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Biomedical subjects

M J Denham

Publications and source records attributed to M J Denham.

At least 19 recordsLinked to original sources

Adverse drug reactions.

The elderly have benefitted considerably from the vast increase in the range of drugs available for prescription. However it is now well recognized that the incidence in adverse drug reactions increases with age. This is mainly due to altered pharmacodynamics and pharmacokinetics as well as multiple prescribing and the effect of illness rather than the effect of age per se. Since adverse drug reactions are such a potent cause of illness, it is sensible for doctors to follow simple rules when prescribing for the elderly.

Aged

Evaluation of the safety of enalapril in the treatment of heart failure in the very old.

We have introduced enalapril, in doses equal to or less than the 2.5 mg currently recommended, as an adjuvant to digoxin and diuretics in 17 patients of mean (SD) age 83 (5) years with severe heart failure. Only eleven patients tolerated its introduction. Unlike those reported in younger patients, all but one of the adverse drug reactions occurred 8 h or more after the first dose. Aged patients started on ACE inhibitors should be observed in hospital until stabilized on a maintenance dose. Three patients had an adverse reaction which differed in nature from those previously reported: acute confusional state, ataxia and mesenteric ischaemia. Ten patients were discharged on 5 mg or 10 mg maintenance doses of enalapril. In nine of them improvement on triple therapy was sustained for a minimum of three months. ACE inhibition was lost in the other patient when her compliance with enalapril therapy fell to around 75%: monitoring compliance is essential when ACE inhibitors are used in low dosages. Enalapril was withdrawn during follow up in three patients because of symptoms of mesenteric ischaemia and in four because of dramatic deterioration of renal function. One of the latter was found subsequently to have severe bilateral atheromatous renal artery stenosis. When isosorbide dinitrate was substituted for enalapril, symptoms of mesenteric ischaemia resolved and renal function returned to baseline. Continuing surveillance for adverse effects is essential in patients of this age group with severe heart failure, and the risk of occult renal artery stenosis requires regular biochemical screening during follow up.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Pressure sores: effect of Parkinson's disease and cognitive function on spontaneous movement in bed.

It has previously been shown that the incidence of pressure sores is related inversely to the amount of movement made during the night. The present study of 30 in-patients of geriatric units suggests that the measurement of mean lateral displacement of the centre of gravity may better characterize those at risk than the total amount of movement. The mean displacement was reduced in Parkinson's disease and in dementia. The prevalence of pressure sores was markedly increased where Parkinson's disease and dementia coexisted.

Aged

The paradox of using a 7 day antibacterial course to treat urinary tract infections in the community.

1. We have studied determinants of outcome of 7 day courses of treatment in 77 middle aged and elderly patients, in whom the general practitioner's diagnosis of urinary tract infections had been confirmed microbiologically. Bacteria were sensitive to cephalexin or trimethoprim. Where there was no preference, treatments were allocated randomly. Compliance was monitored using a pill box with a concealed electronic device which recorded openings of the box. 2. Prescribing trimethoprim, 200 mg twice daily, was more effective than cephalexin, 250 mg four times daily (cure rates 93 and 67%) (P less than 0.006). Those cured and not cured were not distinguished by age, gender, genitourinary history, or infecting organism. 3. Compliance as measured by box openings was worse for cephalexin than for trimethopim (P = 0.01). However, both totality and pattern of compliance were similar in patients cured and not cured by cephalexin. Thus rigid adherence to a conventional course did not promote cure: fewer doses could have been prescribed. 4. Estimating compliance is essential to clinical trials where medication is self-administered. Poor compliance may establish over exacting regimens. Counting box openings did overestimate compliance, but counting residual tablets overestimated it grossly: given the number of openings less than the ideal, there should have been 171 residual tablets, only 55 were found.

Aged

Prescribing digoxin in geriatric units: the unexplained variability in dosage requirements.

Some physicians regard patients of Geriatric Units as a homogeneous population with respect to digoxin dosage requirements. Others advocate the use of pharmacokinetic models in prescribing digoxin for the elderly. Sixty in-patients of Geriatric Units were studied and the results compared with those previously obtained from 129 patients of other adult Units; all were receiving maintenance digoxin. For each patient the dose required to achieve a mean steady-state serum digoxin concentration of 1.6 nmol X l-1, the standardized dose, was calculated, assuming proportionality between the dose given and the concentration achieved. A mean of four estimates of standardized dose for each individual was used in the analysis. Threefold ranges of standardized dose covered the requirements of approximately 85% of patients both of Geriatric Units (62.5 to 187.5 micrograms per day) and of other adult Units (125 to 375 micrograms per day). The variables, serum creatinine concentration, sex, age, and body weight were of relatively little value in predicting the standardized dose for the patients in Geriatric Units. There was a sub-group of these in-patients for whom the standardized dose was extremely large.

