Search PubMed⌕ Search

Biomedical subjects

P W Nicholson

Publications and source records attributed to P W Nicholson.

At least 37 records · Page 2Linked to original sources
PubMed1991

Measurement of axial rotation: its relevance to screening for night-time hypokinesia in old age and parkinsonism.

A novel device for continuous monitoring of axial rotation of a recumbent person is described. It is self-applicable and small enough to be mailed. A field trial showed that parkinsonian patients change their position less frequently than did their spouses: the difference became smaller where the age of the spouse was equal to or greater than that of the sufferer. The most marked difference between sufferers and their spouses was with respect to total angular displacement, which was nearly four times greater in the spouses. Further work is needed to show whether impaired rotation predates clinical idiopathic Parkinson's disease and so acts as a useful predictor. Measurement of axial rotation seems valuable in judging risk of pressure sores and gauging improvement in mobility in response to therapeutic interventions.

Aged↗
PubMed1991

Objective outcome criteria in trials of anti-parkinsonian therapy in the elderly: sensitivity, specificity and reliability of measures of brady- and hypo-kinesia.

1. We compare the sensitivity and specificity of chosen outcome criteria in a placebo-controlled, randomised cross-over study of the efficacy of maintenance therapy with the levodopa/carbidopa combination (Sinemet Plus) alone. Patients were characterised by having idiopathic Parkinsonism with no overt fluctuations in control in relation to individual doses of medication. 2. The effect of omission of a morning dose of maintenance therapy on simple timed tests of mobility and manual dexterity, and on distance/time parameters of gait was studied in fourteen patients (aged 64 to 88 years). Measurements made 2, 4 and 6 h after morning active and placebo treatments were standardised by taking the pre-treatment measurement on that day as baseline. 3. In a linear model, which allowed for the structure of the study, neither the total time taken by each patient to get up from a chair, walk an individually set distance, turn, return to and sit in the chair, nor the rate of progress at fastening the same set of buttons, was sensitive to the treatment effect. 4. Three of the gait parameters, free walking speed, mean stride length and mean double support time, were sensitive to the treatment effect. Correction for the speed of each walk, caused some reduction in the sensitivity of stride length to treatment effect, but that of double support time remained. Speed, and double support time or stride length, appeared to be complementary in defining the treatment effect. 5. The linear modelling revealed the complexity of the treatment effect. Although active treatment, by comparison with placebo, increased free walking speed (P = 0.019), the more levodopa found in the plasma following treatment, (P = 0.0005) and the greater the increment in the concentration of its peripheral metabolite, 3-O-methyldopa (P = 0.006), the less the beneficial effect. This model may reflect reduced uptake into the brain and/or an adverse effect of parent drug or a metabolite. 6. The specificity of free walking speed for the treatment effect was good, as was that of mean stride length, after it had been corrected for speed of each walk, and of mean double support time, after correction for speed and incorporation of the change in lying blood pressure accompanying treatment into the model. 7. The measurements of gait parameters were ranked according to reliability.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1991

Capsules for frozen sectioning of small specimens.

It was necessary to make sections of small unfixed specimens which had been frozen while still immersed in their normal culture medium. The principal difficulty stemmed from the poor sectioning quality of the frozen culture medium. A capsule is described which has a narrow well in which the tissue specimen fits snugly within a small amount of culture medium. After freezing, the whole capsule is sectioned and the resulting sections, being nearly devoid of culture medium, are of good quality.

Culture Techniques↗
PubMed1990

Parkinsonian abnormality of foot strike: a phenomenon of ageing and/or one responsive to levodopa therapy?

