Fetal bile acids in congenital biliary atresia —production in the liver and clinical significance

The 1-hydroxy bile acids have been said to be fetal bile acids. These bile acids were evaluated in eight patients with congenital biliary atresia (CBA) using gas chromatography-mass spectrometry. At the time of operation 1,3,7,12-tetrahydroxy-5-cholan-24-oic acid (CA-1-ol) and 1,3,7-trihydroxy-5-cholan-24-oic acid (CDCA-1-ol) were 0.46 ± 34 g/ml and 0.72 ± 0.45 g/ml, respectively, which was significantly higher than in the control group. The percentage CA-1-ol of total bile acids showed a tendency to decrease as age advanced. The grade of hepatic fibrosis ranged from F₂ to F₃ and the values and percentages of CA-1-ol and CDCA-1-ol were relatively higher in F₂ than F₃ patients. The percentage of total bile acids gradually increased in patients without sufficient bile flow but fell sharply after Kasai's procedure in the patients with sufficient bile flow. It appears that fetal bile acids are produced in the livers of CBA patients in the same way as in fetal liver, and that production continues in patients without good bile secretion even after Kasai's procedure. These results suggest that these hydroxylases are reactivated in CBA patients.     

The value of the routine chest roentgenogram in the cardiological evaluation of infants and children. A prospective study

The value of the routine chest roentgenogram was studied in 284 patients, newly admitted to our paediatric outpatient department. Emergency patients were excluded from the study. In 141 cases the initial diagnosis after history, physical examination and ECG was no heart disease, while in 143 cases it was heart disease. After a follow up of up to 4 years, 170 children appeared to have no heart disease and 114 definite heart disease. In 7.7% of cases the chest roentgenogram made at the first visit to the outpatient department led to a change in policy, whereas in only 3.8% was the chest roentgenogram in someway helpful in establishing the correct diagnosis. Amongst those children with initial diagnosis of innocent murmur, the chest roentgenogram led to a diagnosis of heart disease in only 2.8% of cases. It is concluded that for the differentiation heart disease or no heart disease, a chest X-ray film is not indicated. In children with heart disease the chest X-ray film is also of little value, and is mostly to be used only for documentation.Partly presented at the Jahrestagung der deutschen Gesellschaft für pädiatrische Kardiologie, Düsseldorf, 1–2 Oktober 1984     

High resolution CT of the lungs in acute disseminated tuberculosis and a pediatric radiology perspective of the term “miliary”

High resolution CT (HRCT) of the lungs in six children with acute disseminated tuberculosis was evaluated. There was a wide variation in the HRCT appearances. This covered differences in size, distribution and concentration of nodular opacities. Coalescence of nodules and the presence of intestitial thickening was variable. The recognition of acute disseminated tuberculosis is important for diagnosis and has prognostic implications. The use of the term acute disseminated tuberculosis rather than miliary tuberculosis is advocated.     

Pubertal development in male hypopituitarism

The spontaneous or therapeutically induced pubertal development of 65 male patients with idiopathic hypopituitarism was analysed. Spontaneous puberty occurred in 82% of the patients with prepubertal isolated growth hormone deficiency and in 32.5% of those with impairment in the secretion of more than one pituitary hormone.Out of this group, 36 patients could be studied longitudinally. In 15 patients, the onset of spontaneous puberty was delayed, on average, 3.2 years. It started at a bone age of 10.36±1.25 years and followed a pattern similar to that of normal boys. Testosterone levels at each pubertal stage were not different from those of normal boys. Mean peak height velocity reached 7.27±1.82 cm/year. In 21 patients with gonadotropin deficiency, hCG treatment was started at a chronological age of 19.04±2.17 years and a bone age of 12.94±0.80 years. Plasma testosterone attained normal adult levels in the majority of boys, while the development of sexual characteristics showed a wide variation. Mean growth velocity during the first year of hCG therapy reached 6.11±2.47 cm/year. Partial gonadotropin deficiency was diagnosed in two boys.Although testosterone seems today to be, for practical reasons, the replacement therapy of choice, hCG treatment is an alternative for hypopituitary patients with absent gonadotropin function.Abbreviations IGHD isolated growth hormone deficiency - MPHD multiple pituitary hormone deficiency - hCG human chorionic gonadotropin - hGH human growth hormone - PHV peak height velocity     

The contribution of protein catabolism to metabolic decompensation in 3-hydroxy-3-methylglutaric aciduria

