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Biomedical subjects

M Feely

Publications and source records attributed to M Feely.

At least 37 records · Page 2Linked to original sources

Use of a pharmacological indicator to monitor compliance with thyroxine.

Poor compliance with medication is often suspected, but difficult to confirm. The compliance of fourteen newly diagnosed hypothyroid patients was assessed using both TSH levels and low-dose phenobarbitone as a pharmacological marker. The study confirms the value of phenobarbitone as an indicator of compliance over a protracted period and suggests that it could be used to differentiate under-treatment from poor compliance.

Adult

N-desmethylclobazam: a possible alternative to clobazam in the treatment of refractory epilepsy?

The development of anticonvulsant tolerance during 10 days treatment with either clobazam or its principal metabolite, N-desmethylclobazam (NDMC), was compared in mice using an i.v. infusion of pentylenetetrazole as the convulsive stimulus. Subsequently the anticonvulsant activity of NDMC was assessed in patients with refractory epilepsy. In mice, a highly significant tolerance (P less than 0.001) developed to clobazam (10 mg kg-1 twice daily). During the same period, there was no significant change (P greater than 0.05) in the protection afforded by NDMC (40 or 80 mg kg-1 twice daily) although some reduction in anticonvulsant activity was apparent. NDMC (30 mg once daily) was given to nine patients with frequent complex partial and/or grand mal seizures who had become tolerant to the anticonvulsant effect of clobazam. Seven of the patients had been free from benzodiazepine therapy for at least 2 weeks, while the other two patients were switched directly from clobazam. Eight of the nine patients showed a favourable response to NDMC. In the seven who had been given a holiday from clobazam the response to NDMC was similar to the initial response to clobazam and was achieved at plasma NDMC concentrations in the same range as those seen during clobazam administration (1000-3000 ng ml-1). It is concluded that NDMC is active as an anticonvulsant in man and there is evidence from the animal studies to suggest that it may be preferable to clobazam.

Adult

Low-dose phenobarbitone as an indicator of compliance with drug therapy.

1 To assess the potential value of low-dose phenobarbitone (PB) as a marker of compliance we studied the relationship between plasma level of PB and dose (2-16 mg daily) following 3 or 4 weeks treatment in healthy volunteers (n = 26) and in-patient volunteers (n = 7). 2 Also, to simulate poor compliance, PB levels were measured in some volunteers following alternate-day (n = 6) or short-term (n = 5) treatment with similar doses. These levels, expressed as the level: dose ratios (LDRs), did not overlap with those obtained following 3 or 4 weeks of daily PB intake. 3 To evaluate the efficacy of this marker in patients taking other drugs we gave a group of out-patients (n = 24) compound tablets containing B vitamins and a small dose (16 mg) of PB; their compliance over 2-5 weeks was assessed both by measuring plasma levels of PB and residual tablet counting. 4 In the latter study, as well as providing absolute evidence of good compliance by many patients, the plasma levels of PB proved particularly valuable when non-compliant individuals 'forgot' to bring their residual tablets. 5 We suggest that phenobarbitone, in doses low enough to be non-sedative and non-enzyme inducing, is potentially useful as a pharmacological indicator of compliance with drug therapy.

Adult

Benzodiazepine cross-tolerance in mice extends to sodium valproate.

Slow intravenous infusion of pentylenetetrazol was used to measure the convulsive threshold in mice. The anticonvulsant effects of clobazam, clonazepam, diazepam, lorazepam, sodium phenobarbitone and sodium valproate were assessed in naive animals and compared with the effects of the same compounds in animals which had been pretreated (twice daily for 3 days) with one of the benzodiazepines or sodium valproate. Cross-tolerance was observed between all the benzodiazepines but not between benzodiazepines and sodium phenobarbitone. Animals pretreated with the benzodiazepines were cross-tolerant to valproate, but the converse was not true; nor did sodium valproate induce tolerance to itself.

Animals

Doctors' unawareness of the drugs their patients are taking: a major cause of overprescribing?

We studied the accuracy of both hospital and general practitioners' records of current drug treatment in consecutive patients who attended a general medical review clinic. Either the hospital or the general practitioner's records (obtained in a questionnaire), or both, were inaccurate for over 70% of 59 patients interviewed with their medicine. Most of the errors were due to patients taking drugs in addition to those shown in their records. Some of these were inappropriate, and many seemed unnecessary. It appears that neither hospital doctors nor general practitioners are fully aware which drugs their patients are taking, and this may contribute to overprescribing. We believe that considerable financial savings might be made if patients brought all their medicines to every consultation.

Awareness

Tolerance to the anticonvulsant effect of clonazepam in mice: no concurrent change in plasma concentration.

Clonazepam was administered for 10 or more days on three different dose regimens (0.5, 0.25 and 0.08 mg kg-1 twice daily) to mice given pentetrazol by slow intravenous infusion. Plasma concentrations of clonazepam were assayed by high performance liquid chromatography. Tolerance developed to the anticonvulsant effect of clonazepam at all doses but was incomplete and could be overcome by increasing the dose. With the 0.5 and 0.25 mg kg-1 regimens there was no significant change in the drug plasma concentrations during development of tolerance; on the lowest dose, levels were below the limits of accurate detection. Anticonvulsant tolerance does not seem to be the result of a disturbance in clonazepam metabolism.

Animals

Intermittent clobazam for catamenial epilepsy: tolerance avoided.

Clobazam, 20 or 30 mg/day was given for 10 days around menstruation in successive menstrual cycles to 13 women who had responded favourably to this drug in an earlier short-term placebo controlled cross-over study. Three patients have been successfully treated, with complete freedom from seizures around menstruation, for 3-3 1/2 years and two others responded favourably until pregnancy made treatment inappropriate. A further four patients did well during a shorter period (6-13 months) of follow-up. An increase in seizures between periods of clobazam therapy was observed in three patients, and led to the withdrawal of this drug in two of them. However, tolerance to the antiepileptic effect of clobazam was not observed in any patient, even though nine were treated for 1 year or more. In only once case was it necessary to discontinue treatment because of sedative side effects.

Adult

Chondroblastoma of the skull.

A case of chondroblastoma of the temporal bone is reported, and the pathology of the lesion outlined. The rarity of these neoplasms in the skull makes accurate prognosis impossible.

Adult

Antibiotic prophylaxis in neurosurgery. A randomized controlled trial.

A randomized trial was performed to support the contention that prophylactic antibiotics can reduce the incidence of postoperative neurosurgical wound infections. The regime outlined by Malis was followed. Vancomycin and gentamicin were administered systemically just prior to surgery and streptomycin was added to the irrigating solution. Patients were randomly assigned to two groups: control and treated. The infection rate in the control group was 3.5% and in the treated group 0.5%.

Adult