Pretransplant management and small bowel-liver transplantation in an infant with microvillus inclusion disease.
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Atrophy↗
Biomedical subjects
S S Kaufman
Publications and source records attributed to S S Kaufman.
Human hepatocyte transplantation: gene therapy and more?
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Cell Transplantation↗
Correlation of mucosal disaccharidase activities with histology in evaluation of rejection following intestinal transplantation.
Following intestinal transplantation, we have found that recovery from severe rejection may be difficult to identify. In this study we sought to ascertain whether concurrent determination of mucosal disaccharidase activities and histologic assessment improves the accuracy of diagnosis of rejection. Histologic changes were graded blindly using a standard set of diagnostic criteria, and these changes were compared over time to maltase, sucrase, lactase, and palatinase activities in four pediatric patients under treatment for severe rejection. The histologic criteria, which included magnitude of enterocyte loss, degree of granulation tissue, severity of villus atrophy, and frequency of apoptosis and cryptitis, were found to correlate with one another over time irrespective of outcome (r = 0.72 to r = 0.85). Enzyme activities were also correlated with each other over time (r = 0.64 to r = 0.80). However, the correlation between histologic diagnosis and enzyme activity was weaker (r = -0.48 to r = -0.57). Furthermore, neither histologic nor enzyme evaluation early in the course of rejection predicted ultimate clinical outcome. The results of this investigation show that determination of mucosal disaccharidase activity provides no additional useful information concerning efficacy of anti-rejection therapy as compared to histologic analysis alone.
Child↗
Use of disodium pamidronate in children with hypercalcemia awaiting liver transplantation.
We report four children with advanced liver disease awaiting liver transplantation who developed moderately severe hypercalcemia (range: 1.65-2.40 mmol/L) while receiving total parenteral nutrition. Hypercalcemia had been unresponsive to cessation of calcium intake and therapy with loop diuretics and calcitonin. One or two intravenous doses of disodium pamidronate (35-50 mg/m2) resulted in normalization of plasma calcium concentration within 2-4 d in all four children. Pamidronate may be useful for children with hypercalcemia associated with liver disease.
Child↗
Transplanted small bowel and expression of the insulin-like growth factor binding proteins.
The insulin-like growth factor binding proteins (IGFBPs) act to modulate the growth and differentiation of the gastrointestinal mucosa by regulating cellular responses to the important mitogens, the insulin-like growth factors (IGFs). The transplanted small bowel must maintain the normal growth factor interrelationships and signaling pathways despite the potential of host rejection. Ostomy effluent of patients after small bowel or combined liver/small bowel transplantation was assayed for IGFBPs to investigate the effect of rejection on the IGF-IGFBP axis. Seventeen patients were studied over an 18-month period. The transplanted small bowel produced no measurable IGFBPs in the ostomy effluent under normal circumstances. However, when rejection was taking place the ostomy effluent was found to have measurable IGFBP levels in 6 of 12 episodes, the 6 episodes occurring in 6 different patients. Mostly, the IGFBPs present did not exhibit a serum-like pattern indicating the secretion of IGFBPs into the effluent was not the result of loss of mucosal barrier integrity. There were no statistically significant differences in protein content of the ostomy fluids in the presence or absence of rejection. Our results suggest that the gastrointestinal IGF axis is altered during some instances of transplanted small bowel rejection, with increased secretion of IGFBPs.
Adolescent↗
Intolerance to protein hydrolysate infant formulas: an underrecognized cause of gastrointestinal symptoms in infants.
The purpose of this study was to determine the effectiveness of an amino acid-based infant formula in infants with continued symptoms suggestive of formula protein intolerance while they were receiving casein hydrolysate formula (CHF). Twenty-eight infants, 22 to 173 days of age, were enrolled; each had received CHF for an average of 40 days (10 to 173 days) and continued to have bloody stools, vomiting, diarrhea, irritability, or failure to gain weight, or a combination of these symptoms. Sigmoidoscopy with rectal biopsy was performed in all infants. The infants then received an amino acid-based infant formula, Neocate, for 2 weeks. After 2 weeks of treatment, 25 of the infants demonstrated resolution of their symptoms and underwent challenge with CHF. Of the 25 who were challenged, eight tolerated the CHF and the remainder had recurrence of their symptoms. The histologic features in these infants varied from eosinophilic infiltration to normal. We conclude that not all infants with apparent formula protein-induced colitis respond to CHF and that these infants may have resolution of their symptoms when fed an amino acid-based infant formula.
Dietary Proteins↗
Influence of bacterial overgrowth and intestinal inflammation on duration of parenteral nutrition in children with short bowel syndrome.