Adult

A quinine a day keeps the leg cramps away?

A double-blind, placebo-controlled, cross-over trial of quinine in leg cramps occurring at rest was conducted in 22 elderly cramp sufferers. Despite demonstration of impaired quinine elimination in the elderly, prescription of the traditional dose of 300 mg quinine bisulphate at night failed to produce a significant (P = 0.1) reduction in the number or severity of cramps. There was a significant relationship between serum quinine concentration and attenuation of cramps. However, the simple expedient of increasing the nightly dose of quinine may carry the concomitant risk of cinchonism.

Aged

Parkinson's disease in the elderly: response to and optimal spacing of night time dosing with levodopa.

1. Insomnia is an even more frequent complaint in elderly patients with Parkinson's disease than might be expected from the effect of age alone on sleep. 2. A double-blind, placebo-controlled trial in eleven patients with Parkinson's disease of mean (s.d.) age 80(5) years, showed that nocturnal dosing with levodopa produced a clinically significant improvement in sleep both as assessed subjectively and by measurement of number of spontaneous moves in bed. 3. Despite the long interval between tablet administration and morning assessment, walking time was faster on mornings following active treatment.

Carbidopa

Therapeutic drug monitoring of digoxin: help or hindrance?

A major role of therapeutic drug monitoring services is to advise on the dose of a drug which would be required to bring the concentration in the blood to within specific 'therapeutic' limits. Monitoring digoxin usage constitutes a substantial part of the work load. We have examined the potential variability in recommendations for digoxin dosages based on a series of serum digoxin measurements in each of 80 out-patients. In over a third of cases a dose, which seemed to be optimal on the basis of the first assay result, would have produced concentrations outside the conventional therapeutic range when the measurement was repeated. This was despite careful supervision of medication and the timing of the blood sample in relation to its administration. In routine practice the apparent variability in dose requirements would be far greater. Objectives of therapeutic drug monitoring services remain the same, the way forward would seem to lie in their taking on a heavy commitment to counsel and supervise patients before repeated blood sampling. However, effort and resources might be better channelled into producing simple prescribing aids relating the risk of cardiotoxicity directly to the size of the maintenance dose and the individual's renal function.

Aged

Beta-thromboglobulin and the diagnosis of thrombosis in elderly patients.

The plasma concentration of beta-thromboglobulin was estimated in elderly in-patients using a radio-immuno-assay technique. There were highly significance differences between the mean values of patients with arterial or venous thrombosis, as compared with controls. The ability of the test to detect thrombosis above the inguinal ligament means that it is a useful addition to the existing battery of tests for detecting thrombosis.

Aged

Capillary fragility in elderly in-patients.

Capillary fragility has been examined in 110 elderly patients, excluding those patients who might have been expected to have abnormal fragility. Nonetheless, fragility appeared to be greater in elderly patients than in younger subjects. It was much increased in the non-paralysed arm of hemiplegic patients but not in the paralysed arm--perhaps because petechiae were obscured by trophic changes. Capillary fragility was significantly correlated with systolic blood pressure but not with age. This suggests that higher values in elderly patients may be related to the high prevalence of arteriosclerosis rather than to age itself.

Aged

Thyroid function tests in the elderly in the community.

A study of the well elderly living at home has demonstrated that the ranges for serum thyroxine (T4), triiodothyronine (T3) uptake and free-thyroxine index (FTI) are much narrower than those for the sick elderly in-patient. The prevalence of thyroid disease appears similar in both types of elderly population.

Aged

The value of blood cultures in geriatric practice.

Forty-nine of 498 (10%) blood cultures taken in a 14-month period in a geriatric department were positive. These cultures were taken from 295 patients. Respiratory infections, recent onset of confusion, non-specific malaise and suspected sub-acute bacterial endocarditis were the most common clinical indications for the test. Twenty-seven of the 49 positive cultures were considered significant, the remainder being regarded as due to skin contaminants. This yield was found to be of clinical value, particularly in chest infection when the responsible organism often could not be cultured from the sputum.

Aged

Pathological validation of auscultation of the elderly heart.

Systolic murmurs present in 129 geriatric patients followed to post-mortem were assessed as mitral or aortic in origin by simple clinical assessment alone. Post-mortem examination contradicted clinical findings in only 2% of cases. Mitral valve pathology, mostly post-inflammatory scarring or mucoid degeneration, was present in 50% of the cases with murmurs. There was a significant correlation between the presence of murmurs, particularly mitral murmurs, and congestive cardiac failure, and there was also a significant correlation with age. A tendency for aortic systolic murmurs to be associated with a higher mean systolic blood pressure was not significant and there was no significant association between systolic murmurs and ischaemic heart disease.

Aged