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Biomedical subjects

P E Hyman

Publications and source records attributed to P E Hyman.

At least 19 recordsLinked to original sources
PubMed1995

Intestinal motility and jejunal feeding in children with chronic intestinal pseudo-obstruction.

BACKGROUND/AIMS: Total parenteral nutrition is responsible for most of the morbidity and mortality of childhood chronic intestinal pseudo-obstruction (CIP). The aim of this study was to determine if there are manometric patterns associated with the success of jejunal feedings in children with CIP. METHODS: Eighteen children with CIP (age range, 1-9 years; mean, 4 years; 11 boys and 7 girls) were studied. All patients required parenteral nutrition or failed to thrive while receiving gastrostomy feedings. All underwent an antroduodenal manometry before surgical placement of a jejunostomy. Continuous drip jejunal feeding with an elemental formula was subsequently initiated. Follow-up after jejunal feeding was 1.6 years (range, 6 months to 4 years). Jejunal manometry was performed 2 months to 1 year after jejunostomy. RESULTS: Jejunal feeding eliminated the need for parenteral nutrition in all 9 patients with migrating motor complex (MMC) and in 3 of 9 patients without MMC (P < 0.01). The MMC was present or absent in both antroduodenal and jejunal manometry in 14 of 18 children (77.7%). In 10 of 18 children (55%), duodenal and jejunal manometry showed similar qualitative abnormalities. CONCLUSIONS: In selected children with CIP who fail gastrostomy feeding, jejunal tube feeding is an alternative to parenteral nutrition. The presence of MMCs is associated with a successful adaptation to jejunal feeding.

Child↗
PubMed1995

Age-related changes in colon motility.

To assess age-related changes, we analyzed 32 colon manometry studies of children referred for motility studies and found not to have colonic disease. Colon motility was recorded by endoscopically placed water-perfused catheters. There was an inverse correlation between the number of high-amplitude propagated contractions and age, before and after administration of a meal; colonic contractions different from the high-amplitude propagated contractions increased with age.

Adolescent↗
PubMed1994

Effect of erythromycin on antroduodenal motility in children with chronic functional gastrointestinal symptoms.

To evaluate the effects of erythromycin on antroduodenal motility in children with chronic functional gastrointestinal symptoms, we studied 35 consecutive subjects referred for diagnostic motility studies. We recorded fasting motility for > 4 hr, then infused in random order either 1 or 3 mg/kg erythromycin intravenously over 1 hr and continued the study for another hour. Erythromycin induced phase III in 18 of 20 children who had phase III during fasting compared to only one of 15 who did not (P < 0.001). The antral motility index increased after erythromycin (1596 +/- 323 vs 436 +/- 242 mm Hg/30 min before erythromycin, P < 0.005) but the duodenal motility index did not change. The antral motility index was greater in children receiving 3 mg/kg than in those receiving 1 mg/kg (1968 +/- 391 vs 1226 +/- 285 mm Hg/30 min, P < 0.01), but duodenal motility indices did not differ. Only one child receiving the lower dose erythromycin complained of abdominal pain, nausea, or vomiting vs 9 of 19 the children receiving the higher dose (P < 0.02). In summary, in children with chronic functional gastrointestinal disorders, erythromycin rarely induced phase III in patients who did not have it during fasting. When different doses erythromycin are compared, 1 and 3 mg/kg are equally efficacious in inducing phase III episodes; the lower dose is associated with fewer side effects and the higher dose produces a higher antral motility index.

Adolescent↗
PubMed1994

Gastroesophageal reflux: one reason why baby won't eat.

