Search

Asthma is a complex syndrome in which bronchial inflammation and smooth muscle hyperactivity lead to labile airflow obstruction. The commonest form of asthma is that due to atopy, which is an immune disorder where production of IgE to inhaled antigens leads to bronchial mucosal inflammation. The ultimate origins of asthma are interactive environmental and genetic factors. The genetics is acknowledged to be heterogeneous, and one chromosomal region of interest and controversy has been 11q13. To clarify the nature of the chromosome 11q13 effect in atopy and asthma, we conducted a genetic association study in subjects with marked atopic asthma and matched controls, which incorporated the study of 13 genetic variants over a distance of 10-12 cM and which took account of detailed immune and clinical phenotyping. Association with high IgE levels was limited to the interval flanked by D11S1335 and CD20 in a 0.8-Mb interval and was greatest for variants of Fc epsilon RI beta and HTm4; these variants also associated with asthma (recurrent wheeze with labile airflow obstruction and need for regular inhaler treatment). At the more telomeric marker, D11S480, variants associated with asthma, but not with high IgE levels. The data might support the possibility of multiple loci relevant to atopic asthma on chromosome 11q13.

Asthma is a complex syndrome in which bronchial inflammation and smooth muscle hyperactivity lead to labile airflow obstruction. The commonest form of asthma is that due to atopy, which is an immune disorder where production of IgE to inhaled antigens leads to bronchial mucosal inflammation. The ultimate origins of asthma are interactive environmental and genetic factors. The genetics is acknowledged to be heterogeneous, and one chromosomal region of interest and controversy has been 11q13. To clarify the nature of the chromosome 11q13 effect in atopy and asthma, we conducted a genetic association study in subjects with marked atopic asthma and matched controls, which incorporated the study of 13 genetic variants over a distance of 10-12 cM and which took account of detailed immune and clinical phenotyping. Association with high IgE levels was limited to the interval flanked by D11S1335 and CD20 in a 0.8-Mb interval and was greatest for variants of Fc epsilonRIbeta and HTm4; these variants also associated with asthma (recurrent wheeze with labile airflow obstruction and need for regular inhaler treatment). At the more telomeric marker, D11S480, variants associated with asthma, but not with high IgE levels. The data might support the possibility of multiple loci relevant to atopic asthma on chromosome 11q13.

Interest in the neurology of the newborn has been largely stimulated by the new advances of imaging; CT, cranial ultrasonography and MRI which for the first time allowed diagnosis of brain lesions in the live infant which in the past could only be made by post mortem examinations. (Ultrasound in particular, as it is safe, cheap and portable has been eminantly suitable for routine use in the nurseries to study the incidence, timing and evolution of the lesions in the neonatal period. While MRI is expensive and more difficult to perform it gives superb anatomical definition and is also safe for repeated examinations. It is thus very suitable to follow the evolution of the lesions into infancy). The aim of this presentation is to illustrate how an integrated approach with the combined use of imaging and clinical evaluations lead to a better understanding of antenatal and perinatal factors which may be responsible for the production of these lesions on one hand and the impact of these lesions on later development on the other.

Summary: This study investigates the birthweight, gestational age, and body proportions of home births in a malarious area of Papua New Guinea. A population based cohort of pregnant women was followed longitudinally through pregnancy. Within the first few days of birth anthropometric measures were taken and a gestational age assessment made. Of the 121 live singleton infants, forty per cent were low birthweight and the preterm rate was 4 per cent. Infants appeared to be proportionally growth retarded. Low birthweight was associated with short maternal stature, and preterm delivery with maternal illness. Mean birthweight derived from hospital statistics of babies born to women from the same area was higher than the mean derived from this population based study.

Three restriction fragment length polymorphisms (RFLPs) of the fibrinogen genes were used in 91 individuals to investigate the role of genetic variation at this locus in the determination of plasma fibrinogen. The strongest association was with a polymorphism detected with the β-fibrinogen probe and the enzyme Bcl I. The probe detects two alleles, designated B1 and B2. The individuals with the genotype B1B had a mean fibrinogen of 2·74 g/l; those with B2B2 had a mean fibrinogen of 3·69 g/l (a level previously associated with a strongly increased risk of ischaemic heart disease); and those heterozygous for the two alleles, with the genotype B1B2, had a mean of 2·98 g/l. Genetic variation at the fibrinogen gene locus accounted for 15% of the total phenotypic variance in fibrinogen.

Findings on cranial ultrasonography strongly suggested the diagnosis of a localized infarct in four premature infants. CT was performed to differentiate between hemorrhagic and nonhemorrhagic lesions, and magnetic resonance imaging was used to obtain information about the late effect of the lesions. The clinical findings, imaging findings, and later outcome in these premature infants were compared with the existing knowledge of this type of lesion in the full-term infant. A localized infarct appears to carry a good prognosis in the premature infant and should be differentiated from other types of lesions, such as periventricular leukomalacia or parenchymal hemorrhage, which are more common in the premature infant and carry a worse prognosis.

