Eur J Pediatr

Anti-thymocyte globulin, cyclosporin A and granulocyte colony-stimulating factor for severe aplastic anaemia complicating paediatric liver transplantation.

Year 1998
Hadzic N. Layton M. Heaton ND. Rela M. Baker AJ. Mieli-Vergani G.
Department of Child Health, King's College Hospital, Denmark Hill, London, UK.
We describe a sustained trilineage haematopoietic response to intensified immunosuppressive therapy with anti-thymocyte globulin, cyclosporin A and recombinant human granulocyte colony-stimulating factor in a 4-year-old girl, who developed severe aplastic anaemia after orthotopic liver transplantation for fulminant liver failure induced by non A-E hepatitis. The outcome was successful and allows the following. CONCLUSION: Intense immunosuppression in combination with haemopoetic growth factors and antimicrobial prophylaxis should be considered as first line therapy in severe aplastic anaemia after orthotopic liver trans-plantation.

Early and severe neurological features in a Wilson disease patient compound heterozygous for two frameshift mutations.

Year 1998
Angius A. Dessi V. Lovicu M. De Virgiliis S. Pirastu M. Cao A.
Istituto di Ricerca sulle Talassemie ed Anemie Mediterranee CNR, Cagliari, Italy.
We describe a patient with Wilson disease who presented at 11 years of age with neurological symptoms and subsequent rapid progression of neurological impairment but absent hepatic manifestations. Molecular analysis showed compound heterozygosity for two frameshift mutations, 2299insC and 214delAT, which most likely result in an absent or inactive protein product. Mutation-phenotypic analysis indicates that this genotype does not explain the severe phenotype, suggesting the presence of modifying factors. CONCLUSION: Wilson disease may present even in childhood or adolescence with neurological abnormalities in the absence of hepatic manifestations.

Thymic cyst haemorrhages and transient cholestasis in a 4-week-old infant.

Year 1998
Koopman LP. Plotz FB. Meuzelaar JJ. Knoester H.
Department of Paediatrics, University Hospital Groningen, The Netherlands.
We report a 4-week-old boy with acute respiratory distress, due to massive haemorrhages in multiple thymic cysts. A right hemithymectomy was performed because of mechanical obstruction of the trachea by the cysts. The origin of the multilocular thymic cysts remained unclear. Most likely, these haemorrhages were caused by vitamin K deficiency, although the infant received vitamin K prophylaxis. In addition, he developed transient cholestasis, but the aetiology remained unclear. It is postulated that massive haemorrhages in thymic cysts produce large amounts of bilirubin, causing sludging of bile excretions in the liver. Four weeks after the operation, all laboratory findings were normal and 6 months after the operation the boy is still healthy. CONCLUSION: This case report shows that respiratory distress in an infant can be caused by multiple haemorrhages in multilocular thymic cysts.

Safety and efficacy of interferon retreatment in children with chronic hepatitis B.

Year 1998
Ballauff A. Schneider T. Gerner P. Habermehl P. Behrens R. Wirth S.
Department of Paediatrics, University of Essen, Germany.
More than 50% of children with chronic hepatitis B do not respond to treatment with alpha-interferon. Since these patients continue to display high viral replication and progressive liver disease, retreatment should be considered. To date it has not been well evaluated whether a second course of treatment could increase the response rate. In two alpha-interferon retreatment trials in adult patients the response rate, defined by seroconversion from HBeAg to anti-HBe, ranged between 11% and 44%. One beta-interferon retreatment study in children reported a seroconversion rate of 32%. Regrettably, none of the studies included a control group observing the 'spontaneous' seroconversion rate after a first interferon cycle. Thus, a nonrandomized alpha-interferon retreatment study in children including control patients was performed. Alpha-interferon for retreatment was administered 3 times a week for 16-24 weeks in 15 children (5-16 years) at least 6 months after ceasing the first cycle. Four children received 5 MU/m2 of a natural alpha-interferon and 11 children 9 MU/m2 recombinant alpha-interferon 2b. Follow up was 18-47 months after initial treatment. In parallel, a control group of 19 unretreated children with comparable clinical and demographic data was followed for 12-39 months. HBeAg seroconversion was observed in 5 (33%) of the retreated children and in 5 (26%) of the control patients during follow up. The difference is not significant. In the initially nonresponding children, those with high ALT levels before the first treatment showed late HBeAg seroconversion more frequently than those with low ALT levels (P=0.017) irrespective of retreatment. The ALT level before retreatment was not a predictor for response. CONCLUSIONS: A second cycle of alpha-interferon during the 3 years following the first treatment in nonresponding children with chronic hepatitis B can be safely performed but did not increase HBeAg/anti-HBe seroconversion compared with the spontaneous seroconversion rate of patients without retreatment.

