Booster vaccination and 1-year follow-up of 4–8-year-old children with a reduced-antigen-content dTpa-IPV vaccine

Reduced-antigen-content pertussis vaccines designed initially for booster vaccination of adolescents and adults can also be used to vaccinate pre-school age children. Combination vaccines, which reduce the number of administered injections, combine multiple antigens including inactivated poliovirus (IPV), which is recommended in this age group in some countries. This randomised, controlled study compared a combined diphtheria-tetanus-acellular pertussis-inactivated polio-containing booster vaccine, dTpa-IPV (Boostrix™ Polio, n = 822), to separately administered dTpa (Boostrix™) and IPV (IPV Mérieux™, n = 136) in 4–8-year-old children who had previously received four doses of DTPa. Additional serological assessment was performed 1 year after the booster dose. One month after vaccination, seroprotection/vaccine response rates were similar for both groups. At least 99.9% of the subjects had protective antibodies against diphtheria, tetanus and polio, and at least 90.1% had a vaccine response to pertussis antigens after dTpa-IPV. Reactogenicity of dTpa-IPV was comparable to dTpa + IPV. Fever and grade 3 loss of appetite occurred more commonly after dTpa-IPV, whereas swelling and grade 3 pain occurred more frequently after separately administered dTpa + IPV (P < 0.05 for all). However, 95% CIs overlapped in all cases. Large swelling reactions after dTpa-IPV occurred less commonly than have been reported after a fifth dose of DTPa. One year after the booster, 98.6% of the subjects tested continued to have protective antibodies against diphtheria, tetanus and polio, and at least 81.2% were seropositive for pertussis components. The reduced-antigen-content dTpa-IPV vaccine was immunogenic, well tolerated and safe in pre-school age children. It provides immunity against four diseases in a single injection, with the potential reactogenicity benefit of a reduced-antigen dose. Source of financial support: GlaxoSmithKline Biologicals, Rixensart, Belgium.     

In vivo recording of the glucose- and disaccharide-evoked potentials from the human jejunum in infancy

Using a pair of Ag–AgCl electrodes, the sugarevoked potentials (PD) were recorded from the jejunum of human infants in vivo by infusion of Ringer's solution containing glucose or a disaccharide through an intestinal tube. One of Ag–AgCl electrodes was fixed inside the tip of the intestinal tube and the other was placed in the hypodermis. The sugars tested were d-glucose, lactose, maltose and d-xylose. In the case of d-glucose, a simple Michaelis-Menten relation was seen between the amplitude of PD and concentration, and the values of Kt and PD _max for the control infants were 14.4±2.8 mM and 11.4±2.3 mV, respectively (mean±SD, n=8). Disaccharides gave a similar relationship over a wide range of concentrations except for very high concentrations, where Lineweaver-Burk plots of the data deviated slightly upward from the linear plot obtained at lower concentrations. Extrapolation of the linear segment of the plots for the disaccharide-evoked potential crossed the ordinate at the same point as the line for glucose-induced potentials. The mean magnitude of PD _max for glucose in infants with intractable diarrhea was significantly lower (about 56%) than that in the control infants, but the Kt values were not significantly different. The ratios of PD induced by 100 mM maltose to PD induced by 100 mM glucose in the patients with intractable diarrhea were not different from those in controls, while the ratios of PD induced by 100 mM lactose to PD induced by 100 mM glucose were decreased. At the recovery stage of intractable diarrhea, the magnitude of PD _max for glucose and the ratio of PD induced by 100 mM lactose to PD induced by 100 mM glucose were increased to the control level.No problems were encountered in the present study and the method may be useful in examination of digestion and absorption of sugars in infants.     

Biofeedback in spina bifida

The use of anorectal manometry as a biofeedback technique in the treatment of constipation and fecal incontinence in patients with spina bifida is described. The technique was applied in ten incontinent spina bifida patients aged 3 to 16 years. To evaluate our results we used the concept of controlled incontinence, i.e., voluntary defecation at set times, with the patient remaining clean the rest of the time as a base. A total of 80% satisfactory results was obtained. Offprint requests to: J. M. Gil-Vernet     

Fetal bile acids in congenital biliary atresia —production in the liver and clinical significance

