Zur konstitutionellen Dysotosis enchondralis,insbesondere zur Pfaundler-Hurlerschen und Morquioschen Krankheit

Zusammenfassung Eingehende Stellungnahme zur konstitutionellen Dysostosis enchondralis. Anerkennung als Dachbegriff und Befürwortung desselben. Umgrenzung seines derzeitigen Inhalts, als welcher die Dysostosistypen Ribbing und Morquio, die Dysostosis multiplex v. Pfaundler-Hurler, die Cystinkrankheit sowie bisher mehr-minder vereinzelt dastehende Beobachtungen zu nennen sind. Stellungnahme zu manchen der letzteren und zur multiplen Epiphysenstörung. Ablehnung röntgenoskopischer Unterscheidungsmöglichkeit zwischen Formen mit epiphysär, meta- und epiphysär bzw. metaphysär lokalisierten Veränderungen als klinisches Ordnungsprinzip.. —Ins Einzelne gehende Erörterung der Abgrenzung zwischen Dysostosis Morquio und dem lipoidfernen Symptomenkomplex der klassischen sowie der Spätform der Pfaundler-Hurlerschen Krankheit. Skeletröntgenoskopische Abtrennung zwischen Späthurler und Morquio erscheint vorerst unmöglich. Tabellarische Zusammenstellung der Unterschiede zwischen den genannten Affektionen. — Abschließend kurze Ausführungen zur Pleonosteosis familiaris Léri.     

Serum creatinine and creatinine clearance in healthy neonates and prematures during the first 10 days of life

Normal serum creatinine (Scr) and creatinine clearance (Ccr) values during the first 10 days of life were obtained in 63 very premature (28–32 weeks of gestation), premature (33–37 weeks) and term infants (38–42 weeks). Scr fell, and Ccr rose less markedly in the very premature infants. Scr was 80 mol/l on the 1st day of life both in very premature and premature infants, and 77 mol/l in full-term neonates. After 10 days, Scr was 73, 53 and 35 mol/l respectively. There was an exponential correlation between Ccr and gestational age, indicating rapid maturation of glomerular function.Abbreviations Scr serum creatinine - Ccr creatinine clearance - GA gestational age - GFR glomerular filtration rate     

Age-dependency of alpha- and beta-adrenoceptors on thrombocytes and lymphocytes of asthmatic and nonasthmatic children

Among the possible mechanisms which may cause wheezing or asthmatic episodes a genetically determined -adrenoceptor blockade and a hyperresponsiveness of -andrenoceptors has been postulated. Evidence to support this hypothesis stems from an increased bronchial sensitivity to -blockers, a reduced formation of cyclic AMP in response to -adrenergic stimulation and enhanced -adrenergic responses in asthmatic subjects. The recent development of techniques for measuring the specific, high-affinity binding of radiolabeled -and -adrenergic antagonists made it possible to study - and -adrenoceptors in vitro. Based upon the assumption that a change in the number and/or affinity of adrenergic receptors might be a general phenomenon, we have performed - and -receptor binding studies on lymphocytes and platelets from wheezing infants and asthmatic children as well as of infants, children, and adults not suffering from these diseases.Using ¹²⁵[I]-cyanopindolol (ICYP) and ³[H]-yohimbine (HYOH) as highly specific ligands for - and -adrenoceptors, the following results were obtained: (1) Lymphocytes and platelets from control subjects and asthamatics bound similar amounts of ICYP and HYOH and thus showed no differences either in the number or the affinity of - and -adrenoceptors. Lymphocytes and platelets of wheezing and nonwheezing infants also bound the same amounts of the radioligands. (2) In asthmatic children receiving 4×2 puffs salbutamol -adrenoceptor were down-regulated and this may mimic -adrenoceptor blockade. (3) When subjects were divided into four categories according to age (0–5, 5–10, 10–20 years, adults) the number of -adrenoceptor binding sites showed an age-dependent increase. The number and affinity of -adreneceptor binding sites on platelets was neither influenced by age nor disease.It is concluded that the - and -adrenoceptors of wheezing infants and asthmatic children at least on blood cells are normal. However the -adrenoceptors show an age-dependent maturation process, which may account for an unresponsiveness to -adrenoceptor agonists in wheezing infants.Supported by a grant from the Ministerium für Wissenschaft und Forschung, NRWPresented at the 19th Workshop for Pediatric Research, University of Göttingen, March 10–11, 1983     

Decreased β2-adrenoceptor density and decreased isoproterenol induced c-AMP increase in juvenile type I diabetes mellitus: An additional cause of severe hypoglycaemia in childhood diabetes?