Leucine and protein metabolism were studied using stable isotope techniques in 6-year-old twins with 3-hydroxy-3-methylglutaric aciduria during acute metabolic decompensation. The decompensation was preceded by prolonged fasting in twin 1 and by an upper respiratory infection in twin 2. Twin 2 was also studied when well (control study). During infection, leucine oxidation (36 mol/kg per hour), protein catabolism (6.0 g/kg per day) and urinary excretion of major leucine metabolites (104 mol/kg per hour) were all increased compared with the control study (16 mol/kg per hour, 4.7 g/kg per day and 28 mol/kg per hour respectively). During fasting, leucine oxidation (18 mol/kg per hour) was unchanged and protein catabolism (4.1 g/kg per day) was decreased despite substantially increased urinary metabolite excretion (87 mol/kg per hour) compared with the control study. These results indicate that protein mobilisation and leucine oxidation played important roles in metabolic decompensation during infection but not during fasting. It is likely that the increased metabolite excretion during fasting arose primarily from fatty acid catabolism, indicating the importance of this substrate in metabolic decompensation in 3-hydroxy-3-methylglutaric aciduria.     

Growth and growth hormone in children during and after therapy for acute lymphoblastic leukaemia

Growth impairment and growth hormone (GH) deficiency have been reported in children treated for acute lymphoblastic leukaemia (ALL). We have studied growth and GH secretion in a group of 50 patients, affected by ALL, during a 2- to 5-year period after diagnosis, and in 12 long-term-survivors. We observed a significant decrease in growth velocity during the 1st year (in particular during the first 6 months) of therapy and a catch-up growth after the end of therapy. Longterm survivors did not exhibit a significant reduction of height standard deviation score (SDS), as compared to height SDS at diagnosis. None of the patients showed GH deficiency. Our data indicate that chemotherapy significantly affects growth of patients treated for ALL, whereas radiotherapy-at the doses used in this study-does not induce GH deficiency, at least not within 9 years after diagnosis.     

Neutrophil chemotaxis in infants delivered by caesarean section

We evaluated polymorphonuclear leucocyte (PMN) chemotaxis and cortisol levels in cord blood from 15 healthy term infants delivered by caesarean section and from 15 healthy vaginally delivered term infants. Mean neutrophil chemotaxis was significantly higher in infants delivered by caesarean section (78.3±23.4m) than in vaginally delivered infants (57.8±16.6 m;P=0.01). Mean blood cortisol level was significantly lower in infants delivered by caesarean section (9.14±2.76 g/dl) than in infants born by vaginal delivery (20.71±6.98 g/dl;P=0.0001). No relationship was found between PMN chemotaxis and blood cortisol level. The higher neutrophil chemotactic activity observed in infants delivered by caesarean section could be related to general maternal anaesthesia.     

Silent carrier β-thalassaemia due to a severe β-globin mutation interacting with other genetic elements

Beta-thalassaemia is caused by the presence of two mutated -globin genes, one inherited from each parent. We describe two families in which the diagnosis of -thalassaemia intermedia was delayed because one of the parents, an obligatory heterozygote, had normal haematological parameters (silent carrier -thalassaemia). DNA analysis revealed that these silent carriers were heterozygous for a point mutation in the polyadenylation signal (AATAAA-AATAAG). This defect is known to cause a moderately severe -thalassaemia phenotype. In one case, concurrent deletional -thalassaemia was found in the silent carrier, which may have contributed to the mild phenotype. The increasing availability of DNA analysis should allow prompt diagnosis of such cases. Silent carrier -thalassaemia presents a diagnostic challenge to the clinician who evaluates children with anaemia.     

Veränderungen von Produktion und Metabolismus des Cortisol bei gesunden Säuglingen nach dreitägiger Depot-ACTH-Gabe

Zusammenfassung Es wird über die Harnausscheidung von Pregnan-3-17-20-triol und Pregnan-3-20-diol nach einer dreitägigen Belastung mit Depot-ACTH bei gesunden Säuglingen berichtet.Die Basalmittelwerte liegen für Pregnantriol zwischen 33 und 37 g/d, für Pregnandiol zwischen 70 und 81 g/d. Nach ACTH kommt es zu einer Zunahme der Ausscheidungsgröße beider Substanzen, wobei sich das Verhältnis für Pregnantriol zu Pregnandiol gegenüber den Basalwerten umkehrt.Diese Umkehrung wird einerseits als Ausdruck einer intensiven Ausnutzung der für die beiden letzten Stufen der Cortisolsynthese maßgeblichen Hydroxylasen aufgefaßt, andererseits auf Grund der deutlichen Zunahme der Pregnantriolausscheidung eine funktionelle Limitierung der C-11-und C-21-Hydroxylase zur Diskussion gestellt.Die gegenüber der des Pregnantriol niedrige Pregnandiolausscheidung ergibt einen Hinweis, daß möglicherweise die Limitierung der enzymatischen Aktivität bei der Differenzierung der einzelnen Corticosteroide im Laufe der Umwandlungen in Richtung Endprodukt zunimmt.

