Reduced levels of growth hormone, insulin-like growth factor-I and binding protein-3 in patients with shunted hydrocephalus

OBJECTIVE: Children with hydrocephalus are characterised by slow linear growth in prepuberty, accelerated physical maturation during puberty, and reduced final height. We aimed to study the possible roles of growth hormone, insulin-like growth factor-I (IGF-I), and IGF binding protein-3 (IGFBP-3) in this growth pattern. STUDY DESIGN: One hundred and fourteen patients with shunted hydrocephalus (62 males) aged 5 to 20 years, of whom 17 had spina bifida (six males), and 73 healthy controls (38 males) were studied. Anthropometric measures, body mass index, and body fat mass were assessed and the stage of puberty was determined. Serum growth hormone and plasma IGF-I and IGFBP-3 concentrations were measured. RESULTS: The patients comprised 44 (26 males) who were prepubertal and 70 (36 males) pubertal or postpubertal, while 32 of the controls (19 males) were prepubertal and 41 (19 males) pubertal or postpubertal. The prepubertal children with hydrocephalus had lower IGF-I (p = 0.002) and IGFBP-3 concentrations (p < 0.001) than the controls, and the pubertal children had four times lower basal growth hormone concentrations (p < 0.001). There was a correlation between height SD score and IGF-I levels in the total patient population (r = 0.23; p = 0.01). Peripheral IGF-I concentrations peaked at pubertal stages 2-3 in the female patients and at stage 4 in the controls. The prepubertal patients on antiepileptic treatment, carbamazepine in most cases (73%), had higher IGF-I (p = 0.01) and IGFBP-3 concentrations (p = 0.03) than those who had never been treated with antiepileptic drugs, but still lower IGFBP-3 levels than the controls (p = 0.01). CONCLUSION: Based on these findings, it can be concluded that reduced growth hormone secretion may contribute to the pattern of slow linear growth and reduced final height observed in these patients.     

Prevalence of coeliac disease in siblings of patients with Type I diabetes is related to the prevalence of DQB1*02 allele

Aims/hypothesis: Coeliac disease is more prevalent among patients with Type I (insulin-dependent) diabetes mellitus and coeliac disease-related antibodies have been reported to increase in frequency in their first-degree relatives. Our aim was to find out if coeliac disease is more common among siblings of children with Type I diabetes than in the normal population. Methods: IgA endomysium antibodies were measured by indirect immunofluorescence in 550 subjects (mean age 11.8 years, range 3.1–26.9 years) with a sibling with Type I diabetes. We performed jejunal biopsy on as many subjects with positive antibodies as agreed. HLA-DQB1 genotyping was done in 427 subjects. Results: Endomysium antibodies were positive in nine subjects (1.6 %). Jejunal biopsy was diagnostic for coeliac disease in five out of seven patients. An additional patient with coeliac disease, one already on a gluten-free diet, was identified by questionnaire. The prevalence of coeliac disease was 1.1 %. Five of six patients with coeliac disease had HLA-DQB1^*02 allele, compared with 118 of 421 of those without coeliac disease (p = 0.009). The sixth patient was positive for HLA-DQB1^*0302 allele, which was also found in 241 of 421 of those without coeliac disease (p = 0.4). Conclusion/interpretation: We found the prevalence of coeliac disease among siblings of children with Type I diabetes to be similar to figures reported from recent population-based studies and to be correlated with the prevalence of coeliac disease associated HLA-DQB1 alleles. We propose that routine screening for coeliac disease among all first-degree relatives of patients with Type I diabetes is not warranted. [Diabetologia (2001) 44: 1051–1053] Received: 11 January 2001 and in revised form: 27 April 2001     

