Ranitidine, 75 mg, over-the-counter dose: pharmacokinetic and pharmacodynamic effects in children with symptoms of gastro-oesophageal reflux.

BACKGROUND: The use of over-the-counter antacids has increased in children under the age of 12 years, and has been followed by an apparent increase in the use of over-the-counter histamine-2 receptor antagonists. However, the pharmacokinetic and pharmacodynamic effects of over-the-counter histamine-2 receptor antagonists in the paediatric population are largely unknown. AIM: To evaluate the pharmacokinetics and pharmacodynamics of a single dose of the over-the-counter histamine-2 receptor antagonist, ranitidine, 75 mg, in children with symptoms of gastro-oesophageal reflux disease. METHODS: Children aged between 4 and 11 years with symptoms of heartburn suspected to be due to gastro-oesophageal reflux disease were recruited at six clinical centres. Following a single dose of either oral ranitidine, 75 mg (n=19), or placebo (n=10), recording of intragastric pH and serial blood sampling were carried out for 6 h. RESULTS: The estimated pharmacokinetic parameters of ranitidine, 75 mg, were as follows: the median Cmax value of 477 ng/mL occurred within a median of 2.5 h after dosing, and the median half-life was 2.0 h. The intragastric pH began to rise approximately 30 min after dosing with ranitidine to a peak of pH; 4. The pH in the ranitidine group remained higher than that in the placebo group throughout the 6-h evaluation period. Adverse events were generally mild. CONCLUSIONS: Ranitidine, 75 mg, significantly increased the intragastric pH in children aged 4-11 years. The pharmacokinetic and pharmacodynamic profiles were similar to those in adults. Ranitidine, 75 mg, appears to be effective for the control of intragastric acidity for 5-6 h in children aged 4-11 years.

Nonendoscopic removal of percutaneous endoscopic gastrostomy tubes: morbidity and mortality in children.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) tubes are often removed by cutting the tubing at skin level and allowing the internal components to pass through the gastrointestinal tract. This technique is commonly used in adults, but little information is available concerning its safety in younger patients. METHODS: To assess the safety of this approach in children, the clinical courses of all patients who had undergone PEG tube removal in our pediatric gastroenterology unit over a 3-year period were reviewed. RESULTS: Five of 11 patients in whom the internal components were allowed to pass developed significant complications. Three required subsequent endoscopic removal of the internal component due to persistent vomiting, one died from complications of esophageal perforation caused by the retained internal component, and one developed a gastrocutaneous fistula containing the retained bumper 2 years after PEG tube removal. Significant complications occurred more often in the younger and smaller patients. CONCLUSIONS: Small children are at greater risk than adults for developing serious complications associated with unremoved PEG tube internal components. If passage of the internal components cannot be confirmed after 2 weeks, chest and abdominal radiographs should be obtained.

Environmental tobacco smoke exposure and gastroesophageal reflux in infants with apparent life-threatening events.

OBJECTIVE: To study the hypothesis that environmental tobacco smoke exposure in infants diagnosed with an apparent life-threatening event (ALTE) could be a contributing factor to gastroesophageal reflux. METHODS: Thirty-four polygraphic recordings of combined esophageal pH study and respiration in infants with ALTE, age 4.1 +/- 4.9 months, range 0.4-27 months, were studied. This group of children had uncomplicated perinatal history, no congenital anomalies, no neuropathology, and no drug exposure. A written questionnaire was administered to the parents to determine the following: environmental variables, degree of environmental tobacco smoke (ETS) exposure (number of cigarettes/day), and nutrition (breast vs. bottle feeding). RESULTS: There was a strong correlation between pH study parameters and ETS exposure (p < 0.005). The esophageal pH parameters were markedly elevated in the ETS-exposed group and in this group there was a linear relation between the number of cigarettes smoked per day and reflux index, as well as reflux > 5 min/hr (p < 0.05, r = 0.46). Nursing mothers were less likely to be smokers (18.2% vs. 34.0%). The only significant respiratory finding was in the obstructive/mixed apnea group; there was strong association between ETS exposure and high reflux index (p < 0.05). CONCLUSION: We conclude that ETS exposure represents a significant contributing factor to GER. Pediatricians should systematically ask questions about the infant environment, explain the risk of ETS exposure to the caretaker, and recommend that children should remain in a smoke-free environment.

