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Biomedical subjects

J Baird-Lambert

Publications and source records attributed to J Baird-Lambert.

At least 19 recordsLinked to original sources
PubMed1992

Liver function tests in persons receiving anticonvulsant medications.

Liver function tests were carried out in 206 adults and children taking anticonvulsants to ascertain the prevalence of biochemical abnormalities in asymptomatic patients. It was observed that serum gamma-glutamyl transpeptidase was elevated in 74.6% of patients, alkaline phosphatase in 29.7% and alanine aminotransferase in 25.2% of cases. These figures are similar to those previously reported in the literature and probably reflect hepatic enzyme induction by the anticonvulsants. It is suggested that there is no value in the routine performance of liver function tests in patients with epilepsy. However, such patients should be informed of the symptoms of hepatic dysfunction and asked to report for liver function tests should they have such symptoms.

Adolescent↗
PubMed1987

1-Methylisoguanosine: interaction with central adenosine receptors and lack of antagonism of its in vivo effects by a benzodiazepine antagonist.

1-Methylisoguanosine, a marine natural product analogue of adenosine, with moderate activity as a benzodiazepine receptor ligand, has previously been shown to have muscle-relaxant and hypothermic activity in mice in vivo. The present experiments showed that the benzodiazepine antagonist Ro15-1788 did not block the in vivo muscle-relaxant and hypothermic effects of 1-methylisoguanosine, suggesting that these particular actions are not due to interactions with benzodiazepine receptors. When applied by microiontophoresis near spontaneously-active neurones or neurones activated by ACh, DL-homocysteate or glutamate in the ventrobasal thalamus of anaesthetized rats, 1-methylisoguanosine had a depressant action; it was similar to adenosine in potency and in its ability to be antagonized by 8-(parasulphophenyl)theophylline. The depression was usually longer lasting than that caused by adenosine, consistent with previous neurochemical data showing it to be resistant to adenosine deaminase and a poor substrate for the uptake system for adenosine in the CNS. These results suggest that the major pharmacological/behavioural actions of 1-methylisoguanosine in vivo are more likely to be caused by an interaction with adenosine receptors, rather than with benzodiazepine sites.

Animals↗
PubMed1987

Identifying patients who might benefit from free phenytoin monitoring.

Guidelines for measuring free drug concentrations in serum have become necessary due to the easy availability of these assays as a result of the introduction of commercial kits. The present study was performed to identify patients or groups of patients in whom the serum free phenytoin fraction varied from normal, such that they might benefit from measurement of serum free phenytoin. Three hundred fourteen samples submitted for routine phenytoin analysis were studied by enzyme-modified immunoassay technique (EMIT). Thirty-eight patients on phenytoin monotherapy and without other factors thought to affect protein binding of this drug had a mean (+/- SD) free phenytoin fraction of 9.8 +/- 1.8% of total concentration (mean serum albumin concentration 43.4 +/- 3.9 g/L). The free fraction was elevated by administration of comedications which are themselves highly protein bound, and in those patients who were hypoalbuminaemic (serum albumin less than 30 g/L). The groups studied were not mutually exclusive, but stepwise regression analysis showed that other factors known to affect serum albumin (e.g., age greater than 65 years, liver or renal disease, or pregnancy) did not, in themselves, produce a significant effect on free phenytoin fraction. Similarly, an elevated total serum phenytoin concentration was not a significant factor in producing an elevation in free phenytoin fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1986

Studies on several pyrrolo[2,3-d]pyrimidine analogues of adenosine which lack significant agonist activity at A1 and A2 receptors but have potent pharmacological activity in vivo.

5'-Deoxy-5-iodotubercidin was previously reported to cause potent muscle relaxation and hypothermia when injected i.p. into mice. In normotensive rats, i.v. injection reduced blood pressure and heart rate. 5-Iodotubercidin possessed the same in vivo activities whereas tubercidin was pharmacologically almost inactive. None of these compounds interacted significantly with Al adenosine receptors, as determined by their ability to displace 3H-N6-phenylisopropyladenosine or 3H-5'-N-ethylcarboxamidoadenosine bound to rat brain membranes. Furthermore these compounds were much weaker than adenosine as agonists of adenosine-stimulated adenylate cyclase in guinea-pig brain slices (A2 receptors). A previous report showed that 5'-deoxy-5-iodotubercidin and 5-iodotubercidin were very potent inhibitors of adenosine kinase from rat or guinea-pig brain and were potent inhibitors of 3H-adenosine uptake into brain slices; relative to the halogenated derivatives, tubercidin was quite weak as an inhibitor of adenosine kinase and of adenosine uptake. We therefore propose that a significant part of the in vivo activity of the two halogenated tubercidin analogues may not be due to a direct agonist action at A1 and/or A2 adenosine sites (as proposed for a number of other metabolically-stable analogues of adenosine) but may result from an inhibition of reuptake of endogenously-released adenosine; the increased extracellular levels of adenosine resulting from this action could then interact directly with membrane receptors. Consistent with this, low concentrations of 5'-deoxy-5-iodotubercidin were shown to significantly potentiate the effects of exogenous adenosine on blood pressure and heart rate in anaesthetized rats and on adenosine-stimulated cAMP generation in guinea-pig brain slices. None of these compounds interacted with central benzodiazepine receptors. The cardiovascular and behavioural effects of 5'-deoxy-5-iodotubercidin and 5-iodotubercidin were blocked by theophylline; results from the cardiovascular studies suggest there may be different adenosine receptors in heart and blood vessels.

