[The abused and neglected child in Switzerland]. / L'enfant maltraité et négligé en Suisse.

Pediatricians form part of children's and young people's most important extra-familial relations. They are thus especially well placed: first, to discover abuse of any kind, and second to put in motion the first years of measures of assistance for the children and their families. The first years of life are decisive for effective prevention of abuse and neglect, and for the development of a healthy personality. In this part of life, pediatricians are virtually the only "social outposts". Nevertheless, in Swiss pediatrics the concept of child protection is still in the initial stages. While we should warmly welcome the fact this problem was at last the main theme of an annual meeting, it must be remembered that this was only the first time. For a long time now no one has doubted that in our, thus far socially privileged country, a frighteningly large number of children and adolescents are victims of abuse. Since the publication of the report "Mauvais traitements des enfants en Suisse" (1992) a representative questionnaire to parents has shown that in this country and now, as before, over a third of parents use corporal punishment on their children. It has been calculated that e.g. 21,800 babies aged between 0 and 2.5 years are beaten, 4800 of them even with implements. There are no data on psychological and sexual maltreatment. Despite this shocking incidence of abuse, only a total of 72 cases (6% of all recorded cases) were reported over one year by pediatric practitioners in the "1989 prospective study". We cannot accept that this reflects a lack of social concern. Many other shortcomings appear to be involved: lack of briefing on the problems of child abuse during medical training, post-graduate and continuing studies, inadequate arrangements for interdisciplinary work, discouragement and early delegation to pseudo-experts, distrust of the efficacy of available aids (but sometimes overestimation of one's own possibilities) and last but not least, a still highly idealized image of the family which prompts one to reject the possibility of abuse. The Swiss Pediatric Society is urgently called upon to focus closer attention on this subject, and in so doing to take advantage of the increasingly widespread concept that child abuse must be regarded as resulting from a disturbance of the child's social network. Here the pediatrician can find an effective, decisive and also--above all--preventive role.

Persistent microalbuminuria in adolescents with type I (insulin-dependent) diabetes mellitus is associated to early rather than late puberty. Results of a prospective longitudinal study.

Microalbuminuria is generally accepted to be highly predictive of overt diabetic nephropathy which is the leading cause of end-stage renal failure and, consequently, of death in patients with type 1 (insulin-dependent) diabetes mellitus (IDDM). Its early identification and therapy are exceedingly important. We studied prospectively the occurrence of microalbuminuria (MA) in relation to puberty and its pubertal stages in 164 children and adolescent patients (83 girls and 81 boys) with IDDM. Analysing 100 healthy subjects, normal values for albumin excretion (range: 0-10.1 micrograms/min/1.73 m2) according to sex and the different pubertal stages were defined. No significant difference between the groups were noted and, therefore, 20 micrograms/min per 1.73 m2 (3 SD above the mean) was generally defined as cutoff for MA. Of the patients with IDDM studied, 20% (20 females and 12 males) developed persistent MA (22.1-448.2 micrograms/min/1.73 m2) during the study period of 8 years. The first manifestation of persistent MA was in 69% (13 females and 9 males) during stages of early and midpuberty; and in 28% (6 females and 3 males) at a late pubertal stage or at the end of puberty. The only child who developed MA before the onset of puberty (range: 23.5-157.4 micrograms/min/1.73 m2) was found to have dystopic kidney. Therefore, all patients with IDDM should be screened for MA regardless of diabetes duration, sex and level of diabetes control beginning at the very first stage of puberty and neither earlier nor after puberty as suggested by the American Diabetes Association.

Fetal haemoglobin levels in adult type 1 (insulin-dependent) diabetic patients.

Glycated haemoglobin levels (HbA1 and HbA1c) are established parameters of long-term glycaemic control in diabetic patients. Depending on the method used, fetal haemoglobin interferes with the assays for glycated haemoglobin. If present in high amounts, fetal haemoglobin may lead to overestimation of glycated haemoglobin levels, and therefore, of average blood glucose concentration in diabetic patients. Glycated (HbA1c) and fetal haemoglobin levels were measured by high pressure liquid chromatography in 60 (30 female) adult Type 1 (insulin-dependent) diabetic patients of Swiss descent, and were compared with levels obtained from 60 normal, non-diabetic control subjects matched for age and sex. Fetal haemoglobin levels were significantly higher in the diabetic patients (0.6 +/- 0.1%, mean +/- SEM; range: 0-3.6%) than in the control subjects (0.4 +/- 0.1%, p < 0.001). Elevated fetal haemoglobin levels (> or = 0.6%) were found in 23 of 60 diabetic patients (38%) compared to 9 of 60 control subjects (15%; chi 2 = 8.35, p < 0.01). In addition, fetal haemoglobin levels in diabetic patients are weakly correlated with glycated haemoglobin (HbA1c) (r = 0.38, p < 0.01). Fetal haemoglobin results were confirmed with the alkali denaturation procedure, and by immunocytochemistry using a polyclonal rabbit anti-fetal haemoglobin antibody. A significant proportion of adult patients with Type 1 diabetes has elevated fetal haemoglobin levels. In certain patients this may lead to a substantial over-estimation of glycated haemoglobin levels, and consequently of estimated, average blood glucose levels. The reason for this increased prevalence of elevated fetal haemoglobin remains unclear, but it may be associated with poor glycaemic control.

