Association of the interleukin-23 receptor gene variant rs11209026 with Crohn's disease in German children.

AIM: Genome-wide association studies have described variants within the interleukin-23 receptor (IL23R) locus to be associated with Crohn's disease (CD) and ulcerative colitis (UC). We investigated the association of rs11209026 (p.Arg381Gln) and rs7517847 (c.799-3588T>G) into German paediatric inflammatory bowel disease (IBD) patients and analysed IL23R transcriptional activity in colonic tissues. METHODS: The rs11209026 and rs7517847 nucleotide substitutions were determined in 353 German children with IBD (221 CD, 132 UC) and 253 controls using pre-designed TaqMan((R)) SNP genotyping assays. In selected IBD patients and controls, IL23R mRNA expression was measured using real-time PCR. RESULTS: The prevalence of the rs11209026 A allele was lower in CD patients, but not in UC patients, when compared with controls (1.8% vs 7.1%, p < 0.01). The rs7517847 variant, in contrast, was associated neither with CD nor with UC. IL23R expression was variable in IBD patients compared with controls without significant overexpression or downregulation. CONCLUSION: Our study provides additional support for the strong protection of the rs11209026 (p.Arg381Gln) variant against paediatric CD. IL23R was expressed in both CD and UC with a great variability. However, expression levels showed no significant association with the disease.

[Severe aplastic anaemia in six children after non-A-E hepatitis without hepatic failure]. / Schwere aplastische Anämie bei 6 Kindern nach Non-A-E-Hepatitis ohne Leberversagen.

Aplastic anaemia can coincide with non-A-E hepatitis. Treatment follows a standardised study protocol of the German Society of Paediatric Oncology and Haematology (GPOH). Patients receive immunosuppression and/or bone marrow transplantation. We present six cases of aplastic anaemia after non-A-E hepatitis with different courses. In four of these children illness first presented with acute gastroenteritis. Five out of six children fully recovered, two of these with immunosuppression alone, three after bone marrow transplantation. One patient died due to complications of the bone marrow transplantation. In two patients steroid therapy was carried out to treat the hepatitis. This did not have any effect on the course of their aplastic anemia. We emphasise this common combination of aplastic anemia following non-A-E hepatitis. This overview underlines the necessity of regular blood testing after non-A-E hepatitis. Often gastroenteritis seems to precede illness thus perhaps indicating an infectious trigger.

Serum leptin, gonadotropin, and testosterone concentrations in male patients with anorexia nervosa during weight gain.

Amenorrhea in female patients with anorexia nervosa is associated with low leptin secretion, thus suggesting a causal link. In an attempt to address the hypothesis that leptin also influences the hypothalamo-pituitary-gonadal function in males, we studied three male patients with acute anorexia nervosa longitudinally. Serum levels of leptin, LH, FSH, testosterone, and SHBG were measured on a biweekly basis during weight gain. Leptin levels at low body mass index values were below the 5th percentile. During weight gain, leptin levels reached or surpassed the 95th percentile. The temporal dynamics of body mass index and fat mass were closely related to those of leptin concentrations in serum. Leptin increments were paralleled by increments of gonadotropins, testosterone, and the free androgen index (FAI). In each of the patients, serum concentrations of leptin were positively correlated with those of testosterone (P = 0.0001, P = 0.01, P = 0.07, respectively) and FAI (P = 0.0001, P = 0.0001, P = 0.09, respectively). In addition, in the combined data set of all patients changes of leptin over time were positively correlated with changes in LH (P = 0.01), FSH (P = 0.0001), testosterone (P = 0.002), and FAI (P = 0.002). In conclusion, these data suggest that leptin might also play an important role in the regulation of the hypothalamo-pituitary-gonadal axis and fertility in underweight males as has previously been shown in underweight females.

Heterotopic auxiliary liver transplantation in a 3-year-old boy with acute liver failure and aplastic anemia.

