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Biomedical subjects

J Oxley

Publications and source records attributed to J Oxley.

35 records · Page 2Linked to original sources
PubMed1984

A clinical trial of single dose rectal and oral administration of diazepam for the prevention of serial seizures in adult epileptic patients.

The clinical anticonvulsant efficacy of single dose rectal and oral administration of diazepam 20 mg was examined in two double-blind placebo-controlled trials in adult epileptic patients. All subjects suffered from drug resistant epilepsy and frequently experienced serial seizures. Diazepam was administered rectally as a new experimental suppository formulation immediately after a seizure and was highly effective in preventing recurrent fits within a 24 h observation period (p less than 0.001). Pharmacokinetic studies revealed a wide range of serum diazepam concentrations 60 min after administration of the suppository (mean serum diazepam level 190 +/- 73 (SD ng/ml). In a similar study oral administration of diazepam 20 mg significantly reduced the incidence of serial seizures compared with a placebo (p less than 0.01) and the mean 60 min serum diazepam level was 273 +/- 190 (SD) ng/ml.

Administration, Oral↗
PubMed1983

Acute effects of intravenous phenytoin on the frequency of inter-ictal spikes in man.

Phenytoin was administered intravenously to six adult epileptic patients in doses ranging from 500--1000 mg (equivalent to 5.6 mg/kg--20 mg/kg body weight). A significant decrease in the frequency of inter-ictal spikes in the EEG was seen and this effect was most marked 10--20 min after the infusion, when the mean spike count was reduced to 27% (s.d. 17%) of the control (P less than 0.05). In one subject the decrease in inter-ictal spikes coincided with a decrease in fit frequency. Adverse reactions affecting the vestibular system occurred in three patients at doses of 15--20 mg/kg. No cardiovascular complications were observed in any subject. The overall results suggest that doses of 7.5--10 mg/kg would be sufficient to significantly reduce the frequency of inter-ictal spikes in the EEG.

Adult↗
PubMed1983

A controlled trial of cinromide.

A double-blind controlled trial of cinromide in 25 adult subjects with refractory epilepsy using the maximum tolerated dose showed that it possessed no significant antiepileptic properties.

Adolescent↗
PubMed1983

Prolactin and gonadotrophin changes following generalised and partial seizures.

Postictal values of prolactin, LH and FSH have been recorded in patients with both generalised tonic-clonic and partial seizures. Elevations of prolactin and LH were seen immediately and at 20 minutes in males and females with generalised attacks. At sixty minutes values for prolactin had fallen to baseline levels, but LH remained elevated. FSH values were increased in females only, at twenty and sixty minutes. Following partial seizures prolactin was elevated, especially with complex partial seizures, at twenty minutes. These results are discussed in the light of known electrophysiological mechanisms relating to partial seizures, and clinical guidelines for the use of neurohormonal tests in the evaluation of seizures are suggested.

Consciousness↗
PubMed1982

Bioavailability of diazepam after intravenous, oral and rectal administration in adult epileptic patients.

1 The absorption of single doses of diazepam in six adult epileptic subjects following intravenous, oral and rectal administration were studied in order to evaluate the usefulness of the latter in emergency situations in the adult. 2 Diazepam tablets (Valium, Roche) and rectal solution (Valium solution for intravenous administration) produced similar peak serum concentrations after delays of 15-90 min. 3 Two suppository formulations showed statistically significant differences in absorption characteristics. 4 Serum diazepam levels above 400 ng ml-1 (suggested to be necessary for a satisfactory anticonvulsant effect) were reached in only a few subjects after rectal doses of 10-20 mg of solution, and then usually after a delay of over 2 h.

Administration, Oral↗
PubMed1982

Absorption of diazepam from the rectum and its effect on interictal spikes in the EEG.

