Peter Lanning

Valproate-induced hyperandrogenism during pubertal maturation in girls with epilepsy.

Valproate is effective for treatment of a variety of seizure types both in adults and in children with epilepsy, but it induces obesity and polycystic ovaries in a considerable proportion of adult women, particularly when the medication is started before the age of 20. In the present study we evaluated reproductive endocrine function in 41 girls, 8 to 18 years old, taking valproate for epilepsy and in 54 healthy control girls. Among the girls taking valproate, 16 were prepubertal, 11 were pubertal, and 14 were postpubertal, and the corresponding numbers were 20, 13, and 21 in the control group. The mean serum testosterone concentrations of prepubertal, pubertal, and postpubertal girls taking valproate were significantly higher than those of the control girls at the same pubertal stage. Hyperandrogenism, defined as serum testosterone levels higher than the mean + 2SD in the control girls at the same pubertal stage, was seen in 38% of prepubertal, 36% of pubertal, and 57% of postpubertal girls taking valproate. In addition, postpubertal girls taking valproate were more obese than the controls and the mean serum insulin‐like growth factor binding protein‐1 concentration of pubertal and postpubertal hyperandrogenic girls taking valproate was lower than in valproate‐treated girls without hyperandrogenism. Valproate may induce hyperandrogenism in girls with epilepsy during the sensitive period of pubertal maturation, and the frequency of hyperandrogenism increases with pubertal development. This emphasizes the importance of careful endocrine observation of girls taking valproate for epilepsy. Ann Neurol 1999;45:444–450

Incidence, ultrasonic patterns and resolution of nephrocalcinosis in very low birthweight infants

Saarela T, Vaarala A, Lanning P, Koivisto M. Incidence, ultrasonic patterns and resolution of nephrocalcinosis in very low birthweight infants. Acta Pædiatr 1999; 88: 655‐60. Stockholm. ISSN 0803‐5253

EARLY CLOSURE OF PATENT DUCTUS ARTERIOSUS WITH INDOMETHACIN IN PRETERM INFANTS WITH IDIOPATHIC RESPIRATORY DISTRESS SYNDROME

ABSTRACT. Thirty‐seven preterm infants with idiopathic respiratory distress syndrome were prospectively studied for the effect of the early closure of patent ductus arteriosus with indomethacin on the course of idiopathic respiratory distress syndrome. Serial retrograde aortograms were performed in all infants in order to visualize the ductus arteriosus, apart from three patients, who died early and were evaluated aortographically only once. The ductus was initially open in 27 infants and closed in 10 infants. The infants with open ductus arteriosus were randomly divided into two groups. The first group consisted of 13 infants, in whom the ductus was closed with indomethacin at a median age of 18 hours. The other 14 infants served as controls. Total time on assisted ventilation and duration of exposure to additional oxygen were significantly shorter in medicated infants than in controls. Oxygenation of infants with an initially closed ductus was better from birth and duration of their ventilatory assistance and oxygen exposure were shorter than in infants with initial ductal shunting. The data suggest that the early closure of the patent ductus arteriosus with indomethacin in distressed preterm infants has a favourable effect on the course of idiopathic respiratory distress syndrome.

Ultrasonic features of the Osgood-Schlatter lesion.

Summary: Ultrasound was used to compare the knees of 10 boys and four girls with typical clinical Osgood–Schlatter lesions with 27 symptomless knees. The normal sonographic changes of the tibial tubercle with advancing age are described. In all children with Osgood–Schlatter lesions, the distal patellar tendon thickened and became more echogenic than normal tendons, and an anechoic zone of edema was seen anterior to the tibial tuberosity. Four knees disclosed a thin shell-like elevated fragment of the tibial tuberosity seen as an echogenic surface. In 12 knees, single or multiple fragments of the tibial tuberosity were easily shown. Ultrasound is proposed as a simple, fast, and reliable method for the diagnosis of the Osgood–Schlatter lesion.

Operative realignment of patellar malalignment in children

Realignment operations were performed on 57 knees to correct patellar malalignment in children between 1985 and 1991. Three different operative techniques were used: the lateral release, the lateral release and medial reefment, and the Roux-Goldthwait patellar tendon transposition. Roentgenographic values were measured before and after the operation by Laurins method. The mean follow-up time was 4 years 2 months, after which 20 knees were excellent, 20 good, 11 fair, and six poor, according to Insalls criteria. The effect of the operation on pathological roentgenographic values was obvious, and the malalignment of the patella was in most cases corrected. There are differences in the improvement effected by these three techniques. The lateral release and medial reefment correct the patellar tilt most effectively, and the Roux-Goldthwait operation, the lateral patellar deviation. The lateral release seems to be the appropriate technique for mild malalignment.

Prematurity-associated nephrocalcinosis and kidney function in early childhood.

