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Biomedical subjects

M de Silva

Publications and source records attributed to M de Silva.

At least 19 recordsLinked to original sources
PubMed1996

Randomised comparative monotherapy trial of phenobarbitone, phenytoin, carbamazepine, or sodium valproate for newly diagnosed childhood epilepsy.

BACKGROUND: The medical treatment of childhood epilepsy is largely influenced by clinical trials in adult patients. We know of only one randomised comparative trial (of two drugs) in newly diagnosed childhood epilepsy. We have undertaken a long-term, prospective, randomised, unmasked, pragmatic trial of the comparative efficacy and toxicity of four standard antiepileptic drugs used as monotherapy in children with newly diagnosed epilepsy. METHODS: Between 1981 and 1987, 167 children aged 3-16 years, who had had at least two previously untreated tonic-clonic or partial seizures, with or without secondary generalisation, were randomly allocated treatment with phenobarbitone, phenytoin, carbamazepine, or sodium valproate. The protocol was designed to conform to standard clinical practice. Efficacy was assessed by time to first seizure after the start of treatment and time to achieving 1-year remission. FINDINGS: The overall outcome with all four drugs was good. 20% of children remained free of seizures and 73% had achieved 1-year remission by 3 years of follow-up. We found no significant differences between the drugs for either measure of efficacy at 1, 2, or 3 years of follow-up. The overall frequency of unacceptable side-effects necessitating withdrawal of the randomised drug was 9%. This total included six of the first ten children assigned phenobarbitone; no further children were allocated this drug. Of the other three drugs, phenytoin (9%) was more likely to be withdrawn than carbamazepine (4%) or sodium valproate (4%). INTERPRETATION Our data will inform choice of drug and outcome with four of the standard drugs available for newly diagnosed tonic-clonic or partial seizures with or without secondary generalisation in children.

Adolescent↗
PubMed1996

Inheritance of chromosome 7 is associated with a drug-resistant phenotype in somatic cell hybrids.

A major form of drug resistance in tumour cells known as classical multidrug resistance (MDR) is associated with the overexpression of the mdr1 gene product, the membrane protein P-glycoprotein (P-gp), which acts as an energy-dependent drug efflux pump. In this study the inheritance of P-gp expression was examined using hybrids formed after somatic cell fusion between a drug-sensitive human T-cell leukaemia cell line, CEM/CCRF, and a drug-resistant derivative, CEM/A7, which is characterized by a clonal chromosomal duplication dup(7)(q11.23q31.2). Fourteen hybrids, chosen at random, were analysed by reverse transcriptase-polymerase chain reaction (RT-PCR) and by binding studies involving the monoclonal antibody MRK16, which recognises an external P-gp epitope. Only two hybrids were positive for both MRK16 antibody labelling and mdr1 mRNA. Partial karyotypic analysis of all hybrids revealed that only the MRK16-positive hybrids contained the duplication in chromosome 7 seen in the CEM/A7 parental MDR line. Therefore, P-gp overexpression in the MRK16-positive hybrids may be linked to the inheritance of chromosome 7 from CEM/A7 and possibly associated with the chromosome 7 abnormality.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Nodular fasciitis of the nose in a child.

Nodular fasciitis is an unusual benign tumour composed of fibroblasts. It presents as a rapidly growing mass arising from subcutaneous or deep fascia. Less than 20% of cases occur in children. Diagnosis can only be made by histopathological examination of a biopsy of the lesion. A case of nodular fasciitis presenting as a mass arising from the right nasal cavity in a 19-month-old female is presented. The lesion was successfully eradicated by surgical removal. There has been no recurrence at 4-year review. Nodular fasciitis is a benign condition that may mimic malignancy clinically and histologically. Recognition of this condition is important to avoid unnecessarily aggressive treatment. Relevant clinical, radiological and histological features are discussed.

Ethmoid Bone↗
PubMed1995

Neuropsychological function and MRI abnormalities in neurofibromatosis type 1.

This study investigated the relationship between MRI abnormalities and cognitive function in neurofibromatosis type 1.40 children aged eight to 16 years underwent comprehensive neuropsychological, medical and neuroradiological assessments. MRI scans revealed a characteristic pattern of T2-weighted signals ('UBOs') located primarily in the basal ganglia, brainstem and cerebellum in 25 of the children. Reductions in global IQ, attention, and visuopatial and executive functions were shown to occur in association with the presence of UBOs. These findings establish a link between changes in neuropsychological functions and MRI abnormalities in NF-1, and further support neuropathological findings which suggest that UBOs may be a manifestation of delayed or disordered myelination.

Adolescent↗
PubMed1995

Reducing donor exposure in preterm infants requiring multiple blood transfusions.

Preterm infants frequently require multiple blood transfusions. Traditionally, 'fresh' (less than seven days old) blood has been used but this often results in transfusions from multiple donors. To reduce donor exposure the policy for top-up transfusions was changed. A unit of blood under five days old with additional satellite packs was ordered for each infant and used up to its expiry date, allowing up to eight transfusions from a single donation to be given. The mean (SD) number of transfusions per infant in 43 infants transfused according to previous policy and in 29 transfused according to the new policy was similar at 5.6 (4.0) and 5.3 (3.1), respectively. However, donor exposure fell following the change in policy from 4.9 (3.5) to only 2.0 (0.9). Only one infant was exposed to more than three donors compared with 24 infants in the control group. Plasma potassium concentrations were not significantly different following transfusion of blood stored for up to 33 days. This simple change in policy has reduced donor exposure in infants requiring multiple top-up transfusions.