Gastroesophageal reflux (GER) is the movement of gastric contents retrograde into the esophagus. Sometimes the refluxate is seen as emesis, but often reflux is "silent," meaning that there are no discrete symptoms during an episode. In adults, the most common symptom of GER is heartburn, whereas in infancy excessive crying and malaise are symptoms that prompt investigation for GER, with or without esophagitis. Symptoms of esophagitis in infancy may include arching (hyperextension) of the torso and refusal of feedings. Tube feedings may be required to treat infants with failure to thrive who refuse oral feedings. Paradoxically, tube feedings increase the number of GER episodes. A hypothetical explanation for refusal of food in infancy is that pain with swallowing (odynophagia) or heartburn are consequences of peptic esophagitis. As a result, infants will learn to refuse food if it hurts or if they fear that it will hurt to eat. Another possible mechanism is visceral hyperalgesia, a neuropathic condition in which prior experience changes sensory nerves so that previously innocuous stimuli are perceived as painful. Some infants may have especially sensitive sensory nerves in the upper gastrointestinal tract, which predisposes visceral hyperalgesia to develop. Thus pain occurs from luminal distension or acid reflux in the absence of tissue damage. The evaluation of babies who won't eat includes a careful history and physical examination to exclude the possibility of chronic systemic illness. Refusal to feed is an unusual manifestation of a common condition: GER disease. The initial tests for GER usually include a barium swallow study to assess the upper gastrointestinal anatomy, endoscopy and esophageal biopsy to assess esophagitis, and an intraesophageal pH study, which is useful in "silent" reflux to quantitate the duration of esophageal acid exposure and to correlate discrete symptom episodes with periods of reflux. The treatment of infants and toddlers who refuse to eat because of pain resulting from visceral hyperalgesia or reflux esophagitis involves removing the pain associated with eating and making eating a pleasurable experience. Treatment for esophagitis may include maintaining an upright posture after meals and thickened feeds, medication to improve gastrointestinal motility or to decrease acid secretion, or fundoplication.

Esophagitis, Peptic↗
PubMed1994

Antroduodenal manometry in children and adults with severe non-ulcer dyspepsia.

BACKGROUND: Nonulcer dyspepsia is common in adults but has been recognized only recently in children. METHODS: We compared signs, symptoms, and antroduodenal motility findings in 34 children and 35 adults with severe nonulcer dyspepsia. RESULTS: Symptoms and signs were similar in the two groups. Ten children (29%) and one adult (3%) required tube feedings (p = 0.01). Abdominal surgery had been performed on 6 of 34 (18%) children and 18 of 35 adults (51%) (p < 0.01), without relief of symptoms. Esophageal manometry was abnormal in 5 of 23 (22%) children and 6 of 31 (19%) adults. Antroduodenal manometry was suggestive of neuropathy in 25 children and 26 adults and of myopathy in 3 children and 2 adults. Absence of phase 3 of the migrating motor complex was found in 4 children and 17 adults (p = 0.01). Antroduodenal manometry was normal in six children and seven adults. CONCLUSION: Signs, symptoms, and discrete manometric abnormalities of childhood nonulcer dyspepsia resembled those of adult nonulcer dyspepsia. Manometric findings in nonulcer dyspepsia resembled those reported in chronic intestinal pseudo-obstruction, suggesting that these conditions are on a continuum of enteric neuromuscular diseases.

Adolescent↗
PubMed1992

Effect of cell culture on rabbit colonic smooth muscle bradykinin receptors.

The aim of this study was to assess the effect of cell culture on the bradykinin receptor of rabbit colon myocytes. In longitudinal muscle strips prepared from distal colon, bradykinin stimulated dose-dependent contraction that was 62% of the maximal response to bethanecol. At 4 degrees C, [3H]bradykinin binding to fresh muscle homogenates from the distal colon was time dependent, saturable, and linearly related to tissue concentration. Specific binding of 0.6 nmol/L [3H]bradykinin was 80% +/- 2% of total binding. In competitive binding studies, Hill coefficients approached unity, suggesting the presence of a single class of receptors. The order of potency was bradykinin greater than [D-Phe7]bradykinin much greater than des-Arg9, [Leu8]bradykinin, which is consistent with results of a B2 receptor subclass. Colon myocytes from the longitudinal muscle layer achieved confluence and were harvested for studies after 12-14 days in culture. Bradykinin receptors were of high affinity [disassociation constant (Kd) = 672 pmol/L] and numbered 10,217 +/- 2567/cell. To show that the receptors on cultured myocytes were functional, the effect of bradykinin was measured (a) on intracellular calcium concentration using Fura 2 and (b) on prostaglandin E2 concentration in the culture media using radioimmunoassay. In cells grown to confluence on cover slips and preloaded with Fura 2, bradykinin stimulated the threshold response at 1 nmol/L and maximal response (increased intracellular calcium concentration from 229 to 633 nmol/L) at 1 mumol/L. Bradykinin, 100 nmol/L, increased Prostaglandin E2 in the culture media threefold. In summary, colon myocytes express functioning bradykinin receptors, which, unlike muscarinic receptors, persist in culture. Bradykinin appears to be a suitable agonist for studies of receptor-mediated intracellular events in cultured colon myocytes.

