Double-blind, placebo-controlled trial of famotidine in children with abdominal pain and dyspepsia: global and quantitative assessment.

To determine the benefit of using an H2-receptor antagonist in children with abdominal pain and dyspepsia, 25 such children were enrolled in a double-blind, placebo-controlled trial of famotidine. Global and quantitative pain assessments were done before and after each treatment period. The quantitative assessment was calculated based on the abdominal pain score that was the sum of three components. Based on the global evaluation, there was a clear benefit of famotidine over placebo (68% vs 12%). Using the quantitative assessment, however, the mean improvement of the score using famotidine versus placebo was not statistically significant (3.37+/-3.53 vs 1.66+/-2.7). There was a significant improvement in this score during the first treatment period regardless of medication used (period effect: P = 0.05). A subset of patients with peptic symptoms demonstrated a significant drug effect that outweighed the period effect (drug effect: P = 0.01; period effect: P = 0.02). We conclude that famotidine subjectively improves the symptoms of children with recurrent abdominal pain but not objectively using the derived score. However, famotidine is significantly more effective than placebo among children with peptic symptoms. The use of this simple scoring scale may facilitate selecting those children who will benefit from H2-receptor antagonist therapy.

Restorative proctocolectomy in children with ulcerative colitis utilizing rectal mucosectomy with or without diverting ileostomy.

BACKGROUND: Controversies continue concerning the best way to perform restorative proctectomy (RP) for ulcerative colitis (UC). Can rectal mucosectomy and hand-sewn ileoanal anastomosis (IAA) withstand the challenge posed by extrarectal dissection with a double-stapled technique and no mucosectomy? Is a diverting ileostomy mandatory after RP? METHODS: The authors describe 30 consecutive children with UC who underwent RP with rectal mucosectomy and hand-sewn IAA. The authors assess the results and compare the first 14 patients (group 1) treated with temporary diverting ileostomies with the next 16 consecutive patients (group 2) without diverting ileostomies. RESULTS: The average age (13.8 years in group 1 v 10.4 in group 2), duration of illness before resection (3.2 years in group 1 v 1.5 in group 2), and gender breakdown (10 of 14 were girls in group 1, 10 of 16 were girls in group 2) were similar between the two groups. Outcome was not significantly different between the two groups. Average bowel movements per 24-hour period was 5.5 in group 1 and 4.2 in Group 2. Occasional nighttime staining occurred in two patients in group 1 and five in group 2. No one suffered daytime staining in group 1, and one patient had occasional daytime staining in group 2. Average quality of life (on a scale of 0 to 5) as assessed by the patients or parents was 4.4 in group 1 and 4.9 in group 2. There were 10 total complications in group 1. One child required a permanent stoma for ileoanal separation. Two patients required reoperations for complications caused by the diverting ileostomy. The single instance of peritonitis was in group 1 caused by anastomotic leak after ileostomy closure. There were five total complications in group 2, of which, two required temporary stomas for ileoanal separations. CONCLUSIONS: RP with rectal mucosectomy and hand-sewn IAA in children with UC provides good functional results. Peritonitis did not occur in the absence of diversion. Eliminating routine diverting ileostomy avoids the considerable complications and morbidity from the stoma and its closure.

Growth failure as the first expression of malnutrition in children with human immunodeficiency virus infection.

BACKGROUND: To define the onset, pattern, and earliest manifestations of malnutrition related to HIV infection. METHODS: A retrospective cross-sectional analysis of changes in weight and growth in a group of 54 children with perinatally acquired HIV infection was conducted. Eight children had asymptomatic HIV infection, 26 had symptomatic infection, and 20 had symptomatic infection and were referred for nutritional support. RESULTS: We found an early decline in the rate of linear growth with a relative preservation of the weight-for-age. Weight-for-height measurements were preserved until there was advanced HIV-related disease. CONCLUSIONS: This pattern can result in a false impression of adequate nutrition and emphasizes the importance of longitudinal growth data of the child with HIV infection. Evidence of linear growth failure before clinical wasting is apparent is an absolute indication for aggressive nutritional support.

Clinical outcome of ulcerative proctitis in children.

