Serum growth hormone levels measured by radioimmunoassay and radioreceptor assay: a useful diagnostic tool in children with growth disorders?

Serum GH levels were measured by RIA and RRA in 133 subjects (19 healthy controls and 114 patients with various growth disturbances, aged 2.3-24.8 yr). Serum samples obtained from 147 stimulation tests representing a total of 1065 samples were analyzed by both methods, and the results compared. The data are expressed in absolute values and in RRA/RIA ratios. The area under the curve after a stimulation test (area GH) was calculated by planimetry. RIA was performed by the classical double antibody method using a polyclonal anti-serum. For the RRA, human cultured lymphocytes (IM-9 cells) were used, and 125I-labeled human GH was purified by high performance liquid chromatography. The same human GH standard was used in both assay systems. In control subjects a significant (P less than 0.0001) positive correlation was found at all ages between GH levels measured by RIA and RRA (r = 0.69 after insulin and r = 0.77 after glucagon). The RRA/RIA ratio (mean +/- SEM) for the peak GH level was 0.88 +/- 0.05, and the area under the GH curve was 0.85 +/- 0.05. The peak mean RRA/RIA ratios were significantly lower (P less than 0.05 and P = 0.03, respectively). No relationship was found with the absolute value of either peak or area GH. In patients with growth delay and Turner's syndrome, lower GH levels were found than in control subjects in both assay systems. The RRA/RIA ratios were also lower. In the other patients with some growth disorder, normal GH levels and ratios were found. In patients with renal failure, high levels of RIA-GH and RRA-GH were found, with a normal RRA/RIA ratio. In patients with documented pituitary GH deficiency, GH-releasing factor administration resulted in an increase in GH levels that was identical in both assays. The RRA/RIA ratio remained constant throughout the test. No correlation was found between the ratio and the absolute value of either RIA-GH or RRA-GH regardless of the stimulation test used. It is concluded that the presence of an abnormal GH molecule is extremely rare in patients with short stature. Thus, the presence of a bioinactive hormone is not a common cause of growth failure. During provocative testing some changes in the ratio may occur that do not appear after GH-releasing factor, further illustrating the different mechanisms involved in GH secretion.

Properties of thyroid-stimulating hormone and cortisol secretion by the human newborn on the day of birth.

Secretory activation of the thyroid and adrenal glands is a hallmark of the neonatal adaptation to extrauterine life. TSH and cortisol play key roles in these axes. The highest serum concentrations of TSH attained over the full span of human life are normally found shortly after birth. Serum cortisol is also known to be elevated in the immediate postnatal period. However, the dynamics of TSH and cortisol secretion have hitherto not been documented on the day of birth. To study the properties of neonatal TSH and cortisol secretion, we obtained arterial blood at regular intervals (every 20 min for 6 h) from nine polycythemic newborns (gestational age, 34-41 weeks) on the first and/or fourth days after birth during a therapeutic, standardized, isovolumetric, partial exchange transfusion. One premature infant had received betamethasone antenatally. The serum TSH level of an infant with congenital hyperthyroidism of transplacental origin was also measured at the postnatal age of 1 h. Deconvolution analysis of the profiles revealed that all infants displayed a combination of basal and pulsatile TSH release. Bursts of TSH secretion occurred at a median interval of 133 min. The median serum TSH half-life was 75 min. On the day of birth, basal TSH secretion and the amplitude of pulsatile TSH secretion were higher than 3 days later. Cortisol was secreted exclusively in a pulsatile fashion. Bursts of cortisol release occurred at a median interval of 69 min. The median serum cortisol half-life was 60 min. Cortisol secretion appeared to shift gradually from a high frequency, low amplitude pattern early on the first day toward a lower frequency, higher amplitude pattern 3 days later. TSH and cortisol secretion were low in the infant who received betamethasone prenatally. Serum TSH was undetectable in the infant with congenital hyperthyroidism. In conclusion, serum TSH concentrations in the human newborn appear to be elevated on the day of birth as a result of amplified basal and pulsatile TSH release, then fall rapidly through a mechanism that decreases the amplitude of TSH secretion and are affected by modulation of the fetal thyroid axis. From the day of birth onward, cortisol was found to be released in an exclusively pulsatile mode, with characteristics that appear to depend on postnatal age and prenatal glucocorticoid exposure.