Animals↗
PubMed1992

Use of colonic manometry to differentiate causes of intractable constipation in children.

We evaluated colon manometry as a means of differentiating causes of intractable constipation in children. We studied pressure changes in the transverse, descending, and rectosigmoid colons of 23 children with intractable constipation. All patients had a history of less than one bowel movement per week for longer than 2 years without resolution after conventional medical management. The possibility of Hirschsprung disease was excluded in all. On the basis of pathologic and manometric studies of the upper gastrointestinal tract, 10 patients had a diagnosis of gastrointestinal neuropathy and two had a diagnosis of myopathy. The other 11 patients had functional fecal retention; this diagnosis was based on history and outcome of therapy. On the day of study we used endoscopy to place a manometry catheter into the transverse colon and recorded intraluminal pressure for longer than 4 hours. After obtaining a baseline recording, we gave the patient a meal to assess gastrocolonic response. Colonic contractions were recorded in 21 of 23 children. Children with functional fecal retention could be differentiated from those with neuropathy by examination of the postprandial record. After a meal children with functional fecal retention had (1) an increase in motility index (3.4 +/- 0.5 while fasting vs 9.1 +/- 1.3 postprandially; p less than 0.001), and (2) at least one high-amplitude propagated contraction (in 10 of 11 children). The patients with neuropathy had no high-amplitude propagated contractions (p less than 0.001 vs group with functional fecal retention) and motility index in these children did not increase significantly after a meal (2.7 +/- 1.0 while fasting vs 2.9 +/- 1.3 postprandially). The two children with hollow visceral myopathy had no contractions. We conclude that in children with severe chronic constipation the colonic results of manometry differentiate patients with functional fecal retention from those with neuropathy or myopathy of the colon.

Child↗
PubMed1992

Postnatal changes in the substance P receptor on rabbit gastric smooth muscle.

We used radioligand binding to tissue homogenates and isometric contraction of muscle strips to characterize the substance P (SP) receptor on gastric smooth muscle from 1- (newborn) and 7-day-old and 4- and 11-wk-old (weanling) rabbits. Scatchard analysis for newborns was curvilinear, suggesting the presence of multiple binding sites. In newborns the dissociation constant (Kd) of high-affinity binding site was 2.2 +/- 0.3 nM, and the maximum binding (Bmax) was 0.57 +/- 0.06 pmol/mg DNA. The number of high-affinity binding sites decreased with age, disappearing by 11 wk. The Kd for the low-affinity site was more than two orders of magnitude greater than that of the high-affinity site. In competitive binding studies with [3H]SP, the order of potency for the neurokinins was SP much greater than neurokinin A (NKA) greater than neurokinin B (NKB), suggesting that the high-affinity binding sites were NK-1 receptors. [125I]NKA is also bound to newborn tissue homogenate with high affinity. With [125I]NKA the order was NKA greater than SP greater than NKB, suggesting that NK-2 receptors were also present. In contraction studies, atropine and tetrodotoxin had no effect on tachykinin-stimulated contraction, suggesting solely myogenic tachykinin effects on this tissue. In newborn rabbits, the potency and efficacy of SP and NKA were similar. The half-maximal effective dose (ED50) of SP was nearly two orders of magnitude less in newborn rabbits than in weanlings; the potency of NKA did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1992

Characterization of colonic circular smooth muscle cells in culture.

