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Objective: Review the clinical results of 24 years of intestinal lengthening procedures at one institution. Methods: Retrospective review of a single center experience comparing the outcome of 2 intestinal lengthening procedures (Bianchi and serial transverse enteroplasty [STEP]) in terms of survival, total parenteral nutrition (TPN) weaning, and complications. Results: Sixty-four patients, including 14 adults, underwent 43 Bianchi and 34 STEP procedures between 1982 and 2007. Three patients had prior isolated liver transplants. The median (range) remnant bowel length before first lengthening was 45 (11-150) cm overall; (Bianchi = 44 cm, STEP = 45 cm) and 68 (20-250) cm after lengthening; (Bianchi = 68 cm, STEP = 65 cm). Actual survival is 91% overall (Bianchi 88%, STEP 95%) with median follow-up of 3.8 years (Bianchi = 5.9 years, STEP = 1.7 years). Average enteral caloric intake in pediatric patients was 15 kcal/kg before lengthening and 85 kcal/kg at 1 year after lengthening. Sixty-nine percent of patients are off TPN at most recent follow-up, including 8 who were weaned from TPN after intestinal transplantation. Liver disease (when present) was reversed in 80%. Surgical complications occurred in 10%, more commonly requiring reoperation after Bianchi than STEP. Intestinal transplantation salvage was required in 14% at a median of 2.9 years (range = 8 months to 20.7 years) after lengthening. Conclusions: Surgical lengthening with both Bianchi and STEP procedures results in improvement in enteral nutrition, reverses complications of TPN and avoids intestinal transplantation in the majority with few surgical complications. Intestinal transplantation can salvage most patients who later develop life-threatening complications or fail to wean TPN.

Late graft loss (LGL) and late mortality (LM) following liver transplantation (LT) in children were analyzed from the studies of pediatric liver transplantation (SPLIT) database. Univariate and multivariate associations between pre- and postoperative factors and LGL and LM in 872 patients alive with their primary allografts 1 year after LT were reviewed. Thirty-four patients subsequently died (LM) and 35 patients underwent re-LT (LGL). Patients who survive the first posttransplant year had 5-year patient and graft survival rates of 94.2% and 89.2%, respectively. Graft loss after the first year was caused by rejection in 49% of the cases with sequelae of technical complications accounting for an additional 20% of LGL. LT for tumor, steroid resistant rejection, reoperation in the first 30 days and >5 admissions during the first posttransplant year were independently associated with LGL in multivariate analysis. Malignancy, infection, multiple system organ failure and posttransplant lymphoproliferative disease accounted for 61.8% of all late deaths after LT. LT performed for FHF and tumor were associated with LM. Patients who are at or below the mean for weight at the time of transplant were also at an increased risk of dying. Frequent readmission was also found to be associated with LM.

To examine the outcome of technical variant liver transplant techniques relative to whole organ liver transplantation in pediatric liver transplant recipients.Technical variant liver transplant techniques comprising split, reduced, and live-donor liver transplantation evolved to address the need for timely and size appropriate grafts for pediatric recipients.Analysis of data from the Studies of Pediatric Liver Transplantation (SPLIT) registry, a multicenter database of 44 North American pediatric liver transplant programs. The outcome (morbidity and mortality) of each of the technical variants were compared with that of whole organ recipients.Data were available on 2192 transplant recipients (1183 whole, 261 split, 388 reduced, and 360 live donor). Recipients of all technical variant graft type were significantly younger than whole organ recipients, but on average spent 2.3 months less on the waiting list. Thirty-day post-transplant morbidity was increased for each type of technical variant relative to whole organ (45.1% whole, 66.7% split, 65.5% reduced, 51.9% live-donor). Biliary complications (30 day: 7.5% whole, 18.8% split, 16% reduced, 17.5% live-donor) and portal vein thrombosis (30 day: 3.6% whole, 8% split, 8% reduced, 7.5% live-donor) were more common in all technical variant types. Graft type was an independent predictor of graft loss (death or retransplantation) in a multivariate analysis. Split and reduced (relative risk = 1.74 and 1.77, respectively) grafts had a worse outcome when compared with whole organ recipients.Technical variant techniques expand the pediatric donor pool and reduce time from listing to transplant, but they are associated with increased morbidity and mortality.

