Daniel B. Caplan

NUTRITIONAL ISSUES IN PEDIATRIC INFLAMMATORY BOWEL DISEASE

Malnutrition, characterized by weight loss, growth failure and micronutrient depletion, are prominent features of inflammatory bowel disease (IBD) in the pediatric age group. Accurate evaluation of the patients nutritional status and appropriate nutritional support, whether enteral or parenteral, constitute integral parts of the management of the growing child with IBD. Over the past two decades, a number of studies have supported the potential use of nutritional therapy to induce remission and to control disease activity in symptomatic Crohns disease. More recently, preliminary studies on the use of dietary supplements of marine-oil-derived omega-3 fatty acids have also indicated a beneficial effect in IBD patients. In parallel with these clinical trials, scientific research has recently focused on the concept that specific dietary alterations can modulate the immune response. Components of the diet that may have particular relevance to mucosal immunity and the pathogenesis of IBD include polyunsaturated fatty acids, nucleotides, and amino acids such as glutamine and arginine. Future research in the interactions between specific nutrients and the immune system will likely increase our understanding of the causes of IBD, as well as enhance the development of novel nutritional therapies for IBD patients.

METABOLIC RISK FACTORS FOR STONE FORMATION IN PATIENTS WITH CYSTIC FIBROSIS

PURPOSE Cystic fibrosis is characterized by chronic pulmonary disease, insufficient pancreatic and digestive function, and abnormal sweat concentrations. Patients with cystic fibrosis also have an increased incidence of nephrolithiasis. We compared the results of metabolic evaluation in patients with cystic fibrosis with and without nephrolithiasis. MATERIALS AND METHODS A total of 496 patients were evaluated at our center, including 98 with a mean age of 25 years who had cystic fibrosis and complete metabolic evaluation available between 1996 and 2000. Of these patients 13 (13%) had a history of nephrolithiasis. The records were reviewed for clinical characteristics and all patients underwent metabolic evaluation, including serum electrolyte measurement and 24-hour urine collection. Statistical analysis was done to compare the stone versus nonstone groups. RESULTS The incidence of nephrolithiasis in our study was 3%. We identified 13 patients 16 to 41 years old (mean age 27) with nephrolithiasis, of whom 62% had had multiple episodes. Flank pain was the presenting symptom in 9 of the 13 cases (69%). Renal ultrasound and computerized tomography were the most common imaging modalities. In 9 cases stones were passed without intervention, extracorporeal shock wave lithotripsy was required in 2 and ureteroscopy with stone extraction was done in 2. Calcium oxalate was the dominant stone composition in the 9 patients in whom stone analysis was performed. Metabolic evaluation of the stone versus no stone groups showed elevated urinary oxalate (45.5 versus 42.5 mg./24 hours), relative calcium oxalate supersaturation (5.3 versus 7.2) and decreased urinary citrate in the 2 groups. There was a statistical difference in citrate excretion with lower levels in stone formers (102 versus 218 mg./24 hours, p = 0.0007). CONCLUSIONS Patients with cystic fibrosis have an increased incidence of nephrolithiasis and are at high risk for recurrence. Metabolic evaluation is indicated in all patients with cystic fibrosis and urolithiasis since most have hyperoxaluria, urinary calcium oxalate supersaturation and decreased urinary citrate. Correcting detected stone risk factors in these cases may decrease stone recurrence.

Seroprevalence of Helicobacter pylori infection in cystic fibrosis and its cross-reactivity with anti-pseudomonas antibodies.

BACKGROUND The prevalence of Helicobacter pylori infection and its role in gastroduodenal disease in cystic fibrosis (CF) are controversial. Additionally, serologic determination of infection in this population may be inaccurate because of cross-reactivity with other bacterial species. The seroprevalence of H. pylori in a cohort of patients with CF and its cross-reactivity with Pseudomonas antibodies were investigated. METHODS A research enzyme-linked immunosorbent assay (ELISA), and three commercial serologic assays (PyloriStat; BioWhittaker, Walkersville, MD, U.S.A.; Flexsure; SmithKline Diagnostics, Inc., San Jose, CA, U.S.A.; and HM-CAP; EPI, Stony Brook, NY, U.S.A.) at three independent laboratories determined the seroprevalence of anti-H. pylori IgG antibodies in 70 patients with CF. Cross-reactivity between solid-phase H. pylori antigens and Pseudomonas antibodies was ascertained by a competitive inhibition assay, preadsorbing sera of patients with CF with whole cell proteins from different Pseudomonas species, and serum reanalysis by each assay. Western blot analysis before and after adsorption was performed to identify potential cross-reactive antigens. RESULTS The research ELISA, Flexsure, Pyloristat, and HM-CAP initially showed H. pylori seropositivity of 47%, 28%, 24%, and 37%, respectively. Postadsorption seropositivity declined to 8%, 0%, 0%, and 15%, respectively. All patients with research ELISA true-positive results were confirmed endoscopically to have H. pylori infection. Western blot analysis showed a 31-kDa H. pylori protein with antigenic epitopes common to both bacterial species. CONCLUSIONS Cross-reactivity between solid-phase H. pylori antigens and anti-Pseudomonas antibodies occurs in patients with CF. A high index of suspicion should be assumed in evaluating results of serologic H. pylori tests in this population. Preadsorption of CF sera with Pseudomonas proteins should be used in serologic testing.

