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Biomedical subjects

M P Feely

Publications and source records attributed to M P Feely.

At least 19 recordsLinked to original sources
PubMed1990

Effect of warfarin on plasma concentrations of vitamin K dependent coagulation factors in patients with stable control and monitored compliance.

There is a discrepancy in the results of reported studies of levels of vitamin K dependent coagulation factors in patients on warfarin therapy. This may have arisen partly because of the problem of assuring compliance with therapy in outpatients. The plasma concentrations of the vitamin K dependent clotting factors II, VII, IX and X were studied in 23 outpatients whose adherence to prescribed warfarin therapy was determined using a pharmacological indicator of compliance. In these patients, who were shown to have consistently good compliance and stable anticoagulant control over a period of 3-6 months, the activities in plasma of the four coagulation factors were not equally suppressed. Factor IX levels were significantly greater than those of factor VII (P less than 0.0001) which in turn were significantly greater than the levels of factor II (P less than 0.0001) or factor X (P less than 0.0001). There was no significant difference between the levels of factors II and X which were depressed to a similar extent. The proportion of variability of the International Normalized Ratio (INR) explained by linear regression was 51-77% and a model was derived to predict the INR from the mean of the levels of the four clotting factors. The concentrations of the coagulation factors II, VII, IX and X are likely to be highly dependent on the degree of compliance with warfarin therapy which should be taken into account when investigating the behaviour of these factors.

Aged↗
PubMed1990

Hyperthyroidism, inappropriate plasma TSH and pituitary adenoma in three patients, two receiving long-term phenothiazine therapy.

Hypersecretion of TSH by a pituitary adenoma is thought to be a rare form of hyperthyroidism. We describe three such patients, each of whom presented with clinical hyperthyroidism and a diffuse goitre, without eye signs or dermatopathy. Two were receiving long-term phenothiazine, one of these was also acromegalic. Plasma thyroxine, free T4 and tri-iodothyronine were repeatedly raised in each; plasma TSH was grossly elevated in one and inappropriately normal in the other two. Plasma TSH did not rise in response to thyrotrophin-releasing hormone or metoclopramide and was not suppressed by L-dopa in any patient. Anti-thyrotrophin receptor antibodies were undetectable. Skull radiographs showed erosion and expansion of the pituitary fossa and CT scans confirmed a pituitary mass in each patient. A pituitary adenoma was removed by transphenoidal surgery in two patients and a TSH-secreting adenoma was confirmed by immunocytochemical staining and electron microscopy. Both patients were clinically euthyroid post-operatively but still had evidence of TSH excess. Pituitary surgery was technically unsuccessful in the third patient. Although two patients had hyperthyroidism of long duration, all three were diagnosed within one year of the introduction of a sensitive TSH assay to our laboratory. A TSH-secreting pituitary adenoma may be a more common cause of hyperthyroidism than has been believed.

Adenoma↗
PubMed1989

Poor compliance is a major factor in unstable outpatient control of anticoagulant therapy.

Control of oral anticoagulant therapy in outpatients is often unsatisfactory. The contribution of poor compliance with prescribed warfarin to unstable anticoagulant control was investigated prospectively using low-dose phenobarbitone as an indicator of compliance in 30 out-patients, 15 with stable and 15 with unstable control. Following entry to the study, there was no significant change in anticoagulation (p = 0.36) in the group with stable control. In the group who previously had unstable control, there was a significant change in INR (p = 0.0045) and anticoagulant control greatly improved. It appears that the considerable fluctuation in INR seen in many of the latter patients before the study was due to poor compliance and that entering them into the study modified their behavior. Two patients in this group who continued to have unstable anticoagulant control were shown to be poorly compliant using the phenobarbitone indicator. The results suggest that, in outpatients, poor compliance is the major cause of unstable anticoagulation with warfarin.

Ambulatory Care↗
PubMed1988

Use of a pharmacologic indicator to compare compliance with tablets prescribed to be taken once, twice, or three times daily.

By use of an interview, return tablet count, and a pharmacologic indicator (low-dose phenobarbital), we compared compliance with tablets prescribed to be taken once, twice, or three times daily. One hundred seventy-nine patients with type II diabetes were randomly allocated to take one 2 mg phenobarbital tablet once, twice, or three times daily for 28 days. Phenobarbital level/dose ratios indicated that compliance was similar with once- and twice-daily regimens, and both were better than thrice-daily dosing. Mean return tablet counts suggested that compliance was best with the once-daily regimen; both twice- and thrice-daily regimens were similarly inferior. This difference between the techniques may be explained by the inadequacies of the residual tablet count, which identified only 13% of cases identified by phenobarbital. We conclude that compliance with the once-daily regimen was best, but that compliance with a twice-daily regimen was very similar, and both were superior to dosing three times a day.

Drug Administration Schedule↗
PubMed1988

The use of a pharmacological indicator to investigate compliance in patients with a poor response to antirheumatic therapy.

Twenty-six patients with rheumatoid arthritis which was poorly controlled despite high dose D-penicillamine were studied. Compliance was assessed by standard methods (return tablet count and interview). In addition low-dose phenobarbitone was included in the penicillamine formulation as a pharmacological indicator of compliance. Using these techniques incomplete compliance was apparent in 11 patients (42%). All such patients were identified by the pharmacological marker. Only one admitted poor compliance at interview and only six returned more than a few tablets too many. The reason for the high incidence of poor compliance in this selected group is not apparent but it may represent a significant cause of failure with D-penicillamine therapy. The use of low-dose phenobarbitone may have wider applications in the investigation of patients with other conditions who fail to respond adequately to treatment.