The 1-hydroxy bile acids have been said to be fetal bile acids. These bile acids were evaluated in eight patients with congenital biliary atresia (CBA) using gas chromatography-mass spectrometry. At the time of operation 1,3,7,12-tetrahydroxy-5-cholan-24-oic acid (CA-1-ol) and 1,3,7-trihydroxy-5-cholan-24-oic acid (CDCA-1-ol) were 0.46 ± 34 g/ml and 0.72 ± 0.45 g/ml, respectively, which was significantly higher than in the control group. The percentage CA-1-ol of total bile acids showed a tendency to decrease as age advanced. The grade of hepatic fibrosis ranged from F₂ to F₃ and the values and percentages of CA-1-ol and CDCA-1-ol were relatively higher in F₂ than F₃ patients. The percentage of total bile acids gradually increased in patients without sufficient bile flow but fell sharply after Kasai's procedure in the patients with sufficient bile flow. It appears that fetal bile acids are produced in the livers of CBA patients in the same way as in fetal liver, and that production continues in patients without good bile secretion even after Kasai's procedure. These results suggest that these hydroxylases are reactivated in CBA patients.     

Elevated CSF cyclic AMP concentrations in patients with inflammatory diseases of cerebral and extracerebral origin

Cyclic 3–5 adenosine monophosphate (c-AMP) concentrations were measured in cerebrospinal fluid (CSF) from children admitted to the hospital because of suspected meningitis. c-AMP levels were found to be markedly elevated (P<0.001) during the acute phase of most of the purulent meningitis patients, as well as in patients with acute aseptic meningitis. In convalescent patients after purulent meningitis mean c-AMP concentrations remained elevated (P<0.01) beyond the normalization of the routine parameters in CSF. In addition, a variety of febrile inflammatory conditions of extracerebral origin produced elevations (P<0.001) of c-AMP although CSF by routine criteria was normal. The results suggest that c-AMP might serve as a sensitive indicator of transient cellular metabolic disturbance in the brain.Abbreviations CSF cerebrospinal fluid - c-AMP cyclic 3–5 adenosine monophosphate - WCC white cell count     

Recurrent,familial Reye-like syndrome with a new complex amino and organic aciduria

Five of 13 siblings from a Jewish-Ashkenazi family suffered from recurrent Reye-like episodes. During attacks, these patients excreted -keto-adipic, -hydroxy-adipic, and -aminoadipic acids, branched-chain keto acids and saccharopine in addition, to lactic, pyruvic, and dicarboxylic acids characteristic of Reye syndrome. The serum concentrations of citrulline and -aminoadipic acid were elevated and carnitine was at the upper limit of the normal range. Serum acetoacetate level was 4–5 times the -hydroxybutyrate level, but the pyruvate/lactate ratio was normal. Notably, plasma ketone bodies were lower than expected from the degree of catabolism. When the patients were symptom-free, no abnormal amino or organic acids in serum or urine were detected. These findings might be interpreted as a functional impairment at three different biochemical sites: fatty acid -oxidation, dehydrogenase complexes of the pyruvic, -ketoglutaric, -ketoadipic, and branched-chain keto acids, and pyruvate carboxylase. We suggest that in this hereditary disorder a toxic substance, exogenously or endogenously derived, interfered at multiple sites in different metabolic pathways.     

The unreliability of mean corpuscular volume and mean cellular hemoglobin determinations in the diagnosis of α-thalassemia in newborn infants

Mean corpuscular volume (MCV) and mean cellular hemoglobin (MCH) were determined by means of a Hemalog 8/90 electronic counter in 51 full-term newborn infants with -thalassemia-2 and 15 with -thalassemia-1, as well as in 150 normal newborn infants. The mean MCV and MCH values were 92 fl±06 and 33.26 pg±2.22 in the normal newborn infants, 82 fl±07 and 29.40 pg±2.60 in the -thalassemia-2 subjects, and 73 fl±06 and 26.07 pg±2.05 in the -thalassemia-1 subjects. Four of the 150 normal newborn infants had MCV's<79 fl and MCH's<29.00 pg whereas 5 of the -thalassemic subjects had MCV's>90 fl and MCH's>32.00 pg. We conclude that MCV and MCH determinations are unreliable in the diagnosis of -thalassemia in the neonatal period.     