Diet,cow's milk protein antibodies and the risk of IDDM in Finnish children

Summary Associations of infant feeding patterns and milk consumption with cow's milk protein antibody titres were studied in 697 newly-diagnosed diabetic children, 415 sibling-control children and 86 birth-date-and sex-matched population-based control children in the nationwide Childhood Diabetes in Finland study. IgA and IgG antibody titres to the proteins of cow's milk formula, BLG and BSA, and IgM antibody titres to cow's milk formula proteins were measured by ELISA. Several inverse correlations were observed between the duration of breast-feeding or age at introduction of dairy products and antibody titres, and positive correlations were observed between milk consumption and antibody titres in all three populations studied. Multivariate analyses which included the infant feeding variables, milk consumption and current age simultaneously showed that the earlier the introduction of dairy products and the greater the consumption of milk was, the higher several antibody titres were. High IgA antibody titres to cow's milk formula were associated with a greater risk of IDDM both among diabeticpopulation-control and diabetic-sibling-control pairs when adjusted for other cow's milk antibody titres, dietary variables and in diabetic-sibling-control pairs also for ICA. The results suggest that young age at introduction of dairy products and high milk consumption during childhood increase the levels of cow's milk antibodies and that high IgA antibodies to cow's milk formula are independently associated with increased risk of IDDM.Abbreviations IDDM Insulin-dependent diabetes mellitus - BLG betalactoglobulin - BSA bovine serum albumin - ICA islet cell antibodies - IAA insulin autoantibodies - OR odds ratio - CI confidence interval     

Epilepsy in hydrocephalic children

Epilepsy and epileptogenic activity in EEGs were studied in 168 shunt treated hydrocephalic (HC) children, the mean age at first operation 1.62 years (SD 1.87). 80 patients (47.6%) suffered from epileptic seizures during the follow-up period (mean 8.9 years). The epileptic seizures appeared before the initial shunting, and after the first shunt implantation in 43 (25.6%). There was no correlation between epilepsy and the aetiology of HC, number of shunt revisions, or shunt infections. Sixteen patients suffered from seizures during the neonatal period. Generalized spike and wave activity (SWA) was seen in EEG in eight out of these, and only one was seizure-free at the end of the follow-up period. All eight patients with epileptic seizures during the neonatal period without generalized SWA in EEG were seizure-free, however. SWA was seen in the first EEG prior to shunting in 75/168 patients (44.6%). All those patients who did not receive prophylactic medication, developed epileptic seizures, whereas 68.1% of those who received prophylactic anticonvulsive medication remained free of seizures. Partial epilepsy after shunting manifested itself in 15 patients, but this did not correlate with the side of the shunt or with the side of the SWA in the EEG. Slit ventricles (SLV) developed in 75 patients during the follow-up period, while the ventricles remained normal or dilated in 66 cases (27 patients had no CT follow-up). Epilepsy manifested itself in 8 out of these 141 patients (2 SLV, 6 non-SLV) during the first postoperative year, and in 29 patients in the SLV group and one in the non-SLV group at some time after the first postoperative year.     

Accelerated pubertal development in patients with shunted hydrocephalus

OBJECTIVE: To evaluate pubertal development and peripheral concentrations of gonadotrophins and sex hormones in children with shunted hydrocephalus compared with healthy controls. STUDY DESIGN: 114 patients (52 females, 62 males) and 73 healthy controls (35 females, 38 males) aged 5 to 20 years were analysed for stage of puberty, age at menarche, testicular volume, basal serum follicle stimulating hormone (FSH), luteinising hormone (LH), sex hormone binding globulin (SHBG), testosterone and oestradiol concentrations, and free androgen index. RESULTS: Male gonadal and male and female pubic hair development occurred significantly earlier in the patients than in the controls. The mean age at menarche was significantly lower in the female patients than in their controls (11.7 v 13.2 years; p < 0.001), and lower than it had been for their mothers (v 13.1 years; p < 0.001). Relative testicular volume was higher in the male patients than in their controls (1.2 standard deviation score (SDS) v 0.2 SDS; p < 0.001). The prepubertal patients had higher basal LH (0.13 U/l v 0.08 U/l; p < 0.001) and SHBG (132.3 nmol/l v 109.1 nmol/l; p < 0.01) than the controls. Both the prepubertal and pubertal females had significantly higher basal FSH than their controls (1.57 U/l v 1.03 U/l; p < 0.05, and 4.0 U/l v 2.9 U/l; p < 0.01, respectively). CONCLUSIONS: Hydrocephalic children experience accelerated pubertal maturation, reflected in a younger age at menarche in females and an increased testicular volume in males. This may be because of enhanced gonadotrophin secretion, possibly resulting from unphysiological variations in intracranial pressure.     

