[CMV infections in the mother and newborn].
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Biomedical subjects
Publications and source records attributed to R Regev.
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We present new data obtained by 23Na nuclear magnetic resonance spectroscopy, which can distinguish free intracellular sodium from cell-bound sodium, showing that the intracellular concentration of Na+ the halophilic eubacterium Vibrio costicola is only 5 to 20% of that in the extracellular medium. Previous methods could not distinguish free intracellular Na+ from that bound to cell structures, and it was believed that in halophilic eubacteria the total monovalent cation concentration inside matched that of the NaCl outside. Information obtained by the newer technology raises fundamental questions about the ways in which these organisms and others which live in hypersaline environments function and cope with osmotic stress.
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The synthesis and uptake of intracellular organic osmolytes (compatible solutes) were studied with the aid of natural abundance 13C NMR spectroscopy in two unrelated, moderately halophilic eubacteria: Ba1 and Vibrio costicola. In minimal media containing 1 M NaCl, both microorganisms synthesized the cyclic amino acid, 1,4,5,6-tetrahydro-2-methyl-4-pyrimidinecarboxylic acid (trivial name, ectoine) as the predominant compatible solute, provided that no glycine betaine was present in the growth medium. When, however, the minimal medium was supplemented with glycine betaine or the latter was a component of a complex medium, it was transported into the cells and the accumulating glycine betaine replaced the ectoine. In Ba1, grown in a defined medium containing glucose as the single carbon source, ectoine could only be detected if the NaCl concentration in the medium was higher than 0.6 M; the ectoine content increased with the external salt concentration. At NaCl concentrations below 0.6 M, alpha,alpha-trehalose was the major organic osmolyte. The concentration of ectoine reached its peak during the exponential phase and declined subsequently. In contrast, the accumulation of glycine betaine continued during the stationary phase. The results presented here indicate that, at least in the two microorganisms studied, ectoine plays an important role in haloadaptation.
Eighteen infants were entered into a randomized, placebo-controlled trial of dexamethasone therapy for chronic lung disease. Initial ventilation requirements were similar in the two groups, although all infants were in headbox oxygen on entry to the trial. The dexamethasone-treated infants showed a significantly more rapid improvement during the 1st week of treatment, although the overall duration of oxygen therapy was similar in both groups. Cranial ultrasound examination revealed new periventricular abnormalities in three out of the five dexamethasone-treated infants who had previously normal scans, compared with none of four similar placebo-treated infants. A large trial, focussing on potential complications, is now needed.
Seventeen infants with extensive cystic leukomalacia without associated intraventricular hemorrhages were compared with 34 infants with normal cranial ultrasound findings and 34 infants with large intraventricular hemorrhages to establish whether different risk factors could be elicited for these lesions. Adverse obstetric factors that were associated with extensive leukomalacia were the place of birth (outborn [ie, not born at our hospital but transferred here after delivery]) and the need for emergency cesarean section. Neonatal risk factors, with the exception of gestational age, were equally distributed between the infants with the two types of lesions. The results of this study suggest that extensive cystic leukomalacia and large hemorrhages have similar predisposing factors, but the type of lesion that develops depends on the maturity of the infant.
Head growth was correlated with outcome in 12 infants with major intracranial haemorrhages and in 9 with extensive cystic leukomalacia. Decreasing head growth was associated with a poor neurodevelopmental outcome whereas a normally growing head did not necessarily correlate with a normal outcome.
The evolution of ultrasound findings in 59 infants with transient periventricular densities is described and the neurodevelopmental outcome of 53 of these infants was compared with 92 of 107 infants with normal ultrasound scans, born during the same 24-month period. Four of the 53 infants with transient periventricular densities developed spastic diplegia and 24 developed transient dystonia, whereas only 8 of the 92 children with normal ultrasound scans demonstrated this finding (P less than 0.001). Persistence of the densities for more than 10 days and the presence of densities in the trigone were especially related with subsequent problems. Postmortem findings in two infants and MRI studies in six infants also suggested that transient periventricular densities represent the milder end of the spectrum of periventricular leukomalacia.
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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.
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.
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Ultrasonography or computed tomography scanning of the brain was performed in 10 infants with congenital myotonic dystrophy between the age of 1 day and 2 months, and showed intracranial abnormalities in all. Ventricular dilation was diagnosed in eight (80%), subarachnoid hemorrhage in one, and white matter infarcts in one. The common finding of ventricular dilation is probably related to developmental brain abnormality dating back to fetal life, because it was already present in three infants scanned on the first day of life. Neonatal asphyxia was present in seven infants, associated with intraventricular hemorrhage in two. The relationship between these changes and mental retardation, which is a common feature in this disease, is unclear.
Continuous monitoring by electroencephalography (EEG) was performed in 31 preterm infants with echodense ultrasound lesions using the Oxford Medilog four channel recorder. In 12 infants these densities preceded cyst formation, eight in the periventricular and four in the subcortical region. In the 19 other infants the densities resolved. The most severe EEG depression occurred in the four infants with subcortical cysts, who also had the poorest outcome. Six of eight infants with periventricular lesions had lesser degrees of abnormality though all infants had moderate to severe handicap at follow up. Similar abnormalities were seen on EEG recording in three infants in whom the densities resolved without cyst formation and these infants also had an abnormal outcome. An abnormal EEG recording provides a sensitive early guide to the severity and prognosis of these lesions, even before they can be seen on ultrasonography.
The growth of nine infants with Krabbe's disease was followed longitudinally by repeated measurements of head circumference, length and weight. All infants showed early slowing and then arrest of growth, leading progressively to microcephaly and severe failure to thrive.
The ultrasound findings of eight premature infants who developed extensive cystic leucomalacia after the first two weeks of life are reported. Ultrasound examinations should be considered after any clinical deterioration in preterm infants up to 40 weeks' postmenstrual age to avoid missing cases of extensive cystic leucomalacia.
Krabbe disease (globoid cell leukodystrophy) was found with very high incidence (6/1,000 live births) in a large Druze kindred in Israel. The clinical data on 12 of the affected children demonstrated clinical variability even though these children are homozygous for the same mutation by descent from a common ancestor.
A fluorescent substrate 12-(N-methyl-N(7-nitro-2-oxa-1,3-diazol-4-yl) aminododecanoyl sphingosyl beta-D-galactoside ('NBD galactocerebroside') was synthesized and used for the detection of galactocerebrosidase activity. The enzyme determinations using this substrate were found to be extremely sensitive yielding unambiguous results. This substrate was used for the prenatal diagnosis of a fetus affected with Krabbe disease; the diagnosis was later confirmed in the aborted fetus.