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Summary In this paper we report about the urinary excretion of Pregnan-3-17-20-triol and Pregnan-3-20-diol in infants between 4 and 8 months after a three-day load-test with ACTH-depot.The basal mean-values are between 33 to 37 g/die of Pregnantriol and between 70 to 81 g/die of Pregnandiol. After ACTH-load there is an increase of the excretion of both substances whereas the ratio of Pregnantriol and Pregnandiol gets reciprocal. We consider this beeing a sign of an intensive utilization of the hydroxylating enzymes involved in the two last steps of cortisol synthesis. On the other hand it is possible that there is a functional limit in the activity of C-11-and C-21-hydroxylating enzymes regarding the clear increase of Pregnantriolexcretion.The relatively low values of Pregnandiol opposite to these of Pregnantriol may refer to the possibility that the limitation of the enzyme activities increases in way of performing the different corticosteroids.

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Die Arbeit wurde mit Unterstützung durch die Deutsche Forschungsgemeinschaft durchgeführt.     

Ureteral reimplantation en bloc for refluxing duplicated ureters

Vesicoureteric reflux (VUR) is a major problem in completely duplicated ureters. So far, the treatment of choice has been the reimplantation of the two ureters in their common sheath, the ureterocystoneostomy en bloc according to Politano-Leadbetter's or Cohen's procedure. In recent years, some pediatric surgeons and urologists have questioned the efficacy of this method. We therefore analyzed 62 children with 69 duplicated ureters treated en bloc by Politano-Leadbetter's procedure during the 20-year period 1971 – 1990. Postoperative follow-up was up to 16 years. We noted only 1 recurrence of reflux as well as 2 stenoses. Long-term results as far as function was concerned were also favorable in 40 duplicated renal units. Thus, ureteral reimplantation en bloc remains a simple and safe procedure for treating VUR in completely duplicated ureters.     

“Autistisches” Verhalten im Kindesalter und seine Ursachen

Zusammenfassung Zum Autismusproblem wird über zwei Kinder und deren Familienanamnesen berichtet. Eines dieser Kinder stammt aus einer Verwandtenehe. In den Familien beider Kinder kommen auffallende, im mitmenschlichen Kontakt gestörte Persönlichkeiten vor. Im Zusammenhang damit werden die von Asperger dargestellte autistische Psychopathie und der von Kanner beschriebene frühkindliche Autismus (early infantile autism) besprochen und anschließend wird der aktuelle Stand ätiologischer und therapeutischer Probleme diskutiert.

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Summary The present paper deals with the problem of autism reporting on two children and the histories of their families. One of these children descends from parents related to each other. In the families of both children individuals disturbed in human relationship are to be found. In this connexion the autistic psychopathy described by Asperger and the early infantile autism described by Kanner are reviewed and finally the present knowledge of etiological and therapeutical problems are discussed.

     

Left-sided posterior mediastinal thymus-MRI findings

Anomalous descent of the thymus may result in ectopic thymic tissue in the neck and/or the mediastinum and can mimic an abnormal mediastinal mass. We present one case of a posterior mediastinal mass that was diagnosed as a posterior mediastinal thymus utilizing CT plus MRI.     

Serum iron,serum transferrin and transferrin saturation in healthy children without iron deficiency

Serum iron, serum transferrin and transferrin saturation were studied in 253 healthy, non-anaemic children 4, 8 and 13 years old, and in 60 healthy, non-anaemic adults having serum ferritin values 15 g/l. One hundred and ninety-six children had serum ferritin values 15 g/l (i.e. replete iron stores), 35 had intermediate ferritin values from 10–14 g/l and 22 had ferritin values <10 g/l (i.e. depleted iron stores). Iron replete children showed a gradual rise in serum iron and transferrin saturation values with age. Serum iron and transferrin saturation values were lower (P<0.001, P<0.0001) and transferrin values high (P<0.0001) in iron replete children compared to adults. Iron replete children had a 2.5 centile transferrin saturation value of 5%; 19.9% of these children had saturation values <15% and 8.2% had values <10%. In iron depleted children a transferrin saturation value <7% yielded the highest diagnostic efficiency as regards exhausted iron stores, although with a low predictive value of a positive test. The transferrin saturation is unsuitable as a single diagnostic criterion in the evaluation of iron deficiency in children and should always be combined with other indicators of iron status.     