OUTCOME AFTER CHILDHOOD ENCEPHALITIS

The prognosis for 73 children treated for encephalitis between 1973 and 1983 was evaluated. 70 children participated in a follow-up examination 2.4 to 12.9 years after the acute phase of the disease. The 61 school-aged children had lower performance and full-scale IQs than their randomly selected, age- and sex-matched controls. Visual acuity was more often reduced, and they more often had focal slowing on EEG and electronystagmogram abnormalities. Clinically, these differences were not significant. Encephalitis with a poor prognosis occurred seldom, the incidence being 3.5 cases per one million children at risk annually. These results show that the prognosis for childhood encephalitis is much better than anticipated on the basis of experience mainly with herpes simplex virus encephalitis.     

Cerebral palsy and additional handicaps in a 1-year birth cohort from northern Finland--a prospective follow-up study to the age of 14 years

In a 1-year birth cohort from the two northernmost provinces in Finland, Oulu and Lapland which comprised of 12 058 liveborn infants, the total number of children affected with cerebral palsy (CP) was 69. The cumulative incidence up to the age of 14 years was 5.7 per thousand. A prenatal aetiology was present in 32%, a perinatal aetiology in 36% and a postnatal aetiology in 19% whereas in 13.0% of the cases the cause remained untraceable. A total of 50 children (73%), had 1 or more additional handicaps. Mental retardation (IQ less than 85) was present in 70%, epilepsy in 48%, a visual defect in 19% and impaired hearing in 7%. The impact of the total handicaps is also illustrated by the fact that only 33% of the children were able to attend a normal school. The incidence of 5.7 per thousand recorded here is clearly higher than in studies from several other countries, as the cumulative incidence is usually reported to vary between 2 and 3 per thousand.     

Cell-free plasma DNA as a predictor of outcome in severe sepsis and septic shock

BACKGROUND: Increased concentrations of cell-free DNA have been found in plasma of septic and critically ill patients. We investigated the value of plasma DNA for the prediction of intensive care unit (ICU) and hospital mortality and its association with the degree of organ dysfunction and disease severity in patients with severe sepsis. METHODS: We studied 255 patients with severe sepsis or septic shock. We obtained blood samples on the day of study inclusion and 72 h later and measured cell-free plasma DNA by real-time quantitative PCR assay for the beta-globin gene. RESULTS: Cell-free plasma DNA concentrations were higher at admission in ICU nonsurvivors than in survivors (median 15 904 vs 7522 genome equivalents [GE]/mL, P < 0.001) and 72 h later (median 15 176 GE/mL vs 6758 GE/mL, P = 0.004). Plasma DNA values were also higher in hospital nonsurvivors than in survivors (P = 0.008 to 0.009). By ROC analysis, plasma DNA concentrations had moderate discriminative power for ICU mortality (AUC 0.70-0.71). In multiple regression analysis, first-day plasma DNA was an independent predictor for ICU mortality (P = 0.005) but not for hospital mortality. Maximum lactate value and Sequential Organ Failure Assessment score correlated independently with the first-day plasma DNA in linear regression analysis. CONCLUSIONS: Cell-free plasma DNA concentrations were significantly higher in ICU and hospital nonsurvivors than in survivors and showed a moderate discriminative power regarding ICU mortality. Plasma DNA concentration was an independent predictor for ICU mortality, but not for hospital mortality, a finding that decreases its clinical value in severe sepsis and septic shock.