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Biomedical subjects

E M Brett

Publications and source records attributed to E M Brett.

At least 55 records · Page 3Linked to original sources

Falsely increased digoxin concentrations in samples from neonates and infants.

Several previous studies have suggested the presence of a digoxin-like immunoreactive substance in the serum of infants. In this study we examined eight different immunoassay kits to confirm the presence of such a substance. The kits were evaluated using serum from newborns and infants who were not receiving digoxin. We investigated the relationship of this digoxin-like immunoreactive substance to substances that are present in unusual concentrations in newborn sera. These substances included fatty acids, cholesterol, triglycerides, bilirubin, protein, and albumin. No relationship could be established. Since serum steroid concentrations are known to be increased in the newborn and since digoxin is essentially a steroid derivative, we looked at steroids separately and collectively to see whether they mimicked the immunoreactivity of digoxin. We found that pooled steroids did indeed mimic digoxin and might be implicated as the immunoreactive substances.

Adult↗

Altered ratio of carbamazepine-10,11-epoxide/carbamazepine in plasma of children: evidence of anticonvulsant drug interaction.

A method of measuring carbamazepine-10,11-epoxide (CBZ-10,11-EPOX) has been developed and used to monitor plasma concentrations in children suffering from various forms of epilepsy. Children stabilised on standard doses of CBZ alone showed a ratio of CBZ-10,11-EPOX/CBZ of 18.92 +/- 8.08, expressed as a percentage of the CBZ concentration, while those on multiple-drug therapy (with the exception of benzodiazepines and phenobarbitone) showed both increased values of CBZ-10,11-EPOX/CBZ ratio and increased absolute concentrations of CBZ-10,11-EPOX in plasma. These changes correlated with clinical side-effects which could not be attributed to CBZ itself or to the other drugs administered concurrently.

Anticonvulsants↗

Correlation between plasma carbamazepine-10,11-epoxide concentration and drug side-effects in children with epilepsy.

Ninety children with epilepsy were treated with carbamazepine (CBZ) alone or with other anticonvulsant drugs. Side-effects were noted in 14 patients. When 25 patients treated with CBZ alone (group 1) were compared with 27 on CBZ and sodium valproate (group 2) and with 38 on CBZ and one or more other anticonvulsants (group 3), the incidence of side-effects was two in group 1 (of whom one patient had a toxic plasma level of CBZ), but 12 in groups 2 and 3 combined. In all but three of the 14 patients with side-effects, plasma levels of CBZ were within the 'therapeutic range'. A significant difference was found between the carbamazepine-10,11-epoxide (CBZ-10,11-EPOX) levels in plasma and CBZ-10,11-EPOX/CBZ ratio in patients with and without side-effects. For five patients on CBZ and other drugs, changes in treatment resulted in changes in side-effects, and also in CBZ-10,11-EPOX levels. Three of these patients showed an interaction between CBZ and sodium valproate, with a correlation between plasma CBZ-10,11-EPOX and side-effects when either drug was introduced or withdrawn, the plasma levels of CBZ itself and of sodium valproate being within the 'therapeutic range'.

Adolescent↗

Delta bilirubin in serum of pediatric patients: correlations with age and disease.

At least four bilirubin fractions can be separated and identified by liquid chromatography, the least understood being the "delta" fraction (B delta), which apparently is covalently bound to albumin. To learn more about the incidence and significance of B delta, we assayed serum from 539 infants and children, both by the chromatographic method and the routine colorimetric Jendrassik-Grof method. The proportion of B delta appeared to correlate with both age and disease course. For infants younger than 28 days B delta generally was less than 2% of total bilirubin; for hyperbilirubinemic older infants and children the median B delta value was 35%. High B delta (greater than 50% of total bilirubin) in newborns was associated with intra- and extra-hepatic cholestasis, biliary cirrhosis, biliary atresia, and hepatitis. Among older infants and children, a proportion of low B delta (less than 10%) was found in hemolytic anemias, sepsis, shock, and other non-hepatic jaundice. In several cases, when low B delta was accompanied by increased conjugated bilirubin, the prognosis was very poor. Delayed clearance of B delta from the circulation together with its reactivity in direct diazo methods may interfere with interpretation of values for conjugated bilirubin as measured by classical methods.

Aging↗

Involvement of the central nervous system in congenital muscular dystrophies.

Three children, two siblings and one unrelated child, with congenital muscular dystrophy with central nervous system (CNS) involvement are discussed. The siblings appeared to suffer from a relatively mild myopathy with progressive brain disease, of which brain biopsy in one showed astrocytic proliferation in the white matter. In the patient with severe muscle disease, autopsy showed widespread patchy demyelination in the white matter and developmental abnormalities in the cerebral and cerebellar cortex. These patients differ from the Japanese (Fukuyama) cases of CMD in the severity of the changes in the cerebral white matter, and from Santavuori's cases in the absence of ocular abnormalities and hydrocephalus. Their unique nosology is discussed.

Adolescent↗

Value of computerised tomography in children with non-specific mental subnormally.