Differential effects of oestrogen treatment on the proportionality of growth in tall girls

We studied the differential inhibitory effects of conjugated oestrogens on lower leg length and standing height increments in 17 excessively tall girls compared to a control group of 17 tall healthy untreated girls. Standing height, lower leg length and body weight were recorded at weekly or monthly intervals. Standing height velocity dropped from 150 m/day to 122 m/day, whereas daily weight gain increased from 17 to 48 g/day during oestrogen treatment. The oestrogen induced decrease of standing height velocity could be explained by a marked inhibition of lower leg growth velocity from 42 m/day to 30 m/day (native data) or 35 m/day to 8 m/day (data corrected for weight gain) (P<0.001), whereas no differences of trunk growth velocity could be detected. Thus, the findings strongly suggest that pharmacological doses of oestrogens only affect epiphyseal growth.     

Unusual CNS presentation of neuroblastoma

Neuroblastoma is a common tumor of childhood, usually occurring in children under 4 years of age [1]. We report a case of a 10-year old child who initially presented with a large calvarial mass representing a solitary site of metastasis from an occult adrenal neuroblastoma. The sunburst pattern of the calvarial metastasis noted in this case is rarely seen with neuroblastoma. The age of our patient, solitary focus of metastasis at presentation, and imaging appearance of the tumor are very uncommon findings of neuroblastoma.     

Die α-Amylase-Aktivität im Harn gesunder Schulkinder

Zusammenfassung Durch die Einführung der Mikro- und Ultramikromethode von Street u. Close zur Bestimmung der -Amylase-Aktivität in die klinischen Laboratorien wurde die Überarbeitung der bisherigen Normalwerte dieses Enzyms in den einzelnen Altersklassen und Körperflüssigkeiten erforderlich.In dieser Studie wurden 210 Schulkinder im Alter zwischen 6 und 12 Jahren auf ihre -Amylase-Ausscheidung im Harn untersucht. Der Test wurde unter Standardbedingungen an einer Greifswalder Oberschule mit einer dreistündigen Sammelperiode zwischen 7.45 Uhr und 10.45 Uhr durchgeführt. Wie schon in früheren Untersuchungen konnte auch an diesem Probandengut ein altersbezogener Anstieg der -Amylase-Aktivität und der Gesamtausscheidung der -Amylase mit dem Harn in der Zeiteinheit innerhalb zweier Altersklassen festgestellt werden. Geschlechtsgebundene Differenzen wurden nicht gefunden.Der Normalbereich der -Amylase-Aktivität im Harn für Schulkinder im Alter zwischen 6 und 12 Jahren wurde zwischen 40 und 250 SCE pro 100 ml Harn und die Gesamtausscheidung innerhalb von 3 Std mit 25-200 SCE bestimmt. Es besteht eine Korrelation zwischen der -Amylase-Ausscheidung mit dem Harn und dem spezifischen Gewicht des Harns. Die eigenen Befunde werden mit neueren Angaben der Literatur verglichen und interpretiert.

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The -amylase activity in the urine of healthy school children

Summary The introduction of new laboratory methods requires a review of the normal values. The micro- and ultra micro method for the determination of -amylase activity by Street and Close, already used successfully by many laboratories, allows the determination of enzyme activity in many biological fluids but calls for a re-assessment of the so-called normal values. In this study the results of determinations done on 210 school children are presented. The tests were perfomed with urine samples from a three hour period, collected under standard conditions. An exact statement of the quantity of -amylase excreted with the urine per unit of time was thus made possible.The 210 children belonged to two age-groups: either 7–8 or 11–12 years old. The three parameters determined from the three hour sample were: Quantity, specific weight, and -amylase activity. We were able to confirm our own earlier findings that the enzyme activity increases with age, in both, activity and quantity. Significant sex-dependent differences were not observed. The normal range of values of -amylase concentration in urine was found to be between 40 and 250 SCU (Street-Close Units) per 100 ml urine and the total excretion within three hours ranged from 25-200 SCU. A correlation between -amylase concentration and specific weight of the urine was not observed. This form of test implies an improvement of the diagnostic possibilities.