Abstract To assess the impact of prematurity-associated nephrocalcinosis on kidney function later in life, 20 premature children with neonatal nephrocalcinosis and 20 controls, matched for birth weight and postnatal age but without nephrocalcinosis, were examined (birth weight 905±209 vs. 957±226 g; study age 4.7±1.1 vs. 4.6±0.9 years). Distal tubular acidification capacity was measured with the oral acetazolamide test, in which the response was abnormal in 1 out of the 20 children with a history of nephrocalcinosis, but in none of the controls. Urinary calcium and β2-microglobulin excretion were higher in the children with nephrocalcinosis, but no differences were found in fractional excretion of sodium and potassium or tubular reabsorption of phosphate. Estimated creatinine clearance was not different between the groups. Of the 6 children with nephrocalcinosis lasting beyond 2 years of age, 5 had had chronic lung disease neonatally and exhibited a tendency for compensated respiratory acidosis at the time of the examination. Neonatal nephrocalcinosis seems to lead to some signs of renal tubular dysfunction in early childhood of preterm infants. Glomerular function, however, appears not to be specifically disturbed by nephrocalcinosis.

Growth and lipid metabolism in girls and young women with epilepsy during pubertal maturation.

Summary:  Purpose: To assess growth and the serum lipid profile in girls with epilepsy receiving monotherapy at a mean age of 12.6 years and approximately 6 years later.

Nephrocalcinosis in full-term infants receiving furosemide treatment for congestive heart failure: a study of the incidence and 2-year follow up.

Abstract In order to study the incidence and course of nephrocalcinosis in full-term infants with congestive heart failure receiving long-term furosemide treatment, 36 such infants (median age 2.9 months, range 1.2–8.0) and 36 full-term control infants not receiving any diuretics (median age 3.4 months, range 1.1–8.4) were studied by renal ultrasonography and random urine calcium variables. The infants with nephrocalcinosis were followed at 3–6 month intervals up to 2 years of age, or until ultrasonic resolution. Nephrocalcinosis was found in 5 out of the 36 (14%) treated infants, but in none of the controls (P = 0.03). The dose of furosemide was higher in the infants with nephrocalcinosis than in those without (1.9 ± 0.6 vs. 1.3 ± 0.4 mg/kg per day; P = 0.01). The urinary calcium concentration was higher in the infants receiving furosemide than in& controls and a similar trend was observed in the urinary calcium/creatinine ratio, but& these variables did not differ between the study infants with and without nephrocalcinosis. Ultrasonic resolution of nephrocalcinosis was observed in 3 of the 5& infants at 12 months, but in the other 2 the condition still persisted at 24 months. Conclusions Long-term furosemide treatment in full-term infants with congestive heart failure entails a considerable risk of developing nephrocalcinosis. Renal ultrasonography is warranted in these patients within a few months after initiation of the treatment and in the case of nephrocalcinosis alteration of the diuretic regimen is to be considered.

Clinical characteristics and factors affecting growth in long-term survivors of cancer

We evaluated clinical characteristics and growth in 51 (24 males) long-term survivors of childhood cancer (median follow up 12.7 years). Patients were shorter, had a higher proportion of body fat and higher systolic blood pressure than their controls. The change in relative height during treatment was -0.83 standard deviation score (S.D.S.) in patients with cranial irradiation and -0.32 S.D.S. in patients without cranial irradiation; the figures after treatment were -0.56 and 0.20 S.D.S., respectively. Half (r2 = 0.50) of the variation in growth retardation during therapy could be explained by the cumulative doses of 6-mercaptopurine (6-MP) and vincristine and relative height at diagnosis. Cranial irradiation, increased relative height at diagnosis and young age at diagnosis were significant predictors of growth failure over the total observation period, explaining 43% of the variation. We conclude that long-term survivors of childhood cancer have impaired linear growth, increased body fat mass and elevated systolic blood pressure. Young children who are tall for their age at diagnosis and treated with cranial irradiation have the highest risk of impaired growth after the diagnosis. High doses of 6-MP seem to contribute significantly to growth retardation during therapy.

Axial radiography or CT in the measurement of patellofemoral malalignment indices in children and adolescents

The present study compares the repeatability of patellofemoral malalignment (PFM) indices obtained by 20 degree flexion axial radiography (AR) and computerized tomography (CT) with 0 degree and 20 degree flexion of the knees in children and adolescents. Thirty-one patients with a mean age of 14.2 years (range 8 to 19.2 years) suffering from PFM were examined using these two radiographic techniques. The lateral patellofemoral angle (LPA), the lateral patellar tilt (LPT), and the lateral patellar displacement (LPD) were measured by by two different investigators on different occasions, and the agreement of these indices between CT and AR was evaluated according to Bland and Altmans statistical method. LPT and LPD obtained by AR were more reliable and repeatable than those obtained by CT. The quadriceps muscle contraction exacerbates PFM indices significantly with the knees in full extension (P = 0.0001). LPT and LPD measured at 20 degrees AR show reliably the two pathological components (the patellar tilt and the lateral patellar displacement) of PFM which are necessary for diagnosis and treatment planning. CT with quadriceps contractions is better in qualitative screening of more subtle cases of PFM.