1. Normally during walking, the heel strikes the ground before the forefoot. Abnormalities of foot strike in idiopathic Parkinson's disease may be amenable to therapy: objective measurements may reveal response which is not clinically apparent. Occult changes in foot strike leading to instability may parallel the normal, age-related loss of striatal dopamine. 2. The nature of foot strike was studied using pedobarography in 160 healthy volunteers, aged 15 to 91 years. Although 16% of strikes were made simultaneously by heel and forefoot, there were no instances of the forefoot preceding the heel. No significant effect of age on an index of normality of foot strikes was detected (P greater than 0.3). 3. The effect on foot strike of substituting placebo for a morning dose of a levodopa/carbidopa combination was studied in a double-blind, cross-over trial in 14 patients, aged 64 to 88 years, with no overt fluctuations in control of their idiopathic Parkinson's disease in relation to dosing. On placebo treatment there was a highly significant (P = 0.004) reduction in the number of more normal strikes, i.e. heel strikes plus simultaneous heel and forefoot strikes. The effect appeared unrelated to the corresponding difference between active and placebo treatments in plasma concentration of levodopa or a metabolite of long half-time, 3-O-methyldopa (3OMD). However, it correlated negatively (P less than 0.05) with the mean of the 3OMD concentrations. 4. It appears that some abnormalities of foot strike due to Parkinson's disease are reversible. Employing test conditions, designed to provoke abnormalities of foot strike, might be useful in screening for pre-clinical Parkinson's disease.

Adolescent↗
PubMed1990

Screening for aminoglycoside auditory toxicity in the old.

1. We have investigated 22 patients receiving gentamicin, mean (s.d.) age 78 (6) years for auditory toxicity, using a standard audiometric technique in a sound-treated room (Study 1). 2. Use of a portable audiometer might allow a larger and more representative proportion of patients treated with aminoglycosides to be screened for ototoxicity. A method for detecting high frequency loss suitable for use in the ward was evaluated in 12 volunteers aged 27 (4) years (Study 2). 3. The error inherent in taking hearing at the start of treatment as a reference point was measured in 16 patients, aged 81 (8) years, prescribed non-ototoxic antibacterials (Study 3). 4. A significant (P = 0.05) reduction in hearing threshold was detected in Study 1, although psychometric tests revealed unchanged or improved ability to co-operate. This occurred only at 4000 Hz, the highest frequency used. The magnitude of this loss, mean 2.5 dB, was similar to that of the improvement in threshold detected (P = 0.0004) early in the course of treatment in Study 3. Thus, underestimation of ototoxicity is likely. 5. If a change of threshold of 10 dB or more is taken arbitrarily to represent a real change in hearing, then there was a significant excess of patients in Study 1 with losses at 4000 Hz only (P = 0.032). The six with such losses at this frequency were older than the rest. However, there was a significant (P less than 0.02) positive correlation between log mean predose serum gentamicin concentration and age. Thus, it remains to be determined whether presbyacusis sensitizes those hair cells which it does not destroy to toxic damage. 6. The cumulative dose of gentamicin (for a course of the duration given) was calculated according to published prescribing aids. There was no systematic reduction in the ratio of the dose recommended by a given aid to the dose prescribed in the six with hearing losses as defined above. 7. In Study 2, thresholds obtained at 6000 Hz in the open ward were, on average, 0.9 dB higher than in the sound treated room, but the effect of venue did not reach statistical significance. In the morning thresholds were marginally, but significantly (P = 0.04), lower than in the afternoon. Precision, as measured by the standard deviation of replicate determination, was independent of test conditions. Using multiple (ten) threshold determinations appeared to improve resolution.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1990

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)

Aged↗
PubMed1988

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↗
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↗
PubMed1988

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↗
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↗
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↗
PubMed1985

Geometrical factors in the cardiac nuclear probe.

The design of the collimator for the assessment of left ventricular function with a non-imaging detector is considered. When certain simplifying assumptions are made concerning the distribution of the background and the ventricular activity, the statistical variation in the calculated ventricular count rate is examined for various detector-collimator combinations. For detectors with sufficient diameter to give reasonably low counting errors it is shown that the focused multihole type of collimator is preferable and the optimum parameters of this are given. It is shown that when the simplifying assumptions are relaxed there is still a preference for the use of a focused multihole collimator.

Animals↗
PubMed1981

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↗