Veränderungen von Produktion und Metabolismus des Cortisol bei gesunden Säuglingen nach dreitägiger Depot-ACTH-Gabe

Zusammenfassung Es wird über die Harnausscheidung von Pregnan-3-17-20-triol und Pregnan-3-20-diol nach einer dreitägigen Belastung mit Depot-ACTH bei gesunden Säuglingen berichtet.Die Basalmittelwerte liegen für Pregnantriol zwischen 33 und 37 g/d, für Pregnandiol zwischen 70 und 81 g/d. Nach ACTH kommt es zu einer Zunahme der Ausscheidungsgröße beider Substanzen, wobei sich das Verhältnis für Pregnantriol zu Pregnandiol gegenüber den Basalwerten umkehrt.Diese Umkehrung wird einerseits als Ausdruck einer intensiven Ausnutzung der für die beiden letzten Stufen der Cortisolsynthese maßgeblichen Hydroxylasen aufgefaßt, andererseits auf Grund der deutlichen Zunahme der Pregnantriolausscheidung eine funktionelle Limitierung der C-11-und C-21-Hydroxylase zur Diskussion gestellt.Die gegenüber der des Pregnantriol niedrige Pregnandiolausscheidung ergibt einen Hinweis, daß möglicherweise die Limitierung der enzymatischen Aktivität bei der Differenzierung der einzelnen Corticosteroide im Laufe der Umwandlungen in Richtung Endprodukt zunimmt.

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Summary In this paper we report about the urinary excretion of Pregnan-3-17-20-triol and Pregnan-3-20-diol in infants between 4 and 8 months after a three-day load-test with ACTH-depot.The basal mean-values are between 33 to 37 g/die of Pregnantriol and between 70 to 81 g/die of Pregnandiol. After ACTH-load there is an increase of the excretion of both substances whereas the ratio of Pregnantriol and Pregnandiol gets reciprocal. We consider this beeing a sign of an intensive utilization of the hydroxylating enzymes involved in the two last steps of cortisol synthesis. On the other hand it is possible that there is a functional limit in the activity of C-11-and C-21-hydroxylating enzymes regarding the clear increase of Pregnantriolexcretion.The relatively low values of Pregnandiol opposite to these of Pregnantriol may refer to the possibility that the limitation of the enzyme activities increases in way of performing the different corticosteroids.

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Die Arbeit wurde mit Unterstützung durch die Deutsche Forschungsgemeinschaft durchgeführt.     

15β-Hydroxylated steroids may be diagnostically misleading in confirming congenital adrenal hyperplasia suspected by a newborn screening programme

In a Swiss screening programme for detection of congenital adrenal hyperplasia (CAH), 27 of over 120,000 newborns examined from 1992 to 1994 were further studied because of persistingly high 17 hydroxyprogesterone (17OHP). Out of 27, 11 were later confirmed to have CAH by specific gas chromatography of urinary steroids and ACTH test at age 3–4 months. Of 27, 11 were born at term (7 confirmed 21-hydroxylase deficiency, one 11-hydroxylase deficiency). Out of 27, 16 were preterm newborns. Of them, only 2 were confirmed to have CAH (one 21-, one 11-hydroxylase deficiency). In 3 cases with high 17OHP, but later not confirmed CAH, what appeared to be a pregnanetriolone peak in the gas chromatograms was shown to be 3, 15, 17-pregnenetriol. This compound may be misleading in confirming the diagnosis of CAH. 15-Hydroxylated compounds occur in fetuses, neonates, and amniotic fluid. Since human tissues do not have l5-hydroxylating capacity, their origin is unclear. However, since some bacteria (Bacillus megatherium) and mycelial fungi (fusaria) are known to hydroxylate steroids in position 15, it is likely that this compound is formed by micro-organisms in the enterohepatic circulation of newborns or their mothers.Presented in part as an invited lecture at the symposium on congenital adrenal hyperplasia in honour of Claude Migeon, Baltimore MD, June 11.–13., 1995, and at the 34th Annual Meeting of the European Society for Paediatric Endocrinology, Edinburgh UK, June 25–28, 1995     

Undescended testes: early versus late maldescent

A review of 468 orchidopexies was undertaken to ascertain the importance of a complete hernial sac extending to or beyond the testis. A hernial sac was present in 84% (171/202) of testes in patients under 5 years of age, in contrast to 23% (61/266) in patients over 5 years. It seems reasonable to presume that the failure of the hernial sac to close is secondary to failure of normal descent, which in turn is due to antenatal factors and may be classified as early maldescent. In the older age group maldescent is due to failure of the last stage of descent, which should occur in the 5- to 10-year prepubertal age period (late maldescent, or the ascending testis). The cause of late maldescent is not due to a short processus, as this increases in length with age (approximately 0.5 cm/year), unless the persistence of the processus itself is the cause. A classification of early or late maldescent is suggested.     