BACKGROUND: Auxiliary liver transplantation offers an alternative method to conventional transplantation in acute liver failure. It is especially challenging for children because lifelong immunosuppression may be avoided. However, experience with this procedure is rare and there is controversy about whether to place the graft orthotopically or heterotopically. METHODS: We present the case of a 3-year-old boy with acute liver failure due to non-ABC hepatitis complicated by aplastic anemia who underwent auxiliary liver transplantation. Segments 2 and 3 of the graft were implanted heterotopically in the right lower abdomen. RESULTS: Good liver function was immediately restored. Aplastic anemia resolved 3 weeks after transplantation. Immunosuppressive therapy was discontinued after 14 months, and the graft was left to atrophy. Thirty-nine months after transplantation the boy is alive and well with normal liver function tests and normal blood cell counts. CONCLUSIONS: Heterotopic auxiliary liver transplantation allowed recovery of the native liver in a child with acute liver failure and aplastic anemia due to non-ABC hepatitis.

Interrelation between whole-body turnover rates of RNA and protein.

In our search for new non-invasive methods to determine metabolic and nutritional state, we have identified several specific, modified, urinary one-way catabolites of rRNA, tRNA and mRNA which permit the assessment of the whole-body turnover of these RNA classes. A comparison of the steady-state turnover of RNA and the proteins actin plus myosin (determined using urinary 3-methylhistidine) in preterm infants and adults showed that preterm infants have about 3 times higher average turnover rates per unit body weight than adults of tRNA and rRNA as well as of actin plus myosin, whereas calculated mRNA turnover was 6 times higher in preterm infants than in adults. These as well as our recent observations of RNA turnover in different mammals are compared here with data on whole-body protein turnover and basal metabolic rates (BMR) in different mammalian species including man, for which data are available. The turnover rates of tRNA, rRNA, protein and energy (BMR) can be described by the relation, turnover = const. x body mass (exp.), the extrapolated exponents being 0.69-0.78. This suggests a common underlying principle, possibly energy turnover, as cause for the coordinated whole-body turnover rates of RNA and protein in the steady state.

[Possible pathophysiologic, diagnostic and therapeutic implications of new findings on leptin secretion within the scope of anorexia nervosa]. / Mögliche pathophysiologische, diagnostische und therapeutische Implikationen neuer Befunde zur Leptinsekretion im Rahmen der Anorexia nervosa.

OBJECTIVES: Leptin is a hormone synthesized in adipocytes and secreted into the bloodstream. It plays an important role in the regulation of body weight, the adaptation to semi-starvation and in reproductive function. Hence, clinical studies pertaining to anorexia nervosa can serve to further elucidate the functions of this hormone in light of the unique features of this disorder. METHODS: Circulating concentrations of leptin are exceedingly low during the acute stage of anorexia nervosa. Which symptoms result from these diminished concentrations must be clarified. Furthermore, research is required to evaluate whether or not a too rapid weight gain might induce a physiological counter-regulation which would predispose to renewed loss of weight. RESULTS: This review summarizes findings to date pertaining to leptin secretion in patients with anorexia nervosa. In addition, possible diagnostic, pathophysiological and therapeutic implications are discussed.

[Intraabdominal and hepatic infections in pediatric cancer patients]. / Gastrointestinale und hepatobiliäre Infektionen.

Common complications involved in treating pediatric patients with cancer are bacterial, viral and fungal infections of the gastrointestinal tract including esophagitis, gastritis, duodenitis, colitis and hepatobiliar infections. In many cases there are multiple factors that predispose these patients to gastrointestinal infections, such as granulocytopenia, T-cell dysfunction, and mucosal damage. In addition, newer therapies have changed the spectrum of infection that is seen in these patients. The profound T-cell suppression associated with therapies such as stem cell transplantation has led to the emergence of previously rare infections including cytomegalovirus and adenovirus. This article provides the recommendations of the Infectious Diseases Working Party of the German Society for Pediatric Infectious Diseases (DGPI) and the German Society for Pediatric Hematology/Oncology (GPOH) for diagnosis, prevention, and management of local as well as invasive infections of the gastrointestinal tract.