Persistent müllerian duct syndrome: a case report.

The persistent Müllerian duct syndrome is a rare disorder of sexual development. We report on a 4 month-old male who presented with a left-sided inguinal hernia and undescended testes. During the repair of the hernia 2 testes, 1 fallopian tube and an uterus were observed. The clinically suspected diagnosis of hernia uteri syndrome was confirmed by laboratory investigations. At the age of 18 months laparotomy was performed and the 2 fused gonades were descended into the right scrotum.

Risks of alternative nutrition in infancy: a case report of severe iodine and carnitine deficiency.

A 7.5-month-old infant with failure to thrive, developmental delay, muscular hypotonia, a visible goitre and severe osteopenia is described. Laboratory examination revealed a markedly increased serum TSH with low free T4, severe iodine and carnitine deficiency. The infant was breastfed until the age of 2.5 months and was then given a mixture of almond extract in water. The mother is a strict vegan and the father a lactovegetarian. The nutritional intake of the child was severely depleted in calories (-46%), calcium (-73%) and iodine (-88%). The restrictive alternative nutrition was responsible for the various deficiency disorders.

Increasing incidence of hypoglycemic coma in children with IDDM.

OBJECTIVE: To examine the incidence of hypoglycemic coma in children with insulin-dependent diabetes mellitus (IDDM) over 8 yr from 1981 to 1988 and to investigate the importance of residual beta-cell function of HbA1 levels and other variables as risk factors for hypoglycemic coma. RESEARCH DESIGN AND METHODS: The study consisted of 155 children with IDDM aged less than 16 yr at study entry. Mean age at onset of diabetes was 7.9 yr (range 1.1-15.6 yr). We made a prospective assessment of hypoglycemic coma episodes, with a standardized questionnaire, over a total observation time of 816.6 person-yr. Three monthly clinical and laboratory examinations, which included determinations of C-peptide and HbA1 levels, were conducted. We compared children with hypoglycemic coma (cases) with children without hypoglycemic coma (controls) in a case-control analysis matched for diabetes duration. Yearly incidence of hypoglycemic coma, calculated as the number of subjects having an attack in 1 yr divided by the cumulative number of person-years for that year, was measured. Univariate and multivariate odds ratios were calculated from logistic regression. RESULTS: Over the first 4 yr, the average yearly incidence was 4.4/100 person-yr compared with 7.4/100 person-yr during the later 4 yr (P less than 0.0001). This tendency was accompanied by intensification of insulin treatment with an increase in the mean number of daily injections and a decrease in mean HbA1 levels. In the case-control analysis, absent residual beta-cell function was the most important risk factor for hypoglycemic coma (adjusted odds ratio 7.8, 95% confidence intervals 2.0-31.2), followed by near-normal HbA1 levels (adjusted odds ratio 4.5, 95% confidence intervals 1.9-10.5). CONCLUSIONS: In this group of children, improvement of glycemic control apparently led to an increase in the incidence of severe hypoglycemia. In children with recurrent hypoglycemic coma and undetectable C-peptide levels, it may be safer to aim for somewhat less tight glycemic control.

Unsustained central sexual precocity in four girls.

Four girls who presented with breast enlargement at 4-5.8 years of age have been followed without specific therapy for up to 4 years. Three had normal CT brain scans, one had normal skull and sella x-rays. Stimulation of gonadotropins by LHRH was excessive in all but plasma estradiol levels were only intermittently elevated. Initially, bone age was advanced and height velocity was increased in three of the four. Ultrasound visualized an enlarged uterus in two and waxing and waning ovarian cysts in all. The clinical course was characterized by persistence of physical signs over at least 3.4 years in one patient, fluctuation in another, and marked regression in two. We propose that some patients with central precocious puberty may spontaneously have a nonprogressive course which has to be considered when evaluating the efficiency of drugs interfering with puberty.

[Hypoglycemia in childhood diabetes]. / Hypoglykämien bei Diabetes im Kindesalter.