OBJECTIVES: Massive intestinal resection results in short bowel syndrome and necessitates prolonged parenteral feeding. The purpose of this work was to assess the impact of late complications of short bowel syndrome, including intestinal bacterial overgrowth and enterocolitis, on the duration of parenteral nutrition (PN) in comparison with factors evident in the neonatal period. METHODS: Retrospective chart review. RESULTS: Of 49 children, 42 were weaned from parenteral nutrition after a treatment course of 17 +/- 14 months. In these 42, postresection small intestinal length equaled 81 +/- 65 cm; 45% had an ileocecal valve. Small intestinal length in the seven children who were PN dependent was 31 +/- 30 cm (p < 0.05); none had an ileocecal valve (p < 0.05). Bacterial overgrowth occurred in all seven PN-dependent children and in 23 of 42 children eventually weaned from PN (p < 0.05). When bacterial overgrowth was identified before weaning (n = 12), the duration pf PN was 28 +/- 17 months, but when bacterial overgrowth was first identified only after weaning (n = 11), the duration of PN was 16 +/- 13 months (p < 0.05). Small intestinal inflammation correlated with bacterial overgrowth (r = 0.69). Those children with severe enteritis identified before weaning remained on the PN regimen for 36 +/- 15 months, in comparison with 21 +/- 14 months in those with mild enteritis and 13 +/- 11 months in those without inflammation (p < 0.02). CONCLUSIONS: Although the length of small intestine remaining after resection is the best immediate predictor of final success in terminating PN in children with short bowel syndrome, PN is prolonged by bacterial overgrowth and associated enteritis in those who will ultimately be weaned.
Bacteria↗
Introduction of 6-mercaptopurine in Crohn's disease patients during the perioperative period: a preliminary evaluation of recurrence of disease.
BACKGROUND: Recurrence of Crohn's disease after surgery is a common occurrence, pointing to the need for a strategy to prevent recurrent disease. We report the postoperative course of 10 patients who required intestinal resections for complications related to Crohn's disease. METHODS: All patients had a Pediatric Crohn's Disease Activity Index score of 10 or greater. Among these patients, 5 began treatment with 6-mercaptopurine in the perioperative period. All 10 had received various combinations of prednisone and salicylate compounds. Patients who were given 6-mercaptopurine did not discontinue the medication until 2 years after the surgery. RESULTS: To date, none of the five patients who were placed on 6-mercaptopurine have had recurrence of their Crohn's disease (mean disease-free period 32.6 +/- 18.4 months). Among those five patients not receiving 6-mercaptopurine there have been three relapses (mean time to relapse 3.7 +/- 1.2 months). Log-rank sum analyses of Kaplan-Meier survival curves show benefit to patients receiving 6-mercaptopurine in preventing relapses after intestinal resection (p < 0.05). CONCLUSIONS: Although the underlying pathophysiologic reasons leading to the high relapse rate after intestinal surgery in Crohn's disease are unknown, we conclude that treatment with 6-mercaptopurine in the perioperative period may be warranted to help prevent the recurrence of Crohn's disease after surgery.
Adolescent↗
Gastroenteric inflammation in children with ulcerative colitis.
This is a retrospective review of five pediatric cases of inflammatory bowel disease with gastroduodenal as well as pancolonic inflammation. The presumptive diagnosis was Crohn's disease in all. Three of five also had microscopic ileitis. Chronic active gastritis was present at diagnosis in all five and duodenitis in four of five. None ever had noncaseating granulomas in any location. Prolonged (mean, 22 months) and ineffective trials of multiple medical therapies were carried out before subtotal proctocolectomy, which allowed the diagnosis of ulcerative colitis to be made in all children. Surgery remained curative after follow-up of over 1 yr (mean, 16 months). This experience confirms that gastroduodenal inflammation occurs in children with ulcerative colitis. Presence of gastroduodenal inflammation does not ensure the diagnosis of Crohn's unless other characteristic features of Crohn's are present. Accurate discrimination between Crohn's and ulcerative colitis remains important in management of pediatric inflammatory bowel disease to facilitate timely surgical referral. Upper gastrointestinal tract inflammation in ulcerative colitis warrants further study.
Adolescent↗
Ranitidine therapy for esophagitis in children with developmental disabilities.
Esophagitis is common in children with cerebral palsy. Because histamine2-receptor antagonists such as ranitidine have not been uniformly effective, we treated disabled children with esophagitis with greater than usual doses. Endoscopy and pH monitoring were used to monitor dose and response to treatment. A dose of 9.3 +/- 0.9 mg/kg/day did not improve visual or microscopic esophagitis after 3 months. A dose of 14.8 +/- 3.9 mg/kg/day resulted in only slight microscopic improvement, but symptoms were improved. There was no correlation between esophageal reflux index at enrollment and either severity of esophagitis or response to treatment. Elevation of gastric pH by ranitidine was infrequent. These results affirm that pH monitoring does not reliably identify disabled children with reflux esophagitis nor does ranitidine reliably heal this disorder.