The receptor-binding properties of isolated rabbit colonic circular smooth muscle cells in primary culture have been investigated. In intact smooth muscle, acetylcholine, acting through M2 muscarinic receptors, and vasoactive intestinal polypeptide (VIP), acting through VIP receptors, are two of the principal neurotransmitters mediating contraction and relaxation, respectively. The muscarinic receptor was present in very high levels (600,000 receptors/cell) on freshly isolated colonic smooth muscle cells as shown by binding of the muscarinic receptor antagonist N-methylscopolamine (NMS). However, NMS binding sites decreased rapidly when the cells were placed in primary culture. After 21 h in culture, specific binding of [3H]NMS decreased to 20%, and after 48 h to less than 10% that of preculture values. This loss was not associated with a change in receptor affinity, since Kd was unchanged for the receptors still present. In contrast, high-affinity VIP receptors were expressed on cultured smooth muscle cells but could not be detected on freshly isolated cells. Cultured cells responded to VIP with an increase in intracellular adenosine 3',5'-cyclic monophosphate (cAMP), indicating that the VIP receptors were functionally coupled to adenylate cyclase. Cultured cells also responded to calcitonin gene-related peptide (CGRP) and forskolin with increased production of intracellular cAMP. In contrast, neither VIP nor CGRP elicited an increase in intracellular cAMP when added to freshly isolated cells. Furthermore, freshly isolated cells had a greatly diminished response to forskolin, suggesting that the isolation procedure not only destroyed cell surface receptors for VIP and CGRP, but also damaged the cells sufficiently to decrease cellular adenylate cyclase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Developmental changes in gastric mucus gel thickness: responsiveness to 16,16-dimethyl prostaglandin E2 and mucosal protection in the rat.

The gastric mucosa of newborn rats is sensitive to the damaging effects of acid and ethanol. We measured gastric mucus gel thickness in newborn, suckling, and weaned rats by inversion microscopic observation. The thickness in newborn rats was 52.2 +/- 6.7 microns and increased with age, reaching 96.8 +/- 5.6 microns in 8-wk-old rats (p less than 0.001). Oral administration of 16,16-dimethyl prostaglandin E2 at concentrations of 10 and 100 micrograms/kg body weight increased mucus thickness in 8-wk-old rats but had no effect in 1-wk-old rats. We also assessed the effect of 16,16-dimethyl prostaglandin E2 on the prevention of gastric mucosal damage induced by ethanol. Oral 16,16-dimethyl prostaglandin E2 reduced damage in 8-wk-old rats, but there was no effect in 1-wk-old rats. These data suggest that the susceptibility of newborn rats to gastric mucosal injury may be related to the relative thinness of the gastric mucus gel layer and the failure of prostaglandins to increase the mucus gel layer thickness.

16,16-Dimethylprostaglandin E2↗
PubMed1992

Diabetic gastroparesis due to postprandial antral hypomotility in childhood.

Nausea, vomiting, chronic abdominal pain, and constipation developed in three children with insulin-dependent diabetes mellitus beginning 1 to 7 years after the onset of diabetes. All three had considerable difficulty in achieving satisfactory glycemic control. All had delayed gastric emptying of solids and postprandial antral hypomotility. Diabetic autonomic neuropathy must be considered in the differential diagnosis of gastrointestinal symptoms even in the young diabetic patient.

Adolescent↗
PubMed1992

Diversion colitis in children with severe gastrointestinal motility disorders.

We found colitis in 11 of 14 children, 4 months to 7 yr after surgical diversion of the colon for chronic intestinal pseudo-obstruction. Colonoscopic examination was incidental during placement of a catheter for colon manometry and transit studies. All 14 children had complained of diffuse, poorly localized abdominal pain, but only three had a history of bloody stools. Diversion colitis had not previously been suspected in six of eight affected children without hematochezia. Biopsies showed a nonspecific acute and chronic inflammation and/or nodular lymphoid hyperplasia. There was no correlation between the duration of the colonic diversion and the severity of the colitis. Diversion colitis may be an indolent inflammatory nidus and a potential cause for repeated bacteremia, abdominal pain, and bleeding.