Emesis in infants as a consequence of feedings.

Emesis is a common symptom resulting from adverse food reactions in infants. In this article the terms food allergy and food intolerance are defined and differentiated. The immunopathophysiology of food allergies is discussed along with useful diagnostic tests. Adverse reactions to common infant nutrients such as cow's milk and soy milk are described, and therapeutic use of "hypoallergenic" formulas is outlined.

Energy expenditure in cystic fibrosis during activities of daily living.

Energy expenditure during various activities of daily living in normally nourished female adolescents with cystic fibrosis was compared with that in matched healthy control subjects. Energy expenditure at rest, during sitting and standing, and during two levels of exercise was increased significantly in patients with cystic fibrosis (122% +/- 14%) compared with control subjects (104% +/- 10%) (p < 0.05), but incremental increases from one level of activity to another did not differ. We conclude that the various activities of daily living are not responsible for increased energy needs in female adolescents with cystic fibrosis.

Contamination of enteral nutrition systems during prolonged intermittent use.

Two related studies were done to determine the incidence of bacterial contamination in enteral delivery systems that were used for 15 and 7.5 hr, rinsed after each use, and reused daily in vitro for 7 and 5 days, respectively. In the first study, systems infusing either a premixed formula (Ensure) or a hand-mixed formula (Vivonex) did not show bacterial growth until the 4th day, 1.0-2.0 X 10 colony-forming units per milliliter (CFU/ml) of Staphylococcus epidermidis. Thereafter there was sporadic growth of different organisms but never increasing growth during the 7 days of infusion. In the second study, systems with Ensure were initially contaminated with Staphylococcus aureus and Escherichia coli and reused for 5 days. S. aureus was eliminated by rinsing, but E. coli persisted in the delivery system at concentrations of 10(3)-10(6) CFU/ml. We conclude that clean enteral nutrition systems can be rinsed after short-infusion periods and reused up to 7 days in vitro without significant contamination; however, once a bag has become heavily contaminated some bacteria cannot be eradicated from the system by rinsing.

Gastroesophageal reflux following percutaneous endoscopic gastrostomy in children.

The frequency and clinical significance of gastroesophageal reflux (GER) in patients after percutaneous endoscopic gastrostomy (PEG) was determined. Ten children, aged 11 months to 15 years, who had normal preoperative extended esophageal pH monitoring were restudied after PEG. Of the ten patients, six developed GER with a pH score significantly higher than their initial one (40.5 +/- 3.3 pre-PEG v 129.5 +/- 24.2 post-PEG, P less than .005). Similarly, the mean post-PEG pH score was higher in patients with GER than in those without a change in score (129.5 +/- 24.2 v 33.8 +/- 2.8, P less than .005). None of these patients was symptomatic for GER immediately after the PEG, but within 10 months of surgery, three of six (50%) developed reflux-related symptoms. These data indicate that clinically significant GER is associated with PEG.

Gastritis with valproate therapy.

We have identified ten children who developed gastritis after prolonged anticonvulsant therapy that included either valproic acid or divalproex sodium. Presenting symptoms were primarily feeding difficulties, including anorexia and refusal to eat. Vomiting was present in two thirds of the patients, with diarrhea, weight loss, and abdominal pain occurring less frequently. Occult blood in stool samples was a late development. All patients responded to therapy with H2-receptor antagonists, oral antacids, or both, with prolonged treatment often necessary to prevent relapse. Although gastrointestinal tract side effects are common with the initiation of valproate sodium therapy, feeding difficulties after long-term treatment are less common. Gastritis should be suspected in children receiving valproate therapy when feeding difficulties arise, particularly if the symptoms are persistent or recurrent.

Randomized study of premedication for esophagogastroduodenoscopy in children and adolescents.