Holzgreve-Wagner-Rehder syndrome: Potter sequence associated with persistent buccopharyngeal membrane. A second observation.

Here we present a second example of the syndrome first reported by Holzgreve et al. [1984] in this journal, i.e., Potter sequence with persistent buccopharyngeal membrane type II, postaxial polydactyly, cleft palate, cardiac anomalies, intestinal nonfixation, and intrauterine growth retardation. This specific complex MCA syndrome is not associated with a detectable chromosome abnormality.

Opitz C syndrome and pseudohypoaldosteronism.

The C syndrome of multiple congenital anomalies is described in a male infant with pseudohypoaldosteronism. The association of these 2 rare autosomal recessive conditions is discussed.

Alagille syndrome (arteriohepatic dysplasia) and del(20)(p11.2)

We report on a boy with Alagille syndrome. Chromosome analysis on a peripheral blood lymphocyte culture showed a de novo deletion of the short arm of chromosome 20 with a 46,XY,del(20)(p11.2) chromosome constitution. This is the second report of a del(20p) in a patient with Alagille syndrome. The possible localisation of this autosomal dominant syndrome on 20p is discussed.

Restrictive dermopathy with distinct morphological abnormalities.

A newborn child is described with the fetal hypokinesia sequence as a consequence of a restrictive dermopathy. Remarkable findings in this infant were neonatal teeth and survival till age 4 months. Ultrastructural examination of the skin showed thin epidermis and absence of elastic fibres.

Determination of enterokinase activity by measuring the disappearance of trypsinogen.

An electrophoretic technique for the determination of enterokinase activity is described. The natural substrate trypsinogen is hydrolysed in the presence of soybean trypsin inhibitor. Under the conditions of assay, neither the trypsin inhibitor nor the trypsin-trypsin inhibitor complex are detected. Enterokinase activity can be determined in biological materials such as duodenal aspirates without any interference from trypsin activity. A significant correlation exists between the present technique and a spectrophotometric technique by which the liberation of trypsin activity is used to determine enterokinase activity.

Sialic acid-deficient serum and cerebrospinal fluid transferrin in a newly recognized genetic syndrome.

Identical twin-sisters with evidence of a demyelinating disease showed multiple serum glycoprotein abnormalities. The association of a low serum iron level and a normal blood haemoglobin suggested an abnormality of transferrin too. This was confirmed by finding a sialic acid-deficiency of this glycoprotein in serum as well as in cerebrospinal fluid.

A new variant of glucosephosphate isomerase deficiency: GPI-Kortrijk.

A new case of glucosephosphate isomerase deficiency in a Belgian family is described. The activity of the enzyme was decreased to about 25-30% of the normal value. Characterization of the defect enzyme showed a decreased thermostability. Heating of the enzyme at 45 degrees C showed a loss of activity of 50% after 90 min. The pH-optimum and the KM-value for fructose 6-phosphate were normal. The electrophoretic pattern showed a faster migration. The variant described here differs from all known variants. Therefore we propose to give to this new variant the name GPI-Kortrijk.

Calcium and phosphorus retention in the preterm infant during total parenteral nutrition. A comparative randomised study between organic and inorganic phosphate as a source of phosphorus.

The preterm infant fed parenterally is prone to some demineralisation due in part to insufficient Calcium (Ca) and Phosphorus (P) retention. In an attempt to augment Ca and P retention, we prepared a standardised parenteral solution containing calcium gluconate and glucose-1-phosphate (Phocytan) as source of phosphorus, yielding a daily supply of 75 mg/kg Ca and 45 mg/kg P. 28 very low birthweight infants were randomly assigned to receive either this solution (high Ca P ; n = 15) or a conventional formulation containing calcium gluconate and potassium mono- and dibasic phosphate delivering 42 mg/kg Ca and 36 mg/kg P daily (low Ca P ; n = 13). In the high Ca P daily retention was respectively 80% and 99% for Ca and P whereas in the low Ca P group, retention was 70% and 82%. Serum parathormone levels were significantly lower in the high Ca P group. We conclude that parenteral nutrition with a new high Ca P supplement results in an augmented Ca and P retention in very low birthweight infants. This may help to prevent neonatal bone demineralization.

Standard two-compartment formulation for total parenteral nutrition in the neonatal intensive care unit: A fluid tolerance based system.