Objectives In a large cohort of children with intestinal failure (IF), we sought to determine the cumulative incidence of achieving enteral autonomy and identify patient and institutional characteristics associated with enteral autonomy. Study design A multicenter, retrospective cohort analysis from the Pediatric Intestinal Failure Consortium was performed. IF was defined as severe congenital or acquired gastrointestinal diseases during infancy with dependence on parenteral nutrition (PN) >60 days. Enteral autonomy was defined as PN discontinuation >3 months. Results A total of 272 infants were followed for a median (IQR) of 33.5 (16.2-51.5) months. Enteral autonomy was achieved in 118 (43%); 36 (13%) remained PN dependent and 118 (43%) patients died or underwent transplantation. Multivariable analysis identified necrotizing enterocolitis (NEC; OR 2.42, 95% CI 1.33-4.47), care at an IF site without an associated intestinal transplantation program (OR 2.73, 95% CI 1.56-4.78), and an intact ileocecal valve (OR 2.80, 95% CI 1.63-4.83) as independent risk factors for enteral autonomy. A second model (n = 144) that included only patients with intraoperatively measured residual small bowel length found NEC (OR 3.44, 95% CI 1.36-8.71), care at a nonintestinal transplantation center (OR 6.56, 95% CI 2.53-16.98), and residual small bowel length (OR 1.04 cm, 95% CI 1.02-1.06 cm) to be independently associated with enteral autonomy. Conclusions A substantial proportion of infants with IF can achieve enteral autonomy. Underlying NEC, preserved ileocecal valve, and longer bowel length are associated with achieving enteral autonomy. It is likely that variations in institutional practices and referral patterns also affect outcomes in children with IF.

Objective: Food protein–induced proctocolitis usually occurs early in life and is characterized by blood-streaked stools and pain during defecation in an otherwise healthy infant. While many infants with food protein–induced proctocolitis respond well to a casein hydrolysate formula, some require an amino acid–based formula. The objective of the study was to measure the change in physician-rated symptom score from enrollment to study completion in infants with presumptive food protein–induced proctocolitis fed with a specific amino acid-based formula. Methods: In this study, infants ≤6 months of age diagnosed with presumptive food protein–induced proctocolitis received an amino acid-based formula for 42 days. Intake, stool patterns, weight, stool occult blood, and questionnaires assessing infant feeding and stool patterns and parental formula satisfaction were collected. Results: The full analysis set included 43 infants. The mean age at enrollment was 59 ± 5 days. A significant improvement was observed from enrollment to exit in physician-rated symptom score (9.1 ± 0.5 to 4.8 ± 0.5, p < 0.0001), the number of infants with occult blood in stool, and weight-for-age Z-scores during the study. Parental satisfaction with the formula was high. Conclusion: The results confirm that the amino acid-based formula studied is efficacious for managing symptoms of presumptive food protein–induced proctocolitis.

Infants and children with chronic diarrhea (CD) often require specialized foods or parenteral nutrition (PN) to achieve adequate nutrient intakes to support growth and development. We assessed the efficacy of an amino acid-based formula (AAF) in supporting growth and improving symptoms in infants and children with CD from multiple etiologies. Two studies were conducted: CD study in children (CD-C) and CD study in infants (CD-I). Each was a single group, baseline-controlled study in which each subject served as his/her own control. At enrollment, all subjects had CD lasting > 2 weeks and had ≥ 4 stools/day. Subjects were fed an AAF for 80 days starting at SD5, and were assessed at SD 28 and 84. CD-C: 18 of 19 subjects completed the study. At enrollment, the mean age was 5.6 ± 0.7 years, the most common diagnosis was short bowel syndrome (SBS) (n = 13), and 5 subjects with SBS were on PN. Subjects achieved significant increases in weight-for-age z-scores (p = 0.026). Over 50% of subjects achieved improvements in clinical outcomes targeted most frequently by their physicians. Of the five subjects on PN at enrollment, four had substantial weight gain and four had their PN requirements decreased. CD-I: 22 of 27 subjects completed the study. At enrollment, the mean age was 3.3 ± 0.3 months, the most common diagnosis was food allergy (n = 20), and no subjects were on PN. Subjects achieved significant increases in weight-for-age z-scores (p = 0.0023), significant decreases in the number of stools/day (p = 0.0012), and improvements in stool consistency (p = 0.0024). Over 80% of subjects achieved improvements in the clinical outcomes targeted most frequently by their physicians. Infants and children with CD fed an AAF for three months displayed significant improvements in weight-for-age z-scores and clinical symptoms. Children dependent on PN also grew well and four of five decreased their dependence on PN. Both trials were registered on ClinTrials.gov (CD-C, NCT01812629 ; CD-I, NCT01820494 ).