Severe hypoglycemic episodes in diabetic children are a serious complication of present medical therapy. With the recent trend towards intensified insulin therapy, the incidence of severe hypoglycemia will probably increase. The pathophysiological mechanisms in the development of severe hypoglycemia are lack of modulation of plasma insulin levels, diminished or abolished glucagon release, delayed epinephrine release, and diminished glucose threshold for awareness of hypoglycemic symptoms, especially in well stabilized diabetics. The consequences of severe hypoglycemia are EEG changes, focal or generalized convulsions, (rarely) partial or generalized epilepsy, and disturbances of cognitive function probably due to neuronal damage. Some of the risk factors can easily be understood and are preventable. A highly increased risk factor is a low HbA1, and a complete lack of endogenous insulin secretion. However, in our experience human insulin is not an additional risk factor. Home blood glucose monitoring for determining the correct insulin dose and food supply is of great prophylactic importance. In the presence of coma in a diabetic child due to hypoglycemia, i.m. glucagon or i.v. glucose should be administered immediately in the correct dose. Following a severe hypoglycemic episode the glucose equilibration should be somewhat less strict. Regular education of the patient on risk factors, prevention and therapy of hypoglycemia is of great importance.

[Basal bolus therapy in adolescent diabetic patients]. / Die Basis-Bolus-Therapie beim adoleszenten Diabetiker.

Between April 1986 and December 1987 30 adolescent patients with type 1 diabetes were changed from a conventional twice daily insulin regimen to the basal-bolus system, using pen-injectors. Actually, 26 patients are still using the new system. A comparison was made over a three-year period with a group of 26 patients on conventional therapy matched for age, sex and diabetes duration. A questionnaire was sent to the pen-injectors for subjective evaluation of the new system. The insulin dose remained unchanged. The incidence of hypoglycemic coma in the control group (4.3 per year/26 patients) was similar to the one in the pen-injector group prior to installation of the new system (4.0 per year/26 patients) and increased, but not significantly, on the new system (8.9 per year/26 patients). In both groups, the relative body weight increased significantly, the increase being greater in the pen-injectors (p = 0.001) than in the controls (p = 0.042); however, the difference of weight gain between the two groups was not significant. Fasting plasma cholesterol and triglycerides did not change. Glycosylated hemoglobin (Hb-A1 corrected for Hb-F) dropped significantly in the pen-injectors three months after installation of the new system (p = 0.026), but reached the preceding level already after six months. In the controls, the Hb-A1 remained constant over the three years. Greater flexibility in lifestyle, easier handling and better subjective diabetes control were the main advantages mentioned by the patients on the new system. Negative statements were the necessity for multiple injections, the high frequency of blood glucose control and strongly increased problems with weight control.(ABSTRACT TRUNCATED AT 250 WORDS)

Oxandrolone in constitutionally delayed growth, a longitudinal study up to final height.

Twenty-seven prepubertal boys and 9 prepubertal girls with constitutionally delayed growth were treated with the anabolic steroid oxandrolone for 12 months and followed until they reached final height. Sixteen boys were treated with a mean dose of 0.12 mg/kg.day [low dose (LD)] and 11 boys with a mean dose of 0.22 mg/kg.day [high dose (HD)]. The girls were treated with a mean dose of 0.1 mg/kg.day. Thirteen boys and 9 girls served as controls. On oxandrolone the mean height velocity increased from 4.0 to 8.6 (boys, LD), from 4.3 to 8.9 (boys, HD), and from 4.3 to 8.3 cm/yr (girls). The immediate posttreatment height velocity was significantly higher than the pretreatment height velocity (P less than 0.05), regardless of whether the patients had entered puberty. On oxandrolone the mean ratios of change in bone age/change in chronological age were 2.0 (boys, LD), 2.3 (boys, HD), and 2.0 yr/yr (girls) and continued to be accelerated during the 6 months after treatment. Height predictions at the onset of treatment and after 6 months off treatment were calculated by three different methods: Bayley-Pinneau (BP), Roche-Wainer-Thissen (RWT), and Tanner Mark II (T II). In the boys (LD) mean height predictions increased significantly by the methods of BP (3.3 cm) and RWT (2.9 cm), but not by the method of T II (0.6 cm). In the boys (HD) no significant change in height predictions was noted. In the girls mean height predictions remained unchanged by BP and RWT, but decreased significantly by T II (-2.5 cm). The difference between final height and initial height prediction was taken as a measure of the influence of the treatment on adult height. In all three treatment groups the difference between final height and initial height prediction, calculated with all three methods, did not differ from the control group. We conclude that oxandrolone treatment for 1 yr has no effect on adult height. In spite of this, the use of an anabolic steroid such as oxandrolone may still have value, as an increase in height velocity and an earlier onset of puberty may benefit short children suffering from psychological problems due to delay of growth and development.

