Screening for minor changes in the distal part of the human dystrophin gene in Greek DMD/BMD patients.

The distal part of the human dystrophin gene is characterised by particular features and seems to play an important functional role. Additionally in recent years several data have implicated minor mutations in this gene region in some patients with mental retardation (MR). In order to screen for pathogenic mutations at the distal part of the human dystrophin gene we have used single-strand conformation analysis of products amplified by polymerase chain reaction (PCR-SSCA) in 35 unrelated male Greek DMD/BMD patients with no detectable deletions. Seven patients also had severe mental retardation. Direct sequencing of samples demonstrating a shift of SSCA mobility revealed six different and pathogenic minor changes, five in DMD and one in a BMD patient. Four of the mutations were found in DMD patients with severe MR. Three of these mutations were localised in exon 66, which presents an interesting similarity with part of the 3' end of the genome of eastern equine encephalomyelitis virus (EEEV). The present data from Greek DMD/BMD patients give further information about the phenotypic effects consequent on mutations in exons at the distal part of the human dystrophin gene.

Hemorrhage, phenobarbital, and fluctuating cerebral blood flow velocity in the neonate.

Fifty-one sequential intubated babies with birth weights of less than 1,751 were evaluated by serial Doppler ultrasound during the first three days of life. These babies were part of a phenobarbital prophylaxis trial cohort study. Subependymal-intraventricular hemorrhage developed in 17 of the babies. Infants with subependymal-intraventricular hemorrhage, whether or not they received pancuronium or phenobarbital, had coefficients of variation comparable to those of babies without hemorrhage. Coefficient of variation values of the right were comparable to values obtained from the left anterior cerebral artery complex and did not appear to be consistently altered by the presence of subependymal-intraventricular hemorrhage. Coefficient of variation values appeared to be consistently greatest on day 1 and lowest on day 2. In addition, the values overall increased as the number of waves used to determine the coefficient of variation enlarged from five to 20. This phenomena, however, was not seen among pancuronium recipients and suggests that movement artifact may be a determinant of coefficient of variation values. We conclude that, when the best 20 waves are chosen to evaluate the coefficient of variation, no association exists between coefficient of variation values and development of subependymal-intraventricular hemorrhage or administration of phenobarbital.

Bilirubin, intraventricular hemorrhage, and phenobarbital in very low birth weight babies.

The relationships among serum bilirubin concentration on days 5 and 7, birth weight, the presence of intraventricular hemorrhage, and the receipt of phenobarbital were examined in a group of 232 newborns weighing less than 1,751 g who were intubated, mechanically ventilated by 12 hours after birth, and whose parents had given permission for a randomized trial of phenobarbital prophylaxis of intraventricular hemorrhage. The ratio of serum bilirubin concentration to birth weight (the bilirubin divided by birth weight index [BBI]) was used to examine the impact of 25 variables on a clinical guideline for therapy of hyperbilirubinemia in newborn infants. A linear regression model was used; the most powerful covariate was a birth weight less than 1.0 kg. The only other variable that reduced the BBI was phenobarbital receipt. The presence of intraventricular hemorrhage and ecchymoses had a significant influence increasing the BBI.

Deep tendon reflexes in premature infants.

Ten classic deep tendon reflexes (DTRs) were evaluated in 62 premature infants of greater than 27 weeks post-conceptional age. The pectoralis major was the most readily elicitable reflex in all infants (100%), regardless of maturity. Achilles, patellar, biceps, thigh adductors, and brachioradialis reflexes also were obtained in at least 98% of babies of greater than 33 weeks gestation. Among these reflexes, less mature infants (less than 33 weeks gestation) had decreased elicitation rates for patellar and biceps reflexes and overall had diminished reflex intensity when compared to older infants (33-36 weeks gestation). By order of decreasing rate, finger flexors, jaw, crossed adductors, and triceps reflexes were less frequently elicited in both groups. Equal DTRs were obtained often in healthy and previously ill infants of less than 33 weeks gestation. Head position had no apparent affect on the ability to elicit reflexes. Theophylline therapy tended to intensify the Achilles reflex and the quiet, wakeful state appeared to be the most optimal state for the elicitation of DTRs.