Diagnosis of the first Japanese patient with 3-oxo-delta4-steroid 5beta-reductase deficiency by use of immunoblot analysis.

Year 1998
Kimura A. Kondo KH. Okuda KI. Higashi S. Suzuki M. Kurosawa T. Tohma M. Inoue T. Nishiyori A. Yoshino M. Kato H. Setoguchi T.
Department of Paediatrics and Child Health, Kurume University School of Medicine, Japan.
A 3-oxo-delta4-steroid 5beta-reductase (5beta-reductase) deficiency is difficult to diagnose because severe liver damage can result in a similar pattern of metabolite excretion. We investigated the usefulness of immunoblot analysis for diagnosis of 5beta-reductase deficiency and quantitatively analysed urinary bile acids by gas chromatography-mass spectrometry in a 5-month-old Japanese boy with severe neonatal cholestasis associated with hypertyrosinaemia. A liver sample was examined by immunoblot analysis using monoclonal antibodies against 5beta-reductase. Urinary 3-oxo-delta4 bile acids accounted for 88.3% of total bile acids, 5alpha-bile acids for 0.9%, and primary bile acids for 9.1%. Immunoblot analysis of the liver tissue showed an indistinct band of 5beta-reductase. CONCLUSIONS: These findings suggest that this patient had a secondary 5beta-reductase deficiency due to severe liver damage, even though 3-oxo-delta4 bile acids constituted more than 70% of total urinary bile acids. However, the patient may possibly have had an inherited 5beta-reductase deficiency.

Pyostomatitis vegetans in childhood.

Year 1998
Al-Rimawi HS. Hammad MM. Raweily EA. Hammad HM.
Paediatric Department, Jordan University of Science and Technology, Irbid-Jordan.
Pyostomatitis vegetans is an oral eruption, characterized by small pustules, ulcers and erythematous vegetations of the labial and buccal mucosae as well as labial-attached gingivae. Its importance lies in its high correlation with inflammatory bowel disease. It is commonly associated with skin and inflammatory bowel disease and is rare in children. We here report a sister and brother with onset of the disease at the age of 5 and 7 years, respectively. It is the first report of familial pyostomatitis vegetans occurring in the youngest patients hitherto reported. CONCLUSION: The observation of two sibs with pyostomatitis, vegetans pyoderma gangrenosum and inflammatory bowel disease suggest a hereditary disposition to this rare triad.

Pulmonary evolution of cystic fibrosis patients colonized by Pseudomonas aeruginosa and/or Burkholderia cepacia.

