Effect of growth hormone and oxandrolone treatment on glucose metabolism in Turner syndrome. A longitudinal study.

In 18 girls with Turner syndrome, glucose tolerance was studied before treatment and after 6 and 24 months of growth-promoting treatment with recombinant human growth hormone (24 IU/m(2)/week; 8 mg/m(2)/week) and oxandrolone (0.06 mg/kg/day), as well as after termination of the treatment. One girl developed an overt non-ketotic diabetes mellitus 50 months after termination of treatment. The results of the remaining 17 girls in whom the effect of treatment on glucose metabolism was reversible are presented as a group. Their median age at the beginning of the treatment was 10.4 years (range 6.9-15.9), and 15.0 years (range 12.1-19.9) at the final assessment. There was a moderate, but not significant rise in fasting glucose throughout the course of the longitudinal study. At oral glucose tolerance testing (oGTT), the area under the curve for glucose rose significantly (p = 0.013) during the period of treatment and returned to the basic value thereafter. Fasting insulin and especially the integrated insulin values (AUCi; area under the curve for insulin) during oGTT increased continuously during treatment, declined after termination of treatment but were still significantly (p = 0.04) higher than before treatment. Considering the fact that in untreated girls with Turner syndrome the fasting insulin and the AUCi increase with age, one can conclude that the insulinaemia returned to age-specific norm after termination of treatment. Thus the effect of a combined growth hormone and oxandrolone growth-promoting treatment on glucose metabolism was fully reversible in these 17 girls with Turner syndrome.

Mutation of ornithine transcarbamylase (H136R) in a girl with severe intermittent orotic aciduria but normal enzyme activity.

Ornithine transcarbamylase deficiency shows X-linked inheritance with partial dominant expression in carrier females. We studied a girl with intermittent severe orotic aciduria and mild hyperammonaemia despite apparently normal enzyme activity in the liver. Sequence analysis of all 10 exons of the ornithine transcarbamylase gene revealed a novel A-->G exchange (A502G) in exon 5 which changes His-136 to arginine in the ornithine transcarbamylase protein. Km values for carbamyl phosphate and ornithine determined in the patient's liver were comparable to those of wild-type enzyme but, unlike the wild-type enzyme, the mutant enzyme was unstable upon freezing and thawing. Electron microscopy revealed several giant mitochondria with paracrystalline inclusions. The results are compatible with the assumption that the mutant enzyme cannot form a functional complex with carbamyl phosphate synthetase and the ornithine carrier, resulting in decreased availability of substrates and diminished enzyme activity in vivo.

Impact of different doses of ethinyl oestradiol on reduction of final height in constitutionally tall girls.

Fifty-two tall girls were treated for constitutionally tall stature with different ethinyl oestradiol (EE) dosages. They were divided into three different treatment groups: group B (100 micrograms EE/day; n = 11); group C (300 micrograms; n = 25) and group D (500 micrograms; n = 16) and compared with an untreated group A (n = 21) matched for age, height, bone age (BA) and height prediction. Using the height prediction method TW II, EE treatment reduced final height compared with the untreated girls in a weak dose-dependent manner, 2.3 cm (100 micrograms/day), 3.0 cm (300 micrograms/day), and 3.8 cm (500 micrograms/day). Such a dose dependency was not found on applying the Bayley-Pineau height prediction method (100 micrograms/day; 4.1 cm; 300 micrograms/day: 4.2 cm; 500 micrograms/day: 4.5 cm). However, there was a striking inverse correlation of the BA at the onset of treatment with the height reduction achieved using the TW II method (r: -0.43; P < 0.001). Importantly, girls with a BA below 12 years at the onset of treatment experienced a height reduction of more than 6 cm. CONCLUSION The EE dose used in the range of 100-500 micrograms/day is not crucial for the amount of height reduction in tall girls. In general high dose EE treatment should be given restrictively, and especially so in girls with a BA (TW2 RUS-ZH) above 12.0 years.

Effectiveness of single versus double volume exchange transfusion in newborn infants with AB0 hemolytic disease.

The effectiveness of early single volume exchange transfusion (ET; 80 ml/kg) was compared with that of early double volume exchange transfusion (160 ml/kg) for treatment of hemolytic disease of the newborn caused by AB0 incompatibility. Twenty full-term infants with AB0 hemolytic disease were randomized into the two treatment groups. The groups were comparable for gestational age, body weight, hemoglobin values, reticulocyte count, maximum serum bilirubin levels, rate of rise of serum bilirubin before ET, antibody titer, and age at time of ET (all p greater than 0.05). The efficacy of treatment was similar in both groups taking into account the mean bilirubin level after ET, post-ET bilirubin, duration of phototherapy following ET, and frequency of second ET (all p greater than 0.05). However, platelet count immediately after ET was lower in the double volume ET group as compared to the single volume ET group (p less than 0.01). Hemoglobin values immediately after ET were higher in the double volume ET group (p less than 0.01). At ten days of life no differences were detectable. The results of this study indicate that the effectiveness of single volume ET for treatment of full-term infants with jaundice due to AB0 incompatibility is at least comparable to that of double exchange ET. Furthermore, the lesser aggressive approach determines less complications such as a decrease of platelet count.