Seventy-six children had computerized tomography scans as part of an investigation of mental subnormality; most of them are severely retarded and all those over age 5 years attend special schools. Seventy-two per cent of the children had normal scans. Twenty per cent showed cerebral atrophy and in only 8% was there a specific abnormality (agenesis of corpus callosum, arachnoid cyst, communicating hydrocephalus). None of these findings had any positive prognostic implication. Sedation or general anaesthesia was required for all except one child. Injection pethidine compound was used for children under age 5 years or less than 30 kg in weight, and trimeprazine orally was used for older children. The radiation exposure was high--5.6 rad per scan, which is 100 times greater than that from a posteroanterior and lateral chest x-ray film. For these reasons computerised tomography scans cannot be recommended as a routine part of the investigation of children with non-specific mental subnormality.

Adolescent↗

Effects of sodium valproate in 100 children with special reference to weight.

Excessive weight gain occurred in a patient who was taking sodium valproate and phenytoin. The sodium valproate was therefore withdrawn but the rapid weight loss that ensued led to phenytoin intoxication. Hence a retrospective analysis was conducted of 100 children with epilepsy treated with sodium valproate. Fit control improved in 77 and was best in children with generalised epilepsy. None of the reported severe side effects, such as acute liver disease and pancreatitis, were encountered. Milder but troublesome side effects, however, occurred in 65 patients. The commonest was increased weight gain, which occurred in 44 cases. Others were transient gastrointestinal disturbances (20), lassitude (nine), transient hair loss (six), transient enuresis (seven), and aggressive behaviour (four).

Adolescent↗

The possible adjuvant role of bordetella pertussis and pertussis vaccine in causing severe encephalopathic illness: a presentation of three case histories.

The clinical and some laboratory details of three children who had severe neurological sequelae after either infection with Bordetella pertussis or immunisation with diphtheria, tetanus and pertussis vaccine and oral polio vaccine are reported. Each of these patients had had a recent or concurrent viral illness. The severity of their encephalopathic illness may have been due to an adjuvant role of B. pertussis or a component of the vaccines they received.

Adjuvants, Immunologic↗

Total-calcium measurement in serum from neonates: limitations of current methods.

In the routine analysis for calcium in serum from neonates we noted large discrepancies in icteric samples analyzed by several different methods. The present investigation was undertaken to demonstrate the magnitude of the problem of bilirubin interference in calcium analysis and to assess the specific applicability of commonly used micro-methods in the pediatric or neonatal laboratory. The intention is not to advocate any single methodology but rather to point out inadequacies that must be considered. Colorimetric and fluorometric methods correlated poorly with an atomic absorption spectroscopic method for samples from pediatric patients. In addition, we noted significant interference proportional to the concentration of bilirubin. A fluorescence titration method was shown to be unacceptable for pediatric use because of the variable and unpredictable response to bilirubin interference. The study emphasizes the need for thorough invesigation of methods before they are put to use in the specialized pediatric setting.

Bilirubin↗

A bioluminescence micromethod for measuring chloramphenicol in serum.

Bioluminescence provides a sensitive analytical approach for the measurement of low concentrations of ATP and can be used to monitor any reaction in which ATP is consumed or synthesized. We describe a quick, sensitive method involving bioluminescence for the quantitation of chloramphenicol in serum. Chloramphenicol acetyl transferase catalyzes the acetylation of chloramphenicol in the presence of acetyl coenzyme A. ATP is consumed when the acetylation reaction is coupled to the acetyl coenzyme A synthetase reaction. Residual ATP is then assayed with the firefly luciferin-luciferase reaction. The procedure can be completed in less than 1 h and requires as little as 20 microliter of serum. The response of the assay is linear with concentration through a range of 2 to 20 mg/L and shows good correlation with a gas-chromatographic method (r = 0.978) and a radioenzymic method (r = 0.985). No significant interference was found from five other antibiotics tested. The small sample requirement makes the assay especially applicable to infant and pediatric monitoring, where the effects of toxicity are greatest.

Chloramphenicol↗

Hereditary sensory neuropathy with spastic paraplegia.

Five cases of spastic paraplegia with a progressive symmetrical sensory neuropathy producing ulceration and osteomyelitis of the hands and feet are reported. The pathology in one patient, who died of secondary amyloidosis, was similar to that found by Denny-Brown in hereditary sensory radicular neuropathy with severe loss of posterior root ganglion cells and loss of myelinated fibres in both peripheral nerves and posterior columns of the spinal cord. A sural nerve biopsy in another case showed a striking loss of both myelinated and unmyelinated fibres, with some evidence of degeneration and regeneration. The inheritance is probably by an autosomal recessive gene. The prognosis in the more severe form of the disorder is poor.

Adolescent↗

The Börjeson-Forssman-Lehmann syndrome: a new case.

A new case of the Borjeson-Forssman-Lehmann syndrome is described with details of anthropometry, dermatoglyphs, endocrine function studies and mental state. Comparisons are made with the five previously reported cases. The diagnosis is based on the clinical appearance. Endocrine studies gave normal results and the patient's short stature is not due to growth hormone deficiency. There is no evidence for primary hypogonadism.

Abnormalities, Multiple↗

Limitations of immunochemical measurement of ceruloplasmin.

We describe a quantitative immunochemical method for the nephelometric measurement of ceruloplasmin. Results are compared with those from a radial immunodiffusion technique. We examine factors affecting the results, such as antiserum source and calibrators, and list reference limits for a pediatric population.

Age Factors↗