Blood Donors↗
PubMed1994

Sclerosing cholangitis in children with inflammatory bowel disease.

BACKGROUND: Primary sclerosing cholangitis (PSC) with inflammatory bowel disease (IBD) has been rarely reported in children. AIM: To describe the clinical presentation, sequential liver function test abnormalities, radiological bile duct anomalies and liver histology in four children with PSC and IBD. METHODS: Over a period of 18 years, four of 130 patients with IBD developed abnormal liver function tests. Three of the four patients had ulcerative colitis and the other Crohn's disease. All four patients had baseline and follow-up liver function tests, percutaneous transhepatic cholangiography and a needle biopsy of the liver. RESULTS: The four patients at presentation had minimal symptoms or signs of liver disease. All had elevation of serum transaminases, gamma glutamyl transferase and/or alkaline phosphatase. Three had the typical onion skin fibrosis of bile ducts. Percutaneous transhepatic cholangiography demonstrated irregularity and beading of the hepatic and common bile ducts in three patients. The other with normal cholangiography had fibrosing cholangitis on liver biopsy and was considered to have small duct disease. CONCLUSIONS: We conclude that yearly biochemical assessment of liver function should be performed on all children with IBD, and if abnormal should raise the suspicion of PSC. The latter diagnosis can be confirmed by liver biopsy and cholangiography.

Biopsy, Needle↗
PubMed1994

Specific learning disability in children with neurofibromatosis type 1: significance of MRI abnormalities.

To determine whether previously reported areas of increased T2 signal intensity on MRI examination in children with neurofibromatosis type 1 (NF 1) are associated with deficits in development and learning common in this population, we evaluated 51 children with NF 1 (aged 8 to 16 years). Forty children completed the full assessment protocol (MRI, medical, psychometric, speech therapy, and occupational therapy assessments). The mean Full Scale IQ scores for the entire study population showed a left shift compared with the normal population, and the distribution of IQ scores was bimodal, suggesting that there are two populations of patients with NF 1--those with and those without a variable degree of cognitive impairment. There was no association between lower IQ scores and any clinical variable. Areas of increased T2 signal intensity unidentified bright objects (UBO+) were present in 62.5% of the study population, and their presence was not related to clinical severity, sex, age, socioeconomic status, macrocephaly, or family history of NF 1. However, compared with children without areas of increased T2 signal intensity (UBO-), the UBO+ group had significantly lower mean values for IQ and language scores and significantly impaired visuomotor integration and coordination. Children with areas of increased T2 signal intensity were at a much higher risk for impaired academic achievement. Children without increased T2 signal on MRI (UBO-) did not significantly differ from the general population in any measure of ability or performance. Areas of increased T2 signal on MRI represent dysplastic glial proliferation and aberrant myelination in the developing brain and are associated with deficits in higher cognitive function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Selective inhibition of luteinizing hormone action by ethanol in cultured human granulosa cells.

To extend further our previous observations on the inhibition of luteinizing hormone (LH)-induced increases in steroid secretion by ethanol (EtOH) (Alcohol. Clin. Exp. Res. 14:522-527, 1990), cultured human granulosa cells were pretreated with several EtOH concentrations (0-100 mM), and cells were stimulated with human LH (25 ng/ml) or human follicle stimulating hormone (FSH) (100 ng/ml) and the secretion of 17-beta-estradiol (E2) and progesterone (P) was measured. EtOH significantly increased basal E2 secretion in a dose-related manner (0-20 mM); however, in the same concentration range EtOH did not produce consistent changes in FSH-stimulated E2 secretion. In contrast, EtOH decreased LH-stimulated E2 secretion between 0-20 mM such that at 20 mM EtOH, the positive effect of LH was abolished. EtOH increased P secretion by 40% at 20 mM and at 100 mM, there was a 100% increase. The FSH-stimulated P secretion was not consistently changed by EtOH, whereas LH-stimulated P secretion was decreased in a dose-dependent manner. LH/human chorionic gonadotropin (hCG) receptors in cells exposed to EtOH showed a 15% (p < 0.01) and a 47% decrease at 20 mM and 50 mM EtOH, respectively. At 50 mM EtOH, there was a decrease in LH/hCG receptor number from 2900/cell to 1670/cell, without a change in receptor affinity for hCG and 50 mM EtOH decreased LH/hCG receptors in intact granulosa cells in a time-dependent manner. These results indicate that the selective effects of EtOH on LH action in human granulosa cells may be mediated in part by an action on LH/hCG receptors.

Cells, Cultured↗
PubMed1993

Hemiplegia due to posterior cerebral artery occlusion.

BACKGROUND: Hemiplegia is a rare manifestation of posterior cerebral artery occlusion. The acute clinical picture may be difficult to differentiate from occlusion of the middle cerebral artery. A mechanism for the hemiplegia has not been conclusively determined. CASE DESCRIPTION: We describe a patient with hemiplegia secondary to posterior cerebral artery occlusion by an embolized fragment of a prosthetic valve. Computed tomographic scan showed the foreign body just distal to the origin of the posterior cerebral artery with infarction of its vascular territory. These findings were later confirmed at autopsy. There was no radiological or autopsy evidence of involvement of the other cerebral arteries or their territories. CONCLUSIONS: The patient provides further evidence that occlusion of the posterior cerebral artery just distal to its junction with the posterior communicating artery may produce contralateral hemiplegia without oculomotor nerve nucleus involvement.

Adolescent↗