Little is known about the receptor and post receptor mechanisms of sympathoadrenal signal transmission in type I diabetes mellitus. Therefore, we examined the maximum binding of granulocyte ₂-adrenoceptors and the in vitro c-AMP accumulation in lymphocytes of 24 children and adolescents with diabetes mellitus and 14 similarly aged healthy subjects. The number of high affinity ₂-adrenoceptors on granulocytes correlated significantly with unstimulated (r=0.6,P<0.004) and with isoproterenol stimulated c-AMP values in lymphocytes (r=0.68,P<0.0007) showing the proportional changes of ₂-adrenoceptors and c-AMP in two different cells. The number of ₂-adrenoceptors on granulocytes was significantly reduced in diabetic as compared to healthy children (median 1397, range 599–3405 vs. 2205, 825–3200 ₂-adrenoceptors per granulocyte,P=0.014). Moreover, the percentage in vitro stimulation of c-AMP by isoproterenol in lymphocytes was significantly reduced in diabetic children as compared to healthy individuals (120%, 39%–278% vs. 225%, 66%–500%,P=0.012). These results indicate a decreased sympathoadrenergic signal transmission in peripheral blood cells as a model for the liver probably contributing to severe hypoglycaemia in diabetic children.     

Clinical experience with continuous intravenous sedation using midazolam and fentanyl in the paediatric intensive care unit

Twenty-four patients in a paediatric intensive care unit mostly undergoing cardiac surgery, received a midazolam dosage between 50–400 g/kg per hour as a continuous intravenous infusion partly in combination with fentanyl [0,5–2,5 g/kg per hour] for analgesia and sedation. The mean duration of midazolam infusion was 11.6 days (range 38h–40 days). Blood samples for the HPLC assay of serum midazolam concentration were taken and the clearance estimated. The efficiency of sedation in correlation to the midazolam concentration was evaluated by a clinical sedation score. Serum midazolam concentrations between 100–400 g/l were sufficient for sedation. Dosage had to be increased during therapy according to an increased midazolam clearance. The evaluation of the sedation score showed that sedation of artifically ventilated infants and young children can be established by continuous intravenous infusion of midazolam.Dedicated to the 65th birthday of Prof.Dr. Erich Gladtke     

Evaluation of delta-aminolaevulinic acid excretion in random urine samples of children

Urinary delta-aminolaevulinic acid (-ALA) excretion was evaluated in random urine samples of 191 healthy children, aged 2–14 years, with blood lead levels <0.8 mol/l (mean ± SD: 0.34±0.13), erythrocyte zinc-protoporphyrin <70 mol/mol haem (mean ± SD: 50.4±8.0) and blood haemoglobin >6.8 mmol/l (mean ± SD: 8.2±0.5). It was found that uncorrected -ALA concentration and -ALA/creatinine ratio are age-dependent, whereas the ratio of -ALA/logarithm of creatinine concentration (mean ± SD: 55.3±13.5 mol/log mmol) is independent of age and sex. The authors recommend the use of this parameter for the assessment of -ALA excretion in random urine samples in children     

Pharmacodynamics and pharmacokinetics of esmolol,a short-acting β-blocking agent,in children

