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C Weller

Publications and source records attributed to C Weller.

At least 19 recordsLinked to original sources
PubMed1992

Objective evidence for tolerance, against a background of improvement, during maintenance therapy with controlled release levodopa/carbidopa.

We have investigated whether the potential benefits of a controlled release formulation of levodopa (200 mg)/carbidopa (50 mg), Sinemet CR, are realised during maintenance therapy. Eight sufferers from idiopathic Parkinsonism, mean age 69.9 y, were studied: all exhibited "end of dose" effect within 4 h of a dose of their maintenance therapy with levodopa (100 mg)/carbidopa (25 mg) in a conventional release formulation, Sinemet Plus. They received, in random order, initial single dose challenges with one tablet of Sinemet Plus, one and two tablets of Sinemet CR and placebo alone, each on a separate day. After a mean of 21 weeks on maintenance therapy with Sinemet CR, subsequent single dose challenges with Sinemet CR and placebo were made. Objective measures of performance and blood sampling for assay of plasma concentrations of levodopa and the major peripheral metabolite, 3-0-methyldopa (30MD) were carried out immediately before (10.00 h) and serially until 6 h after each challenge. The overall mean stride length was significantly greater in relation to the subsequent (679 mm) than the initial (517 mm) placebo challenge. Moreover, stride length immediately before the challenges was significantly greater on the subsequent occasions. Improved performance, also seen for free walking speed, was not explained by plasma levodopa or 30MD concentrations. In the initial challenges, the mean increment in stride length achieved by active treatment, as compared with placebo, did not differ significantly between the one (210 mm) and two (235 mm) tablet doses of Sinemet CR: a maximal response had been obtained.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Reduced axial rotation in the spouses of sufferers from clinical idiopathic parkinsonism.

Axial rotation during recumbency was used to quantify the tendency towards parkinsonism with respect to one cardinal sign, brady/hypokinesia. Twenty-four elderly sufferers from idiopathic parkinsonism, their spouses, and 40 control subjects were studied. Significant differences in total angular displacement over 7 h were found between sufferers and their spouses (83% of grand mean) and between spouses of sufferers and controls (31%). These differences could not be accounted for by age or cognitive function. Moreover, the total angular displacement of the spouses was independent of whether they shared a bed with the sufferer. Neither the sufferers and their spouses, nor the 20 couples who constituted the control group, showed any relationship between partners with respect to angular displacement. These findings do not favour learned behaviour, or selective mating as an explanation of reduced movement in spouses of sufferers. Significantly more of the control couples had a single cardinal sign in both partners than expected on the basis of the frequency of a single sign in one partner. Environmental factors operating in adult life could be involved in the pathogenesis of parkinsonism.

Aged↗
PubMed1992

Hypothesis: age-associated changes in gait represent, in part, a tendency towards parkinsonism.

In 144 healthy, active, asymptomatic volunteers (aged 30-88 years), age explained 33% of the variance in free walking speed. This could not be ascribed simply to differences in physique at maturity, since height had a more important effect on speed (p less than 0.0001) than did leg length (p less than 0.01). Multiple linear regression was used to fit models for speed, by selection from four sets of variables: common physical, body sway, functional anatomy of spine and lower limbs, and psychometric. The best model (which included age) explained little more of the variance (41%) than did age alone. Moreover, incorporation of age into the alternative model, built in its absence, still contributed significantly (p less than 0.0001) to the variance explained. The effect of age on gait appeared to be complex, with an increment in double support time disproportionate to the reduction in speed. We formulate by exclusion, the hypothesis that age-associated changes in gait represent, in part, a tendency towards parkinsonism.

Adult↗
PubMed1992

Gait on a shoestring: falls and foot separation in parkinsonism.

A novel device for monitoring gait, which can be used in confined spaces, is described. In addition to distance/time assessment of gait, it measures foot separation whilst walking. A field trial illustrates its potential in the investigation of falls.

Accidental Falls↗
PubMed1992

Effect of captopril on functional, physiological and biochemical outcome criteria in aged heart failure patients.