Sisters with α-mannosidosis and systemic lupus erythematosus

Alpha-mannosidosis is an autosomal recessive disorder caused by deficiency of lysosomal -mannosidase (LAMAN). Here, we report two sisters with -mannosidosis who developed systemic lupus erythematosus (SLE). The sisters were both homozygous for a one bp deletion within the LAMAN gene resulting in a truncated gene product. The coincidence of -mannosidosis and SLE are discussed with regard to both clinical and molecular findings. Conclusion:-mannnosidosis may contribute to the onset of systemic lupus erythematosus in predisposed patients.Abbreviations ACR American College of Rheumatology - LAMAN lysosomal -mannosidase - SLE systemic lupus erythematosus     

The umbilicus in gastroschisis: aesthetic considerations

Preservation of the umbilical cord attachment (UCA) in gastroschisis (GS) is still not routine practice. In a prospective series of 36 children with GS, it was always possible to preserve the UCA, even in those undergoing a temporary silo and delayed closure. Reconstruction by umbilical cord capping left no additional scar and achieved a normal abdominal wall. Mild cellulitis in 3 infants resolved on antibiotics, and an initial umbilical weakness in 7 did not require additional surgery. We conclude that preservation of the UCA should be an integral part of surgical technique for all infants with GS. Reconstruction by umbilical cord capping alone achieves an unscarred abdominal wall with an umbilicus of normal shape and position.     

Adrenoceptors and the lung: their role in health and disease

- and -Adrenoceptors have each been divided into two subgroups (₁, ₂, ₁ and ₂). The basic mechanisms underlying the adrenoceptor/effector coupling are complex and vary for the -, but not for the -subpopulations. Adrenoceptors of the bronchi and the lung show a special pattern of distribution and response, ensuring that the airway system works as a functionary unit. Dysfunctions of adrenoceptormediated effects have been suggested to contribute to some important paediatric disorders such as hyaline membrane syndrome, wet lung, bronchial asthma, cystic fibrosis, and pertussis. Drugs which act on the adrenergic system influence some of these disorders directly. Further studies applying modern techniques to receptor research are needed in order to clarify the basic mechanisms involved in receptor-mediated lung disorders and the activity of drugs in lung tissue.Abbreviations AC adenylate cyclase - ADP adenosine diphosphate - -R -adrenoceptor - cAMP cyclic adenosine monophosphate - CF cystic fibrosis - GDP guanosine diphosphate - GTP guanosine triphosphate - IAP islet activating protein     

Severe combined immunodeficiency caused by a splicing abnormality of the <Emphasis Type="Italic"> CD3δ </Emphasis>gene

CD3 deficiency is a recently identified rare form of severe combined immunodeficiency. We analysed the CD3 gene in a Japanese family with severe combined immunodeficiency. The patients lacked T-cells with normal numbers of B-cells and natural killer cells in peripheral blood. We found a novel homozygous mutation in the splicing acceptor site of intron 2 (IVS2–2AG) in these patients. Analysis of patients mononuclear cells revealed the CD3 splicing abnormality. Chest X-ray films and computed tomography revealed small sized thymuses in these patients. Conclusion:The CD3 gene should be analysed in patients with severe combined immunodeficiency lacking T-cells with normal B- and natural killer cells irrespective of the thymus size.     

Final height and pubertal development in 55 children with idiopathic growth hormone deficiency,treated for between 2 and 15 years with human growth hormone

Sixty patients with the diagnosis of idiopathic growth hormone deficiency have been followed till final height was reached, after hGH treatment lasting between 2 and 15 (average 5.4) years. Twenty-six had total and 13 partial isolated growth hormone deficiency (IGHD); 10 had GHD plus gonadotrophin deficiency (GnD); six had multiple pituitary hormone deficiency (MPHD) and five, labelled transient prepubertal GHD, had normal responses in the insulin tolerance test when retested after the end of treatment.The final height of the patients with IGHD averaged 2.3 SD below the population mean, or 2.0SD below their midparent mean. Half the boys, but only 15% of the girls, ended above the population 3rd centile. There was no difference in final height between those with total and partial deficiency nor between patients treated prepubertally and those in whom treatment started in early puberty. In the 39 patients with IGHD the correlation of final height with midparent height was 0.72, a figure identical to that occurring in the normal population. Though final height was chiefly influenced by parental height, it was also affected by the degree of smallness when treatment began being lowered by an average of 2.5 cm for every SD that the patient's height at beginning of treatment lay below the average of all IGHD children, parents' heights being allowed for.Since untreated patients end at about 6 SD below the mean, treatment during the age span represented in these patients recovered 4SD, but failed to recover the remainder. The lost 2 SD may be due to the late start of treatment (averaging 11 years of age even in our prepubertal patients). Our findings emphasise the importance of early diagnosis, so that future patients never drop to 4 or 5 SD below mean height for age, but only to 2 or 3.Patients with IGHD plus GnD had final heights averaging 1.5 SD below the population mean and those with MPHD 1.0 SD below. This was entirely due to their developing longer legs than the patients with IGHD, the final sitting heights being the same. The long legs were due to treatment with sex steroids being started relatively late. Patients with IGHD who entered puberty spontaneously did so late in time and in the boys pubertal development was normal. In the girls there was a disturbance in the normal relationship of pubertal events and in two menarche never occurred.     