Rectal administration of several different preparations of diazepam to a group of adult volunteer patients with epilepsy produced variable rates of absorption. Peak serum concentrations following 10 mg, 20 mg, and 30 mg of diazepam solution were achieved between 13-60 min, 10-120 min, and 30-90 min respectively. An experimental diazepam "solid solution" suppository was found to have significantly better absorption characteristics compared with the commercially available Valium suppository. Diazepam solution 20 mg was administered rectally in 10 adult epileptic patients with frequent spontaneous interictal spikes in their EEGs. A highly significant reduction in spike frequency was seen compared with placebo. The effect was most marked 10-20 min after administration of diazepam, when the mean spike count fell to 39 +/- 35 SD percent of the control value (p less than 0.01), and this corresponded with a mean serum diazepam level of 210 +2- 125 ng/ml.

Adolescent↗
PubMed1981

Rectal diazepam in the treatment of absence status: a pharmacodynamic study.

Rectal administration of diazepam is highly effective in terminating absence status as judged by reduction of spike-wave activity in the EEG. Pharmacokinetic studies indicate that diazepam can have antiepileptic properties at serum levels well below those previously reported as being necessary to achieve a therapeutic effect.

Adult↗
PubMed1980

Effects of sodium valproate on the serum protein binding of phenytoin, and on liver enzyme activity.

The effect of a single dose of sodium valproate on the serum protein binding of phenytoin was studied in 6 epileptic patients receiving phenytoin maintenance therapy. Phenytoin was significantly displaced by valproic acid, but the free concentration of phenytoin was unchanged because of redistribution to tissues. As a result of this effect, total serum phenytoin concentration was significantly lowered. Induction of metabolism probably does not play a part in this interaction because antipyrine half-lives and urinary D-glucaric acid excretion were not altered by chronic administration of sodium valproate to 8 patients receiving this drug alone.

Antipyrine↗
PubMedDate not supplied

Renin gene expression in fetal kidneys of pregnancies complicated by twin-twin transfusion syndrome.

Twin-twin transfusion syndrome (TTTS) complicates one in five monochorionic pregnancies and is generally associated with high mortality and morbidity. One twin (the recipient) grows appropriately and has polyhydramnios while the other (the donor) may have a reduced growth velocity and severe oligohydramnios. The disparities in amniotic fluid volumes represent differences in fetal urine output. These differences occur secondary to hemodynamic changes, in which the vascular arrangement of placental anastomoses in TTTS leads to unidirectional flow from the donor to the recipient twin. A better understanding of the pathophysiology may contribute to improved management of this morbid condition. We studied three consecutive prospectively diagnosed stillborn twin pairs affected by early-onset TTTS. Renin gene expression was studied in sections of fetal kidneys with immunocytochemistry using a renin antiserum and with in situ hybridization using riboprobes complementary to renin mRNA, and renin-secreting cells (RCC) were counted. The overall maturation of the renal cortex was assessed by the percentage of immature glomeruli. The donor twin kidneys were smaller than those of the recipients, but the maturation of the renal cortex was not significantly different (28.2% immature glomeruli in the donor and 24.4% in the recipient kidney). The donor kidney showed increased renin gene expression with hyperplastic juxtaglomerular apparatuses (JGAs) that contained excess RCCs (median 20.02 [25th-75th centiles, 5.4, 25.1 RCCs per 100 glomeruli]). In contrast, the recipient kidney was virtually devoid of these cells (0.04 [0, 0.36] RCCs per 100 glomeruli; P < 0.05). In the donor kidney, increased renin release may, by a local action, contribute to renal vasoconstriction and oliguria. Increased renin and/or angiotensin II in the blood passing through the placental anastomoses may, by an endocrine action, suppress renin synthesis in the recipient kidney, thereby increasing renal blood flow and causing polyuria and polyhydramnios. These changes in the renal RAS could thus contribute to the pathogenesis of TTTS. The renal renin changes noted here may represent a contributory or compensating mechanism, the success of which may dictate the overall survival of the twin pregnancy and allow better understanding of the pathophysiology and perhaps therapy that may be employed in this condition.

Adult↗