Jeffrey S. Hyams

Relationship of functional and antigenic interleukin 6 to disease activity in inflammatory bowel disease

BACKGROUNDnIntestinal and peripheral blood mononuclear cell interleukin 6 (IL-6) production in inflammatory bowel disease might present an increased quantity of IL-6 into the systemic circulation. The aim of the present study was to examine the relationship of circulatory IL-6 to the clinical and laboratory expression of inflammatory bowel disease in children.nnnMETHODSnSera were obtained from 26 children with ulcerative colitis, 49 with Crohns disease, and 29 control patients. Serum functional IL-6 was measured by a bioassay and antigenic IL-6 by enzyme linked immunosorbent assay.nnnRESULTSnFunctional and antigenic serum IL-6 levels were higher in Crohns disease than in ulcerative colitis or controls (P < 0.0001) and higher in ulcerative colitis than controls (P < 0.04). In Crohns disease affecting the colon, functional and antigenic serum IL-6 levels were greater than in disease limited to the small bowel (P < 0.002). Increasing disease severity was reflected by increasing antigenic but not functional IL-6 levels in both Crohns disease (P < 0.001) and ulcerative colitis (P < 0.02). Serum antigenic IL-6 levels were related to acute phase reactants in both diseases (P < 0.001) whereas functional levels were not.nnnCONCLUSIONSnOur results underscore the importance of using both functional and antigenic methodologies in examining the relationship of circulating cytokines to the clinical manifestations of inflammatory bowel disease.

Corticosteroids and growth.

Les corticosteroides favorisent le catabolisme et peuvent donc gener la croissance. Par contre utilises judicieusement, ils peuvent la permettre en traitant une affection qui entrave la croissance. Revue de quelques elements eclairant sur ces rapports confus: constatations cliniques, rapports avec les mediateurs hormonaux de la croissance et le metabolisme du collagene, effets a long terme

Cyclosporine treatment of autoimmune chronic active hepatitis

A 14-yr-old boy with a 5-yr history of autoimmune chronic active hepatitis refractory to corticosteroid therapy was given cyclosporin A (5 mg/kg X day). Before cyclosporine therapy, serum aminotransferase levels were 20 times normal and immunoglobulin G was 4 g/dl. Within 2 wk of starting cyclosporine therapy, aminotransferase levels decreased; by 2 mo they were almost normal, and at 1 yr into therapy they were normal. A decrease in cyclosporine dosage was associated with an increase in aminotransferase levels, which then again decreased as the dose was increased. Severe growth failure observed during previous corticosteroid therapy reversed during cyclosporine treatment and the patient displayed catch-up growth. No significant side effects were noted after 1 yr of cyclosporine therapy. Further evaluation of cyclosporine in the treatment of corticosteroid-unresponsive autoimmune chronic active hepatitis appears warranted.

Chronic abdominal pain caused by sorbitol malabsorption

7. Willems JL, Monnens LAH, Trijbles TMF, et al: Leighs encephalomyelopathy in a patient with cytochrome c oxidase deficiency in muscle tissue, Pediatrics 60:850, 1977. 8. Atkin BM, Buist NRM, Utter MF, et al: Pyruvate carboxylase deficiency and lactic acidosis in a retarded child without Leighs disease, Pediatr Res 13:109, 1979. 9. Van Biervliet JPGM, Bruinvis L, Ketting D, et al: Hereditary mitochondrial myopathy with lactic acidemia, a De ToniFanconi-Debre syndrome and a defective respiratory chain in voluntary striated muscle, Pediatr Res 11:1088, 1977. 10. Chesney RW, Kaplan BS, Colle E, et al: Abnormalities of carbohydrate metabolism in idiopathic Fanconi syndrome, Pediatr Res 14:209, 1980. 11. Hackett TN Jr, Bray PF, Ziter FA, et al: A metabolic myopathy associated with chronic lactic acidemia, growth failure and nerve deafness, J PEDIATR 83:426, 1973.

Effect of metoclopramide on prolonged intraesophageal pH testing in infants with gastroesophageal reflux.

The effect of metoclopramide (MCP) on prolonged intraesophageal pH testing was evaluated in 42 infants with gastroesophageal reflux (GER). Following a baseline period of intraesophageal pH monitoring, MCP was administered by injection at 0.1 mg/kg/dose (10 patients), 0.2 mg/kg/dose (11 patients), or 0.3 mg/kg/dose (21 patients). The percentage of time of intraesophageal pH less than 4, reflux frequency, and acid clearance time were calculated for each subject before and after MCP for both 5% dextrose and formula feedings. These parameters were further separated into 2-hour or shorter and more than 2-hour postprandial periods. No significant differences with either type of feeding were noted at either 0.1 or 0.2 mg/kg/dose. Significant decreases in the percentage of time the intraesophageal pH was less than 4 (30.0 +/- 2.9 versus 15.6 +/- 3.1, p = 0.001), the reflux frequency (episodes/hour; 6.5 +/- 0.9 versus 4.0 +/- 0.6, p = 0.004), and the acid clearance time (minutes/episode; 3.8 +/- 0.7 versus 2.2 +/- 0.3, p = 0.047) were noted in the 2-hour or shorter period following 5% dextrose feedings but not following the formula feedings in the subjects receiving 0.3 mg/kg/dose. Three of the 42 study patients developed increased irritability, and one developed dystonia following MCP. These data suggest that if a clinical trial of MCP in infants with GER is performed, a larger dose of the medication than previously appreciated might be required.