The nutrient requirements of most (pre) term newborns receiving intensive care appear to be relatively fixed. The range of optimal fluid load however, is perceived as being quite narrow and highly variable in time. We designed four amino acid-dextrose mixtures for a standardized neonatal parenteral nutrition, delivering a fixed amount of nutrients in four dilutions with water and corresponding to a fluid load of 90, 110, 130 or 170 ml/kg per day. The addition of a lipid emulsion completes the TPN. In a pilot study, we followed the weight of 30 very low birthweight infants on this parenteral nutrition. After a stabilisation period, the weight gain was found to be similar to the normal fetal weight accretion in utero. We have now infused these solutions in to more than 1000 infants, without significant complications. These formulations proved to have substantial advantages compared to the individualized prescription in terms of availability, safety and time- and cost-effectiveness.

Treatment of Pseudomonas lung infection in cystic fibrosis with piperacillin plus tobramycin versus ceftazidime monotherapy: preliminary communication.

Twenty-one patients with cystic fibrosis and chronic Pseudomonas lung infection were treated at random with ceftazidime, 150 mg/kg/day, or with piperacillin, 300 mg/kg/day, and tobramycin, 10 and more mg/kg/day for 14 days. On admission and at discharge, body weight, erythrocyte sedimentation rate, white blood cell count, and differential were determined. Pulmonary function analysis and chest X-rays were also obtained on both occasions as was sputum bacteriology. After hospitalization, the patients were followed in the outpatient department for 14-26 months. Both treatments were associated with significant improvement in most of the parameters that were studied, but neither treatment was superior.

Pulmonary mechanics during respiratory distress syndrome in the prediction of outcome and differentiation of mild and severe bronchopulmonary dysplasia.

Pulmonary mechanics was prospectively and longitudinally studied in a cohort of 58 infants who suffered from respiratory distress syndrome. The aim was to determine if early compliance and resistance measurements had additional value to simple clinical variables in predicting poor outcome ie nonsurvival or severe bronchopulmonary dysplasia (BPD) at 28 days. Second, we wanted to determine whether and when the recently described type 1 (mild) BPD and type 2 (severe) BPD could be differentiated by means of lung function tests. In a logistic model, neither lung compliance nor pulmonary resistance at days 1 and 4 of life were selected as predictive variables. On the other hand, gestational age and the ventilatory index no. 1 (ventilator frequency x maximal inspiratory pressure) on day 3 were the best early predictors of poor outcome. Type 2 BPD was characterized by a lower lung compliance and a higher pulmonary resistance than type 1 BPD, although the differences were only significant at 28 days. In conclusion, pulmonary function tests were not helpful in the early prediction of poor outcome at 28 days. They might, however, be of value in the follow-up of BPD patients after 28 days.

Gastrointestinal manifestations in cystic fibrosis.

CFTR, or cystic fibrosis transmembrane conductance regulator, the gene product that is defective in cystic fibrosis, is present in the apical membrane of the epithelial cells from the stomach to the colon. In the foregut, the clinical manifestations are not directly related to the primary defect of the CFTR chloride channel. The most troublesome complaints and symptoms originate from the oesophagus as peptic oesophagitis or oesophageal varices. In the small intestinal wall, the clinical expression of CF depends largely on the decreased secretion of fluid and chloride ions, the increased permeability of the paracellular space between adjacent enterocytes and the sticky mucous cover over the enterocytes. As a rule, the brush border enzyme activities are normal and there is some enhanced active transport as shown for glucose and alanine. The results of continuous enteral feeding of CF patients clearly show that the small intestinal mucosa, in the daily situation, is not functioning at maximal capacity. Although CFTR expression in the colon is lower, the large intestine may be the site of several serious complications such as rectal prolapse, meconium ileus equivalent, intussusception, volvulus and silent appendicitis. In recent years colonic strictures, after the use of high-dose pancreatic enzymes, are being increasingly reported; the condition has recently been called CF fibrosing colonopathy. The CF gastrointestinal content itself differs mainly from the normal condition by the lower acidity in the foregut and the accretion of mucins and proteins, eventually resulting in intestinal obstruction, in the ileum and colon. Better understanding of the CF gastrointestinal phenotype may contribute to improvement of the overall wellbeing of these patients.

Feeding behaviour in preterm neonates.