BACKGROUND: Although the course of ulcerative proctitis in adults has been well described, little data are available concerning its clinical behavior in children and adolescents. This study sought to characterize the presentation, response to therapy, and long-term course of ulcerative proctitis in the pediatric population. METHODS: A retrospective chart review was conducted at five pediatric gastroenterology centers. RESULTS: A total of 38 subjects (mean age 11.6 years) were identified with ulcerative proctitis (mean follow-up 4.3 years). Symptoms were mild at diagnosis in 74% and moderate or severe in 26%. Thirty-two percent had a complaint of constipation at presentation. Cessation of symptoms was noted in 68% within 3 months of therapy, an additional 24% within 6 months, and 8% were still symptomatic despite 6 months of therapy. During any subsequent yearly follow-up interval, -55% of patients were asymptomatic, 40% had a chronic intermittent course, and < 5% were continuously symptomatic despite therapy. Eight subjects were treated with oral corticosteroids, one with 6-mercaptopurine, and one with cyclosporine. Extension of inflammation proximal to the rectosigmoid occurred in 11 of 38 subjects (29%), 0.5-11.3 years postdiagnosis. Seven of the 13 subjects (54%) followed for > or = 5 years had proximal extension of disease, and two had undergone colectomy. CONCLUSIONS: Despite a mild presentation in most subjects, ulcerative proctitis seems to have a high risk of proximal extension of disease. The overall response to therapy seems to be similar to that reported for ulcerative colitis in children. Follow-up endoscopic evaluation of patients with ulcerative proctitis seems warranted, especially in the setting of recurrent or recalcitrant symptoms.

Recurrence of autoimmune hepatitis in children after liver transplantation.

BACKGROUND: Liver transplantation is recognized as the appropriate treatment for end-stage liver disease due to chronic active autoimmune hepatitis. While it was initially thought that the disease did not recur after transplant, it is now generally accepted that adult patients may develop recurrent disease, with studies reporting a recurrence rate of < or = 25%. We have noted a higher incidence of recurrent autoimmune hepatitis in our pediatric patients undergoing liver transplant, with a high incidence of associated morbidity. METHODS: We reviewed the records of six children followed up for autoimmune hepatitis who underwent orthotopic liver transplant for complications of end-stage liver disease. RESULTS: Of the six, five developed recurrent autoimmune hepatitis at a mean time of 11.4 months after transplant. The disease was aggressive, leading to cirrhosis and retransplant in three patients, within 1 year of recurrence. A second recurrence of disease occurred in all three retransplanted patients. One patient has received a third liver transplant, one has died, and one patient is asymptomatic on medical therapy. Autoimmune hepatitis recurred in all four patients receiving tacrolimus. CONCLUSION: We conclude that liver transplant for autoimmune hepatitis is likely to be palliative for most pediatric patients. Potent immunosuppressives such as tacrolimus do not protect against the development of recurrent autoimmune hepatitis.

Cyclosporine as an alternative to surgery in children with inflammatory bowel disease.

Five children with ulcerative colitis for whom surgery was recommended were treated with cyclosporine. The five had received corticosteroids for 1-24 months. The group included two patients with acute-onset ulcerative colitis and three with acute exacerbations of intractable corticosteroid-dependent chronic ulcerative colitis. The average age at initiation of cyclosporine therapy was 13.8 years (range, 11.5-16); all five patients were boys. Cyclosporine was initiated in the hospital by continuous i.v. infusion. Trough levels of 400-600 ng/dl (measured by radioimmunoassay) were achieved, at which point oral cyclosporine was given and oral dosage was adjusted to similar levels. Significant hypertension requiring medical attention was seen in one patient. Of the two recently diagnosed acute cases, one failed to respond and required subtotal colectomy after 2 weeks of treatment, and the other, despite an initial response, had a subtotal colectomy 10 months later. Of the three corticosteroid-dependent children, none was able to be weaned from corticosteroids and all underwent subtotal colectomy. Our experience emphasizes that the appropriate role of cyclosporine as therapy for children with ulcerative colitis is yet to be determined. Cyclosporine was not effective as an alternative to surgery in our patients.

Osseous metaplasia in benign colorectal polyps.

We report two unique cases of metaplastic ossification occurring within a tubulovillous adenoma and a juvenile polyp. In both lesions, well-formed bony spicules were present that were adjacent to living epithelial cells. The metaplastic bone revealed vimentin positivity and cytokeratin negativity. The pathogenesis of osseous metaplasia in colorectal tumors remains unclear, but the process seems to have no clinical significance.

Orthotopic liver transplantation for urea cycle enzyme deficiency.

