A double-blind randomised placebo-controlled evaluation of three doses of botulinum toxin type A (Dysport) in the treatment of spastic equinovarus deformity after stroke.

BACKGROUND/OBJECTIVES: Calf muscle hypertonicity following stroke may impair walking rehabilitation. The aim of this study was to assess botulinum toxin (Dysport) in post-stroke calf spasticity. METHODS: A prospective, multicentre, double-blind, placebo-controlled, dose-ranging study was performed to evaluate dysport at 500, 1,000 or 1,500 units in 234 stroke patients. They were assessed at 4-week intervals over 12 weeks. RESULTS: The primary outcome measure, 2-min walking distance and stepping rate increased significantly in each group (p < 0.05, paired test), but there was no significant difference between groups (including placebo). Following dysport treatment, there were small but significant (p = 0.0002-0.0188) improvements in calf spasticity, limb pain, and a reduction in the use of walking aids, compared to placebo. Investigators' and patients' assessments of overall benefit suggested an advantage for dysport over placebo, but this was not significant. Sixty-eight patients reported 130 adverse events, with similar numbers in each group. The few severe events recorded were not considered to be treatment-related. CONCLUSION: Dysport resulted in a significant reduction in muscle tone, limb pain and dependence on walking aids. The greatest benefits were in patients receiving dysport 1,500 units, but 1,000 units also had significant effects. Dysport 500 units resulted in some improvements. Since few adverse events were reported, this therapy is considered safe and may be a useful treatment in post-stroke rehabilitation of the leg. Possible reasons why functional improvements in gait parameters were not observed are also discussed.

The effect of body weight and age on frequency of repairs in lower-limb prostheses.

INTRODUCTION: Overweight patients sometimes present a practical problem for provision of lower-limb prostheses. Most information about the effect of body weight on the endurance of prostheses is based on laboratory tests. This is a retrospective study based on an audit to study the effect of body weight and age on the frequency of repairs. SUBJECTS: One hundred and sixteen patients were involved (98 male), age 16-96 years, mean=58.7 years; weight 47-140 kg, mean=88 kg; 68 were transtibial amputees and 48 were transfemoral amputees. Causes of amputation were trauma (49), peripheral vascular disease (29), and others (38). Amputation was done 1-66 years prior to assessment, mean=13.66 years. Period of use of current prostheses was 0.5-28 years, mean=3.5 years. RESULTS: One hundred and one repairs were done in a period of 6 months. The number of repairs was found to correlate significantly with weight (P value<0.001) and inversely with age (P value=0.003). No significant correlation was found between repairs and gender, cause of amputation, or level of amputation. CONCLUSION: Body weight and age of amputee are determining factors in the frequency of repairs of lower-limb prostheses. However, a larger study for a longer period will be needed to confirm our finding.

The Barthel Index and its relationship to nursing dependency in rehabilitation.

OBJECTIVES: To investigate the clinical application of the Barthel Index as an indicator of nursing dependency in a younger disabled unit. DESIGN: A prospective study of 132 patients (mean age 49) with chronic neurological problems. SETTING: A younger disabled unit at a District General Hospital, Oxford. MAIN OUTCOME MEASURES: The Barthel Index, and total nursing hours. RESULTS: The Median Barthel Index was 7 (95% confidence interval 6-9). The mean nursing hours were 2.7 +/- 1.7 (CI 2.41-2.99). Spearman rank order correlation coefficient between the Barthel Index and nursing hours was r = -0.69 (CI -0.79 to -0.59). CONCLUSIONS: Regression analysis showed that it was possible to use the Barthel Index as an indicator of nursing dependency particularly in physical care, and that it was independent of age and diagnosis.

Bedside screening for aphasia: a comparison of two methods.

A prospective study was carried out in 50 consecutive patients referred with suspected aphasia in order to compare the Frenchay Aphasia Screening Test (FAST) with the Sheffield Screening Test for Acquired Language Disorders (SST). The study included 32 men and 18 women with a mean (SEM) age 53.9 (2) years. The comprehension scores on the FAST were correlated with receptive skills on the SST r = 0.74 (P < 0.001). For expression, the correlation coefficient was r = 0.92 (P < 0.001) and the total scores of the two tests correlated closely r = 0.89 (P < 0.001). There was a positive correlation between total score on the FAST and the Short Orientation, Memory and Concentration test (SOMC) r = 0.86 (P < 0.001), and the total scores on the SST and SOMC r = 0.91 (P < 0.001). The Barthel index also correlated positively with the FAST r = 0.59 (P < 0.001) and SST r = 0.63 (P < 0.001). The study demonstrated that the two tests are simple, short and similar in their predictive value for the screening and diagnosis of aphasia. The SST was found to have additional advantages, as it does not require any special equipment or stimulus cards, and it was not affected by visual neglect.

Intra-arterial monitoring of the antihypertensive effects of once-daily amlodipine.