In 100 bottle-fed preterm infants feeding efficiency was studied by quantifying the volume of milk intake per minute and the number of teat insertions per 10 ml of milk intake. These variables were related to gestational age and to number of weeks of feeding experience. Feeding efficiency was greater in infants above 34 weeks gestational age than in those below this age. There was a significant correlation between feeding efficiency and the duration of feeding experience at most gestational ages between 32 and 37 weeks. A characteristic adducted and flexed arm posture was observed during feeding: it changed along with feeding experience. A neonatal feeding score was devised that allowed the quantification of the early oral feeding behavior. The feeding score correlated well with some aspects of perinatal assessment, with some aspects of the neonatal neurological evaluation and with developmental assessment at 7 months of age. These findings are a stimulus to continue our study into the relationships between feeding behaviour and other aspects of early development, especially of neurological development.

Thrombosis of the right umbilical artery, presumably related to the shortness of the umbilical cord: an unusual cause of fetal distress.

This case report concerns a late pregnancy complication, clinically apparent as severe variable decelerations in the first stage of labor. Emergency cesarean section delivered a mildly asphyxiated full-term newborn infant. Examination of the umbilical cord revealed a thrombus of the right umbilical artery, near the fetal side, confirmed by histological examination. The total length of the umbilical cord, only 30 cm, was below the limit necessary for uncomplicated delivery of the fetus near term. Transient stretching during fetal descent is thought to be responsible for constriction of the umbilical arteries, blood flow sludging and thrombosis. Although only a few cases have been reported, thrombosis of the umbilical vessels has to be considered whenever the fetal heart rate pattern shows unexplained variable decelerations.

Antenatal ultrasound diagnosis of fetal malformations: possibilities, limitations and dilemmas.

The antenatal ultrasound diagnosis of fetal abnormalities in 150 fetuses over the period 1975-early 1983 is reported. The perinatal outcome of the whole series has been assessed. The most frequently encountered malformations involved the central nervous system (34.9%), the nephro-urological system (17.2%), and the gastro-intestinal tract, abdominal wall and diaphragm (17.1%). Neonatal findings in incompletely explained polyhydramnions, fetal hydrops, and severe intrauterine growth retardation are also commented upon. Numerical chromosomal abnormalities were present in at least 13.3% of the malformed fetuses. The accuracy of the antenatal ultrasound diagnosis in a defined subgroup with congenital malformations resulting in perinatal death was analysed: in 76.9% one (or more) malformations were correctly diagnosed or relevant information was obtained. Comment is made on the obstetrical management and its inherent dilemmas, with appropriate references to the literature. Antenatal ultrasound, together with complementary techniques, can reach an acceptable level of accuracy, but associated anomalies may be missed. Groups for which there are different prognoses can be assessed, and serve as a guideline in perinatal management. Ethical attitudes, psychological aspects, and the possible promises of fetal treatment are briefly discussed.

Intractable asphyxia at birth: analysis of the underlying conditions.

A review of clinical and pathological data on 10,000 consecutive deliveries revealed that the incidence of unexpected and intractable asphyxia at birth despite adequate resuscitation was 0.24%. Lung hypoplasia appeared to be the underlying non-viable condition in 22 out of 24 infants. Attention is drawn to congenital neuromuscular disorders which were found to be the cause of lung hypoplasia in at least 4 out of 22 infants. Some helpful hints for diagnosis are given which may contribute to the final decision making.

Prenatal indomethacin toxicity in one member of monozygous twins; a case report.

A mother, treated with indomethacin because of premature labour, delivered a pair of monozygous twins at a gestational age of 33 weeks. Because of foetal transfusion syndrome, the first twin was polycythaemic and the second anaemic. The latter was also hydropic, suffered from anuria requiring peritoneal dialysis, and showed signs of severe pulmonary hypertension, probably as a consequence of intra-uterine constriction of the ductus arteriosus. The possible interaction between foetal transfusion syndrome, anuria, premature constriction of the ductus arteriosus and the prenatal administration of indomethacin is discussed. In general, indomethacin should cautiously be used as a tocolytic agent.

Subcapsular hemorrhage of the liver and hemoperitoneum in premature infants: report of 4 cases.

The occurrence of a subcapsular hemorrhage of the liver (SHL) with associated hemoperitoneum in four very low birth weight infants (VLBW) is described. We conclude from the analysis of these four cases and a review of the literature, that the pathogenesis of SHL is multifactorial, which emphasizes the extreme vulnerability of these infants.