Objective: The objective of this study was to determine the efficacy of Lactobacillus casei sps. rhamnosus (Lactobacillus GG) (LGG) in reducing the incidence of antibiotic-associated diarrhea when coadministered with an oral antibiotic in children with acute infectious disorders. Study design: Two hundred two children between 6 months and 10 years of age were enrolled; 188 completed all phases of the protocol. LGG, 1 × 1010 – 2 × 1010 colony forming units per day, or comparable placebo was administered in a double-blind randomized trial to children receiving oral antibiotic therapy in an outpatient setting. The primary caregiver was questioned every 3 days regarding the incidence of gastrointestinal symptoms, predominantly stool frequency and consistency, through telephone contact by blinded investigators. Results: Twenty-five placebo-treated but only 7 LGG-treated patients had diarrhea as defined by liquid stools numbering 2 or greater per day. Lactobacillus GG overall significantly reduced stool frequency and increased stool consistency during antibiotic therapy by the tenth day compared with the placebo group. Conclusion: Lactobacillus GG reduces the incidence of antibiotic-associated diarrhea in children treated with oral antibiotics for common childhood infections. (J Pediatr 1999;135:564-8)

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.

Our objective was to determine the immunologic response to two influenza vaccine doses in 39 children who had undergone liver transplantation. Patients received two doses of trivalent inactivated influenza vaccine 4 weeks apart. Sera were collected 4 weeks after each dose and analyzed by a hemagglutination inhibition assay (HAI) for evidence of antibody response to the antigens A/Taiwan/1/86 (H1N1), A/Beijing/32/92 (H3N2), and B/Panama/45/95. Patients with HAI titers of 1:40 or greater were considered to have protective titers. Twenty-six (67%) patients showed a 1:40 or greater titer response to A/Beijing/32/92 1 month after the first vaccination. Only two additional patients were found to have similar titers after the second dose. A higher proportion of patients with protective titers were on smaller amounts of prednisone for body weight or alternate day low dose (< 10 mg/day) prednisone compared to patients on daily low dose or daily high dose prednisone. Patients with protective titers were significantly older (9.0 +/- 2.8 years) than those without protective titers (4.2 +/- 3.4 years, p = .002) following the first inoculation of the A/Beijing/32/92 vaccine component. Similar results were found for the second vaccination and with the H1N1 antigen. Cyclosporine level, gender, and body mass index were not associated with any outcome measures. We conclude that most liver transplant recipients had a protective antibody titer after a single influenza inoculation, but little further advantage was gained after an additional dose. Vaccination of household contacts of younger patients and those patients on daily prednisone or patient chemoprophylaxis may offer greater benefit in prevention of influenza in liver transplant recipients than multiple vaccine doses with current vaccine preparations.

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 remainder 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.

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 of 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, ΔF508/ΔF508; one patient, ΔF508/N1303K; and three patients, ΔF508/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. (J P EDIATR 1995;127:881-7)

Evidence indicates that the accumulation of glutamine in the brain plays an important role in the pathogenesis and severity of the encephalopathy of acute liver failure (ALF). This study uses in vivo proton magnetic resonance spectroscopy (1H MRS) to assess brain glutamine (GLN) in five cases of acute liver failure. The findings are consistent with prior investigations and suggest that the alpha 1H of the GLN molecule can be used for noninvasive spectroscopic quantitation of brain GLN in patients with ALF.

We determined the incidence and outcome of aplastic anemia among 56 patients who underwent liver transplantation for fulminant liver failure at the University of Nebraska Medical Center between July 1985 and December 1993. Aplastic anemia developed in 6 of 18 (33%) children and 1 of 19 (5%) adults who had fulminant non-A, non-B hepatitis; no cases of aplastic anemia occurred among patients with other causes of fulminant liver failure. None of these patients had evidence of a preexisting hematological disorder or infection with hepatitis C virus (as determined with a second-generation ELISA). Aplastic anemia was diagnosed at a median of 4 wk after the onset of hepatitis, with five cases seen before transplantation. Six patients received antithymocyte globulin to promote remission of aplastic anemia. Three children died (fungal infection in two, intracranial hemorrhage in one)--one at 43, one at 108 and one at 119 days after transplantation--without remission of aplastic anemia. Among the four surviving patients, with median follow-up of 25 mo, complete and partial remission of aplastic anemia have occurred in three and one, respectively. Liver allograft function is stable in all surviving patients. The data demonstrate that aplastic anemia is a common complication among children who undergo liver transplantation for fulminant non-A, non-B hepatitis. It is associated with a high rate of mortality, although most survivors appear to have full hematological recovery.