[Scheduled urine collection using disposable diapers with an acoustic signal emitter]. / Untersuchungen zur zeitgerechten Urinsammlung mit Hilfe von Einmalwindeln mit akustischem Signalgeber.

Usually, urine is collected from infants by means of a urine bag. This procedure has some disadvantages, as it can cause discomfort and may even be painful for the child if repeated application of the bags is necessary. Correct placement is difficult for parents or other untrained people and bag displacement is common especially in older mobile children. Urine collection with disposable diapers followed by urine extraction for analysis might be a simple alternative procedure especially for field studies. Urine output is measured by weighing the diapers. A moisture sensor with a sound signal indicates the moment of urination. Stool contaminated diapers must not be excluded from urine collection, if the stool is quickly removed after defecation using diaper liners. Wet diapers are sealed in plastic bags and may be stored at -20 degrees C until extraction. With a hydraulic press urine is extracted from the diapers for measuring concentrations of urinary constituents. After extracting urine after 1 hour and 10 hours contact time only the pH falls significantly. Concentrations of the other constituents tested (creatinine, urea, phosphorus, calcium, sodium, potassium, magnesium, chloride) and total osmolality are not effected. After freezing the wet diapers for storage osmolality and the concentration of creatinine tend to be slightly lower. For clinical practice these effects can be neglected. However, they must be considered using this urine collection method in research.(ABSTRACT TRUNCATED AT 250 WORDS)

[Quality of life following liver transplantation in childhood]. / Lebensqualität nach Lebertransplantation im Kindesalter.

Orthotopic liver transplantation is now routinely performed in infants and children with end-stage liver disease and acute hepatic failure. Quality of life after transplantation depends on organ function, cure or recurrence of the original liver disease, need for further medical care, and complications associated with immunosuppression. Physical and psychomotor development as well as social integration are special aspects which are important for quality of life considerations in children. To illustrate these aspects we will discuss the clinical course of some of our patients.

Hereditary hemorrhagic telangiectasia with juvenile polyposis--coincidence or linked autosomal dominant inheritance?

Hereditary hemorrhagic telangiectasia (HHT) and familial juvenile polyposis (EJP) are two rare autosomal dominant disorders, Genetic heterogeneity has been shown for HHT and is likely for FJP as well. This paper describes the coexistence of both diseases in a girl and her father in addition to twelve members of five families and two sporadic cases reported in the literature. This implies a new phenotype which may be important in elucidating the underlying genetics in HHT and FJP. Clinical diagnosis of one disease should induce screening for symptoms of the other.

[Speech cannula for children with tracheotomy and oxygen inhalation therapy]. / Sprechkanüle bei tracheotomierten Kindern mit Sauerstoffbedarf.

Because of various possible problems tracheotomy in children should be performed only in urgent cases and should be sewed up as soon as possible. Early language therapy and the use of cannulas with speaking device promote language development. We propose a special silver cannula with speaking device for children with oxygen dependence due to bronchopulmonary dysplasia.

Hyperintense lesions of the globus pallidus on MRI in children with chronic liver disease.

UNLABELLED: In three children with chronic liver disease of different aetiology without obvious hepatic encephalopathy, bilateral and symmetrical hyperintensity of the globus pallidus in T1-weighted images was found on cranial MRI. Reversibility was shown in one child with autoimmune hepatitis after normalisation of liver function tests under immunosuppressive therapy. CONCLUSION: As central nervous system involvement in liver disease is only partially understood, brain imaging by MRI offers a potential additional tool to further elucidate the incidence and time course of previously undetected brain alterations.

Do children have an adequate fluid intake? Water balance studies carried out at home.

