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Biomedical subjects

S M Dobbs

Publications and source records attributed to S M Dobbs.

At least 55 records · Page 3Linked to original sources

Determinants of gait in the elderly parkinsonian on maintenance levodopa/carbidopa therapy.

1. We have used gait analysis to investigate the efficacy of maintenance therapy with a levodopa/carbidopa combination in patients with idiopathic Parkinsonism, who do not have overt fluctuations in control in relation to administration of medication. 2. Fourteen patients (aged 64 to 88 years) receiving maintenance therapy with levodopa and carbidopa (Sinemet Plus) entered a placebo-controlled, randomised cross-over study of the effect of omission of a morning dose of active treatment on distance/time parameters of gait. Measurements made 2, 4 and 6 h after the morning treatment were standardised by taking the pre-treatment measurement on that day as baseline. 3. The mean increase in stride length (7%) and decrease in double support time (20%) on active treatment were small but statistically significant (P less than 0.0001, in each case), there being no significant placebo effect on either gait parameter (P = 0.69 and 0.08 respectively). Neither active nor placebo treatments had any significant (P greater than 0.45 in each case) effect on the lying, standing or postural fall in mean arterial pressure, measurements being made in the same temporal relation to the treatments as was gait. 4. In a generalised linear model, after allowing for the effect (P less than 0.0001) of intrinsic variability in pre-treatment speed as well as for structure of the study, nature of treatment had an effect on stride length over the whole walk, significant at P = 0.002. 5. Pre-treatment postural fall in mean arterial pressure was nearly as significant (P = 0.003) as the nature of treatment in the context of such a model: the greater the fall, the greater the increment in stride length seen following active or placebo treatment. This was probably explained by an acquired tolerance to the fall as the day progressed. 6. The major determinant (P less than 0.0001) of the change in double support time over the whole walk, after allowing for the structure of the study, appeared to be the post treatment mean arterial standing blood pressure. The lower the pressure, the shorter the double support time, and hence, the greater the tendency to a hurried gait. 7. Nature of treatment, when added into the models described in summary points 5 and 6, had no significant effect (P greater than 0.25, in each case).(ABSTRACT TRUNCATED AT 400 WORDS)

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Compliance with anti-tuberculous therapy: a field trial of a pill-box with a concealed electronic recording device.

We have conducted a field trial of a pill-box containing a concealed electronic device for monitoring compliance in 23 consecutive adult out patients taking a rifampicin/isoniazid combination once daily. In 22 cases, the times when the box was opened were successfully recorded for the entire period (mean (SD) 26 (5) days) between successive clinic visits. In the other patient the record terminated after one week, a broken box being returned. Both totality of compliance (as assessed by box openings) and consistency of compliance (the proportion of the total number of intervals between openings which were of 22 to 26 h in length) were significantly greater in those studied in the intensive than in the maintenance phase of therapy. Patients may have taken the reduction in medication at the end of the intensive phase as signalling cure. A computer program has been developed to display the recorded data. This allowed the physician responsible to assimilate at a glance the patient's tablet-taking habits. In routine practice knowledge of the presence of the device may improve compliance and a discussion of the graphical display may prove of value in counselling.

Adult↗

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)

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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.

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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.

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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↗

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↗

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↗

Making a rehabilitation hospital for the elderly work.

We report our efforts to make a rehabilitation hospital work. The simple intervention of introducing a patient record system, in which problems, management, achievements and discharge plans were clearly documented, doubled the number of patients who returned home over an eight-month period. This resulted in greater availability of acute geriatric beds at the District General Hospital (DGH), where two thirds of the elderly medical inpatients occupy beds on other units, and in an improvement in morale of patients and staff. Greater co-operation between geriatric and medical teams in selecting those patients who would benefit from continuing rehabilitation is required. The advantages of accommodating such patients separately from patients with a poor prognosis and those requiring long-term care are discussed.

Aged↗

Gastric adaptation occurs with aspirin administration in man.

Endoscopy has become a standard method to evaluate drug-induced damage to the gastroduodenal mucosa; however, studies defining the time course, extent, and duration of the injury in man are unavailable. We report a systematic endoscopic evaluation of the effect of aspirin administration on the gastric mucosa in normal volunteers. Aspirin (2.6 g/ day) or placebo was administered for 1 or 7 days. Gastroscopy was performed after 1, 2, 4, and 8 days, and every other day thereafter until the lesions resolved. Submocosal hemorrhages and/or focal erosions were present within 24 hr in all subjects. With continuous aspirin administration, injury was maximal within 3 days and then lessened, ie, damage present after 7 days of aspirin was significantly less than after 1 day of therapy. The time to resolution of the damage was also longer following 1 day than after 7 days of aspirin (median 8 days for 1 day of aspirin vs median 3 days for 7 days of aspirin). Thus, gastric mucosal adaptation occurred and was associated both with less damage and with an accelerated healing process. Acute administration of aspirin produced well-defined areas of submucosal hemorrhages within 2 hr of administration; additional doses increased the area of involvement but not necessarily the severity of involvement.