Arterial blood gas derangements associated with death and intracranial hemorrhage in premature babies.

We evaluated to what extent acidosis and alkalosis and their respiratory and metabolic components during the first 12 hours of life occurred prior to early neonatal death and postnatal intracranial hemorrhage among 206 low birth weight, intubated premature babies participating in a clinical trial of phenobarbital prophylaxis for intracranial hemorrhage. Time-weighted indices included the time each baby spent with abnormal values of pH, PaCO2 and HCO3-. Babies whose birth weight was less than 1 kg suffered adversities associated with prolonged pH less than 7.35. Heavier birth weight babies were at increased risk of adversity if their pH fell below 7.2. Babies who were not severely acidotic initially, but became so within hours, were at prominently increased risk of death and hemorrhage. Babies who had a mild increase of PaCO2 between 45 and 60 mmHg were less likely to develop germinal matrix hemorrhage than their peers who had more severe hypercapnia. A time-weighted measure of metabolic deficit correlated with death, but not with hemorrhage. Prolonged exposure to pH greater than 7.55 was associated with reduced risk of subependymal/intraventricular hemorrhage and death, especially in babies below 1 kg birth weight. We conclude that acidosis is an antecedent of intracranial hemorrhage in low birth weight premature babies, that duration of exposure might convey important risk information, and that birth weight is a correlate of vulnerability to some pH disturbances.

Long lasting benefits following the combination of static night upper extremity splinting with botulinum toxin A injections in cerebral palsy children.

AIM: Botulinum toxin A injections and orthotics have been used to manage upper extremity spasticity in hemiplegic children. The authors performed a study to evaluate the necessity and effectiveness of a static night splint following outpatient botulinum toxin A treatment in children with upper limb spastic cerebral palsy. METHODS: Twenty children with upper limb spastic cerebral palsy were treated with botulinum toxin A injections. A static night splint was applied in half of them. Objective assessment of upper limb function was performed at baseline, at 2 and 6 months after botulinum toxin A injection using the Quality of Upper Extremity Skills Test. RESULTS: After botulinum toxin A treatment, both groups showed an improvement on their previous functional level of the injected upper extremity. At 2 months, children in group A showed a 15.4% improvement, whereas children in group B improved by 12.2% from baseline; these were not statistically significant (P=0.326). At 6 months, group A still maintained a 15.9% improvement in function compared to group B which differed only by 4.2% from prebotulinum toxin A baseline; these differences were statistically significant (P=0.000). Complications related to the botulinum toxin A injection were not observed. The static CONCLUSIONS: Static night splinting following botulinum toxin A injections has shown a definite treatment effect in reducing spasticity and improving function in children with upper limb spastic cerebral palsy.

Fasciculation of the eyelids: an additional clue to clinical diagnosis in spinal muscular atrophy.

Fasciculation of the eyelids was observed in five of eleven children with spinal muscular atrophy (SMA); two had severe SMA and three were of intermediate severity. Three other children with intermediate SMA and the two children with mild SMA did not show eyelid fasciculations. This could provide an additional clinical sign to tongue fasciculation and hand tremor in the diagnosis of SMA in childhood.

The maturation of the auditory brainstem response compared to peripheral nerve conduction velocity in preterm and full-term infants.

The maturation of the auditory brainstem response in preterm and full-term infants is compared with that of nerve conduction velocity. There is a linear relationship between wave I latency, the peripheral component of the response, and nerve conduction velocity, but the negative correlation is not high. A poor negative correlation exists between the I-V interval, an index of brainstem transmission, and nerve conduction velocity. The factors governing the maturation of central transmission along the auditory pathway in the brainstem are not related to myelination of peripheral nerves. Abnormal nerve conduction velocities are not related to any particular abnormal brainstem response in a stable external environment.