Unreliability of Rotazyme ELISA test in neonates

Le test ELISA au rotazyme nest pas fiable chez les nouveau-nes exclusivement; seulement 7% des examens positifs au rotazyme se sont averes aussi positifs aux tests de confirmation. On preconise de confirmer la positivite des selles ou rotazyme chez les nouveau-nes asymptomatiques ou ceux avec des reactions faiblement positives, a laide de la microscopie electronique dun ELISA de confirmation ou de lhybridation de lARN

Psychopathology and relationship measures in children with inflammatory bowel disease and their parents.

Children with inflammatory bowel disease and their parents were assessed for DMS-III diagnoses, maternal attachment, marital relationship, life stresses, illness severity and cognitive/affective profile. Eleven of 15 children and 21 of 27 parents had psychiatric diagnoses. Three children were suicidal. Thirteen of 15 mothers had insecure attachment. Marital difficulties and medical severity correlated with life stress. The higher prevalence of psychiatric disorders than epidemiologically and of insecure attachment suggest at-risk relationships.

Colonic hydrogen production in infants with colic

pneumonias in immunocompromised patients. JAMA 1985;253:1769-73. 9. Bellamy EA, Johnston ID, Wilson AG. The chest radiograph in whooping cough. Chest Radiol 1987;38:39-43. 10. Ng VL, York M, Hadley WK. Unexpected isolation of Bordetella pertussis from patients with acquired immunodeficiency syndrome. J Clin Microbiol 1989;27:337-8. 11. Borkowsky W, Steele C J, Grubman S, Moore T, La Russa P, Krasinski K. Antibody responses to bacterial toxiods in children infected with human immunodeficiency virus. J PEDIATR 1987;1 l:563-6. 12. Bernstein L J, Ochs HD, Wedgewood R J, Rubenstein A. Defective humoral immunity in pediatric acquired immune deficiency syndrome. J PEDIAT~ 1985;107:352-7. 13. Mendez H, Fikrig S, Deforest A, Clark JL. Response to childhood immunizations in children with human immunodefi. ciency virus (HIV) infection [Abstract]. In: IV International Conference on AIDS, Stockholm, Sweden, June 12-16, 1988:342. 14. Pittman M. Pertussis toxin: the cause of the harmful effecls and prolonged immunity of whooping cough: a hypothesis. Rev Infect Dis 1979;1:401-12. 15. Manclark CR, Cowell JL. Pertussis. In: Germanier R, ed. Bacterial vaccines. Orlando, Fla.: Academic Press, 1984:6% 106. 16. Report of the Task Force on Pertussis and Pertussis Immunization-1988. Pediatrics 1988;81(6 Pt 2):939-84.

Pancreatitis following scoliosis surgery in children and young adults.

Forty-four patients undergoing single-stage surgery for scoliosis were monitored for biochemical and clinical evidence of pancreatitis. Six patients (14%) developed elevation of both serum amylase and lipase levels. Four of these had symptoms or signs suggestive of pancreatitis. Mean intraoperative blood loss was significantly higher in the group with pancreatitis. No significant differences were noted with regard to age, surgical technique, degree of initial or residual deformity, or length of surgery. The patients with pancreatitis required a longer average period of fasting time. Patients with prolonged ileus or abdominal pain after scoliosis surgery should be investigated for possible pancreatitis.

Characterization of Circulating Interleukin-1 Receptor Antagonist Expression in Children with Inflammatory Bowel Disease

The cytokines IL-1β and IL-6 appear to be important in the pathogenesis of inflammatory bowel disease (IBD). Recently, a naturally occurring interleukin-1 receptor antagonist, designated IL-1ra, which inhibits IL-1β activityin vitro andin vivo has been described. The purpose of the present study was to assess the circulating levels and relative relationships of IL-1ra, IL-1β, and IL-6 in children with IBD of varying severity. Serum/plasma samples were obtained from 32 children with ulcerative colitis, 45 with Crohns disease, and 24 control patients. Cytokine assays were performed by enzymelinked immunoassay. IL-1ra levels were significantly elevated in children with ulcerative colitis or Crohns disease of moderate/severe activity compared to patients with inactive/mild IBD or control subjects (P<0.001). IL-1β was only detectable in the circulation of two subjects with severe colitis (one ulcerative colitis, one Crohns disease), and both had extremely elevated IL-1ra levels. IL-1ra levels were significantly related to IL-6 levels for patients with IBD (P<0.00001). Our results suggest that circulating IL-1ra appears in increasing concentrations in children with mounting degrees of disease severity as determined by clinical scoring methods as well as by the level of IL-6. Future work will need to address the clinical and prognostic value of measuring circulating IL-1ra in individuals with inflammatory bowel disease.