Summary Esmolol, a short-acting intravenous cardioselective -blocking agent, was evaluated for age-dependent pharmacodynamic and pharmacokinetic features in 17 young patients (6 months to 14 years). A loading dose (500 g/kg/min) alternating with a maintenance dose (25–200 g/kg/min, titrating by 25 g/kg/min every 4 min) was infused until the heart rate or mean arterial pressure decreased 10%. Cardiac index, left ventricular shortening fraction, and systemic vascular resistance were measured at baseline, peak esmolol effect, and recovery. Serum esmolol concentrations were obtained to determine the half-life and the elimination rate constant.Esmolol reduced the heart rate, blood pressure, shortening fraction, and cardiac index in all patients, but it did not change systemic vascular resistance. Maintenance esmolol dose was 118 ±49 g/kg/min, and the half-life was 2.88±2.67 min. Blood pressure and heart rate returned to normal within 2–16 min, but cardiac index and shortening fraction took longer to recover. There were no statistically significant age-dependent pharmacodynamic effects, but blood pressure decreased prior to heart rate and cardiac index took longer to recovery in patients who weighed15kg. The pharmacokinetic profile in young patients was similar to that of older patients, but the half-life was shorter. The only side effeect was transient nausea and vomiting in one patient. Esmolol is a safe and efficacious -blocking agent in young patients.     

Clinical trial of sulfonated immunoglobulin preparation for intravenous administration

S-sulfonated -globulin (GGS), derived from human -globulin by selective sulfonation, retains the dimensional structure and antibody activity of 7S -globulin. GGS does not bind with complement, and is therefore suitable for intravenous administration. Fc activity is recovered through in vivo conversion to intact globulin following IV administration.A total of 414 administrations of GGS was made to 48 patients with primary immunodeficiency syndrome. The frequency of episodes of fever, cough, and infections suffered by these patients who had been treated with other globulin preparations for about one year before the administration of GGS was compared with that following replacement GGS therapy for about one year. Symptomatic relief on administration of GGS was confirmed to be excellent.The administration of 100 mg/kg/BW of GGS resulted in the IgG level rising to 220 mg/dl, with a decrease to 100 mg/dl after one week. The IgG level at two weeks was 70 mg/dl. It is possible to maintain an IgG level of 200 mg/dl by administration of 100 mg/kg/BW of GGS once every 3–4 weeks.     

Amine im menschlichen Stuhl

Zusammenfassung Die p- und m-Tyraminausscheidung wurde quantitativ im Stuhl von Neugeborenen, Säuglingen und Schulkindern unter verschiedenen Kostformen untersucht. Der p-Tyramingehalt von normalen Säuglingsstühlen (Naßgewicht) lag zwischen 0,030–0,460 Mol/g Stuhl, der normaler Stühle von Schulkindern zwischen 0,005 und 0,102 Mol/g Stuhl. m-Tyramin ließ sich in Säuglingsstühlen nicht nachweisen. Die Konzentration im Stuhl von Schulkindern überschritt sicher nicht 0,008 Mol/g Stuhl.

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Summary The excretion of para- and meta-tyramine in faeces was estimated in newborns, infants, and children during the application of various diets. The p-tyramine content of normal stools of infants (wet weight) amounted 0.030–0.460 moles per gr. faeces and that of children 0.005–0.102 moles per gr. m-Tyramine was not detected in the faeces of infants. If this substance is found at all in faeces of children it does not exceed 0.008 moles per gr. of faeces.

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Mit Unterstützung durch die Deutsche Forschungsgemeinschaft.     

Adrenocortical reserve of neonates born of long-term,steroid-treated mothers

Since corticosteroids have been shown to be transferred across the human placenta, prolonged administration of these drugs during gestation could be expected to suppress the response of the neonatal adrenal gland. Plasma cortisol levels, before and 30 min after the injection of ACTH (36 g/kg), were determined in six neonates who were exposed in utero to prolonged maternal administration of prednisone. The basal plasma cortisol levels of these neonates (6.15±2.57 g%; mean±SEM) were similar to values obtained in eight healthy neonates (5.19±1.36g%). The increment of cortisol levels after ACTH stimulation (16.4±2.07 g%) of the study patients was larger (P<0.01) than the change (10.3±0.82 g%) observed in six older controls. These results indicate a normal neonatal adrenal reserve after prolonged exposure to corticosteroids during fetal life.     

Concurrent jejunal atresia with “apple peel” deformity in premature twins

Jejunal atresia with apple peel deformity is a rare congenital malformation that is generally believed to result from in utero vascular accidents. We report this case due to the rare occurrence of jejunal atresia with apple peel deformity affecting both members of a set of twins in whom no apparent cause for the atresia exists.     