1. Captopril was evaluated as an adjuvant to diuretic and digoxin therapy in heart failure in old age, using walking ability, minute ventilation and oxygen consumption and plasma atrial natriuretic factor (ANF) concentration as measures of outcome. 2. Twenty patients, mean (s.d.) age 81 (6) years, entered a double-blind, randomised, crossover study of three treatments, a twice daily regimen of captopril (AA), at a dosage established by titration against serum angiotensin converting enzyme (ACE) activity, the same dosage in the morning with placebo at night (AP), and twice daily placebo (PP). Each treatment lasted 3 weeks. A 2 week run-in period on triple therapy, with AA captopril, was used to assess stability and compliance. Seventeen completed all treatments: three completed two. 3. Any benefit of captopril was modest and there was deterioration in gait on the titrated dosage 3 months afterwards (P = 0.04). Efficacy in the old may be greatest when the titrated dose (25 or 50 mg) is given once daily: the multiple daily doses recommended may be unnecessarily demanding. 4. Walking performance was measured by gait analysis (GA) at free walking speed and by a simple walking test (SWT), in which patients stopped at the first relevant symptom. There was a consistent tendency for four measures of performance (GA: speed, stride length and double support time; SWT distance) to be best on the AP treatment, next best on AA, and worst on PP but for the fifth, SWT speed, AP and AA were similar. The trend appeared most marked for SWT distance, mean (s.e. mean) values for AP, AA and PP being 123 (15), 94 (16) and 75 (16) m, respectively. However, the treatment effect did not reach statistical significance at the 0.05 level. 5. There was no significant difference between treatments in minute ventilation, minute oxygen consumption, or their ratio, either at rest or on exercise. 6. Resting ANF concentrations were nearly four times higher (P = 0.0001) in the patients than those, mean (s.e. mean) 66 (5) pmol l-1, in eleven healthy volunteers of mean age 80 (6) years, and the increase on exercise, seen in the controls (P less than 0.01), was absent. In the patients the resting plasma ANF concentration was significantly affected by treatment (P = 0.03), being less on both AP, 245 (9), and AA, 214 (9) than on PP, 264 (10) pmol l-1 (P = 0.02 and 0.03, respectively). 7. Baseline serum ACE activity was induced on active treatment. The change in ACE activity at 3 h post an active dose was significantly greater on AP than AA (P = 0.005). The increased sensitivity to inhibition during once daily administration was reflected in mean arterial pressure. The pre-dose standing pressure was less on AP than on PP (P less than 0.05), and the change in postural fall (pre-dose minus 2 h post), was greater (P = 0.004), but AA and PP were similar in these respects.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1992

Gait in relation to ageing and idiopathic parkinsonism.

Distance/time measures of gait in 105 sufferers from idiopathic Parkinsonism, who were able to walk unaided, and 144 healthy controls were examined systematically. Those sufferers with overt fluctuations in control were assessed during their "therapeutic window". Free walking speed was lower for a given cadence in the sufferers, but reached a plateau whilst cadence could still be increased. Age, cognitive function and the range of passive hip flexion were important determinants of gait in them. Even minor degrees of cognitive impairment were associated with reduced free walking speed in sufferers: it appears unwise that they were prescribed more sedatives than the controls. The potential benefit of physiotherapy in maintaining joint flexibility was noted. The deficits in speed of individual sufferers, and hence the estimated potential for prophylaxis and treatment, were unrelated to age at presentation. There was no evidence for a limited period of responsiveness to levodopa therapy in this cross-sectional study.

Adult↗
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↗
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

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↗
PubMed1979

A portable pulse-interval modulation telemetry/multiplexing EEG recording system for use in the home.

A portable 6-channel recording system employing time-division multiplexing with cable or radio-telemetry has been developed. The system is very compact and has proved to be reliable when used in a domestic environment. The use of multiplexing, in general, permits an expansion in the number of available channels and a reduction in equipment and tape costs, while the use of pulse interval modulation, in particular, overcomes tape recording limitations which may be encountered with the more common amplitude modulation techniques.

Electroencephalography↗
PubMed1979

Prostatic secretion leukocyte studies in non-bacterial prostatitis (prostatosis).

Non-bacterial prostatitis is a common affliction among men and lacks objective criteria for clear identification. We studied 43 consecutive patients and 20 normal controls for the presence of bacteria and quantitation of prostatic secretion leukocytes. Significantly greater numbers of macrophages per volume of prostatic secretion were found in the patients. Multiple observations of such increased leukocyte proliferation could be used to establish true prostatic inflammation.

Adolescent↗
PubMed1979

Characterisation of protein synthesis in cell-free extracts from different mammalian cells by their sensitivity to inhibitors of polypeptide-chain initiation.

Plasma cells and reticulocytes are differentiated mammalian cell systems specialized in the synthesis of distinct proteins. To study whether a cell specificity of polypeptide-chain initiation in such cell systems can be detected through inhibitors, the sensitivity to several drugs interfering with initiation was compared in cell-free systems with S-30 extracts from these cells. The following was indicated by the experiments: (1) under the selected conditions, the different cell-free systems are comparable with respect to their activity of initiation, and that aurintricarboxylic acid inhibits mRNA binding to the ribosome in plasma cell tumours the same as in reticulocytes. (2) The sensitivity of translation of endogenous mRNAs in reticulocytes and plasma cell tumours to inhibitors of mRNA binding to the ribosome, aurintricarboxylic acid and the homopolynucleotides poly(U) and poly(A), are different. (3) Inhibition of the succeeding reactions of peptide-chain initiation by sodium fluoride and pactamycin was not selective. (4) In both cell systems translation of poly(U) is equally sensitive to aurintricarboxylic acid. (5) In extracts from TEPC 15 myeloma cells synthesis of immunoglobulin L-chains compared with that of the other myeloma proteins is partially resistant to aurintricarboxylic acid, whereas in reticulocytes, no differential sensitivities of individual proteins could be observed. The different susceptibility of the mRNA binding reaction in plasma cell tumours and reticulocytes suggests that the predominant mRNAs of these cells have different affinities to ribosome binding sites.

Animals↗
PubMed1978

Home health care.

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Cost-Benefit Analysis↗