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Biomedical subjects

R J Dobbs

Publications and source records attributed to R J Dobbs.

At least 55 records · Page 3Linked to original sources
PubMed1988

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 Enalapril was withdrawn during follow up in three patients because of symptoms of mesenteric ischaemia and in four because of dramatic deterioration of renal function.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↗
PubMed1988

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↗
PubMed1988

Bringing gait analysis out of the laboratory and into the clinic.

The potential value of objective assessment of gait in geriatric medicine cannot be explored fully whilst gait analysis remains a laboratory research tool, imposing special conditions which often preclude its use in the elderly. We describe a method of gait analysis suitable for the geriatric clinic and illustrate its use in documenting the response to interventions in three patients presenting with falls due to parkinsonism. Irregularity between gait cycles was noted, a finding previously described in Parkinson's disease, dementia and normal old men at a fast walking speed. Such irregularity may prove to be a major risk factor for falls. Where multiple pathologies which disturb gait coexist, measurement of changes in gait in response to treatment may provide a much needed means of audit.

Accidental Falls↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

Prescribing digoxin in geriatric units--exercise and redistribution of drug.

In subjects capable of normal everyday activity, exercise has been shown to lower the serum digoxin concentration by increasing uptake into skeletal muscle. A randomized cross-over study of the effect on the serum digoxin concentration of treatments consisting of rest for, or exercise during, 30 min was carried out in 20 elderly patients undergoing rehabilitation. In one patient exercise was associated with a marked (40%) reduction in the serum digoxin concentration. In the remainder there was a very small, but statistically significant, fall in concentration in the exercise as compared with the rest period. Unexpectedly low serum digoxin concentrations in in-patients of geriatric units, may occasionally be an artefact due to temporary redistribution of digoxin.

Aged↗
PubMed1986

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↗
PubMed1983

Effect of treatment with chlorthalidone and atenolol on response to dilator agents in the forearm resistance vessels of men with primary hypertension.

The forearm resistance vessels of men with primary hypertension respond to verapamil with a greater than normal dilatation relative to that induced by sodium nitroprusside. We have examined the effect on this functional abnormality of treatment with chlorthalidone (50 mg daily in 16 patients) and atenolol (100 mg daily in eight patients and 200 mg daily in two). The responsiveness of the forearm resistance vessels to local intra-arterial infusion of verapamil and sodium nitroprusside was assessed before treatment and again after a minimum of 1 month of drug therapy. Forearm blood flow was measured by venous occlusion plethysmography. Chlorthalidone induced significant reductions in calculated mean arterial pressure, which fell from 135 +/- 4 to 117 +/- 4 mm Hg, and the dilator response to verapamil at 5 micrograms/min, which was reduced from 2.4 +/- 0.2 to 1.5 +/- 0.2 ml min-1 100 ml-1 forearm; the response to sodium nitroprusside at 3.2 micrograms/min was not significantly changed. Atenolol induced significant reductions in mean arterial pressure, which fell from 134 +/- 6 to 123 +/- 6 mm Hg, heart rate which fell from 72 +/- 3 to 55 +/- 2 beats/min, and response to verapamil at 5 micrograms/min which fell from 2.7 +/- 0.2 to 2.1 +/- 0.2 ml min-1 100 ml-1 forearm; the response to sodium nitroprusside was not significantly changed. Both drugs caused reversion towards normal of the relative enhancement of responsiveness to verapamil that was present before treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1982

Response of forearm resistance vessels to verapamil and sodium nitroprusside in normotensive and hypertensive men: evidence for a functional abnormality of vascular smooth muscle in primary hypertension.

1. The response of the forearm resistance vessels to local intra-arterial infusion of verapamil and sodium nitroprusside has been assessed by a plethysmographic method in 23 men with normal arterial pressure and 35 men with primary hypertension. 2. In the 20 patients with hypertension for whom full dose-response curves were determined, the dilator response to verapamil was significantly greater than that in the normal controls, whereas the response to sodium nitroprusside was reduced. 3. Comparison of responses to the two dilators in individual subjects enabled the scattering effect of variables common to both drugs to be reduced. Analysis of the results in this way showed a highly significant difference between the hypertensive men as a whole and the normotensive controls (P less than 0.00001); 24 out of the 35 hypertensive men showed responses that were outside the normal range. 4. The abnormal pattern of response observed in the hypertensive group cannot be accounted for by structural changes in the vessels and strongly suggests a functional abnormality of the vascular smooth muscle.

Adult↗
PubMed1982

Nifedipine in the treatment of hypertension: report of a double-blind controlled trial.