Excessive urinary oxalate excretion after combined renal and hepatic transplantation for correction of hyperoxaluria type 1

A 4.5-year-old boy received a combined liver and kidney transplant for correction of hyperoxaluria type 1. Both organs were from the same donor and functioned primarily. Three months after transplantation, urine oxalate excretion reached a maximum of 10500 mol/24 h and remained above 2300 mol/24 h for the next 2 months. Two months later, oxalate excretion decreased to about 565 mol/24 h, indicating exhaustion of a large oxalate pool. Six months after transplantation plasma oxalate is near normal (4.9 mol/l). With the exception of one episode of acute rejection of the renal transplant, both organs were tolerated well and continue to have a unimpaired function 9 months after transplantation. However, there is increased echogenity on renal ultrasound, indicating oxalate deposits in the grafted kidney. This case illustrates that successful combined transplantation of both liver and kidney can be performed in infants, resulting in cure of the metabolic defect. The prolonged or acute excretion of oxalate may lead to oxalate deposition in the grafted kidney without impaired graft function or early graft loss.     

Maternal tyrosinaemia II: Management and successful outcome

A 25-year-old woman with tyrosinaemia type II was treated from the 5th week of pregnancy with a protein-restricted diet supplemented with a tyrosine/phenylalanine-free amino acid mixture. Tyrosine concentrations were maintained in the range 100–200 mol/l by restricting natural protein intake to 0.16 g/kg per 24h in early pregnancy, with increases up to 0.38 g/kg per 24h in the last trimester. This treatment maintained plasma phenylalanine concentrations in the range 20–40 mol/l. Maternal weight gain and fetal growth were normal, and the mother remained asymptomatic throughout the pregnancy. A normal infant was born at term with length, weight and head circumference between the 25–50 th per centiles.     

Childhood neuromuscular disease with rimmed vacuoles

A 5-year-old boy suffered from a slowly progressive non-familial neuromuscular disease, clinically marked by generalised muscle weakness, atrophy and hypotonia, a myopathic EMG and mildly elevated CK values. His gastrocnemius muscle showed marked myopathy, type I fibre predominance, and numerous rimmed vacuoles. This boy's condition is regarded as a childhood neuromuscular disease with rimmed vacuoles.This paper has been presented at the Annual Meeting of the German Society of Neuropathologists, Bremen, June, 1984     

Rapid effect of intravenous growth hormone (GH)-releasing hormone 1–44 on plasma GH levels in children

Growth hormone releasing hormone (GHRH)-testing was performed in 24 short normal children (16 male, 8 female). Before and after administration of GHRH_1–44 (1g/kg body weight i.v.) blood samples for growth hormone (GH) determination were drawn at-30, 0, 1, 2, 3, 4, 6, 8, 10, 15, 30, 45, 60, and 90 min. Plasma GH increase was apparent 1 min after injection and in 12 patients (7 female) peak plasma GH values were reached within 15 min. In all patients plasma GH levels were greater than 10 ng/ml within the first 8 min following GHRH injection, but in 4 patients this level was not attained when considering only GH values obtained after 15 min. These results demonstrate the capability of the pituitary to rapidly secerete GH in response to GHRH_1–44 in children. Therefore, in this age group blood samples for GH determination should be taken earlier when testing with GHRH_1–44.Abbreviations GHRH growth hormone releasing hormone - GH growth hormone - SD standard deviation     

Iron overload and desferrioxamine chelation therapy in β-thalassemia intermedia

This study on serum ferritin levels ind urinary iron excretion after 12h subcutaneous infusion of desferrioxamine in 10 thalassemia intermedia patients shows that even nontransfusion-dependent patients may have positive iron balance resulting in iron overload from 5 years of age. However, the iron overload found in these patients appears to be much lower than in age matched patients with transfusion-dependent thalassemia major. Iron overload increases with advancing age, as shown by increasing serum ferritin levels and desferrioxamine-induced urinary iron elimination. After a six month trial of 12h continuous subcutaneous desferrioxamine administration there was a significant decline in serum ferritin levels.From this study it seems that iron chelation is indicated in thalassemia intermedia patients over 5 years of age in order to prevent iron accumulation. However, the appropriate treatment schedule should be tailored to the individual needs of each patients, established by close monitoring of serum ferritin levels and desferrioxamine-induced urinary iron elimination.This work was supported in part by grants from Assessorato Igiene e Sanità Regione Autonoma della Sardegna, N.I.H. grant number 5 R01 HL-24173-02, C.N.R. subprogetto finalizzato Malattie Ereditarie dell'Eritrocita contract number 80-02252.83     

