Roger Eeckels

Familial psychomotor retardation with markedly fluctuating serum prolactin, FSH and GH levels, partial TBG-deficiency, increased serum arylsulphatase A and increased CSF protein: a new syndrome?: 90

Identical twin-sisters (born at 36 wks; birthweight 2.2 and 3.0 kg) presented at 2 years of age with marked psychomotor retardation and bone-age of 1 year. Physical growth and phenotype were normal. Repeated investigations revealed: markedly fluctuating basal serum prolactin (778-5652 μU/ml; nl < 800), FSH (17-55 mIU/ml; nl < 10) and GH (2-144 ng/ml; nl < 10), but normal LH; low TBG (1.1 and 1.2 mg/dl; nl 1.6-2.4) also present in the father, with otherwise normal thyroid function including TRH test, arylsulphatase A moderately increased in serum (mean 293 and 272 nmol/ml; nl 30-130) but not in leukocytes, without increase of other lysosomal enzymes, and increasing CSF protein. Normal results were found for GH response to i.m. glucagon, urinary excretion of 17-keto and 17-hydroxysteroids, at funduscopy and for lymphocyte karyotype (Giemsa banding), buffy coat of blood leukocytes and electronmicroscopy of conjunctiva. Sella tursica was normal on x-ray. Cortical and cerebellar hypotrophy was evident on CAT-scan. Electromyography was normal but nerve conduction velocity was delayed (30-31 m/sec; nl 50 ± 1). A nerve and muscle biopsy is planned. At this stage we have no satisfactory explanation for these unusual findings.

A new chromosome anomaly in acute lymphoblastic leukemia (ALL)

SummaryA new chromosome anomaly in acute lymphoblastic leukemia (ALL) is reported. Three, possibly four, patients showed an identical karyotype anomaly, characterized by a (4;11)(q13;q22) reciprocal translocation. This anomaly has not so far been found in lymphoproliferative disorders other than ALL. Two of the patients had congenital leukemia, but the anomaly described appears to be more characteristic of ALL than of congenital leukemia, and may help the clinician in establishing the diagnosis of ALL.

Data cleaning: detecting, diagnosing, and editing data abnormalities.

In this policy forum the authors argue that data cleaning is an essential part of the research process, and should be incorporated into study design.

Respiratory syncytial virus bronchiolitis: A double-blind dexamethasone efficacy study

The efficacy of dexamethasone therapy for primary respiratory syncytial virus bronchiolitis was studied in a double-blind placebo design in 29 previously healthy infants (median age, 194 days). No significant differences were found between the groups in evolution of respiratory rate, oxygen saturation, clinical score, or pulmonary function tests on day 3.

Influence of nutritional status on child mortality in rural Zaire

Although the association between nutritional status and mortality risk is obvious for extreme malnutrition, the issue is not so clear for mild to moderate undernutrition. We have investigated this association in children of 0-5 years in the rural area of Bwamanda, Zaire, where an integrated development project, with good medical facilities, has operated for 20 years. A random cluster sample of 5167 children was taken; newborn infants and immigrants were included at six quarterly survey rounds from October, 1989, until February, 1991. All surveys included clinical and anthropometric assessment of nutritional status. Deaths were recorded up to April, 1992; there were 246 deaths. Marasmus, kwashiorkor, and other causes of death were defined by the verbal autopsy method and checked against medical records kept at the central hospital and the peripheral dispensaries. As expected, we found an increased risk of death in severe malnutrition. When deaths directly attributed to marasmus or kwashiorkor were excluded, mild to moderate stunting or wasting were not associated with higher mortality in the short term (within 3 months of the previous study round) or in the long term (from 3-30 months after study entry). The commonest causes of death were malaria and anaemia. Extreme marasmus and kwashiorkor caused 16% of deaths, and are important causes of death even in this favoured area with an integrated development project. Nutritional interventions should be targeted more selectively so that children with moderate malnutrition can be protected from progression to marasmus or kwashiorkor.

Length of gestation and birthweight in dizygotic twins

Despite the longer gestation of girls, their birthweight is less than that of boys. Because unlike-sex twins provide a natural situation in which to investigate the influence of sex on gestation, we compared birthweight and gestation of 1929 same-sex and unlike-sex dizygotic pairs. Length of gestation in unlike-sex pairs was similar to that of female same-sex pairs, and significantly (0.4 weeks; p=0.02) longer than that of male same-sex pairs. Birthweight of girls from unlike-sex pairs was similar to that of girls from same-sex pairs, but boys from unlike-sex pairs weighed 78 g more than boys from same-sex pairs (p=0.001). These data show that in unlike-sex pairs it is the girl that prolongs gestation for her brother, resulting in a higher birthweight than that of same-sex boys.