In order to compare three premedication regimens, 58 children and adolescents were randomized to three groups: Group I, meperidine intramuscular; Group II, atropine intramuscular and diazepam intravenous; and Group III, meperidine, promethazine, and chlorpromazine intramuscular. Almost all patients required supplemental intravenous diazepam or meperidine to obtain adequate sedation. An endoscopist without knowledge of the medication group scored each patient for adequacy of sedation. Sedation was more effective in Group III than in Groups I and II (p less than 0.005); however, Group III patients were less arousable at completion of the procedure (p less than 0.0005) and had a greater duration of sedation (220 min compared with 56 and 88 min for Groups I and II, respectively, p less than 0.001). Complications were minor and not associated with any specific treatment. The evidence from this study supports the following conclusions: (a) adequate sedation for esophagogastroduodenoscopy in pediatric patients requires sedation with more than one of the drugs used in this study; and (b) the regimen meperidine, promethazine, and chlorpromazine, with diazepam supplement, was superior in providing sedation, but patients required a longer period of recovery than did patients sedated with one of the other regimens.

A randomized study of oral metoclopramide in small bowel biopsy of infants and children.

As an intravenous injection is not used in our premedication of infants and children for small bowel biopsy, we investigated what effects oral metoclopramide might have on small bowel biopsy procedure time and fluoroscopy time. Eighteen infants and children were randomized to receive 0.2 mg/kg metoclopramide or placebo orally, 40-45 min before starting the procedure, and the procedure was monitored for the time required for the biopsy capsule to reach the pylorus, to cross into the proximal duodenum, and to reach the biopsy site. Corresponding fluoroscopy times were recorded as well. Mean total procedure time was less for those treated with metoclopramide, 43.7 +/- 11 min, than for controls, 86.5 +/- 15.5 min (p less than 0.005). Mean total fluoroscopy time was also less in treated patients (40.9 +/- 11.5 s versus control 84.4 +/- 17 s) (p less than 0.005). The effect of metoclopramide occurred in the interval for the biopsy capsule to cross the pylorus (15.1 +/- 2.7 min versus control 60.8 +/- 16.6 min) (p less than 0.005) and in fluoroscopy time required (15.1 +/- 1.9 s versus control 46 +/- 17 s) (p less than 0.005). Oral metoclopramide is effective in reducing procedure time for small bowel biopsy, and its predictable action facilitates reduction in fluoroscopy exposure.

Gastroparesis in neonatal myotonic dystrophy.

Myotonic dystrophy in the neonate is commonly accompanied by facial diplegia, generalized muscular hypotonia, talipes equinovarus, and muscular respiratory failure. The gastrointestinal manifestations of this disease include poor sucking, choking, regurgitation, aspiration, and swallowing difficulties. Gastroparesis can be a major contributor to the feeding difficulties experienced by these infants. We report on an infant with congenital myotonic dystrophy in whom a severe gastric motility problem was alleviated by metoclopramide therapy. This smooth muscle manifestation may be an important and potentially remediable source of morbidity in these infants.

Preferential decrease in thymus dependent lymphocytes during storage at 4 C in anticoagulant.

Human lymphocytes stored at 4 C either as leukocyte concentrates (LCs) in citrate-phosphate-dextrose (CPD) or as whole blood anticoagulated with CPD show a rapid and marked decrease in the relative and absolute numbers of thymus derived (T) lymphocytes. Determinations were made on cells recoverable on a Ficoll-Hypaque (F-H) gradient. In evacuated LCs, the relative percentage of T cells dropped to less than 10 per cent within 72 hours with a concomitant increase in the relative percentage of bone marrow derived (B) cells to 80 per cent or more. LCs opened to the air and subsequently stored at 4 C displayed an even more precipitous decline in the relative percentage of T cells, reaching a 10 per cent level within 72 hours. The relative percentage of T cells in CPD-anticoagulated whole blood samples stored at 4 C displayed similar decreases, reaching 20 per cent levels within 24 hours. The change in the relative percentage of T cells at the Ficoll-Hypaque interface was shown to reflect a decrease in the total numbers of T cells placed on the F-H gradient with time, since determinations of T and B cell numbers in NH4Cl-treated whole blood showed a 65 to 80 per cent decrease in the numbers of T cells within 24 hours in anticoagulated whole blood held at 4 C. Thus, it may be inferred that the T cell decrease is mediated via some interaction of anticoagulant, storage time, and some component(s) present in both LCs and whole blood.