Low iron stores in infants and children with treated phenylketonuria: A population at risk for iron-deficiency anaemia and associated cognitive deficits

A retrospective study of 53 patients with phenylketonuria (PKU), whose disease was managed with a low-phenylalanine diet, revealed a high incidence of iron depletion (as reflected by subnormal serum ferritin concentrations). Serum ferritin concentrations under 10 g/l were found in one out of six infants aged 5–12 months. Concentrations under 16 g/l were found in 16 of 22 children aged 1–3 years and in 11 of 25 children aged 4–12 years. Dietary iron, estimated from prescribed intakes of medical foods, exceeded the Canadian recommended nutrient intake, suggesting that low stores of iron may be secondary to reduced bioavailability and absorption of iron. These findings suggest that the current dietary management of PKU is associated with an increased risk for low iron stores. Investigators have reported an association in young children between iron-deficiency anaemia and both cognitive and motor disturbances. Children with PKU, already at risk of neurological damage because of phenylalanine neurotoxicity, may be at increased risk as a result of iron depletion. Serum ferritin as well as haemoglobin concentration should be monitored, along with plasma phenylalanine and tyrosine, to ensure optimum treatment of affected children.     

A scoring system in predicting the risk of intestinal stricture in necrotizing enterocolitis

Of 46 infants with a diagnosis of necrotizing enterocolitis (NEC) admitted to the neonatal intensive care unit over the period 1981–1985, 40 have been followed from 2 to 6 years after the acute episode. A contrast enema (CE) to look for intestinal strictures (IS) was performed either during the first months in surgically managed patients, or between 2 and 6 years in asymptomatic patients. Clinical, laboratory and radiology parameters collected during the 7 days following NEC were used to establish a score which was correlated with radiological data obtained after CE. Of the 40 infants, 17 developed symptomatic or asymptomatic IS and 16 of these 17 infants has a score 7. Nineteen of the 23 patients without IS had a score <7. We conclude that the proposed score established on day 8 after onset of NEC helps to identify infants at higher risk of developing IS and for whom closer follow up appears necessary.     

Effective treatment of acute hyperkalaemia in childhood by short-term infusion of salbutamol

Hyperkalaemia is a lifethreatening emergency and infusion of glucose with insulin has so far been regarded as the standard treatment of choice. Recently the -2 stimulatory drug salbutamol has been shown to be an effective agent to treat hyperkalaemia by inducing a shift of potassium into the intracellular compartment. We treated 15 children aged 0.1–14 (mean 5.2) years suffering from acute hyperkalaemia (mean level 6.6±0.54, range 5.9–7.7 mmol/l) with a single infusion of salbutamol (5 g/kg over 15 min). Serum potassium concentrations decreased significantly within 30 min to levels of 5.74±0.53 and 4.92±0.53 mmol/l after 120 min (P<0.001, respectively). No side-effects occurred other than a slight increase in heart rate in 3 patients.Conclusion A single intravenous infusion of salbutamol at a dose of 5 g/kg is a highly effective treatment for hyperkalaemia with minimal clinical side-effects. The effect lasts for at least 120 min and may reverse hyperkalaemia in some patients without further interventions so that salbutamol seems justified as the first choice treatment for this condition in childhood.     

Serum zinc concentration during childhood

Serum zinc concentrations in subjects of different ages were estimated by neutron activation analysis to obtain reliable reference values for the diagnosis of primary or secondary zinc deficiency during childhood. In these healthy individuals a small age-dependent variation of the mean values was found. Serum zinc concentrations were lower in cord blood (mean value: 880×10^–9 g/ml) and in infants (mean value: 820×10^–9 g/ml) than in adults (mean value 1178×10^–9 g/ml). In comparison to these values, the serum zinc concentration in a patient with secondary zinc deficiency and 4 patients with acrodermatitis enteropathica was reduced to about 25% of normal.With support of the Deutsche Forschungsgemeinschaft