Child↗
PubMed1991

Effect of 5-hydroxytryptamine and its antagonists on colonic smooth muscle of the rabbit.

The effect of 5-hydroxytryptamine (5HT) was studied in circular and longitudinal muscle from the proximal and distal colon of New Zealand white rabbits. 5HT stimulated a dose-dependent isometric contraction of distal and proximal circular muscle that was greater than in distal longitudinal muscle (P less than 0.01). 5HT did not stimulate taenia coli longitudinal muscle. The EC50 for 5HT stimulation of distal circular muscle (-7.0 +/- 0.1), distal longitudinal muscle, and proximal circular muscle was similar. Methysergide dose-dependently inhibited the 5HT stimulation of both proximal and distal circular muscle. The IC50 for methysergide inhibition of 5HT (5 x 10(-7) M) stimulation was -5.5 +/- 0.2. Ketanserine and ICS 205-930 did not inhibit 5HT stimulation of colonic muscle. Tetrodotoxin (TTX) decreased the potency, but not the efficacy of 5HT stimulation of proximal and distal circular muscle. Atropine decreased the potency (EC50 = -6.6 +/- 0.1) (P less than 0.05) and the efficacy by 40%. Electrical field stimulation (EFS) caused an on-contraction and off-contraction of distal circular muscle and an on-contraction of proximal circular muscle. 5HT decreased the off-contraction of the distal circular muscle but did not affect the on-contraction of the other muscle strips. 5HT receptor antagonists did not affect EFS of the tissue. The studies suggest: (1) 5HT stimulates circular colonic muscle with greater efficacy than longitudinal muscle, (2) 5HT stimulates circular muscle through a 5HT1 receptor, (3) there is atropine-sensitive and atropine-insensitive 5HT stimulation of circular colonic muscle, (4) 5HT inhibits neurons responsible for the off-contraction in distal circular muscle without affecting the on-contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Perinatal changes in bombesin-stimulated muscle contraction in rabbit stomach and colon.

Bombesin and its mammalian homologue, gastrin-releasing peptide, stimulate smooth muscle contraction and may promote the growth of gastrointestinal tissues. Isometric contraction of strips from circular muscle of the gastric fundus and longitudinal muscle of the distal colon were used to compare changes in the response to bombesin in newborn and weanling rabbits. There was an age-related qualitative change in gastric muscle from biphasic contractions including phasic and tonic components in the newborn to phasic contractions alone in the weanling. The colon contractions were tonic at both ages. In both tissues there was an age-related fivefold increase in stress in response to maximally effective concentrations of bethanechol (P less than 0.05). In contrast, in the stomach age-related decreases in the response to maximally effective concentrations of bombesin were observed, from 2930 +/- 179 mN/cm2 (98% of the maximal response to bethanechol) in the newborn to 565 +/- 81 mN/cm2 (4% of the maximal response to bethanechol) in the weanling (P less than 0.005). In the colon, a twofold increase in response to bombesin was observed, from 446 +/- 59 mN/cm2 (82% of the response to bethanechol) in the newborn to 862 +/- 11 mN/cm2 (29% of the response to bethanechol) in the weanling (P less than 0.05). No age-related changes were observed in the potency of bombesin in either tissue. Neither atropine nor tetrodotoxin altered the contractions in either tissue, suggesting that bombesin interacted directly with myocytes. There was three times as much bombesinlike immunoreactivity in the stomach compared with the colon, but no age-related changes in either tissue. In summary, by the age of weanling the stomach lost the tonic component of contraction and 80% of the efficacy of bombesin-stimulated phasic contraction that had been present in the newborn. The loss of efficacy, absolute in the stomach and relative to bethanechol in the colon, suggest that bombesin may be most important in stimulating motility in the neonatal period.

Animals↗
PubMed1991

Cisapride in children with chronic intestinal pseudoobstruction. An acute, double-blind, crossover, placebo-controlled trial.