Megacystis-microcolon-intestinal hypoperistalsis syndrome: a functional intestinal obstruction in the female newborn.

A fatal case of the megacystis-microcolon syndrome in a newborn girl is presented and two previously unreported findings are discussed. The umbilical hernia is thought to represent a mechanically induced embryological defect, secondary to the expanding nonfunctional megacystis which appears to be the dominant component from an early stage. Hypertrophic changes of the large intestinal wall musculature, adjacent to dilated segments, may indicate an impaired propulsive activity in utero, as a result of defective neurotransmission. The latter is proposed as the common pathophysiological mechanism for both urinary and intestinal malfunction.

Perforation of the intussuscipiens transverse colon: an unusual complication in infancy.

A case of an ileocolic intussusception in an infant is presented, complicated by an unusually "silent" rupture of the intussuscipiens transverse colon. We stress the importance of clinical diagnosis even in the absence of convincing plain film findings. The value of laparotomy is also emphasised in this particular case, where a barium enema could have been potentially hazardous for the patient.

Predictors for survival and normal neurodevelopmental outcome of infants weighing less than 1001 grams at birth.

Between 1979 and 1981, 67 infants weighing 1000 g or less at birth were admitted to the Hammersmith Hospital Neonatal Intensive Care Unit. 29 survived the neonatal period. Low acidosis score, without a metabolic component, was the most powerful predictor of survival. Other factors were gestational age, five-minute Apgar score, the need for ventilatory support, hypoxia, hypercapnia, pneumothorax, hypotension and the presence of a larger PVH. Of the 24 survivors followed up to three years of age, 11 were optimal, nine had some neurodevelopmental deficits and three had moderate functional handicap. Only one child has cerebral palsy and global mental retardation. Five-minute Apgar score and the presence of PDA correlated with normal outcome. None of the 20 obstetrical factors examined appeared to influence either survival or neurological outcome.

Visual evoked responses to light emitting diode (LED) photostimulation in newborn infants.

The use of a Xenon discharge stroboscope to elicit VERs in a neonatal intensive care unit has several disadvantages. To overcome these a photostimulator has been developed which consists of an array of 25 red light emitting diodes (LEDs). The LEDs are driven by pulses of fixed length and current and the output intensity is controlled by the pulse repetition rate. Such a photostimulator is compact and can be hand-held inside a cot or incubator. Using this method VERs have been recorded in healthy full-term and pre-term infants which are comparable in wave form and latency to those elicited by a stroboscope.

Early markers of brain damage in premature low-birth-weight neonates who suffered from perinatal asphyxia and/or infection.

We studied 57 low-birth-weight premature neonates, of whom 29 suffered from perinatal asphyxia and/or infection, while the remaining 28 did not and served as controls. We measured peripheral nucleated red blood cell (NRBC) absolute numbers as well as interleukin (IL)-1beta, IL-6 and tumour necrosis factor (TNF)-alpha cytokine serum levels at 24 h postnatally and on days 3 and 7 following birth. Fourteen of the asphyxiated/infected neonates and 12 controls had neurologic assessments at the corrected postnatal age of 18 months. We found NRBC absolute numbers and serum IL-1beta and IL-6 cytokine levels at 24 h postnatally to be significantly higher in neonates with perinatal asphyxia/infection than in the controls (p = 0.022, p = 0.036 and p = 0.037, respectively). TNF-alpha levels did not differ. Neurologic examination at the corrected postnatal age of 18 months showed 8 out of the 14 children who had been asphyxiated/infected as neonates to have abnormal findings, while 12 children who were used as controls during their neonatal period were normal. Abnormal neurologic findings correlated with high NRBC counts and IL-1beta and IL-6 levels at 24 h postnatally. In conclusion, increased NRBC counts and proinflammatory cytokine levels in asphyxiated/infected neonates represent early markers for subsequent neurologic impairment.