1 The effect of oral nifedipine has been examined in patients with hypertension in whom arterial pressure was not adequately controlled by the combination of a beta-adrenoceptor antagonist (or alpha-methyldopa) and a diuretic. 2 In 42 patients, nifedipine (10 mg capsules) was added to the existing therapy in a final dose of 20-60 mg daily. Six patients had to stop the drug on account of side-effects. In the 36 patients who continued treatment, arterial pressure fell by an average of 24/9 mmHg supine and 26/10 mmHg standing. 3 In 11 of these patients who subsequently completed a double-blind, cross-over, placebo controlled trial, nifedipine (30-60 mg daily) was found to reduce arterial pressure by an average of 19/11 mmHg supine and 21/12 mmHg standing. 4 In all 11 patients who were changed to a sustained release preparation of nifedipine, control of arterial pressure was at least as good as it had been when taking the capsules.

Adult↗
PubMed1981

A method for assessing responses of small arteries in man: effect of physiological and pharmacological stimuli.

1. A method has been developed for estimating resistance to blood flow in the collateral arteries around the elbow. Arterial pressure is recorded continuously from the radial artery and blood flow in the forearm and hand is measured by venous occlusion plethysmography. The brachial artery is occluded for short periods, and the pressure drop across the collaterals and the flow through them are determined. From these observations an index of resistance can be calculated. 2. During 2 min occlusions of the brachial artery, collateral arterial resistance fell progressively to reach a level that was on average 45% lower than the initial resistance (P less than 0.01). 3. There was an inverse relation between distending pressure in the collateral arteries and calculated resistance. 4. Ergotamine tartrate (0.25 mg intravenously) increased collateral resistance by an average of 135%. Glyceryl trinitrate (0.5 mg sublingually) reduced collateral resistance by an average of 45%. Hydrallazine and isoprenaline had an inconsistent dilator effect; the direct action of these drugs may have been offset by the reduction in distending pressure which they induced. 5. The elbow collateral arteries provide a useful model for studying physiological and pharmacological responses of small limb arteries in man.

Adult↗
PubMed1980

Acquired tolerance to dilator action of hydrallazine during oral administration.

1 The effect on forearm blood flow of local intra-arterial infusion of hydrallazine has been studied in twelve patients with essential hypertension and six normal subjects. 2 When the patients with hypertension were not taking hydrallazine by mouth, they responded to intra-arterial infusions with a dose-dependent increase in forearm blood flow that was not significantly different from that in normal subjects. 3 When the patients were taking hydrallazine by mouth, the increase in forearm flow in response to intra-arterial infusions was reduced and forearm vascular resistance did not fall as low as it did in the control study (P less than 0.01). 4 In four patients, the response to intra-arterial hydrallazine was attenuated to a major extent, and in three of these, there was little or no response to oral treatment. In eight patients, the response to intra-arterial hydrallazine did not fall below one half of that in the control study and this minor reduction in sensitivity might be expected to impair, but not abolish, the response to oral treatment. 5 It is concluded that the resistance vessels commonly develop tolerance to the dilator action of hydrallazine during long-term oral therapy. In some patients a high degree of tolerance develops and this is an important cause of failure to respond to oral treatment.

Administration, Oral↗
PubMed1980

Effects of nifedipine on resistance vessels, arteries and veins in man.

1 The effect of nifedipine on peripheral blood vessels has been studied in man. 2 Nifedipine induced dilatation of the forearm resistance vessels when given either by local intra-arterial infusion or sublingually (10 mg). 3 Local infusion of the drug did not relax hand veins preconstricted by infusion of noradrenaline and neither local infusion nor sublingual administration prevented constriction mediated by the sympathetic nervous system. Nifedipine was, however, a potent inhibitor of hand vein contractions induced by high concentrations of potassium provided that the noradrenergic component of the response was suppressed by simultaneous infusion of phentolamine. 4 Sublingual nifedipine (10 mg) did not dilate the elbow collateral arteries. 5 The effects of nifedipine on peripheral blood vessels are similar, but not identical, to those of verapamil. The pattern of action, with dilatation of resistance vessels but not capacitance, resembles that of hydralazine rather than glyceryl trinitrate and this suggest that nifedipine may prove useful in the treatment of hypertension.

Adult↗
PubMed1979

Comparative dilator effect of verapamil and sodium nitroprusside in forearm arterial bed and dorsal hand veins in man: functional differences between vascular smooth muscle in arterioles and veins.

Verapamil and sodium nitroprusside induce a dose dependent dilatation in the forearm arterial bed and preconstricted dorsal hand vein in man. Verapamil is about twenty times more effective in dilating arterioles than veins; sodium nitroprusside is about ten times more effective in veins than arterioles. These differences can be related to functional differences between the two types of vessel.

Adult↗