Adenosine↗
PubMed1985

Effects of prenatal glucocorticoids on renal maturation in newborn infants.

The effect of prenatally administered glucocorticoids on tubular reabsorption of beta 2-microglobulin and elimination half-life gentamicin have been investigated in newborn infants. beta 2-Microglobulin:creatinine ratio was significantly higher in preterm (4.43 +/- 0.88) than in full-term infants (0.89 +/- 0.42), but did not differ between infants exposed to betamethasone in utero and those who were not. Gentamicin pharmacokinetics did not differ between preterm infants who had or had not been exposed to betamethasone. It is therefore concluded that whilst prenatally administered glucocorticoids influence both pulmonary and hepatic maturation, they do not alter either renal tubular reabsorption of beta 2-microglobulin or glomerular filtration rate as estimated by gentamicin half-life.

Adult↗
PubMed1984

Pharmacokinetics of cefotaxime in neonates.

The effects of gestational age on the pharmacokinetics of cefotaxime and its desacetyl metabolite during the first days of life was investigated in a group of four full-term infants and 12 preterm infants of less than 35 weeks gestation. Half of the preterm infants had received betamethasone, a drug known to facilitate hepatic microsomal drug metabolism, whilst the others had not. No significant differences in the pharmacokinetics of cefotaxime were observed between the various groups, with elimination half-life (T 1/2 beta) of cefotaxime ranging from 4.04 +/- 1.52 to 4.56 +/- 1.31 h. The desacetyl metabolite of cefotaxime was present in all post-dose serum samples, irrespective of the gestational age of the baby. Its formation was apparently unaffected by prior exposure to betamethasone. The elimination half-life of cefotaxime is significantly longer in newborn infants than in older children or adults, this increase probably results from decreased renal excretion of the drug, rather than from immaturity in its metabolism. A dose of 50 mg/kg of cefotaxime given every 12 h is appropriate for infants of less than seven days old.

Aging↗
PubMed1984

Changes in response to metrazole during fever in juvenile rats; a new model for febrile convulsions?

Previous models for febrile convulsions have used environmentally induced hyperthermia as the stimulus to induce convulsions. Changes in response to metrazole during yeast-induced fever in juvenile rats are reported here. Animals were more susceptible to metrazole during the rising phase of fever but showed some resistance to its convulsant effects once the fever was established and following defervescence. It is suggested that this may form the basis of a physiologically more appropriate model for the study of the pathogenesis of febrile convulsions.

Animals↗
PubMed1984

Theophylline metabolism in preterm neonates during the first weeks of life.

The effects of prenatal steroids on theophylline metabolism in infants of 27-32 weeks gestation was studied. Although in utero exposure to betamethasone was associated with a more mature theophylline metabolite pattern in the first days of life, initial elimination half-life (t1/2 beta) did not differ significantly between groups. By the second or third week of life the metabolite pattern was similar in all infants. The decline in t1/2 beta seen during theophylline treatment was not directly related to increased metabolite formation. These data suggest that other factors, such as renal clearance, are more important in determining the pharmacokinetics of theophylline in neonates than is hepatic metabolism.

Betamethasone↗
PubMed1982

Phenytoin elimination after intoxication during long-term treatment.

Because of the saturable nature of phenytoin metabolism, intoxication due to overdosage with this drug occurs relatively frequently. The present paper reports on a systematic study of phenytoin elimination in six patients with clinical signs of overdosage and with initial serum phenytoin levels well above the normal therapeutic range (40 mumol/L to 80 mumol/L). On the basis of data obtained, it is recommended that, when a patient presents with symptoms of phenytoin intoxiation, an initial serum phenytoin level should be determined. If this exceeds 130 mumol/L, the drug should be withdrawn for a period of 72 to 84 hours, then the administration should be recommenced at a lower dose.

Adolescent↗
PubMed1982

Potentiation of pharmacological responses to adenosine, in vitro and in vivo.

1. In washed guinea-pig brain slices, adenosine uptake inhibitors potentiated the responsiveness of cAMP to adenosine, while an adenosine deaminase inhibitor, 2'-deoxycoformycin, was without effect. 2. In the isolated guinea-pig ileum, uptake was important in terminating the inhibitory action of adenosine on nerve-mediated contractions whereas the ADA inhibitor did not affect the ileum or its responses to adenosine in any way. 3. Adenosine given to mice (100 mg/kg i.p.) or guinea-pigs (250 mg/kg i.p.) caused a small, transient fall in body temperature, accompanied by skeletal-muscle relaxation. 4. In mice this temperature fall was potentiated by the uptake blocker dilazep, although only marginally so by the uptake blocker dipyridamole. The ADA-inhibitor also potentiated the pharmacological responses to adenosine. 5. Responses to adenosine in the guinea-pig were less affected by treatment with uptake or ADA-inhibitors, except when given in combination.

Adenosine↗
PubMed1982

Pharmacokinetics and tissue distribution of metronidazole in the new born infant.

Metronidazole pharmacokinetics and tissue distribution were studied in 11 infants varying in gestational age from 28 to 40 weeks. Elimination half-life was inversely related to gestational age, and ranged from 22.5 to 109 hours. Hepatic hydroxylation of metronidazole was not evident in infants less than 35 weeks' gestation, unless they had been exposed prenatally to betamethasone. A dosage schedule of 15 mg/kg intravenously as an initial single dose is proposed, and will provide adequate therapeutic levels for 48 hours in the preterm infant and for 24 hours in the term infant. Subsequently a dose of 7.5 mg/kg/12 hours is suggested for the first week of life.

Bacterial Infections↗