Background. Feasibility of repeat lengthening has been demonstrated in animals, but in humans, none of the three clinical case reports have achieved enteral autonomy after secondary lengthening with serial transverse enteroplasty (STEP). Patients and Methods. Institutional Review Board approved retrospective review of a single center series of repeat intestinal lengthening after prior Bianchi lengthening or STEP. Outcome measures examined include patient survival, weaning from parenteral nutrition, and need for intestinal transplantation. Results. Repeat lengthening with STEP was performed 16 times in 14 patients including 2 adults and 7 male patients after prior Bianchi (n=7) and prior STEP (n=7). Median time after initial lengthening to reSTEP was 12 months (2 months–15 years). Median remnant bowel length before initial lengthening was 35 cm (15–110), before reSTEP was 56.5 cm (27–100) and final length after reSTEP was 90 cm (39–120). Survival is 100% with a median follow-up of 14.5 months (1–65 months). Discontinuation of parenteral nutrition (PN) after reSTEP was achieved in 6 of 14 (43%) patients at a median of 3 months (0.5–13 months) after reSTEP. Intestinal transplant salvage was performed in four patients at 7, 9, 13 months, and 4.6 years, respectively, after reSTEP. All four of those undergoing intestinal transplantation have also subsequently discontinued PN. Conclusions. Repeat lengthening is technically feasible after either of the available surgical lengthening procedures (Bianchi and STEP). In the stable patient, who is unable to wean from PN, repeat lengthening led to discontinuation of TPN in almost half of these carefully selected patients and does not preclude intestinal transplantation.

Objective: The aim of this study was to determine whether the type of feeding during the first 4 months of life affects bone mineral density at 4 years of age. Methods: Healthy 4-year-old children were recruited from the offices of primary health care providers. After confirming the type of infant feeding by history, dual energy x-ray absorptiometry analysis was obtained at the University of Nebraska Medical Center and evaluated by a radiologist blinded as to feeding type. Results: One hundred and seventy-eight children completed the study (58% male, 85% Caucasian; mean age, 4.5 years). All children had exclusively consumed human milk (n = 57), an infant formula containing no palm olein oil (n = 56) or an infant formula containing palm olein oil (n = 65) during the first 4 months of life. At 4 years of age, no significant differences were noted in bone mineral content or bone mineral density (P = 0.51 and 0.89, respectively) among the three feeding groups as measured by dual energy x-ray absorptiometry. Total body bone mineral content and bone mineral density varied by gender, with males having significantly higher values than females regardless of feeding type (P = 0.028 and P < 0.001, respectively). Conclusion: There is no association between the use of palm olein formula during the first 4 months of life and subsequent bone mineral content and bone mineral density in healthy 4-year-old children.

Background: Abnormal pudendal nerve function contributes to fecal retention and incontinence in adults. To determine the role of pudendal neuropathy in childhood, we prospectively evaluated pudendal nerve function in normal and encopretic children. Methods: We studied pudendal nerve terminal motor latency in 23 encopretic children and in an equal number of similarly aged, normal children. Anal manometry and electromyography were also obtained in all children. Results: Pudendal nerve latency in the encopretic children equaled 1.58 ± 0.33 msec, which was the same as that in control children. Of the 75 pudendal nerves tested, latency was prolonged in only one encopretic child. In contrast, anal electromyography demonstrated nonrelaxation of the external anal sphincter in 75% of the encopretic children but in only 13% of the normal children (p < 0.001). Anorectal manometry demonstrated, on average, lower anal sphincter pressures at rest and with squeezing in the encopretic children (p < 0.01), but only 17% had sphincter pressures more than two standard deviations below normal. Conclusions: Other than poor relaxation response of the external anal sphincter during evacuation, these data reveal a paucity of functionally important abnormalities in encopretic children. In particular, we find no evidence that abnormal pudendal nerve function is important in the etiology or pathogenesis of encopresis in children.

