittent volvulus such as shown here is not overlooked.

Delayed gastric emptying in infants with gastroesophageal reflux.

The purpose of this study was to investigate the rate of gastric emptying of a liquid meal in young children with symptomatic gastroesophageal reflux of varying intensity. Twenty-three infants (mean age 7.0 +/- 1.4 [SEM] months, range 2 to 14 months) were evaluated for reflux by esophageal manometry, a five-hour pH probe study, and barium swallow. The rate of gastric emptying was determined by using a liquid meal of 4 ounces of cow milk formula labeled with 99mTc sulfur colloid. In seven infants with failure to thrive and objective criteria for severe reflux, the mean gastric emptying was 21.3 +/- 6.4% at one hour. In six infants with reflux and recurrent pulmonary disease, the mean gastric emptying was 19.8 +/- 5.4%. Ten infants with mild reflux, adequate weight gain, and no pulmonary symptoms emptied 44.3 +/- 6.0% of formula at one hour, and six normal adults (mean age 28.3 +/- 2 years) emptied 56.2 +/- 6.5% of formula at one hour. These data suggest that infants with severe GER have significantly delayed gastric emptying, that gastric retention may contribute to the FTT and pulmonary symptoms in these infants, and that abnormal motor function of the gastric fundus may be a significant factor in the pathogenesis of gastroesophageal reflux of infancy.