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Biomedical subjects

C Maguire

Publications and source records attributed to C Maguire.

31 records · Page 2Linked to original sources
PubMed1992

Course of pregnancy and fetal outcome following maternal exposure to carbamazepine and phenytoin: a prospective study.

This prospective study followed the pregnancy course of epileptic women at the Motherisk Program of The Hospital for Sick Children, Toronto. We compared fetal outcome of women treated with carbamazepine (CBZ), those treated with diphenylhydantoin (phenytoin, DPH), and a drug-free control group. Seizures were reported in 15 pregnancies; in a subgroup of 9 women without change in drug or schedule, an increase in seizure frequency was evident in 6, a decrease in 1, and no change in 2, regardless of the drug taken. Of 23 children exposed to CBZ in utero, one was born with a lumbar myelomeningocele and multiple congenital anomalies. Of 21 children exposed to DPH, there was one case of severe developmental delay and four with minor features of fetal hydantoin syndromes (FHS). The three groups did not differ in birth weights or gestational ages of the babies. Although much more experience is needed, as a result of this study and other similar reports, Motherisk now offers women treated with CBZ diagnostic tests to detect neural tube defects during the second trimester of pregnancy.

Abnormalities, Drug-Induced↗
PubMed1991

In vitro screening for anticonvulsant-induced teratogenesis: drug alteration of cell adhesivity.

Anticonvulsant-induced alteration in C6 glioma cell adhesivity has been evaluated in two independent in vitro assay systems. A centrifugal shear assay was employed to determine drug-induced change in cell-substratum adhesivity. Valproate and clonazepam were found to significantly increase cell-substratum adhesivity when cells were cultured at concentrations which were within twice their therapeutic plasma level. A second assay evaluated change in affinity for concanavalin A lectin coated surfaces to determine change in cell surface glycoconjugate expression. Valproate and clonazepam and, to a lesser extent, diazepam significantly decreased drug-exposed C6 glioma cell affinity for concanavalin A lectin coated surfaces. Valproate and clonazepam had approximate IC50 values of 0.75 mM and 75 microM, respectively. These findings are compared and discussed in relation to those obtained with an anti-proliferative assay which has been suggested to predict teratogen potential.

Animals↗
PubMed1990

In vitro screening for anticonvulsant-induced teratogenesis in neural primary cultures and cell lines.

To establish inherent potential for the induction of neural tube defects the ability of selected anticonvulsant agents to interfere with cell division has been established in vitro using an antiproliferative assay in clonal cell lines and a cytotoxicity assay using primary cultures of cerebral cortex neurons at different stages of development. In order to evaluate the relative toxicities of these agents their in vitro effects were determined at 2-3 times the plasma therapeutic level. By these procedures valproate and the benzodiazepines, diazepam and clonazepam, exerted a potent antiproliferative action which could not be attributed to increased cytotoxicity. In contrast phenytoin was markedly cytotoxic but was without an antiproliferative action. This cytotoxicity was most pronounced during the periods of extensive fibre outgrowth. When compared to epidemiological and animal study data, agents which inhibited cell proliferation within twice therapeutic concentration were consistently associated with major neural tube malformations. However phenytoin, found to be positive in the cell cytotoxicity assay, is not associated with neural tube malformations but rather is primarily associated with mental retardation. Thus assessment of antiproliferative activity of anticonvulsant drugs may be one criterion for identification of teratogenic potential during neurulation.

Animals↗
PubMed1990

Hepatic uptake of technetium-99m HM-PAO in a fetus.

The normal biodistribution of technetium-99m HM-PAO ([99mTc]HM-PAO) includes significant uptake in the brain, liver, and kidneys. A pregnant patient studied with [99mTc] HM-PAO to confirm brain death provided an opportunity to examine the transplacental distribution of this radio-pharmaceutical in the unborn fetus. Uptake in the fetus after transplacental delivery is almost exclusively hepatic with a small amount of biliary excretion.

Adult↗
PubMed1988

The expression of an N-CAM serum fragment is positively correlated with severity of negative features in type II schizophrenia.

The expression of a 70-kD serum fragment of the neural cell adhesion molecule (N-CAM) in schizophrenia is described. Schizophrenic patients (n = 40) were found to have statistically significant increases (p less than 0.0001) in serum N-CAM levels when compared to normal individuals (n = 26), and this could not be associated with age or sex. This difference was more marked (p less than 0.0001) between type II schizophrenics (n = 13) and normal individuals (n = 26) than when patients in the overlap group between type I and type II schizophrenia (n = 18) were compared to normal individuals (p less than 0.001). This difference remained significant (p less than 0.01) when overlap patients were compared to those of type II schizophrenia. Furthermore, schizophrenic patients with lower serum N-CAM proved to be better responders to neuroleptic therapy. We suggest that these elevated serum N-CAM levels reflect an increased synaptic turnover rate in this psychotic state.

Adult↗
PubMed1987

Familial idiopathic congestive cardiomyopathy in three generations: a family study with eight affected members.

Idiopathic congestive (dilated) cardiomyopathy with an autosomal dominant inheritance pattern affected eight individuals (four males) in three of four generations of a 63-member kindred of non-consanguineous ancestry. Average age at presentation was 39.5 years (range 32-54). A malignant course with relentless cardiac failure occurred in six cases; one member who died suddenly had been asymptomatic and the eighth is alive but in cardiac failure 44 months after initial presentation. Average time course to death from onset of symptoms suggestive of cardiomyopathy in six affected members was 16 months (range three to 55 months). In three cases, sudden death occurred and was the mode of presentation in one. Myocardial histological examination, available from three cases, showed variation in muscle fibre size with interstitial fibrosis. Forty-two family members in two generations including the propositus (19 males), age range three to 46 years (mean 17.9) when first assessed were prospectively evaluated. Two had basal systolic murmurs and two had right bundle branch block. Excluding the propositus, three members showed Doppler echocardiographic evidence of regurgitation without associated structural anomalies and three had valve prolapse with Doppler echocardiographic evidence of regurgitation. Cardiac chamber dimensions were within normal limits in all members and no cardiac arrhythmias were seen. Among the various therapeutic approaches now available cardiac transplantation, especially in younger patients with unremitting disease, is a potential option which should be considered.

Adult↗
PubMedDate not supplied

Letter and category fluency in Alzheimer's disease: a prognostic indicator of progression?

This study investigated differential patterns of performance by 40 Alzheimer's disease (AD) patients on standardised letter and category fluency tests. The performance of 24 age and education matched controls was used to classify patients as relatively more letter fluency impaired (L < C, n = 15) or more category fluency impaired (C < L, n = 25), and clinical features distinguishing these patient subgroups were investigated. Category performance was equally impaired in both patient subgroups, whereas the L < C subgroups were particularly impaired on letter fluency. The subgroups differed significantly in duration of illness (24 months for L < C group, 47 months for C < L group; t = 2.69, p = 0.01) but did not differ in global dementia severity, age, education, general language ability, or functional status. Data on annual rate of change (ARC) on the Mini-Mental State Examination were available for 26 patients. While not statistically significant, subgroup ARC differences were suggestive of more rapid decline in the L < C patients, consistent with the finding of shorter duration of illness in this group. Word fluency tests may have potential as early predictors of rate of progression in AD.

Aged↗