Hyperammonemia, abnormalities in plasma amino acids and abnormalities of standard liver functions were corrected by orthotopic liver transplantation in a 14-day-old boy with carbamyl phosphate synthetase-I deficiency and in a 35-yr-old man with argininosuccinic acid synthetase deficiency. The first patient had high plasma glutamine levels and no measurable citrulline, whereas citrulline values were markedly increased in Patient 2. Enzyme analysis of the original livers showed undetectable activity of carbamyl phosphate synthetase-I in Patient 1 and argininosuccinic acid synthetase in Patient 2. Both patients were comatose before surgery. Intellectual recovery of patient 1 has been slightly retarded because of a brain abscess caused by Aspergillus infection after surgery. Both patients are well at 34 and 40 mo, respectively, after surgery. Our experience has shown that orthotopic liver transplantation corrects the life-threatening metabolic abnormalities caused by deficiencies in the urea cycle enzymes carbamyl phosphate synthetase-I and argininosuccinic acid synthetase. Seven other patients--six with ornithine transcarbamylase deficiency and another with carbamyl phosphate synthetase-I deficiency--are known to have been treated elsewhere with liver transplantation 1 1/2 yr or longer ago. Four of these seven recipients also are well, with follow-ups of 1 1/2 to 5 yr. Thus liver transplantation corrects the metabolic abnormalities of three of the six urea cycle enzyme deficiencies, and presumably would correct all.

Helicobacter pylori and gastric lymphonodular hyperplasia in children.

The association of gastric lymphonodular hyperplasia and Helicobacter pylori infection has been reported only in children. Lymphonodular hyperplasia of the stomach is a well known radiographic and endoscopic entity. Over the past three decades, it has been associated with many conditions, ranging from a normal variant to a premalignant lesion. We have recently encountered five children with gastric lymphonodular hyperplasia, all of whom had H. pylori infection of the antrum. The literature regarding this association is reviewed, and a possible explanation for this age-dependent expression of H. pylori infection is offered.

Salmonella typhimurium appendicitis.

A child with signs and symptoms of acute gastroenteritis developed localization of her pain to the right lower quadrant. A clinical diagnosis of appendicitis was made and an inflamed appendix was found at surgery. The postoperative period was marked by high spiking fevers and profuse nonbloody diarrhea. Cultures of the appendix and the stool revealed Salmonella typhimurium. Nontyphoidal Salmonella organisms are a rare cause of acute suppurative appendicitis. Intraoperative cultures of the appendix and peritoneal fluid as well as postoperative cultures of the diarrheal fluid were crucial in elucidating the cause of this patient's unusual course.

Sonographic evaluation of portal hypertension in children.

Portal hypertension, an expected consequence of cirrhosis, often has an insidious course in children. A noninvasive technique using abdominal sonography has been previously employed by several investigators as a means of diagnosing this condition. Their technique involves sonographically measuring the diameter of the lesser omentum, which increases as a result of engorged collaterals. In this communication, the method is successfully employed in two children, an infant in whom cirrhosis developed who eventually died from acquired immunodeficiency syndrome, and one whose portal hypertension was relieved after orthotopic liver transplantation. Although successful in these two instances, the theoretical basis on which this technique is based is critically evaluated. Anatomical relationships are reviewed that would caution sonographers who attempt to duplicate these studies. Modifications of the technique that will minimize potential false positive results are also discussed.

Resting energy expenditure in Gaucher's disease type 1: effect of Gaucher's cell burden on energy requirements.

The resting energy expenditure (REE; kcal/d) of 25 patients with Gaucher's disease type 1 was determined by indirect calorimetry. The average observed REE for the group was approximately 44% greater (P less than .01) than that predicted (predicted REE) for these patient's age, sex, height, and weight. The increased caloric requirements of these patients was manifested by a height-for-age less than or equal to the fifth percentile in seven of nine growing children and a muscle mass of less than the fifth percentile in 15 of 19 patients studied. The excess REE (observed REE--predicted REE) for individual Gaucher's disease type 1 patients was directly related to their liver volume as estimated from radionuclide scans and to the mass of the spleen as measured at splenectomy. The relationship between spleen mass and excess REE was demonstrated by an average 22.0% decrease in REE following splenectomy in five patients. Based on these data, the metabolic rate of the splenic tissue removed from the patients was calculated to be 96.8 kcal/d/kg, about twofold to threefold less than that of normal splenic tissue. These findings indicate that the elevated REE observed in these patients resulted from the large mass of Gaucher's cells, which although individually hypometabolic, were cumulatively an excessive metabolic burden. Furthermore, they suggest that indirect calorimetry may be a quantitative tool for measuring disease progression and the effect of therapeutic intervention in Gaucher's disease type 1.