Year 1998
Jacques I. Derelle J. Weber M. Vidailhet M.
Service de Medecine Infantile 1 et 3, Hopital d'Enfants, Centre Hospitalier Regional et Universitaire de Nancy, Vandoeuvre, France.
We analysed the pulmonary evolution (radiological scores and pulmonary function) of 81 cystic fibrosis (CF) patients colonized by Pseudomonas aeruginosa (PA), by Burkholderia cepacia (BC) or by both these bacteria, compared to a control group. Pulmonary function was compared in the age bracket 6-13 years. Functional vital capacity (FVC) and forced expiratory volume (FEV1) values for PA colonized patients were significantly worse than for the control group but better than for children colonized by both organisms. In this last group, the evolution of radiological scores and pulmonary function showed a greater decline 2 years after the first colonization compared to the other groups. FVC and FEV1 values in patients colonized by BC were not worse than these of patients colonized by PA. Moreover, BC affected older patients with advanced lung disease and often previously colonized with PA. These results suggested that co-colonization by PA and BC could be a more deleterious factor on the pulmonary evolution than the isolated colonization by PA or BC, and that BC could be a severity marker rather than a cause. In addition, after starting the utilization of mouthpieces with filter at single use for spirometry in 1993 (without any other change in preventive measures already taken during hospitalization), incidence of BC decreased from 8.2% to zero, and no new case of BC colonization has been observed over the last 4 years. CONCLUSION: Co-colonization of CF patients by PA and BC is more deleterious for pulmonary evolution than colonization by one of these bacteria alone. Re-inforcement of environmental measures during hospitalization (e.g. use of disposable mouthpieces for spirometry) was sufficient to reduce the transmission of BC.

Faecal immunoreactive lipase: a simple diagnostic test for cystic fibrosis.

Year 1998
Munch R. Bragger CP. Altorfer J. Hoppe B. Shmerling DH. Ammann R.
Division of Gastroenterology, University Children's Hospital Zurich, Switzerland. Muench@bluewin.ch
The study evaluates faecal immunoreactive lipase (IRL) measurement in spot stool samples as an index of exocrine pancreatic function in patients with cystic fibrosis (CF). Stool samples (211) from 183 healthy volunteers (age range: 2 days-14.2 years) showed a normal log distribution of IRL values with a median concentration of 71.4 micrograms/g (range: 0.53-4160 micrograms/g). In 156 stool samples from 58 patients with proven CF, the median IRL concentration of 0.4 microgram/g (range: 0.003-107 micrograms/g) was significantly lower (P < 0.001) than that of normal controls. In healthy controls, IRL levels were age related with significantly higher levels (P < 0.001) shortly after birth compared to older children. Stimulation of the exocrine pancreas by oral milk feeding resulted in a significant (P < 0.001) increase in a faecal IRL concentration. Faecal IRL concentrations in meconium were very low and of the same magnitude as in patients with CF. CONCLUSION: Faecal IRL determination had a high diagnostic sensitivity (87%) and excellent diagnostic specificity (97%) in patients with CF. A negative test result (PVneg. 99%) virtually excluded CF under screening conditions.

Manoeuvres to elevate mean airway pressure, effects on blood gases and lung function in children with and without pulmonary pathology.

Year 1998
Naik S. Greenough A. Giffin FJ. Baker A.
Department of Child Health, King's College Hospital, London, UK.
During mechanical ventilation, mean airway pressure (MAP) can be increased by a variety of manoeuvres, for example increasing inspiratory time or elevating the positive end expiratory pressure (PEEP). It seemed likely that the effect on blood gases and lung function of a particular manoeuvre to increase MAP would be influenced by the presence of respiratory pathology and thus the manoeuvre best at improving respiratory status in children with an abnormal chest radiograph appearance would differ from that most efficacious in children without such a problem. The aim of this study was to test that hypothesis. Twenty-two children, median age 15 months (range 2.5 weeks-10 years) were examined. Group 1 (n = 10) had no chest radiograph abnormalities and group 2 (n = 12) lobar collapse and/or consolidation. The patients were studied at baseline settings and at an elevated MAP resulting from (in random order) an increase in inspiratory time (T1), pressure PEEP or peak inspiratory pressure (PIP). In group 1, elevating PIP improved oxygenation and carbon dioxide elimination (P < 0.01) and prolonging T1 improved oxygenation (P < 0.05). In group 2, only raising PEEP significantly improved oxygenation (P < 0.01), but this was associated with carbon dioxide retention (P < 0.01). CONCLUSION: The presence of lung pathology does influence which manoeuvre should be used to elevate MAP to improve blood gases in the paediatric population.