Adolescent↗
Preliminary experience with intestinal transplantation in infants and children.
OBJECTIVE: This report discusses the preliminary experience with intestinal transplantation in children at the University of Nebraska Medical Center. PATIENTS: During the past 4 years, 16 intestinal transplants have been performed in infants and children. Thirteen have been combined liver and bowel transplants, and the reminder were isolated intestinal transplants. Nearly half of the patients were younger than 1 year of age at the time of surgery, and the vast majority were younger than 5 years of age. All but one had short bowel syndrome. RESULTS: The 1-year actuarial patient and graft survival rates for recipients of liver and small bowel transplants were 76% and 61%, respectively. Eight of 13 patients who received liver and small bowel transplants remain alive at the time of this writing, with a mean length of follow-up of 263 (range, 7 to 1223) days. Six patients are currently free of total parenteral nutrition. All three patients receiving isolated intestinal transplants are alive and free of parenteral nutrition. The mean length of follow-up is 384 (range, 330 to 450) days. Major complications have included severe infections and rejection. Lymphoproliferative disease, graft-versus-host disease, and chylous ascites have not been major problems. CONCLUSIONS: Although intestinal transplantation is in its infancy, these preliminary results suggest combined liver and bowel transplants and isolated intestinal transplantation may be viable options for some patients with intestinal failure caused by short bowel syndrome or other gastrointestinal disease in whom long-term total parenteral nutrition is not an attractive option.
Actuarial Analysis↗
Determination of prothrombin activation fragments in young patients with inflammatory bowel disease.
OBJECTIVE: To assess coagulation cascade activation as a potential index of thromboembolic risk in inflammatory bowel disease (IBD). STUDY DESIGN: Fifty plasma samples were obtained during consecutive outpatient encounters with 29 patients (male:female = 20:9) with either Crohn's disease (CD) (n = 23) or ulcerative colitis (UC) (n = 6). Disease activity for CD was determined using the Pediatric Crohn's Disease Activity Index (PCDAI) and for UC using signs/symptoms and mucosal histology. Patients were grouped as active, recently active (not currently active but had been active within the previous 2 months), or inactive. Prothrombin fragment 1.2 (F1.2) was determined by enzyme-linked immunosorbent assay on plasma samples. Lab parameters were compared using the Kruskal-Wallis test with pairwise comparisons made using Wilcoxian rank sum test. RESULTS: Forty-three percent of samples taken during active phases of disease (13 of 30) had elevated prothrombin cleavage byproduct F1.2. Similarly, five of eight encounters (63%) with recently active IBD had elevated F1.2 values. In contrast, none of the patients with inactive disease exhibited F1.2 elevation. Median F1.2 levels in both the active (0.85 nM/L) and recently active (1.4 nM/L) patient groups were greater than that of the inactive group (0.6 nM/L; p < 0.05). CONCLUSIONS: Evidence of coagulation cascade activation in patients with active and recently active IBD suggests an increased risk of thrombogenesis during active disease that extends for a period of time after commencement of medications to induce remission in their disease process. It may be prudent to counsel patients to avoid risk factors associated with thrombotic phenomenon around the time of active IBD.
Adolescent↗
Intestinal transplantation in children.
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Antilymphocyte Serum↗
Clinical denouement and mutation analysis of patients with cystic fibrosis undergoing liver transplantation for biliary cirrhosis.
OBJECTIVE: To describe the clinical characteristics of patients with cystic fibrosis considered for liver transplantation and the clinical outcome after transplantation. METHODS: Patient charts were reviewed. Mutation analysis was performed on blood or liver tissue samples with a panel of 17 mutations. RESULTS: Eight patients (five girls) with cystic fibrosis have undergone orthotopic liver transplantation for biliary cirrhosis. Mean age at transplantation was 12.0 years +/- 7.7 years (range, 9 months to 23 years). Preoperatively, seven patients had mild to moderate pulmonary dysfunction and one moderate to severe pulmonary dysfunction. All patients required pancreatic enzyme replacement, and four patients required insulin for diabetes mellitus. The 1-year survival rate was 75%, with no deaths related to septic events. Mean time of follow-up the six operative survivors was 4.1 years +/- 1.9 years. Pulmonary function testing, in those serially tested, showed that forced expiratory volume in 1 second was maintained or improved and that forced vital capacity improved after transplantation. Mutation analysis showed the following genotypes: four patients, delta F508/delta F508; one patient, delta F508/N1303K; and three patients, delta F508/unknown. CONCLUSIONS: Despite the high risk of transplantation, these encouraging results indicate that liver transplantation should be considered for patients with cystic fibrosis and complications of end-stage liver disease. We could not demonstrate an unusual pattern of CF gene mutations in these patients with severe liver disease. It appeared that immunosuppressive agents did not have a deleterious effect on pulmonary function.
