Päivi Tapanainen

Maternal Hypoxia as a Model for Intrauterine Growth Retardation: Effects on Insulin-Like Growth Factors and Their Binding Proteins

ABSTRACT: Evidence suggests that IGF and their binding proteins play a role in fetal growth, but more knowledge concerning their regulation is essential. We examined the expression of IGF and their binding proteins in experimental intrauterine growth-retarded (lUGR) rat fetuses of hypoxic dams (13–14% oxygen, d 14–21 of gestation). The mean body weight of the fetuses (d 21 of gestation, n = 72) of the six hypoxic dams was 24% lower (p < 0.0001) than the mean weight of the fetuses of six control dams (n = 82). Wet liver weights demonstrated a 20% decrease (p < 0.0001) and placentas a 10% decrease (p < 0.01) compared with control fetuses. The mean serum concentrations of immunoreactive IGF-I in both groups were low but did not differ significantly. The mean serum concentrations of immunoreactive IGF-II, however, were higher in IUGR fetuses. As assessed by Northern blot analysis, there was a 4-fold increase in insulin-like growth factor binding protein-1 (IGFBP-1) mRNA expression in the livers of the IUGR fetuses compared with controls. IGFBP-2 mRNA expression was 6-fold increased in IUGR fetal livers. No difference was found in IGFBP-4 mRNA. An increase in IGFBP-1, −2, and −4 concentrations could be seen by Western ligand blotting in the serum of growth-retarded fetuses compared with control fetuses. This finding was verified by immunoprecipitation with specific antibodies, which demonstrated increases in IGFBP-1 and IGFBP-2. Our results validate the use of maternal hypoxia as an experimental model of intrauterine growth retardation and indicate that increased IGFBP-1 and −2 expression may be of importance in the etiology of fetal growth retardation caused by maternal hypoxia.

Prevalence, segregation, and phenotype of the mitochondrial DNA 3243A>G mutation in children

We studied the prevalence, segregation, and phenotype of the mitochondrial DNA 3243A>G mutation in children in a defined population in Northern Ostrobothnia, Finland.

Pulsatile Secretion of LH and FSH in Prepubertal and Early Pubertal Boys Revealed by Ultrasensitive Time-Resolved Immunofluorometric Assays

ABSTRACT: Pulsatile secretion of LH and FSH was examined in 10 prepubertal (aged 4.5–12.9 y) and seven early pubertal (aged 12.8–14.5 y) boys with ultrasensitive (0.019 and 0.014 IU/L time-resolved immunofluorometric assays. Plasma LH and FSH levels were measured every 15 or 20 min for 6 h during the day and night. The lowest mean LH level in a prepubertal boy was 0.02 IU/L and in eight other prepubertal boys mean LH levels were less than 0.4 IU/L. In early pubertal boys the mean LH levels ranged from 0.3 to 6.5 IU/L. The difference in mean FSH level between prepubertal (0.61 IU/L) and early pubertal boys (1.85 IU/L) was smaller than the difference in LH level. All boys had significant LH and FSH pulses. The LH interpulse interval was 135 ± 86 min (mean ± SD) and 76 ± 65 min for the prepubertal and pubertal boys, respectively (p < 0.01). For FSH, the respective values were 150 ± 122 and 221 ± 157 min (p = NS). The mean LH pulse amplitudes were 11-fold greater in the early pubertal boys than in the prepubertal boys, whereas the mean FSH pulse amplitudes were similar between the two groups. The present method shows that the mean LH levels in prepubertal boys are much lower, and the increase during puberty larger, than previously reported. The increase is apparently due to increased pulse frequency and amplitude. The increase in mean FSH level is smaller and evidently not caused by an increase in pulse frequency or pulse amplitude.

A comparison of different definitions of growth response in short prepubertal children treated with growth hormone.