     

Mild adrenal 3β-hydroxysteroid dehydrogenase deficiency in children with accelerated growth,premature pubarche and/or hirsutism

We studied eight children (seven girls and one boy, of whom three are siblings) with accelerated growth, premature pubarche and/or hirsutism between the ages of 7 and 9.5 years. These patients were studied for the presence of adrenal steroidogenic defect by adrenocortico tropic hormone (ACTH) stimulation testing (Cortrosyn, 0.25 mg iv bolus dose). Baseline and stimulated 17-hydroxypregnenolone (⁵-17P), 17-hydroxyprogesterone (17-OHP), dehydroepiandrosterone (DHEA), androstenedione (⁴-A), testosterone, and cortisol levels were measured. Six children, including three siblings, were diagnosed with a mild form of 3-hydroxysteroid dehydrogenase deficiency based upon the elevated response of serum ⁵-17P and the elevated ratio of ⁵-17P/17-OHP and of DHEA/⁴-A to ACTH stimulation. Thus, a mild form of 3-hydroxysteroid dehydrogenase deficiency may not be uncommon in children with accelerated growth, premature pubarche and/or hirsutism and routine assay of ⁵-steroid metabolites should be generally available.     

15β-Hydroxylated steroids may be diagnostically misleading in confirming congenital adrenal hyperplasia suspected by a newborn screening programme

In a Swiss screening programme for detection of congenital adrenal hyperplasia (CAH), 27 of over 120,000 newborns examined from 1992 to 1994 were further studied because of persistingly high 17 hydroxyprogesterone (17OHP). Out of 27, 11 were later confirmed to have CAH by specific gas chromatography of urinary steroids and ACTH test at age 3–4 months. Of 27, 11 were born at term (7 confirmed 21-hydroxylase deficiency, one 11-hydroxylase deficiency). Out of 27, 16 were preterm newborns. Of them, only 2 were confirmed to have CAH (one 21-, one 11-hydroxylase deficiency). In 3 cases with high 17OHP, but later not confirmed CAH, what appeared to be a pregnanetriolone peak in the gas chromatograms was shown to be 3, 15, 17-pregnenetriol. This compound may be misleading in confirming the diagnosis of CAH. 15-Hydroxylated compounds occur in fetuses, neonates, and amniotic fluid. Since human tissues do not have l5-hydroxylating capacity, their origin is unclear. However, since some bacteria (Bacillus megatherium) and mycelial fungi (fusaria) are known to hydroxylate steroids in position 15, it is likely that this compound is formed by micro-organisms in the enterohepatic circulation of newborns or their mothers.Presented in part as an invited lecture at the symposium on congenital adrenal hyperplasia in honour of Claude Migeon, Baltimore MD, June 11.–13., 1995, and at the 34th Annual Meeting of the European Society for Paediatric Endocrinology, Edinburgh UK, June 25–28, 1995     

Growth response to growth hormone therapy following craniospinal irradiation

Nineteen (12 male, 7 female) children, who have received craniospinal irradiation for the treatment of a brain tumour distant from the hypothalamic-pituitary axis, resulting in growth hormone (GH) deficiency (CS-PRGHD), have been treated with GH. Eight have completed growth. Comparison has been made with the growth of seven untreated children, whose heights and growth rates at presentation were normal despite GH deficiency secondary to irradiation. GH produced a significant increase in growth velocity over the first 3 years' treatment in CS-PRGHD patients with a mean first year increment of 3 cm/year. Patients, treated to completion of growth, showed a significant increase in leg length standard deviation (SD) score (SDS+0.2) compared to that of the untreated (SDS–0.9) (P<0.05). Stitting height SD scores decreased irrespective of GH therapy (by -1.7 for the treated and -2.2 for the untreated). The onset of puberty in the irradiated patients occurred at a mean bone age of 10.7 years in males and 9.9 years in females. This limited the time available for GH therapy. These factors resulted in a decrease in standing height SDS of 0.9 at completion of GH therapy in CS-PRGHD, but a decrease of 1.7 in those not treated with GH. Thus GH therapy failed to induce catch-up growth in irradiated patients, but it did prevent further loss of adult stature, with a mean final height SD score of -3.4 in CS-PRGHD patients.Abbreviations GH growth hormone - CS-PRGHD post craniospinal irradiation growth hormone deficiency - change in - SDS standard deviation score - ALL acute lymphatic leukaemia - IGHD isolated growth hormone deficiency - C-PRGHD post cranial irradiation growth hormone deficiency - FSH follicle stimulating hormone - LH luteinising hormone - BA bone age - TSH thyroid stimulating hormone - CA chronological age     

Solitary ivory vertebra due to primary Ewing's sarcoma

Dense sclerosis of most of the vertebral body has been termed as ivory vertebra. While this condition occurs rather frequently in adults it is not found very often in children.