In 21 healthy children aged 6-11 years water balance studies were performed for 3 days at home. Water intake was assessed from dietary records based on the precise weighing method and water loss was calculated from repeated measurements of body weight and urine collection. Mean values (+/- SD) of all parameters of water balance are presented. Water intake from food and drinks without metabolic water of 43.0 +/- 11.5 g/kg/day or 0.78 +/- 0.17 g/kcal (0.19 +/- 0.04 g/kJ) resulted in a urine volume of 22.5 +/- 7.7 g/kg/day and an osmolality of 24-hour urine samples of 756 +/- 199 mosm/kg. From these data water intake seems to be low in these children. In school-aged children water intake from food and drinks of 1 ml/kcal (0.24 ml/kJ) as recommended for adults (Recommended dietary allowances, 1980) would seem adequate, theoretically resulting in a urine volume of 35 +/- 14 g/kg/day and urine osmolality of 516 +/- 182 mosm/kg based on the data in our children.

Is histological diagnosis of neuronal intestinal dysplasia related to clinical and manometric findings in constipated children? Results of a pilot study.

Neuronal intestinal dysplasia (NID) of the colon has been reported in adults and children with chronic constipation. However, it is unknown whether these histological abnormalities are related to the severity of symptomatology or the findings of anorectal manometry. We studied 57 children (2 weeks to 17 years old, 33 boys) who had chronic constipation and/or soiling or obstructive symptoms early in life and evaluated anamnestic data, symptoms, outcome after 6 months of conventional therapy, rectal biopsies for signs of dysganglionosis, and results of anorectal manometry. In cooperative patients, defectaion dynamics were recorded during manometry with simultaneous surface electromyogram of the external anal sphincter. In 30 older patients, severity of constipation was assessed by measurement of colonic transit time with radiopaque markers. Histology confirmed Hirschsprung's disease in nine (excluded from further analysis), hyperganglionosis of the plexus submucosus (classic NID) in six, heterotopic ganglion cells without hyperganglionosis (abortive NID) in 18, and no signs of dysganglionosis in 24 patients. The rectoanal inhibitory reflex was more often absent or abnormal in children with classic NID (six of six) and abortive NID (11 of 17) compared with children with normal histology (four of 22) (p < 0.001). All other manometric parameters analyzed, colonic transit times, and clinical outcomes were not related to histological diagnosis. In contrast, the severity of constipation and outcome was significantly worse in children with abnormal defecation dynamics. These results suggest that histological signs of NID in the submucous plexus are of uncertain value in assessing the clinical picture and should not influence decisions concerning further treatment, especially surgical interventions.

A partial form of pseudohypoaldosteronism type I without renal sodium wasting.

Multiple target organ involvement in pseudohypoaldosteronism is known but partial defects involving only a single organ system have also been described. In this report we present a girl with early symptoms and a very mild course of the disease without renal salt wasting and with normal sweat osmolality. Sodium content and the sodium/potassium ratio of stool was highly elevated. Increased plasma renin activity and aldosterone concentration as well as a reduced number of aldosterone receptors in mononuclear leucocytes confirmed the diagnosis of pseudohypoaldosteronism. Partial pseudohypoaldosteronism maybe more frequent than currently diagnosed since salt loss can be compensated by intact organ systems, but nevertheless threatens the young patient during illness. Since various degrees of clinical severity of pseudohypoaldosteronism even in the same family have been described, it seems important to identify mild cases in order to monitor younger siblings.

Circadian rhythms of urine osmolality and renal excretion rates of solutes influencing water metabolism in 21 healthy children.

Circadian rhythms of urine excretion, urine osmolality and renal excretion rates of sodium, chloride, potassium, creatinine and urea were studied for 3 days at home in 21 healthy children aged 6-11 years. Urine production as well as renal excretion rates of all solutes studied increased significantly during daytime and had minimum values at night. The peak of potassium and chloride excretion rates occurred earlier in the day than that of sodium. Considering all children together, no circadian rhythm was seen for urine osmolality. However, 9 children had evident but individually different rhythms of urine osmolality, changes which did not seem to correspond to the daily distribution of water intake. Circadian rhythmicity of urine osmolality and renal excretion rates of the main solutes should be considered in diagnostic and therapeutic procedures concerning fluid and electrolyte metabolism.