Background: How to define poor growth response in the management of short growth hormone (GH)-treated children is controversial. Aim: Assess various criteria of poor response. Subjects and Methods: Short GH-treated prepubertal children [n = 456; height (Ht) SD score (SDS) ≤–2] with idiopathic GH deficiency (IGHD, n = 173), idiopathic short stature (ISS, n = 37), small for gestational age (SGA, n = 54), organic GHD (OGHD, n = 40), Turner syndrome (TS, n = 43), skeletal dysplasia (n = 15), other diseases (n = 46) or syndromes (n = 48) were evaluated in this retrospective multicenter study. Median age at GH start was 6.3 years and Ht SDS –3.2. Results: Median [25–75 percentile] first-year gain in Ht SDS was 0.65 (0.40–0.90) and height velocity (HtV) 8.67 (7.51–9.90) cm/year. Almost 50% of IGHD children fulfilled at least one criterion for poor responders. In 28% of IGHD children, Ht SDS gain was <0.5 and they had lower increases in median IGF-I SDS than those with Ht SDS >0.5. Only IGHD patients with peak stimulated growth hormone level <3 µg/l responded better than those with ISS. A higher proportion of children with TS, skeletal dysplasia or born SGA had Ht SDS gain <0.5. Conclusion: Many children respond poorly to GH therapy. Recommendations defining a criterion may help in managing short stature patients.

A practice guideline for treatment of eating disorders in children and adolescents

Eating disorders are diseases of both the body and the psyche. Early treatment focuses on restoration of nutritional status and somatic health, including psycho‐educational counselling and support offered to the patient and his/her family. Diagnosis and treatment require a multidisciplinary approach. Psychological factors related to the condition should be assessed. The most severe weight loss should be reversed before psychotherapeutic treatment. Nutritional counselling is recommended, and the benefits of individual and/or family therapy are considered in accordance with the patients age, development, symptomatology and comorbid psychiatric disorders. Medication is useful in the treatment of bulimia nervosa and certain comorbid symptoms of anorexia nervosa. Early admission to treatment and active therapy are associated with a more favourable prognosis.

Basal insulin switch from NPH to glargine in children and adolescents with type 1 diabetes

Background:u2002 Insulin glargine is a long‐acting insulin analogue increasingly used instead of neutral protamine Hagedorn (NPH) insulin in young subjects with type 1 diabetes.

Evaluation of Growth Hormone Secretion and Treatment

The secretion of growth hormone (GH) is regulated by a complex system that includes both neurotransmitters and feedback by hormonal and metabolic substrates. Over the last few years it has been recognized that GH release varies over a wide spectrum from deficient to excessive secretion. The diagnosis of GH deficiency is based on a combination of anthropometric and clinical signs on the one hand and an inadequate stimulated and/or spontaneous GH secretion on the other. There is no distinct boundary between deficient and sufficient GH secretion. The cut-off limit for normal GH release is accordingly relative and has increased over the past decade from 5 to 10 micrograms/l. The effect of GH therapy on growth can be evaluated only after treatment for at least 6 months. There is, therefore, an indisputable need for methods that would reflect growth response soon after the start of treatment. There are several promising biochemical candidates, e.g. the aminoterminal propeptide of type III procollagen, the carboxyterminal propeptide of procollagen I and the bone Gla-protein, which may turn out to be useful early indicators of the growth response to long-term GH therapy.

Practice-oriented evaluation of medical students during a pediatric course

Examinations should be motivating, inspiring and interesting for students and evaluation should be an essential part of learning. The evaluation is optimal when it is as practical and patient related as possible. To meet these criteria, we have developed examinations that are practice related by using case problems as questions in written examinations and by presenting case problems with slides as an examination. Our aim has been to teach students to seek out knowledge bm the literature by allowing the use of a textbook in solving problem cases in the examination. In order to teach consultation skills in some case problems, students have to write a referral. Furthermore, feedback on the examinations has developed to teach consultation skill by using peer evaluation and peer learning in the feedback. According to principles of objective structured clinical examination, we have developed an exam where the students are evaluated when they are examining real patients in a pediatric ward. The assessment of cli...