Total colectomy with ileo-endomuscular pull-through in the treatment of ulcerative colitis in children*

Since ulcerative colitis is primarily a mucosal disease, total colectomy with rectal mucosectomy and ileo-endomuscular pull-through (Soave) offers many theoretical advantages. The diseased colon is removed, the anal sphincteric mechanism is preserved, and permanent ileostomy is avoided, bladder and sexual function are preserved, and problems with perineal wound healing are avoided. Of critical importance is the state of rectal mucosal disease in the selection of patients for this operation. Our experience with four children in whom the operation has been performed is presented. Postoperative diarrhea has not proved to be a significant problem and continence has been maintained.

Cross circulation between children in hepatic coma and chimpanzees: Clinical, biochemical, and coagulation observations

Two children in profound hepatic coma underwent cross circulation with chimpanzees following unsatisfactory response to conventional medical management and multiple exchange transfusions. One patient awoke dramatically five hours after completion of the procedure and remained conscious and alert altert for 20 days. Biochemical and coagulation derangements were transiently improved, but significant hepatic regeneration did not occur. Further investigation in providing temporary support for such patients with fulminant hepatic failure is necessary.

Platelet-monoamine oxidase activity in Reye's syndrome.

Summary Platelet and liver monoamine oxidase (MAO) activity (mean ± SD) was evaluated in patients with liver-biopsy-proven Reyes syndrome. MAO was measured by a radioenzymatic technique with [3H]tyramine as a substrate. A marked decrease in MAO activity [3.3 ± 2.4 nmol of [3H]4-hydroxyphenylacetic acid formed X (mg protein)-1 x h-1] was observed in platelets on admission in all patients (n = 13) with Reyes syndrome when compared with hospitalized patients without liver disease (n = 8) [9.8 ± 2.5 nmol of [3H]4-hydroxyphenylacetic acid formed x (mg protein)-1 x h-1] and with liver disease (n = 10) [9.1 ± 2.0 nmol of [3H]4-hydroxyphenylacetic acid formed x (mg protein)-1 x h-1]. Following recovery from the disease, platelet MAO approached levels that were not significantly different from those of controls. Contrastingly, reduction of hepatic MAO in Reyes syndrome was similar to that seen in patients with liver disease of different etiologies. These studies suggest that reduced platelet MAO activity is a specific abnormality in Reyes syndrome, and it may be representative of generalized impairment of mitochondrial function in these patients. Furthermore, the pattern of liver and platelet MAO activity in Reyes syndrome may allow for the differentiation of this disease from other hepatopathologic conditions.

Corneal opacities in infancy and childhood

An unusual case of a 24-month-old female with bilateral cloudy corneas first noted in the newborn period is presented. A brief summary of the local and systemic diseases of childhood with which corneal opacities are associated, with an approach to their diagnosis, is included.

1240 PLATELET MONOAMINE OXIDASE (MAO) ACTIVITY IN REYE'S SYNDROME (RS)

In patients with RS we have shown that MAO activity was significantly reduced in liver and tyramine, dopamine, norepinephrine, epinephrine, and octopamine were increased in plasma, urine, and cerebrospinal fluid. The purpose of the present study was to determine whether generalized MAO dysfunction is a metabolic abnormality associated with RS.Platelet and liver MAO activities were evaluated by radioenzymatic technique in RS and control patients. Platelet MAO activity was significantly decreased (p<0.025) in RS patients (n=13) [3.3 ± 2.4 nmoles of [3H]4-hydroxy-phenylacetic acid formed x (mg protein)−1 × hr−1] when compared to control patients without liver disease (n=8) [9.8 ± 2.5 nmoles] and in non-RS liver disease patients (n=9) [9.1 ± 2.0 nmoles]. Following recovery platelet MAO levels in RS patients were not significantly different from controls. In contrast, there were no significant differences between hepatic MAO activities in RS patients and those without liver disease or non-RS liver disease.Conclusion: 1) reduced platelet MAO activity is a specific abnormality in RS and represents generalized mitochondrial dysfunction; 2) the pattern of MAO activities in platelet and liver may differentiate RS from other hepatopathologic states; 3) the disturbance of MAO activity may be responsible for hypercatecholaminemia and neurologic dysfunction in RS patients.

1596 HYPERTYRAMENEMIA AND HYPERPODIACTINEMIA IN REYE'S SYN-DROME: CORROBORaTION OF THE FALSE NEUROTRANSMITTER HYPOTHESIS

Several explanations for the encephalopathy in RS including false neurotransmitter activity have been postulated. Our group has recently demonstrated preliminary evidence of a disturbance in tyrosine metabolism resulting in hypertyraminemia in 14 patients (Ped.64:76,1979). Additionally, we have observed hyperprolactinemia in three cases of stage IV RS (Lancet 2:1097,1979).Utilizing the same radioimmunoassay techniques, plasma tyramines (TM) were measured on 16 additional RS patients. Plasma TM on admission were significantly elevated 6.65 ng/ml ± 1.86 (mean ± S.E.M., range 0.1-36.2) p<0.003 when compared to the control patients without liver disease (range 0.7-1.1 ng/ml). A double antibody RIA was utilized to measure daily serum prolactin in the same 16 RS patients. Mean peak serum prolactin levels for patients presenting in various stages of coma were: I 15.07(7-28), II 13.7(7-33), III 34.7(14-66), IV 50-6(13-73). The mean peak serum prolactins in patients presenting in stages III and IV were significantly higher than those presenting in stages I and II (p<0.01) and positively correlated with admission plasma TM (p<0.04 r=0.61).These findings of hyperprolactinemia and significantly elevated plasma TM in the severely encephalopathic patients indirectly confirm evidence of a “false neurotransmitter” contribution to the encephalopathy. Hyperprolactinemia may select a subpopulation of RS patients with potential to benefit from attempts to correct neurotransmitter disturbance with agents such as L-dopa or bromocriptine.