Fetal Growth: Boys before Girls

At term birth, boys are heavier than girls. This difference is thought to be generated in part by androgen action; its time course has not been deciphered. Androgen action may not only increase weight gain, but may also alter its time course. We have tested this hypothesis by examining the difference in gestational age of 281,894 boys and girls with weights between 500–4,749 g. The age at which children are born with a given weight was found to depend on gender: boys were consistently younger than girls (p < 0.001), the age difference being most pronounced in the lower birth weight classes. Thus, the gender difference in fetal growth appears to be rather pronounced before the third trimester and relatively less marked towards term. In conclusion, the male conceptus seems to grow not only more, but also earlier than the female. Hence, some critical time windows of development may be slightly different in boys and girls, and this phenomenon may be one of the bases for gender differences in the sensitivity to fetal programming.

Congenital folate malabsorption

A Turkish girl presented with a history of fever, diarrhoea, convulsions, recurrent infections and failure to thrive from the age of 5 months. Megaloblastic anaemia was present and profound folate deficiency was evidenced in plasma and in CSF. Treatment with oral folic acid cured the anaemia, diarrhoea and infections but failed to prevent convulsions and the appearance of mental retardation and cerebral calcifications. Loading tests with folic acid and its derivatives led to the conclusion that the folate deficiency was caused by a defect in folate transport both across the gut and the blood-brain barrier. Low plasma concentrations of methionine prompted a therapeutic trial with methionine associated with vitamin B12 and folic acid that spectacularly improved the convulsions.

The glucagon stimulation test: Effect on plasmagrowth hormone and on immunoreactive insulin, cortisol, and glucose in children

Plasma growth hormone (GH), immunoreactive insulin (IRI), cortisol, and glucose were studied before andafter the intramuscular injection of glucagon (0.1 mg. per kilogram) in 80 prepubertal children. Glucose, IRI, GH, and cortisol values rose after the injection of glucagon in normal children. Peak levels were observed at 30 minutes for glucose and IR1, at 120 minutes for GH, and at 180 minutes for cortisol. Blunted responses of GH were observed in some patients with hypothyroidism or celiac disease. Hypopituitary patients had a normal response of glucose and of IR1 but not of plasma GH; plasma cortisol levels incresed following glucagon administration in those patients who otherwise had normal corticotropin reserve. In 32 of 38 children without pituitary disease, GH responses were higher to glucagon than they were to induced hypoglycemia. It is concluded that the glucagon stimulation test is a safe, easy, and reliable test to study pituitary GH reserve in children.

Subcutaneous adipose tissue and lipids in blood in growth hormone deficiency before and after treatment with human growth hormone.

Extract: This study was undertaken to evaluate adipose cell size and number and subcutaneous fat and blood lipids composition in hypopituitary patients before and daring treatment with human growth hormone (HGH). The investigations were performed in 14 prepubertal children 6–17 11/12 years of age, with idiopathic hypopituitarism. Human growth hormone was administered successfully to 6 of these 14 patients for at least 1 year.Before HGH treatment there was a significant reduction of adipose tissue cell number according to chronologic age and to skeletal age. The average adipose cell size was significantly larger than normal. A significant correlation between subcutaneous adipose cell mean weight and tricipital and subscapular skin fold thickness, similar to that observed in normal children, was observed. The distribution of fatty acids in the subcutaneous fat and in the blood lipid composition was normal.During the 1st and 2nd year of HGH treatment, the total number of adipose cells increased rapidly. There was also a highly significant reduction of the average adipose cell size after the 1st year. A significant reduction of the fatty acids unsaturated fraction was observed after the 1st year without further changes after the 2nd year of treatment. The blood lipid composition did not change significantly after either 1 or 2 years of HGH treatment.Speculation: The striking increase in total number of adipose cells observed during HGH administration in hypopituitary patients tends to prove that the adipose tissue organogenesis is not limited to a finite period ending after the 1st year of life.The modifications in composition of adipose tissue triglycerides induced by long term treatment with HGH would mean that the several components of the fatty acid pool are differentially liberated.