The relationship of IgG- and IgM-bound circulating immune complexes and immune dysfunction to glomerular injury was evaluated in 15 children with end-stage liver disease (ESLD) awaiting liver transplantation. Compared with age-matched controls, children with ESLD had significantly (P0.01) increased serum IgG, IgA, and IgM levels, as well as IgG- and IgM-bound circulating immune complexes. Furthermore, they showed a significant (P0.05) depression of C3 and C4 levels compared with controls. Hematuria occurred in 66% of children with ESLD, and the urinary protein/creatinine ratio was also significantly (P0.01) increased compared with controls (4.65 +/- 2.56 vs. 0.16 +/- 0.04 mg/mg). Light microscopy of renal biopsy tissue obtained from 6 children with ESLD at the time of transplantation demonstrated mesangial proliferation and expansion with basement membrane splitting. This was associated with subendothelial deposits on electron-microscopic examination, compatible with a diagnosis of membranoproliferative glomerulonephritis. By immunofluorescence, deposition of IgG, IgA, and IgM occurred in various combinations with co-deposition of complement fragments. We conclude that membranoproliferative glomerulonephritis is a common finding in children with ESLD, probably due to entrapment of circulating IgG- and IgM-bound immune complexes.

The marriage of academic research laboratories to the biotechnology industry has raised some very complex ethical and legal issues regarding commercialization of human body parts, products and derivatives thereof. Current statutes prohibit the sale of one's body or bodily organs although people may legally sell their blood or semen and are generally encouraged to donate certain body parts for transplantation or research both in life and death. No existing legislation, however, clearly addresses ownership rights with respect to human cells and tissues used in research, Commercialization of human biological material, either by the donor or by the recipient, e.g., researcher and/ or pharmaceutical company, is an uncharted area of the law.The question of proprietary rights to one's own cells and tissues did not arise until the biotechnology industry rapidly expanded in the 1980s. Now, human organs, tissues and cells are used in research that may lead to the development of products with tremendous commercial value.

project commonly referred to as the PEG-SOD study. This study raised the question of whether the FDA and HHS requirements for informed consent are unnecessarily restrictive when applied to ER research. In a recent article published in this journal, we reported on the review and approval of the PEG-SOD study by the institutional review board (IRB) of the University of Nebraska Medical Center (UNMC).1 The protocol as described in our article is a multi

• Prenatally acquired cytomegalovirus infection in twins was temporally associated with a discordant development of neonatal hepatitis and extrahepatic biliary atresia. This case presents evidence suggesting an association between perinatal cytomegalovirus infection and selected extrahepatic biliary atresia and neonatal hepatitis. Congenital cytomegalovirus infections and cytomegalovirus hepatitis are also discussed. (AJDC.1991;145:302-305)

In order to determine the relative capacity for bowel adaptation in young versus older rats, 60% bowel resections were performed in seven 3-week-old and seven 8-week-old rats. These animals were then pair-fed with control animals that had undergone sham operations, and after 2 weeks, all animals were killed. Segments of remaining jejunum, midileum, and distal ileum were removed, and mucosa was scraped free using a glass slide. Mucosal wet weight, protein, RNA, DNA, and sucrase content were measured. Data were expressed as percent increase of each mucosal parameter in resected as opposed to control animals, and the two age groups were compared by unpaired t test. When data were examined per centimeter of bowel, increases in all parameters in each segment were substantially greater in the older animals, suggesting that older animals have a greater capacity for mucosal adaptation following massive bowel resection than do young animals. These findings correlate well with clinical experience which suggests that infants with massive bowel resection may require years of parenteral nutrition before total enteral nutrition is possible.

To determine whether zinc has a specific role on intestinal growth and function, three groups of male weanling Sprague-Dawley rats were fed a semipurified zinc-deficient diet: ad libitum fed group received powdered diet and water containing 25 ppm of zinc; force fed (ZN, ZD) groups were fed identical amounts of diet to the ad libitum fed group by intragastric infusion three times per day. The diets were aqueous suspensions made with either deionized water (ZD) or water containing 25 ppm of zinc (ZN), and additional drinking water with (ZN) or without zinc (ZD) was offered ad libitum. Rats were sacrificed after 8 days of feeding. The ZD group showed growth arrest, perioral and periorbital dermal lesions, and abdominal distention within 8 days of feeding. Mucosal DNA, protein, sucrase, maltase, lactase, leucine aminopeptidase, and alkaline phosphatase were significantly decreased in the ZD group, whereas intestinal length, weight, and mucosal weight were unaltered. These results suggest that short-term isolated zinc deficiency impairs growth, digestion, and absorption in the rat small intestine, even in the absence of associated protein calorie malnutrition.