Wilms' tumor producing neuron-specific enolase

A female child with a Wilms' tumor producing neuron-specific enolase (NSE) is presented. The tumor was stage II, with favorable histology, and contained a linear calcification. The NSE was probably composed mostly of enzyme and produced by rhabdomyocyte-like cells in the tumor. Correspondence to: A. Toki     

Pneumothorax complicating bronchiolitis in an infant

Pneumothorax is an uncommon complication of bronchiolitis. This case illustrates an unusual pattern of atelectasis of the right lung with pleural air surrounding the right upper lobe and the remainder of the lung expanded. It is thought that the hyperinflated lung is unable to collapse as a result of the ball valve effect of air trapping.     

Silent carrier β-thalassaemia due to a severe β-globin mutation interacting with other genetic elements

Beta-thalassaemia is caused by the presence of two mutated -globin genes, one inherited from each parent. We describe two families in which the diagnosis of -thalassaemia intermedia was delayed because one of the parents, an obligatory heterozygote, had normal haematological parameters (silent carrier -thalassaemia). DNA analysis revealed that these silent carriers were heterozygous for a point mutation in the polyadenylation signal (AATAAA-AATAAG). This defect is known to cause a moderately severe -thalassaemia phenotype. In one case, concurrent deletional -thalassaemia was found in the silent carrier, which may have contributed to the mild phenotype. The increasing availability of DNA analysis should allow prompt diagnosis of such cases. Silent carrier -thalassaemia presents a diagnostic challenge to the clinician who evaluates children with anaemia.     

Familiärer mangel und α 1

Zusammenfassung Es wird über zwei Kinder aus zwei Familien mit Mangel an ₁ berichtet. Homozygote Defektträger wiesen etwa 15–25%, heterozygote 50–75% des mittleren normalen Serumspiegels auf. Unter 100 Blutspendern fanden sich 5 mit erniedrigten ₁ wie bei heterozygoten Defektträgern.Klinische Auswirkungen des Gendefektes waren im Kindesalter nicht zu erkennen, insbesondere keine Enthemmung der Fibrinolyse.

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₁ deficiency in two families

Two children from two different families with ₁ deficiency are described. Deficient subjects had 15–25% of normal serum ₁ levels in case of homozygosity and 50–75% in case of heterozygosity. Among one hundred healthy blood donors five had serum ₁ levels below 150 mg% corresponding to the levels found in heterozygous deficiency carriers.In the two children described the gene defect had no clinical consequence; fibrinolysis, in particular was not increased.

     

Elevated cytokine levels in tracheobronchial aspirate fluids from ventilator treated neonates with bronchopulmonary dysplasia

Abstract Bronchopulmonary dysplasia (BPD) is a chronic lung disease often occurring in ventilator-treated very low birth weight infants. The aetiology of BPD is multifactorial and pulmonary immaturity, high oxygen concentrations, peak inspiratory pressure levels and large tidal volumes during prolonged mechanical ventilation are important factors. We measured in tracheobronchial aspirate fluid (TAF) the concentrations of the pro-inflammatory cytokines tumour necrosis factor , interleukin-1 (IL-1), IL-6, IL-8, and IL-1 receptor antagonist in infants requiring artificial ventilation for BPD (n=17) or respiratory distress syndrome (RDS) (n=15) or postoperatively after surgery (n=15). The median levels of all studied cytokines in TAF were higher in infants with BPD without local or systemic corticosteroid, treatment compared to the median TAF levels of BPD neonates treated with corticosteroids (P=0.06–P<0.01). The neonates with BPD not treated with corticosteroids also showed higher levels of the five studied cytokines in TAF compared to infants on short-time ventilator treatment (P<0.01–P<0.001) and compared to neonates with RDS (P=0.07–P<0.001). The corticosteroid treated neonates with BPD had TAF cytokine levels approaching those of the control neonates.Conclusion Tumour necrosis factors , IL-1, IL6, IL8 and IL 1 ra were markedly elevated in tracheobronchial aspirate fluids from neonates with bronchopulmonary dysplasia. Corticoid treatment seemed to reduce these levels.