Search PubMed⌕ Search

Biomedical subjects

C Hillemeier

Publications and source records attributed to C Hillemeier.

36 records · Page 2Linked to original sources

Role of peptide histidine isoleucine in relaxation of cat lower esophageal sphincter.

Vasoactive intestinal peptide (VIP) is a candidate as an inhibitory neurotransmitter mediating relaxation of the lower esophageal sphincter (LES) because VIP antiserum reduces LES relaxation in response to neural stimulation. Vasoactive intestinal peptide antiserum, however, does not completely block LES relaxation. Thus it is possible that other neurotransmitters may be involved. Peptide histidine isoleucine has structural homologies with VIP, is synthesized with VIP from a common precursor protein, coexists in some nerve cells, and is coproduced with VIP in some tumors. In numerous organ systems VIP and peptide histidine isoleucine (PHI) produce similar effects, with PHI being less potent than VIP by approximately one log number. In the LES both VIP and PHI produce tetrodotoxin-resistant dose-dependent relaxation, with PHI being almost equipotent with VIP. We therefore tested the hypothesis that PHI may be a second neurotransmitter, partly responsible for relaxation of the cat LES, by using a highly specific rabbit PHI antiserum that exhibits minimal cross-binding with VIP, secretin, and glucagon. In 3 animals, LES and brain tissue were extracted in 0.1 N HCl and assayed with a PHI radioimmunoassay. The antiserum cross-reacted with cat brain and LES showing PHI concentrations greater than 100 ng/g, with the LES containing equal or greater concentrations of PHI than brain tissue. In other animals consecutive LES circular muscle strips were cut, mounted in 1-ml muscle chambers, and stimulated with 6-s square-wave trains of 0.1-, 0.2-, 0.4-, and 0.8-ms pulses at 1, 2, and 5 Hz. These parameters produced relaxation that was completely blocked by tetrodotoxin, and reduced by VIP antiserum, but not affected by adrenergic or cholinergic receptor antagonists. Some strips were incubated in 5% or 10% PHI antiserum, whereas others were incubated in the same concentration of preimmunization serum from the same animal. Incubation in normal serum did not significantly affect relaxation, whereas in the antiserum-treated strips, LES relaxation was reduced by a significant amount (20%-30%) at all parameters of stimulation tested. Incubation in antiserum however had no effect on relaxation induced by VIP (10(-8)-10(-6) M). These data suggest that PHI may play a role in LES relaxation induced by electrical stimulation.

Animals↗

Developmental differences in neurohumoral modulation of the cat lower esophageal sphincter.

It is possible that age-related differences in gastroesophageal function during infancy may predispose the infant to abnormalities. We have therefore evaluated developmental differences in neurohumoral modulation of lower esophageal sphincter function in the cat. These studies were performed in an in vitro setting. In the adult cat, lower esophageal sphincter smooth muscle and postganglionic inhibitory neurons are more sensitive to muscarinic agonists than in the kitten. The circular smooth muscle of the adult lower esophageal sphincter is also more responsive to neurally mediated relaxation, brought about by electrical stimulation. However, there is no difference in response to exogenous vasoactive intestinal peptide between the two age groups. These data suggest that developmental differences in neurohumoral modulation of the lower esophageal sphincter occur in the cat.

Animals↗

Contraction mediated by Ca2+ influx in esophageal muscle and by Ca2+ release in the LES.

Single cells and whole tissue specimens were used in this study to determine sources of Ca2+ utilized for contraction of the circular muscle layer of esophagus and lower esophageal sphincter (LES) of the cat. In vitro circular muscle specimens from the cat esophagus respond to electrical stimulation with phasic contractions at the end of the stimulus, whereas the LES spontaneously maintains tonic contraction and relaxes during stimulation. In Ca2+-free buffer, esophageal contractions rapidly decline and disappear within 10 min after the removal of Ca2+, while LES tone is only partially reduced. Similarly, incubation in a solution containing the Ca2+ influx blocker, La3+, abolishes esophageal contraction but only partially decreases LES tone. Conversely, strontium and caffeine substantially reduce LES tone without affecting the amplitude of esophageal contractions. In single muscle cells isolated by enzymatic digestion from the LES and the body of the esophagus, blockade of extracellular Ca2+ influx by methoxyverapamil (D 600) or ethyleneglycol-bis-(beta-aminoethylether) N,N'-tetraacetic acid abolished esophageal contraction in response to acetylcholine without affecting LES cells, and conversely, strontium abolished LES contraction without affecting esophageal cells. These data are consistent with the view that extracellular Ca2+ is required to initiate esophageal phasic contraction, while the LES has the ability to utilize intracellular Ca2+ to maintain resting tone and to contract in response to acetylcholine.

Acetylcholine↗

Dysphagia lusorum in children.

The association of difficulty in swallowing and an aberrant right subclavian artery is termed dysphagia lusorum. Dysphagia lusorum has been reported not to occur in children. We describe four children who had difficulty swallowing and aberrant right subclavian arteries. Esophageal manometry showed high pulsatile pressure in the area of the aberrant right subclavian artery in each child (12 to 100 mm Hg). Three of the four children underwent surgical correction, and their symptoms resolved. Postoperatively, esophageal manometric findings were normal. We conclude that dysphagia lusorum occurs in children and esophageal manometry shows persistently increased intraesophageal pressure, causing a functional partial obstruction in symptomatic children with dysphagia lusorum.

Cardiac Catheterization↗

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↗

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↗

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↗

Pseudomembranous colitis in a preterm neonate.

This preterm female infant abruptly developed diarrhea and bowel distention at 25 days of age and died within 60 h with fulminating pseudomembranous colitis and proctitis. Toxin-producing C. difficile was recovered from the stool. The pseudomembranous colitis developed 12 days after the last dose of ampicillin was given to the baby. Necrotizing enterocolitis, a condition pathologically distinct from pseudomembranous colitis, was also present.

Ampicillin↗

Gastrointestinal bleeding in the pediatric patient.

Gastrointestinal hemorrhage in infants and children is a catastrophic event but is not associated with significant mortality except in those with a severe primary illness. Upper gastrointestinal bleeding in infants and young children is most often associated with stress ulcers or erosions, but in older children it may also be caused by duodenal ulcer, esophagitis, and esophageal varices. Lower gastrointestinal bleeding may be caused by a variety of lesions among which are infectious colitides, Meckel's diverticulum, bleeding disorders, gastrointestinal allergy, and inflammatory bowel disease. Techniques of diagnosis and management are discussed.

Adolescent↗

Acute pancreatitis in infants and children.

Acute pancreatitis is being encountered more often in children due to antimetabolite therapy, accidental injury, and traumatic battering. Pancreatitis may occur in the absence of traditionally elevated serum amylase and lipase, and initial diagnosis may depend upon ultrasonography. Traditional therapy of enteric rest with nasogastric suction has been supported by the use of parenteral nutrition. Newer pharmaceutical agents have been ineffective in altering the course of the illness or in preventing complications of pseudocyst or abscess.

Acute Disease↗