Transmission of GBV-C/HGV from drug-addicted mothers to their babies.

BACKGROUND/AIMS: In 1995, a new flavivirus, GBV-C/HGV was identified. Little information is available on the clinical manifestations and epidemiology of GBV-C/HGV infection. We investigated the risk of mother-to-infant transmission in a group of GBV-C/HGV RNA positive women and followed up the GBV-C/HGV infected babies. METHODS: Twenty-eight anti-HCV positive women, of whom 25 have been intravenous drug users, and their children were included in the study. RNA was extracted from serum, reverse transcribed and amplified with primers from the NS5 region of GBV-C/HGV and 5'-UTR of HCV in a nested polymerase chain reaction. Amplified DNA fragments were gel purified and sequenced; the sequences obtained were subjected to a phylogenetic analysis. RESULTS: Transmission of GBV-C/HGV occurred in 10 (56%) of 18 infants born to GBV-C/HGV positive mothers; all these women were drug abusers. Only one (5%) of 19 babies whose mothers were HCV RNA positive by polymerase chain reaction, was infected with HCV during the follow up. High sequence homology in the NS5 region of GBV-C/HGV isolates in 10 mother-child pairs suggested mother-to-infant transmission. All 10 babies remained GBV-C/HGV RNA positive during follow up (2-12 months). None of the GBV-C/HGV infected infants became icteric or demonstrated any clinical or biochemical signs of liver disease. CONCLUSIONS: Mother-to-infant transmission of GBV-C/HGV may be high, at least in HCV-infected, drug-addicted women. In GBV-C/HGV RNA positive infants the rate of GBV-C/HGV persistent infection is high, but the infection is not accompanied by any symptoms of liver disease.

Differential diagnosis of cholestasis following allogeneic hematopoietic stem cell transplantation in children: the contribution of serum bile acid levels in relation to other liver function tests.

Hepatic complications associated with cholestasis occur frequently in hematopoietic stem cell transplant recipients. Since bile acid seems to be a sensitive indicator of beginning cholestasis, the authors monitored total serum bile acid levels in addition to the standard liver function tests in 23 recipients of allogeneic transplants between June 1999 and September 2000. The observations suggest that bile acid is an early and sensitive marker of hepatic GvHD but not as specific as bilirubin. For cholestasis in absence of hepatic GvHD bile acid seems to be more sensitive than bilirubin. Routinely monitoring of bile acid after hematopoietic stem cell transplantation is not indicated.

Alpha-interferon treatment in HBeAg positive children with chronic hepatitis B and associated hepatitis D.

The main problem of children with HBeAg positive hepatitis B and associated hepatitis D is progression to liver cirrhosis with decompensation of liver function and need for liver replacement therapy within 15-20 years after infection. To determine whether interferon-alpha (IFN-alpha) therapy has a positive effect on HBV replication and inflammatory activity, we evaluated clinical and serological data of 8 children treated with IFN-alpha and 6 historic control patients without treatment. 4 of the nontreated patients seroconverted from HBeAg to anti-HBe between 7 to 17 years after initial diagnosis and showed decreased inflammatory activity in the liver. In the treatment group, the rate of seroconversion to anti-HBe (3 early, 2 late seroconverters) corresponded well to former trial results obtained in patients exclusively infected by HBV. Serum aminotransferase levels decreased or normalized in seroconverted children. In chronic HBV infection with associated hepatitis D (HDV) infection--compared to the spontaneous course of the disease--IFN-alpha therapy reduced inflammatory activity by earlier seroconversion to anti-HBe in responding patients. Moreover, viral replication and infectivity of hepatitis B was markedly reduced, but no effect on replication of HDV could be documented. Although long-term effects cannot be exactly estimated, at present IFN-alpha remains the only available treatment for HBeAg and anti-HDV positive children and seems to be of benefit for responding patients.