A comparative neurological study was undertaken of growth-retarded or small-for-dates (SFD) and appropriately grown (AFD) full-term infants in a Cape Coloured and a White (London, UK) population. There were no associated complications of pregnancy or labour. Consistent differences were found between SFD and AFD infants in both ethnic groups. In the SFD infants there was an increase in visual and auditory orientation, alertness, startle reflexes, tremors and tone, and some reduction in habituation. The difference between our results and those of earlier authors can probably be accounted for by factor such as use of drugs in labour, perinatal events and different causes of growth retardation, all of which may influence neurological behaviour.

A family with six males affected by X-linked spastic paraplegia (McKusick No. 31290) is described. The disease was accompanied by mental retardation in all patients (severe in four cases with IQ of 40) and by absence of extensor pollicis longus (in four cases). The following X chromosome DNA probes were used in linkage studies: 782, RC8, 99-6, 754, OTC, L128, pDP34, p43-15, DX13, and St14. The mutation is closely linked to the loci DX13 (DXS15) and Stl4 (DXS52) (no recombinants in 11 meioses) and therefore localised to the telomeric region of the long arm of the human X chromosome.

The contribution of early continuous four-channel EEG monitoring to the evaluation of intraventricular hemorrhage in acutely ill preterm infants mechanically ventilated for acute respiratory distress was assessed in a prospective study of 54 infants of less than 34 weeks' gestation. Early abnormal EEG results correlated significantly with later outcome. They often preceded ultrasound evidence of hemorrhage and provided prognostically significant functional correlation with the grade of hemorrhage. Continuous EEG monitoring allows collection of significant data with minimal interference and could contribute to clinical management of high-risk preterm infants.

During a 4-year period, 12 premature infants, all less than 34 weeks of gestation and all with a bilirubin level above 240 mumol/L (14 mg/dL) were determined to have bilateral sensorineural deafness. In order to to investigate how far the hyperbilirubinemia or any a associated factor might have been a causative factor, all infants of 34 weeks of gestation or less who had a serum bilirubin level above 240 mumol/L were investigated. For a period of 4 years, 99 infants meeting these criteria were classified as high risk or low risk on the basis of perinatal risk factors. Eight of the 22 high-risk infants with birth weight less than 1,500 g, but only two of 43 high-risk infants with birth weight greater than 1,500 g were deaf (P less than .05). The deaf infants were also matched with infants of normal hearing who had similar bilirubin levels and the same number of adverse perinatal factors. The mean duration of hyperbilirubinemia was significantly longer in the deaf infants (P less than .02), and they appeared to have a greater number of acidotic episodes while they were hyperbilirubinemic. These findings suggest that in healthy preterm infants with birth weight greater than 1,500 g, high bilirubin levels carry little risk, whereas a serum bilirubin level greater than 240 mumol/L in high-risk preterm infants with birth weight of 1,500 g or less is associated with a high risk of deafness.

NMR scanning is feasible in the newborn period, and is capable of diagnosing most of the problems in this age group, but its general application presents a number of difficulties at present. It cannot be transported to the bedside. Adequate monitoring of ill patients is difficult, and scanning takes a relatively long time. The neonatal brain has an extremely high water content, and NMR scanning procedures require adaptation to apply to these conditions. NMR imaging, however, has already proved extremely useful in the follow-up of neonatal insults. Repeated scanning is possible after closure of the fontanelle without subjecting the infant to ionizing radiation. The scans are able to demonstrate not only the anatomic changes associated with the various lesions, but also how these might affect myelination. Development of better coils and more suitable scanning sequences for neonates and infants are needed to improve image quality and establish the normal range of T1 and T2 values and the normal range of myelination at various ages. Further studies will also establish whether the changes in myelination primarily reflect the pathologic processes occurring in the tissues, such as the amount of gliosis, or are a marker of functional involvement.

The results of serial MR imaging of the brain in 32 patients with neonatal cerebral injury who had two or more examinations are reviewed. By comparison with normal age-matched controls, delayed or deficient myelination was identified in eight patients on follow-up examination. Developmental delay was present in all of these patients. In three patients delayed myelination was identified at the first study and was normal at follow-up. These patients improved clinically. The most severe delays or deficits in myelination and the most severe handicaps were present in patients with subcortical and periventricular leukomalacia. Ventricular size was readily assessed. Development of porencephalic cysts at sites of previous hemorrhage and infarction was recognized. The lack of ionizing radiation is of particular importance in follow-up MR of children, and an increasing role for this technique in pediatric developmental neurology appears likely.

Four neonates who developed an intracranial haemorrhage antenatally are described. In two, there was a congenital deficiency of one of the clotting factors (factor V and factor X respectively) and two had neonatal isoimmune thrombocytopenia.