Lethal osteogenesis imperfecta: abnormal collagen metabolism and biochemical characteristics of hypophosphatasia.

We have examined collagen from a patient with the rare type IIC form of perinatally lethal osteogenesis imperfecta, in whom biochemical characteristics of hypophosphatasia were also apparent. In addition to normal alpha 1(I) and alpha 2(I) chains, there were chains overmodified along their lengths. Unexpectedly, the thermal stability of molecules containing these chains was normal. This suggests the existence of a structural mutation causing delayed triple helix formation, situated in either the alpha 1(I) or alpha 2(I) C-terminal propeptide. Since collagen synthesised by fibroblasts from each of the patient's parents was normal, the mutation was probably newly arising and dominant. In contrast to other reported cases of lethal osteogenesis imperfecta, not only was the secretion of collagen by cultured fibroblasts considerably retarded, but that of non-collagenous proteins was also severely impaired.

Long-term treatment of central precocious puberty with an intranasal LHRH analogue: control of pituitary function by urinary gonadotropins.

Daily subcutaneous doses of luteinizing hormone-releasing hormone (LHRH) analogues are a well-established therapy for gonadotropin-dependent precocious puberty. Reports on intranasally administered analogues, however, are controversial. We studied the effect of intranasal D-Ser(TBU)6-LHRH(BUS) on growth rate, skeletal maturation, and urinary gonadotropins in five girls and one boy with central precocious puberty (CPP) who had been treated for 1.4-2.3 years (mean 1.9). Because of the potential antifertility effects of LHRH analogues, testicular histology was analysed in the boy. In the five children with accelerated growth, the bone age-related velocity of height gain decreased from 10.58 +/- 2.77 to 5.82 +/- 1.8 cm/year (means +/- SD, P less than 0.01), and the ratio of change in bone age to change in chronological age fell below 1. Basal luteinizing hormone (LH), and LHRH-stimulated LH and follicle stimulating-hormone, at pubertal levels before treatment, decreased significantly in all children, normalizing in four (P less than 0.04). During therapy, pituitary function was best controlled by urinary LH, which correlated with clinical data. After 13 months of therapy, testicular histology showed degenerated Sertoli cells, and absence of B- and Ap-spermatogonia and of primary spermatocytes in the boy. We conclude that: (1) Efficient long-term suppression of central precocious puberty--including accelerated growth and skeletal maturation--can be maintained by intranasal dosage of BUS. (2) Urinary LH reflects pituitary function and proves to be a reliable guide to adjustment of the LHRH-analogue dose regimen.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of human and porcine insulin therapies in children with newly diagnosed diabetes mellitus.

A multicenter, longitudinal study of children below the age of 16 years with newly diagnosed Type 1 (insulin-dependent) diabetes treated either with porcine monocomponent insulin (n = 26) or semisynthetic human monocomponent insulin (n = 26) was performed during the first 24 months after onset of diabetes. The two groups were carefully matched for age, duration of disease symptoms, initial metabolic values, islet cell antibodies and HLA-DR antigens. During the 24-month observation period there was no significant difference between the two groups in respect to the clinical course, insulin dosage, HbA1 and residual B-cell activity. No child in either group had a real remission without necessitating insulin therapy. The prevalence of insulin antibodies increased slowly and was 62% in the group treated by human insulin and 52% in the porcine insulin-treated group after 24 months. The titres were generally low and there was no statistical difference between the two groups in respect to insulin antibody formation.

[Effect of meteorologic and air hygiene factors on acute respiratory tract diseases in children--based on the example of the Biel region]. / Der Einfluss meteorologischer und lufthygienischer Faktoren auf akute Erkrankungen der Atemwege bei Kindern--am Beispiel der Region Biel.

In the area of a Swiss town (Biel) and its surroundings, cases of various acute respiratory illnesses among children were recorded and correlated with measured parameters of weather and air pollution (sulfur dioxide, dust) during a period of 17 months. An increase in cases was noted during the fall and winter months, involving low temperatures, high humidity and weather conditions with northerly synoptic winds. Also, correlation of the cases to SO2 deposition values revealed a significant connection that may possibly be simulated by identical seasonal changes. No significant connection could be found between concentrations of SO2 or dust values and frequency of illness.

Current trends in Swiss hospital pediatrics (including pediatric surgery). Increasing importance of collaboration with child psychiatry.