Increased prevalence of fetal haemoglobin in type 1 (insulin-dependent) diabetes mellitus.

Fetal haemoglobin levels were measured in 106 patients with Type 1 (insulin-dependent) diabetes mellitus during a period of two to three years. In 15 patients (14.1%) increased fetal haemoglobin levels (greater than 0.5%), determined by high pressure liquid chromatography, were found in contrast to 3% in a healthy control group (n: 100) of equal age distribution. In children aged over 6 years, elevated fetal haemoglobin levels were measured in 13 diabetic patients (13.3%) in contrast to none of the control group. There was no correlation between fetal haemoglobin levels and duration of diabetes, diabetic control (glycated haemoglobin) and dosage of insulin (U.kg-1, day-1). The 15 patients had a younger mean age at onset of diabetes (5.6 years) than a sex and age matched control group of diabetic patients without increased fetal haemoglobin levels (7.4 years, p less than 0.05). Longitudinal assessment revealed a significant decline of fetal haemoglobin levels with age (p less than 0.005) but a further increase in fetal haemoglobin levels were found in adolescent patients (n: 2). These data indicate a possible effect of insulin-treatment on delaying transition from fetal to adult haemoglobin synthesis or on reactivation of fetal haemoglobin production.

[Hypoglycemia in children with diabetes treated with human or porcine insulin]. / Hypoglykämien bei Kindern mit Diabetes unter humanem oder porcinem Insulin.

If hypoglycemia unawareness in diabetes is related to human insulin, its use would mean an increased risk of unconscious hypoglycemia. In a prospective study in 59 children treated from onset of diabetes by either human or porcine insulin of equal purity for a mean observation period of more than 3 years, no significant difference in the incidence of hypoglycemic coma was detected: 9/29 (31%) of the children treated by human insulin compared to 8/30 (27%) of those treated by porcine insulin had 1 or more severe hypoglycemic episodes. At the time of the first coma there was no significant difference in age, duration of diabetes, insulin dose, or HbA1 between the groups. Thus, human insulin is not considered to be an additional risk factor for the development of hypoglycemic coma in diabetic children.

Antihypertensive and metabolic effects of ketanserin in diabetic patients with mild hypertension.

Ketanserin is a serotonin S2 receptor antagonist with antihypertensive activity. Its effects on blood pressure, glucose metabolism and serum lipids were assessed in 24 patients with diabetes mellitus and mild arterial hypertension in a double blind, placebo-controlled trial. Ketanserin in doses up to 80 mg daily caused a slight decrease of supine BP (from 159/97 +/- 19/11 to 153/90 +/- 20/9 mm Hg; NS/P less than 0.01) and upright BP (from 160/102 +/- 18/13 to 151/93 +/- 12/12 mm Hg; P less than 0.05/NS). However, these pressures did not differ significantly from the levels observed in the placebo group. Supine and upright heart rate, body weight, plasma sodium and potassium, serum creatinine, glucose, C-peptide, glycosylated haemoglobin, serum cholesterol and triglycerides, their lipoprotein fractions, apolipoprotein A1, A2 and B concentrations and the responses of serum glucose and insulin to a standard oral glucose loading test did not change. These findings indicate that the selective S2 receptor antagonist ketanserin did not unfavourably influence glucose and lipid metabolism in diabetic patients with arterial hypertension.

Comparison of fructosamine and glycated haemoglobin in children with type 1 (insulin-dependent) diabetes mellitus.

In six children (age: mean 8.4 years, range 2.2-12.6 years) with newly diagnosed Type 1 (insulin-dependent) diabetes mellitus, plasma fructosamine and glycated haemoglobin (HbA1) were compared in respect to their disappearance during the first month after diagnosis during well controlled glycaemia. The disappearance of the surplus plasma fructosamine and HbA1 was calculated applying exponential equations. The estimated half-lives of fructosamine (mean 57.2 days, range 40.7-77 days) and HbA1 (mean 59.7 days, range 43.3-82 days) were not significantly different, a finding which is left unexplained.

Intermittent microalbuminuria in children with type 1 diabetes mellitus without clinical evidence of nephropathy.