Adult↗

What is the role of prosthesis insertion in esophageal carcinoma?

We review our experience with 13 patients in whom esophageal dilation was used for palliation of malignant esophageal obstruction and with five patients treated with esophageal prostheses for malignant esophagorespiratory fistula. Twelve of the 13 patients with dilation alone received satisfactory palliation and were able to eat a soft or regular diet. Four of five patients with esophagorespiratory fistulas had esophageal dilation followed by insertion of a esophageal prosthesis and received good palliation. Endoscopic insertion of esophageal prosthetic devices has become increasingly popular as a palliative procedure, despite lack of controlled trials either proving efficacy of this therapy or comparing it to radiation therapy with or without dilation of the esophagus. The reported mortality and morbidity rates for esophageal prosthesis insertion are higher than those reported for radiotherapy. There is little to suggest that prostheses are better than or even equal to radiotherapy alone or radiotherapy and bougienage. We review the reported series (greater than 2300 cases) of push-through prostheses insertions in esophageal cancer and compare prosthesis insertion to other therapy. The need for a carefully controlled trial of the different forms of therapy is emphasized, and guidelines for such a study are suggested.

Adenocarcinoma↗

Evaluation of medigoxin in outpatients.

We compared our ability to predict the dose of medigoxin and of digoxin required to achieve a fixed serum concentration (the dose requirement) in 33 outpatients. Preliminary work supported the assumptions that the steady state glycoside concentration achieved was proportional to the daily dose given to an individual, and that the bioavailability of the different tablet presentations was similar for either glycoside. We were not able to predict the dose requirement from patient characteristics with any more certainty for medigoxin than for digoxin. Not only the between-patient variability in dose requirement, but also the within-patient variability, was similar for the two glycosides. However the digoxin used had a dissolution rate of over 90% in 1 h. When comparing medigoxin with digoxin of lower, or more variable dissolution rate, medigoxin may be preferable.

Analysis of Variance↗

Ideal sampling time for drug assays.

Estimation of the mean steady state serum concentration of a drug from an isolated sample apparently requires a knowledge of both the timing of the sample within the dose interval and of the pharmacokinetic constants of the drug in the individual. Data from 80 general medical outpatients receiving maintenance digoxin has been used to derive a relationship between the serum digoxin concentration at any given time (C) and the mean steady state concentration (C), but this did not allow for individual variation in drug handling. It can be demonstrated theoretically that, for a one compartment model with instantaneous drug distribution and first order elimination, the ratio, C/C, is dependent on the half time of the drug, the dose interval and the time of sampling. Moreover, for higher values of half time the ratio is virtually constant at 11 h after a daily dose. This, then, would be an ideal sampling time. The above approach can be extended to any drug provided that its half time is at least 15 h in healthy subjects and that the concentration/time curve approximates to a simple exponential decay during virtually the entire dose interval. Orally administered digoxin meets both of these provisions, the ratio at 11 h being 0.97, which is only slightly different from the 1.02 of the theoretical model. Ideal sampling times and the conditions under which they apply may be derived for other dose intervals.

Blood Specimen Collection↗

A score for prescribing digoxin.

A simple method of selecting a maintenance dose of digoxin, suitable for an adult patient, was derived from data on 129 patients taking digoxin. Eight items of readily available information are required for entry into the prescribing aid: out/inpatient status, sex, age (less/not less than 70 years), weight (allocated to one of four ranges), whether or not chronically house/chair bound, cardiac rhythm (sinus/other), serum creatinine concentration (allocated to one of four ranges), and diuretic therapy (prescribed/not prescribed). The recommended dose is given in terms of size and number of tablets to be prescribed. Using this method 72.3 per cent of patients are expected to achieve mean steady state serum digoxin concentrations within the therapeutic range, 6.5 per cent above and 21.2 per cent below. This performance would be considerably better than that expected from the use of other prescribing aids. If available, routine measurement of the serum digoxin concentration during follow-up is recommended to detect those who might benefit from a change, usually an increase, in dose.

Aged↗