Adolescent↗
Treatment of cyclic vomiting in childhood with erythromycin.
Cyclic vomiting syndrome (CVS) is an unusual cause of episodic emesis in children. It manifests as intermittent episodes of severe vomiting, similar in time of onset and duration, with no symptoms during the intervening period. Dehydration necessitating intravenous fluid therapy may occur. Most therapeutic maneuvers have proven unsuccessful. We report the use of erythromycin as a prokinetic agent in the treatment of cyclic vomiting in 24 children (10 boys, 14 girls). Many patients had mild associated abdominal pain with their vomiting. Fourteen patients had previously been given metoclopramide but none responded. Two patients were mildly developmentally delayed. Twenty-four patients were given oral erythromycin ethylsuccinate, approximately 20 mg/kg/day, in two to four divided doses for 7 days. This dose was repeated as needed when symptoms reappeared. Eighteen of 24 patients reported total resolution of symptoms when re-evaluated at 2 and 6 months. All males responded, eight of 18 responders were female, and all six with partial or no response to therapy were female. This uncontrolled trial suggests that erythromycin may be a useful prokinetic agent in the treatment of CVS in childhood. Because the study was uncontrolled, placebo effect cannot be excluded. Case-controlled, double-blinded prospective trials should be considered to evaluate the effectiveness of erythromycin in CVS.
Adolescent↗
Fulminant hepatic failure with massive necrosis as a result of hepatitis A infection.
Fulminant hepatic failure as a result of hepatitis A is a rarely diagnosed complication entity in developed countries. With the advent of specific serologic markers for acute hepatitis A virus infection, the incidence and pathology of fulminant hepatitis A can be more clearly defined. We describe four patients (one adult, three children; two males and two females, ages 2 1/2-58 years) referred to our institution for orthotopic liver transplantation subsequent to fulminant hepatic failure following hepatitis A infection. All of these patients had a history of residence in or travel to hepatitis A endemic areas. Hepatitis A infection was documented by the presence of serum IgM against hepatitis A virus prior to transplantation. Infection with hepatitis B virus, cytomegalovirus, Epstein-Barr virus, and herpes simplex virus was excluded by clinical and specific serologic examinations. All patients presented with varying degrees of encephalopathy, progressing to coma. Coagulopathy in the form of prolonged prothrombin time and partial thromboplastin time was present in all patients. Peak liver parenchymal enzymes increased to greater than ten times the upper limit of the normal range. Total and direct bilirubin levels increased to > 20 and 10 mg/dl, respectively. Histologic evaluation of the explanted livers showed a spectrum of changes ranging from periportal hepatocellular necrosis with focal parenchymal collapse and prominent bile duct proliferation to massive necrosis with complete loss of hepatic architecture.(ABSTRACT TRUNCATED AT 250 WORDS)
Child, Preschool↗
Magnesium acetate vs. magnesium gluconate supplementation in short bowel syndrome.
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Acetates↗
Treatment of cyclic vomiting in childhood with erythromycin.
Cyclic vomiting syndrome is an unusual cause of episodic emesis in children. It manifests as intermittent episodes of severe vomiting, similar in time of onset and duration, with no symptoms during the intervening period. Dehydration necessitating intravenous fluid therapy may occur. Most therapeutic maneuvers have proven unsuccessful. We report the use of erythromycin as a prokinetic agent in the treatment of cyclic vomiting in 20 children (9 boys, 11 girls). Many patients had mild associated abdominal pain with their vomiting. Thirteen patients had previously been given metoclopramide, but none responded. Two patients were mildly developmentally delayed. Twenty patients were given oral erythromycin ethylsuccinate, approximately 20 mg/kg/day, in 2-4 divided doses for 7 days. This dosage was repeated as needed when symptoms reappeared. Thirteen of 20 patients reported total resolution of symptoms when reevaluated at 2 and 6 months. All males responded, 4 of 13 responders were female, and all seven with partial or no response to therapy were female. This uncontrolled trial suggests that erythromycin may be a useful prokinetic agent in the treatment of cyclic vomiting syndrome in childhood. As the study was uncontrolled, placebo effect cannot be excluded. Case-controlled, double-blinded prospective trials should be considered to evaluate the effectiveness of erythromycin in cyclic vomiting syndrome.
Adolescent↗