Adult↗
PubMed1988

Measuring treatment compliance of men with non-gonococcal urethritis receiving oxytetracycline combined with low dose phenobarbitone.

Of 62 men with non-gonococcal urethritis who entered a study to assess compliance with treatment with oxytetracycline, only 33 could be evaluated. Traditional methods (interview and the absence of oxytetracycline in the urine) showed incomplete compliance in nine. Use of low dose phenobarbitone as a pharmacological marker showed incomplete compliance in a further five patients. In addition, phenobarbitone concentrations gave information on the extent to which individual patients had omitted treatment and provided direct, as opposed to circumstantial, evidence of good compliance by most (18) of those studied. Only three of the 33 patients whose compliance was assessed had evidence of continuing infection at follow up, and there was evidence of incomplete compliance in only one of these patients.

Adolescent↗
PubMed1987

The effect of cimetidine on the single dose pharmacokinetics of oral clobazam and N-desmethylclobazam.

The effect of cimetidine on the single dose pharmacokinetics of orally administered clobazam and N-desmethylclobazam (NDMC) was studied in volunteers. Cimetidine inhibited the elimination of both clobazam and NDMC and inhibited the rate of formation of NDMC from clobazam. The increase in the AUC for NDMC generated from clobazam was relatively greater than that for clobazam itself. This suggests that NDMC elimination is inhibited to a relatively greater extent than clobazam elimination. The increase in AUC for NDMC generated from clobazam was also relatively greater than that for NDMC administered orally. This would suggest that cimetidine either increases the bioavailability of clobazam or reduces that of NDMC. The increases in the AUC for NDMC and for clobazam in some individuals was of a magnitude which is likely to be clinically significant.

Adult↗
PubMed1987

Pharmacokinetics of N-desmethylclobazam in healthy volunteers and patients with epilepsy.

1. The single dose pharmacokinetics of N-desmethylclobazam (NDMC) and clobazam were studied in eight healthy male volunteers. 2. Steady-state pharmacokinetic data are described from four healthy male volunteers and eight epileptic patients taking NDMC. 3. A single 30 mg dose of NDMC produced a greater Cmax (P less than 0.001) and AUC0-infinity (P less than 0.005) and a shorter tmax (P less than 0.05) and t1/2 (P less than 0.01) for NDMC than did 30 mg clobazam. 4. Mean steady-state NDMC concentrations were greater in male patients than in female patients and also in male patients compared with male volunteers. The differences between patients and volunteers might be explained by concomitant antiepileptic medication.

Adult↗
PubMed1986

The effect of low-dose phenobarbitone on three indices of hepatic microsomal enzyme induction.

The effects of low-dose phenobarbitone on three indices of hepatic enzyme induction were studied. Eight healthy volunteers took phenobarbitone 7.5 mg daily for 4 weeks followed by 15 mg daily for 4 weeks; five subjects took 30 mg daily for a further 2 weeks. Phenobarbitone 15 mg daily produced a significant rise in antipyrine clearance (P less than 0.05). Phenobarbitone 30 mg daily produced a further rise, but probably because of the reduced numbers of subjects, this did not achieve significance (P = 0.06). Urinary 6-beta-hydroxycortisol and D-glucaric acid levels did not change significantly and remained within the range seen in subjects not taking enzyme-inducing drugs. We conclude that phenobarbitone 7.5 mg daily produces little (if any) enzyme induction whereas 15 mg, or more, may have the potential to produce drug interactions through enzyme induction.

Adult↗
PubMed1985

Differences between the tolerance characteristics of two anticonvulsant benzodiazepines.

Clobazam (10 mg/kg) and clonazepam (0.25 mg/kg) were administered to mice twice daily by the intraperitoneal route. The development of tolerance to their anticonvulsant effect was compared using a slow intravenous infusion of pentylenetetrazole as the convulsant stimulus. Tolerance to clonazepam developed gradually throughout a 72 h study and did not become significant until the fifth dose. In contrast, tolerance to clobazam occurred extremely rapidly, after only one dose; it was manifested as a single step and no further significant change in protection was observed. Recovery from benzodiazepine tolerance was also studied and seen to occur rapidly with both these compounds; following cessation of dosing, protection was restored to initial levels within 36-48 h.

Animals↗
PubMed1979

Cerebellar infarction.

Cerebellar infarction has been inadequately recognized by clinicians. A review of 75 cases showed that in 55 of them the infarct acted as an expanding mass lesion and compressed the brain stem. Once this occurred, the mortality without operation was very high. With surgical treatment, the mortality was reduced considerably. The computerized tomographic scan is the diagnostic test of choice.

Adolescent↗
PubMed1979

Assessment of the postoperative course of excised brain abscess by computerized tomography.

We present two patients with brain abscess who underwent complete excision with a satisfactory clinical outcome although serial computerized tomography (CT) Scans in the early postoperative period seemed to indicate a large residual abscess in each case. We recommend treatment based on the clinical course rather than the CT scan appearance, indicate that earlier reports on this topic may be misleading, and suggest an explanation for these findings.

Brain Abscess↗