To assess the effect of cisapride on gastrointestinal motility and gastric emptying in children with chronic intestinal pseudoobstruction, 20 children (mean age, 4.9 years; 14 female and 6 male) who required special means of alimentation or who had severe symptoms confirmed by diary during 2 weeks before the study were studied. A motility catheter with recording sites in the antrum and duodenum was placed on the first day of the study and remained in place until the end of the 5-day study. Cisapride (0.3 mg/kg PO t.i.d.) or placebo was given in double-blind randomized crossover fashion, with a 2-day "washout" interval. Antroduodenal motility was recorded on days 2 and 5. Recording consisted of 4 hours of fasting and 2 hours after a complex liquid meal labeled with 99mTc. Gastric emptying was assessed for 1 hour after the meal. Based on manometry, 16 patients had neuropathic and 4 patients had myopathic disorders. Cisapride had no effect on the discrete, qualitative abnormalities found in individual records. Cisapride increased the postprandial duodenal motility index from 1180 +/- 256 mm Hg/30 min after placebo to 2385 +/- 430 mm Hg/30 min (P less than 0.05) but had no significant effect on the antral motility index. Cisapride did not alter the profound delay in gastric emptying; time to reach 50% of initial activity (T1/2) was 105 +/- 20 vs. 93 +/- 19 minutes and percentage of retention after 60 minutes (R60) 56% +/- 4% vs. 58% +/- 4% in control vs. cisapride, respectively. In summary, in children with chronic intestinal pseudoobstruction, cisapride increased postprandial duodenal motility but did not improve gastric emptying.

Child↗
PubMed1991

Anatomic contribution to differences in rabbit colonic muscle contraction.

The aim of this study was to determine if differences in the force of contraction in different regions of the rabbit colon are associated with variations in the histology of the corresponding muscle tissues. Circular and longitudinal muscles were isolated from strips of proximal and distal colonic muscle. Muscle strips stretched to L0 were either stimulated to contract or were processed for electron microscopy. Cross-sections of the smooth muscle cells of the taenia coli had a larger perimeter (P less than 0.001) and were surrounded by increased extracellular matrix (28% of the standardized box) compared with the muscle cells from the other sites in the colon (7%-13%) (P less than 0.001). Cross-sections of the proximal circular muscle cells had a smaller perimeter and were present in a greater number than the cells from other areas of the colon. The distal circular muscle generated a larger force than the other muscles after stimulation with bethanechol or K+ (P less than 0.05). The taenia developed less force than the other muscles (P less than 0.05). Bethanechol was a less potent stimulant for the longitudinal muscles than for the circular muscles (P less than 0.05). This study suggests that (1) the decreased efficacy of bethanechol and K+ stimulation of the taenia coli is caused in part by the smaller number of cells that are available to contract and (2) the increased efficacy for the stimulation of the distal circular muscle compared with the proximal circular muscle is unrelated to the mass of muscle and seems to be related to an inherent property of the muscle.

Animals↗
PubMed1991

Intestinal motility in symptomatic children with fundoplication.

Fundoplication alters the anatomy of the lower esophageal sphincter but should have no direct effects on motility distal to the sphincter. Of 55 children referred for evaluation of symptoms consistent with upper gastrointestinal motor dysfunction, 28 had undergone fundoplication 6 months to 4 years earlier to treat severe gastroesophageal reflux that had failed medical management. All 28 children had symptoms that were unchanged or worsened after fundoplication. In all children, we studied fasting and fed antroduodenal motility, and compared results from groups with and without fundoplication. Abnormalities in antroduodenal motility were found in 25 of 28 of the fundoplication group and in 25 of 27 of unoperated children. We found a wide range of abnormalities, but there were no differences in the types of severity of abnormalities between groups. In summary, in children with severe functional gastrointestinal symptoms, antroduodenal manometry uncovered physiological abnormalities, and fundoplication failed to relieve symptoms. These data suggest that preoperative intestinal manometry could identify children unlikely to benefit from fundoplication.

Adolescent↗