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Biomedical subjects

J Gryboski

Publications and source records attributed to J Gryboski.

16 recordsLinked to original sources

Effect of bethanechol and metoclopramide on upper gastrointestinal motility in the kitten.

Gastroesophageal reflux (GER) during infancy is a disorder of unknown etiology which may be associated with abnormalities of upper gastrointestinal motor function. Bethanechol, a muscarinic agonist, and metoclopramide, a dopamine antagonist, have been utilized as pharmacologic agents in an attempt to improve upper gastrointestinal motility in this disorder. We have studied the effect of these agents on upper gastrointestinal motility in an infant model, the kitten. Bethanechol is found to greatly increase lower esophageal sphincter (LES) pressure and have no effect on esophageal peristaltic amplitude or gastric emptying of a liquid meal. Metoclopramide causes a small and nonsignificant increase in LES pressure, has no effect on esophageal peristalsis, and increases the rate of gastric emptying of a liquid meal. These results suggest that these two agents may have specific actions on the infant's upper gastrointestinal tract.

Animals↗

Developmental characteristics of the lower esophageal sphincter in the kitten.

Gastroesophageal reflux is a common event during infancy. Developmental factors may be responsible for incompetence of the lower esophageal sphincter (LES) in this age group. We used the cat as a model to evaluate in vivo and in vitro the mechanical factors responsible for LES pressure during infancy. We found that in vivo the kitten develops lower LES pressure than the adult cat. For in vitro studies consecutive rings 1.75 mm wide were obtained from the LES region of 3-day-, 1-wk-, 3-wk-, and 6-wk-old kittens and of adult animals. Force-length curves were obtained in standard Tyrode's solution, in Tyrode's solution with high KCl, and in calcium-free Tyrode's solution with ethylenediaminetetraacetic acid disodium salt to determine basal, total, and passive forces, respectively. Active force is given by the difference between total and passive force. The maximum active force generated was lowest in the 3-day-old kittens and increased with age, being highest in the adult cat. Stresses, obtained by normalizing forces for the amount of muscle available, were greater in the kitten than the adult. The ratio of muscle thickness to its inner radius is markedly reduced in the kitten. As intraluminal or LES pressure is given by the product of stress and thickness-to-radius ratio, this might explain why lower pressures are generated despite the higher stresses developed.

Animals↗

Increased intestinal clearance of alpha 1-antitrypsin in patients with alpha 1-antitrypsin deficiency.

To evaluate the possible contribution of enteric losses of alpha 1-antitrypsin (alpha 1-AT) to the low serum levels of alpha 1-AT seen in patients with alpha 1-AT deficiency, we investigated intestinal clearance of alpha 1-AT (C-alpha 1-AT) in five of these patients (mean age 3.4 years) and compared it to that of 10 patients (mean age 3.7 years) with gastrointestinal disorders and normal serum albumin values who served as controls. C-alpha 1-AT was also determined in four patients (mean age 9 months) with noncirrhotic liver disease. The percent of daily alpha 1-AT turnover which could be attributed to stool losses was calculated in these groups of patients. alpha 1-AT was measured in stool and serum by radial immunodiffusion and the clearance calculated. The mean C-alpha 1-AT in the patients with alpha 1-AT deficiency was significantly (p less than 0.05) higher than that of the controls. The liver disease patients had values for C-alpha 1-AT in the range of the controls. Three of the alpha 1-AT deficiency patients had values for C-alpha 1-AT greater than the mean plus 3 SD of the control, but these were not in the range seen in patients with protein losing enteropathy. Mean percent contribution of stool losses to total daily alpha 1-AT turnover was similar in all three groups. We conclude that patients with alpha 1-AT deficiency have increased fecal clearance of alpha 1-AT seemingly unrelated to the liver disease, but that this is not a major cause of the low serum levels.

Child, Preschool↗

High incidence of hypogammaglobulinemia in infants with diarrhea.

Examination of 136 children who were referred to the Pediatric Gastroenterology Clinic at Yale-New Haven Hospital for chronic or severe diarrhea between 1977 and 1981 revealed that 31 patients (22.8%) had serum immunoglobulin levels below the 5th percentile for age. Twenty-four of these 31 patients (77.4%) had normal or near normal serum immunoglobulin levels by their third birthday and most could therefore be classified under the heading "transient hypogammaglobulinemia of infancy," an unexpected finding, as this condition has previously been thought to be rare; only 27 patients with this disorder were reported prior to 1978. While the basic cause of the defect is unknown, it has been linked to a slower than normal maturation of the neonate's ability to secrete immunoglobulins. Comparison of our patients with hypogammaglobulinemia and those with chronic diarrhea but normal immunoglobulins revealed that the former group are younger at presentation (mean, 8.2 months) and at the onset of their diarrhea (3.1 months); the figures for patients without hypogammaglobulinemia were 18.2 and 8.2 months, respectively. Males and females were equally affected, and the diarrhea, which was responsive to a hypoallergenic diet, resolved by 3 years of age as did the hypogammaglobulinemia in nearly all cases. While the etiology of the diarrhea remains obscure, significant problems outside the gastrointestinal tract did not occur. Circumstantial evidence suggests that the most likely cause for the failure of production of IgG, and to a lesser extent IgA antibody, in infants seen with diarrhea may result from a failure of maturation of T cell helper systems rather than any intrinsic defect in the B cell system itself.

B-Lymphocytes↗

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.

Esophagus↗

Esophageal dysfunction in Down's syndrome.

Abnormalities in esophageal function were identified in seven children with Down's syndrome. Three had recurrent episodes of pneumonia from gastroesophageal reflux; two of these and one other patient had esophageal strictures. Two patients with Down's syndrome revealed no evidence of gastroesophageal reflux but did show significant abnormalities in esophageal peristalsis. These data would suggest that ambulatory children with Down's syndrome may be at risk of developing serious sequellae of gastroesophageal reflux. The spectrum of data of these seven patients is discussed, and pertinent prior reports from the literature are reviewed.

Adolescent↗

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.

Adult↗

Pancreatitis in patients with Reye's syndrome.

Three patients who died of a Reye's syndrome had biochemical or pathological evidence of pancreatitis. None of the 38 survivors had clinical or biochemical evidence of pancreatic dysfunction. The use of hypertonic glucose solutions and exogenous insulin may reverse the metabolic abnormalities seen in Reye's syndrome and may spare the pancreas, thereby preventing the development of pancreatitis. In addition, serum calcium and glucose concentrations appear to correlate with pancreatic function and may be of value in detecting the occurrence of pancreatitis. It is our impression that the development of pancreatitis protends a poor prognosis in patients with Reye's syndrome.

Adolescent↗

Esophageal web: a previously unrecognized complication of epidermolysis bullosa.

The course of the esophageal disease in four patients with epidermolysis bullosa dystrophica recessive is examined. Three of four patients experienced web formation, a previously unrecognized finding, and the significance of this lesion in the evaluation and management of these patients is emphasized. One of four patients underwent a successful colonic interposition for severe esophageal disease and the role of this potentially life-saving procedure is discussed.

Adolescent↗

Transient hypertrophic gastropathy in childhood: a protein-losing gastropathy distinct from Menetrier's disease.

Transient hypertrophic gastropathy in a child with similarity of radiographic and clinical features to Menetrier's disease is described. Distinction from Menetrier's disease is emphasized as the condition is characterized by abrupt onset, short duration, eosinophila and good prognosis. The association with hypersensitivity as a possible etiology is more suggestive in this condition. The radiographic changes will often provide the first clue to this condition and rapid reversal of the gastric changes is diagnostic.

Child, Preschool↗