Microalbuminura (MA) was determined in 127 children and adolescents (age 3-21 years) with type 1 (insulin-dependent) diabetes mellitus. Patients with clinical evidence of long-term complications or macroproteinuria were excluded. Urinary albumin excretion was measured in a nocturnal 12-h collection and correlated with the albumin/creatinine ratio of a urine sample freshly voided on the morning immediately following the collection. The patients were divided into group A (n = 83, age less than 16 years, duration of diabetes 1-13 years, mean 4.4) and group B (n = 44, age greater than 16 years, duration of diabetes 1-19 years, mean 8.7) and compared with appropriate controls. MA above 15 micrograms/min was present in 11 of 83 (13.3%) patients in group A and in 7 of 44 (15.9%) in group B. In a repeat urine collection at least 3 months later elevated MA persisted in 1 of 11 (group A) and in 4 of 7 (group B) patients. There was no correlation between increased MA in a 12-h urine collection and the albumin/creatinine ratio in a subsequently voided urine sample. MA was not strictly dependent on age, sex, duration of diabetes, haemoglobin A1, mean arterial blood pressure, plasma creatinine, creatinine clearance or serum beta-2-microglobulin. Further systematic studies and careful follow up are necessary to appraise whether intermittent MA is indeed an early manifestation of incipient kidney disease in children with type 1 diabetes.

[Disease course in 20 patients with an early diagnosis of phenylketonuria and hyperphenylalaninemia]. / Verlauf bei 20 Patienten mit frühentdeckter Phenylketonurie und Hyperphenylalaninämie.

Twenty patients with PKU or hyperphenylalaninemia at ages 0.1 to 15.6 years (median age 6.2 years) were studied prospectively. In all children the condition had been diagnosed when they were neonates on the basis of an abnormal Guthrie test. To maintain plasma phenylalanine levels between 0.2-0.5 mM, dietary restriction of phenylalanine to 20-80 mg/kg daily (median 40 mg/kg) was necessary in 14 children. In children above 8 years, however, these plasma levels were frequently exceeded. In 6 children plasma phenylalanine levels were higher than normal diet. Height, weight and head circumference were within normal range in all patients at all ages. Determinations of DQ/IQ were done at 2, 4, 6 and 8 years of age and revealed values between 90-120 with a median of 102 in the 14 patients who were tested. Only 1 patient had IQ levels between 75-85 and attended special school. Nine other patients were in grade school performing averagely or above. This study confirms that early treatment and long-term follow-up of patients with PKU yield good results. Unsolved problems include duration of dietary treatment and the management of pregnancy in women with PKU.

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.

Bromocriptine treatment in adolescent boys with familial tall stature: a pair-matched controlled study.

Recently, bromocriptine has been proposed as a novel agent for the treatment of excessively tall stature in adolescents. To further test its value, we treated nine boys, aged 10.0-15.4 yr, for 1 yr with bromocriptine (7.5 mg/day). A paradoxical plasma GH response to TRH was demonstrated in four of eight boys before and in five boys after 6 months of bromocriptine treatment. At the onset of therapy, the mean adult height prediction was 202.2 +/- 4.3 (+/- SD) cm (Bayley-Pinneau), 202.1 +/- 4.7 cm (TW Mark II), and 198.6 +/- 5.3 cm (Roche-Wainer-Thissen). After 1 yr of therapy, the mean adult height prediction had changed by -4.5 +/- 2.6 cm (Bayley-Pinneau), -3.4 +/- 2.2 cm (TW Mark II), and -2.6 +/- 1.2 cm (Roche-Wainer-Thissen). These reductions were solely due to a decrease in growth velocity and not to an increased skeletal maturation rate. To substantiate these findings, each treated boy was pair-matched with an untreated tall boy so that their chronological and skeletal ages differed by less than 1 yr. After 1 yr of follow-up, height predictions in the treated boys compared with those in the matched control boys gave significantly reduced results with the Bayley-Pinneau and the Roche-Wainer-Thissen, but not with the TW Mark II, method. Because of this discrepancy it is uncertain whether final height in tall boys will really be reduced by treatment with bromocriptine.

Neonatal diabetes mellitus: evaluation of pancreatic beta-cell function in two cases.

Two cases of neonatal diabetes mellitus, a transient form and a permanent form, are described. Comparing their clinical presentations and courses, we exclude the possibility of an early differential diagnosis based on clinical or laboratory data. We hypothesize that only repeated dynamic evaluations of pancreatic beta-cell function could be useful to differentiate the two forms.

Persistent neonatal hyperinsulinemic hypoglycemia in two siblings successfully treated with diazoxide.

Two siblings with persistent neonatal hyperinsulinemic hypoglycemia are reported. Diazoxide (10 mg/kg/d) was successful in controlling hypoglycemia for eight years and one year, respectively, without serious side effects. Pancreatic surgery was not necessary.