Two anorectic, emaciated infants with central nervous system (CNS) neoplasms are reported. Diagnosis in each case was delayed, because computed tomography of the head was initially falsely negative, and because primary gastroenterologic illness was suggested by the presence of mild inflammation and villous atrophy of the small intestine. This experience indicates that the diagnosis of CNS neoplasm must be aggressively pursued in cachectic infants who refuse to eat, regardless of the results of the initial radiologic studies. Mild histologic abnormalities of the small intestine that may be present in infants with brain tumors probably represent a nonspecific response to starvation and, if unassociated with malabsorption, should not be considered the cause of illness.

We have studied net uptake of zinc from segments of rat duodenum, jejunum, and ileum using in vivo intestinal perfusion. We have also evaluated the effect of pancreatic and bile secretions on duodenal zinc absorption. Segments of duodenum, jejunum, and ileum and duodenum with bile and pancreatic duct obstruction, 10 cm in length, were studied in six rats each. Percentage absorption of zinc as determined by atomic absorption spectrophotomety was greater from the ileum (60.1%) when compared to duodenum (19.1%) or jejunum (20.2%). Exclusion of bile and pancreatic secretions from the lumen increased zinc absorption in the duodenum (32.0%). Postperfusion mucosal zinc content comprised 29.0% of absorbed zinc from jejunum, 7.4% from ileum, 5.2% from duodenum, and 2.7% from duodenum with bile and pancreatic duct obstructed, indicating rapid transport of zinc across epithelial cells after uptake from the duodenum and ileum. Our data indicate that the ileum has the greatest capacity for zinc absorption.

A steerable small bowel biopsy apparatus was evaluated in 56 infants and children over a 15-mo period. A mean time of only 6 min was required to obtain small bowel biopsies. Biopsies were successfully obtained in 92% of patients on the first attempt; repeat attempts were successful in all cases. No complications were encountered. The steerable biopsy tube appears to be a safe and effective means of obtaining small bowel biopsies rapidly in infants and children.

The possibility that somatostatin has a direct inhibitory effect on intestinal D-glucose absorption was studied in rats using intact intestinal loops and everted jejunal segments. Somatostatin infusion in vivo produced a significant fall in plasma glucose concentration (P less than 0.001) and a fall in pooled plasma insulin concentration to 51% of control values. However, somatostatin infusion did not alter significantly from control values the rate of glucose disappearance from the perfused jejunal lumen in vivo or the appearance of gut-derived plasma glucose. The lack of an inhibitory effect of somatostatin on glucose absorption in vivo was confirmed using two in vitro studies. When increasing concentrations of somatostatin (0-10(4) ng/ml-1) were added to both mucosal and serosal solutions, no significant differences were seen for net transmural flux or unidirectional flux of D-glucose in everted jejunal segments. These studies suggest that somatostatin in the rat does not influence plasma glucose concentration by inhibiting intestinal glucose transport at physiological concentrations of glucose and over a wide range of somatostatin concentrations.

Patients undergoing massive small bowel resection for a variety of conditions develop severe nutrient malabsorption which gradually improves through mucosal hyperplasia in the remaining small intestine. Following massive small bowel resection, patients are generally fed elemental diets, often containing high concentrations of medium-chain triglycerides. We evaluated the effect of high percentage medium-chain triglyceride feeding on mucosal adaptation following massive small bowel resection in rats. Twenty 150-g Sprague-Dawley rats were subjected to 60% jejunoileal resection. Another 20 animals received sham operations. One-half of each group were fed a diet containing 83% of the fat as medium-chain triglycerides, the remainder were fed a diet containing 40% medium-chain triglycerides. Animals were pair-fed for 2 wk and subsequently killed. The remaining bowel was removed and unidirectional glucose and leucine uptake were measured using isolated sacs. Mucosal wet weight, protein, and sucrase content were determined. Animals fed medium-chain triglycerides demonstrated decreased mucosal weight in the proximal bowel, decreased mucosal sucrase activity in the proximal bowel, and decreased mucosal leucine uptake in the distal bowel. While medium-chain triglycerides offer an advantage to patients with short bowel syndrome because they are easily absorbed, they may not stimulate the same degree of mucosal adaptation following resection as long-chain triglyceride feedings.

