Biomedical subjects
Publications and source records attributed to M Feely.
The value of early, direct aneurysm clipping in restoring third-nerve function after palsy associated with a posterior communicating artery aneurysm is assessed.
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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.
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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.
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.
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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.
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.
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%.
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The cyclical exacerbations of epilepsy (catamenial epilepsy) were used to assess the antiepileptic effect of a benzodiazepine, clobazam. Doses of 20 mg, and in some cases 30 mg, per day were compared with placebo over predetermined ten-day periods in a double-blind cross-over study. The results were evaluated by preference in a sequential procedure. In 14 of 18 patients who received both treatments clobazam was superior to placebo, and in 4 patients no preference was established. Clobazam completely prevented seizures in most of the patients, and toxic effects were of low frequency and severity.
Electrical stimulation of the infraorbital nerve in the cat resulted in a series of far-field evoked potentials at the vertex. The wave form of these potentials is similar to the auditory brain stem evoked response and the somatosensory far-field response; it is multicomponent, the amplitudes of individual components are of the order of 1 microV, and the latencies are all less than 4 msec. The anatomical origins of these evoked potentials were investigated. The results indicated that contributions due to the afferent trigeminal nerve, the principal sensory nucleus, and the spinal trigeminal nucleus are involved.
We studied post-occlusive reactive hyperaemia using ecg-triggered mercury strain-gauge plethysmography in eight normal subjects treated with incremental doses of aspirin (27.5-1200 mg). The reactive hyperaemic response was measured in the finger (predominantly skin blood flow) and the calf (predominantly muscle). Concentrations of TXB2 and 6-oxo-PGF1 alpha were measured in venous effluent blood from the hand by RIA, following arterial occlusion. Levels of TXB2 were significantly higher at 0-10 and 60-70 seconds (p less than 0.01), and 90-100 seconds (p less than 0.05) following release of occlusion compared to pre-occlusion values. However there was no significant change in concentrations of 6-oxo-PGF1 alpha and therefore by this method release of prostacyclin during reactive hyperaemia in the hand. Aspirin had no influence on finger or calf reactive hyperaemia 90 minutes after dosing, despite marked inhibition of platelet MDA production (75% after 110 mg, maximal inhibition after 1200 mg). These data provide no support for the hypothesis that prostacyclin is involved in the determination of the post-occlusive reactive hyperaemic response in the finger and calf in man.
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