The patients of a general pediatric hospital servicing a representative population are analyzed. 3% of the age group below 16 are admitted, whereof 2/3 as emergencies. The morbidity of boys is distinctly higher than for girls. 1/4 is less than 2 years old. Hospitalization rate for infants is much higher than for older age groups. Surgery slowly outnumbers medicine for inpatients. The most frequent single diagnoses are surgical ones, whereas in medicine diagnoses are scattered over a much broader spectrum. Over 11% of all patients had social, psychosomatic or psychological conflicts significantly contributing to the symptomatology presented, for medicine alone it was one out of five patients! Paternal profession, social failures and family quarrels are important for this cohort. A setting of child psychiatry on a consultant basis should complement the traditional framework of pediatric medicine and surgery; hospital pediatrics can then best offer the necessary structures. The pediatrician's role has to remain central, but additional training is mandatory.

A puzzling triad: anorexia nervosa, high sweat electrolytes and indication to partial exocrine pancreatic insufficiency.

This report describes a 15-year-old girl with anorexia nervosa whose sweat electrolytes and pancreatic exocrine function were abnormal during a state of malnutrition. Both findings normalized when nutrition improved. The patient did not have any evidence of disorders known to be associated with an abnormal sweat test, including most importantly cystic fibrosis. It is postulated that the elevated sweat electrolytes and the pancreatic insufficiency developed in this patient secondary to malnutrition. The pathophysiological mechanism for both phenomena remains obscure. It is recommended that positive sweat tests in malnourished children should be repeated several times in a corrected nutritional state in order to obviate an erroneous diagnosis of cystic fibrosis.

Diseases and tumours associated with virilization: pediatric aspects.

Much light has been shed on the underlying disturbances of virilization syndromes. The clinical aspects remain enormously manifold, and close teamwork between the pediatrician and pediatric surgeon is indispensable. In this chapter, the sources of androgens responsible for virilization and the syndrome of male pseudohermaphroditism are discussed in detail.

[Transient neonatal macrocephaly. The differential diagnosis of abnormally fast-growing skull in newborn infants]. / Passagere neonatale Makrozephalie. Zur Differentialdiagnose des abnorm raschen Schädelwachstums beim Neugeborenen.

In a twin baby of low birth weight a transient abnormally increased growth velocity of the head circumference could be observed. Sodium and water retention were recognized as the underlying disturbance responsible for brain edema. This mechanism is one of several possible etiologic factors leading to macrocephaly in early infancy. Pathogenesis, therapy and prophylactic measures are discussed.

Quality of breast milk: its control and preservation.

The numerous problems of bacterial contamination and proper preservation of breast milk have been examined. Both the many advantages of human milk as the optimal nourishment for the newborn baby and the extensive experiences of veterinary medicine in the handling of milk have been carefully considered. Bacterial multiplication has been studied under various storage conditions. Out of several possible procedures a simple, inexpensive, rapid and reliable dip-slide screening method for determining total bacterial colony counts is described. A clear-cut procedure for the optimal collection of breast milk is presented.

Low- and high-risk non-T and non-B and T-cell acute lymphoid leukemia (ALL) in childhood: different duration of remission and survival.

In a prospective, nonrandomized trial clinical (initial WBC and chest film) and immunological (surface immunoglobulin and rosetting with pretreated sheep red blood cells) criteria were used to stratify 69 children with previously untreated acute lymphoid leukemia (ALL). Forty of 61 evaluable patients had low-risk ALL (initial WBC less than or equal to 20,000/mm3, no mediastinal mass) and were treated less intensively. Twenty-one of 61 patients had high-risk ALL (initial WBC greater than 20,000/mm3 and/or mediastinal mass) and were treated more intensively. Of the high-risk patients 15 had non-T non-B and 6 T ALL. Sixty of 61 patients went into complete remission. After a median observation period of 27 months, 32 of 40 low-risk, 7 of 14 high-risk non-T non-B, and none of 6 high-risk T ALL patients were in continuous first remission. Thirty-six of 40 low-risk, 9 of 15 high-risk non-T non-B, and none of 6 T ALL patients were alive. Despite more intensive treatment, the duration of remission and the survival were significantly shorter in the high-risk than in the low-risk patients. Among the high-risk ALL, non-T non-B ALL did better than T ALL.

Increased risk of diabetes mellitus in beta- thalassemia major due to iron overload.

Frequent transfusions improve the general well being in patients with beta-thalassemia major but carry the risk of iron intoxication including the development of diabetes mellitus. Of 22 patients with beta-thalassemia major (age 3-17 years) only 3 had a normal oral glucose tolerance. The remainder had either borderline or moderately pathological glucose curves. The mean glucose concentration was increased, and the mean insulin concentration and insulin/glucose ratio were diminished. In contrast to the oral test, the i.v. glucose tolerance test gave pathological results in only 2 of 16 patients tested. The i.v. glucose test thus may be less selective than the oral test. The mean insulin concentration was lower also after intravenous glucose, but the early insulin peak was preserved. Arginine infusion led to a normal insulin and growth hormone release. This moderate impairment of insulin release found in most of the patients leaves the hope that an efficient chelating therapy scheme might reverse beta-cell dysfunction.