We investigated the effects of zinc deficiency on body composition by using intragastric force-feeding to obviate decreased food intake and altered eating patterns. Weanling male Sprague-Dawley rats were fed a purified zinc-deficient diet: the ad libitum-fed control group (AL; eight rats) was given powdered diet and water containing 25 ppm zinc; the zinc-replete group (ZN; nine rats) was force-fed a diet blended with water containing zinc in an amount of equal caloric intake to the AL group and allowed access to water containing zinc. The zinc intake of ZN rats was approximately twice that of AL rats based on water intake. The zinc-deficient group (ZD; 13 rats) was fed similarly to the ZN group except deionized water was used for diet preparation and drinking water. After 8 d, body and muscle weight were lower in the ZD group than in the ZN group. Femur weights were similar in the two groups. Serum, liver and femur zinc concentrations were 85, 22 and 42% lower, respectively, in the ZD group than in the ZN group. Serum glucose, relative liver weight, liver glycogen and liver lipids were higher, but muscle and liver DNA were lower in the ZD group than in control groups.

Small bowel neomucosa has been grown on a variety of surfaces. The purpose of this study was to compare the rate of growth and function of neomucosa on colon serosa (CS) and abdominal wall muscle (AM) in New Zealand white rabbits. The terminal ileum was incised for 5 cm and patched with either adjacent CS (23 animals) or AM (19 animals) to create a 2 × 5-cm defect. Gross and histologic examinations of the specimens at 1, 2, 4, and 8 weeks revealed that the rate of growth was similar in both groups. There was minimal lateral ingrowth at 2 weeks, nearly complete coverage of the defects at 4 weeks, and complete coverage of the defect at 8 weeks in more than 85% of animals with mature villi and muscularis mucosae. The ileal diameter at the site of patching increased in both groups from 11.9 ± 2.6 to 16.3 ± 3.2 mm in the CS group and 11.3 ± 2.5 to 15.1 ± 1.8 mm in the AM group (P < 0.01). Glucose uptake was similar in both groups being 65.4 ± 24.1% of control in the CS group and 73.9 ± 29.8% in the AM group. Brush border enzyme activity of sucrase, maltase, and lactase was similar to controls in the AM group but in the CS group activity of sucrase and maltase were significantly less than controls (P < 0.01). Average body weight was increased postoperatively in both groups. There was one anastomotic leak in each group and two cases of partial intestinal obstruction in the abdominal wall group. Both colon serosa and abdominal wall musculature will support the growth of functioning neomucosa with a similar rate of growth and quality of the neomucosa. The use of either in clinical situations should be determined by availability and technical considerations.

Administration of antibiotics has been reported to prevent or minimize liver dysfunction in experimental animals having been subjected to jejunoileal bypass, suggesting that jejunoileal bypass-induced liver dysfunction results from production of toxic substances by bacteria in the defunctionalized bowel. However, improved absorption will also prevent bypass-induced liver injury. We studied the effects of tetracycline on the development of bypass-induced liver dysfunction and compared it to the mucosal adaptation of the intact bowel after bypass. After 6 weeks, rats subjected to bypass but not given antibiotics had decreased levels of serum triglycerides, hepatic cytochrome P-450, and hepatic pentobarbital hydroxylase. Evaluation of intestinal mucosal hyperplasia after bypass indicated that animals given antibiotics after bypass developed greater increases in mucosal DNA content, mucosal protein, and mucosal weight than bypassed animals not receiving antibiotics. We speculate that the beneficial effects of antibiotic administration on liver function after bypass may be a result of improved absorption.

Intestinal tapering and lengthening were performed in a child with short bowel syndrome to prevent the need for home parenteral nutrition. The intestinal lengthening was not successful, presumably because the vascular anatomy was not favorable. Significant clinical improvement and avoidance of home parenteral nutrition resulted from the tapering procedure. These procedures have a role in the treatment of selected patients with short bowel syndrome.