Amlodipine is a dihydropyridine calcium antagonist with a long elimination half life making it suitable for once-daily dosing. This study used sphygmomanometric and intra-arterial ambulatory blood pressure (BP) monitoring to confirm the antihypertensive effect of a once-daily dose of amlodipine over the dosing interval. After a 2-week single-blind placebo run in, amlodipine was administered to 11 patients at a starting dose of 5 mg daily for 2 weeks increasing to 10 mg daily for a further 4 weeks if diastolic blood pressure (DBP) measured sphygmomanometrically was not < 90 mmHg or decreased by > 10 mmHg from baseline values. Intra-arterial blood pressure recordings for 24-hour periods were made at the end of the placebo run in and on completion of the active treatment phase. The effects of isometric and dynamic exercise and head-up tilting (60 degrees) on BP and heart rate were measured during ambulatory monitoring. Mean supine cuff BP was 169/104 mmHg (n = 11) at the end of the placebo treatment period and was reduced to 153/95 mmHg (n = 11) after 2 weeks of amlodipine treatment and 146/92 mmHg (n = 11) after 6 weeks of amlodipine treatment. There was no significant change in heart rate. Intra-arterial ambulatory monitoring showed that BP was controlled for the whole dosing interval with once-daily doses of amlodipine. The normal circadian pattern of BP changes was not altered. BP was reduced by amlodipine during exercise and physiological tests, but there was no postural hypotension and the BP and heart rate responses to exercise were not blunted.(ABSTRACT TRUNCATED AT 250 WORDS)

24-hour blood pressure control with the once-daily calcium antagonist amlodipine.

The efficacy and toleration of once-daily amlodipine (5-10 mg) was studied in 11 patients with mild to moderate hypertension. Continuous intra-arterial blood pressure monitoring was used to study the effects of amlodipine over a 24-h period. Following a 2-week placebo run-in period, amlodipine was given initially as a single-blind 5-mg dose for 2 weeks and increased to 10 mg if required to control blood pressure for a further 4 weeks. Twenty-four-hour intra-arterial blood pressure recordings made after 6 weeks of treatment with amlodipine revealed that amlodipine effectively reduced blood pressure throughout the whole 24-h period without altering the normal circadian pattern. The mean daytime blood pressure was reduced from 165/103 to 147/89 mm Hg (p < 0.05) and the mean nighttime blood pressure was reduced from 137/79 to 121/69 mm Hg (p < 0.05). There was no significant change in heart rate. The mean supine blood pressure measured sphygmomanometrically was reduced from 169/103 mm Hg after placebo to 153/98 mm Hg after 2 weeks of treatment and to 145/92 mm Hg at the end of the study. The results of isometric and dynamic exercise testing showed that amlodipine decreased blood pressure, with no postural decrease on tilting and no change in the proportional increase in blood pressure at peak exercise. Amlodipine was well tolerated although one patient developed ankle edema that would have required discontinuation had she not already completed the study. This study has shown that amlodipine effectively reduced blood pressure for 24 h after once-daily dosing and was well tolerated.

A comparison of single doses of lisinopril and enalapril in hypertension.

Sixteen patients with mild to moderate hypertension were studied in a double-blind crossover comparison of single oral doses of lisinopril 10 mg and enalapril 10 mg. Both drugs caused a marked fall in blood pressure (BP) with a clinically useful effect persisting for 24 h postdose and with no significant difference between treatments in this respect. The time to minimum systolic BP was 2 h (95% confidence limits 0-19 h) longer for lisinopril. The fall in ACE activity at 24 h was 18.5 (8.2-28.8) U/l greater for lisinopril. We conclude that, within the limits of this small study, lisinopril appears to be as effective as enalapril in lowering BP and that it may have a slower onset of action that could be clinically valuable.

24 h blood pressure control with the once daily calcium antagonist, amlodipine.

1. Amlodipine is a novel calcium antagonist which, although pharmacologically similar to other dihydropyridine calcium antagonists, has a long plasma half-life, permitting steady state blood levels to be achieved with a once-daily dose regimen. 2. We have performed a study to examine the effects of this drug on the blood pressure of hypertensive patients over a 24 h period. After a placebo run-in, the drug was administered to 11 patients at a starting dose of 5 mg, and increased to 10 mg after 2 weeks of treatment if the cuff diastolic blood pressure response was unsatisfactory. Cuff measurements were made at entry, after 2 weeks treatment with placebo, after 2 weeks on amlodipine 5 mg once daily, and after a further 4 weeks on amlodipine 5 mg or 10 mg once daily. Intraarterial blood pressure recordings were made at the end of the placebo phase and at completion of the study. 3. Mean supine blood pressure measured sphygmomanometrically was 168/103 (n = 11) mm Hg at entry, 169/104 (n = 11) mm Hg at the end of the placebo phase, 153/95 (n = 11) mm Hg after 2 weeks of treatment and 146/92 (n = 11) mm Hg at the end of the study. Blood pressure curves plotted for each phase of the study revealed an effective 24 h duration of action. Mean daytime blood pressure was reduced from 165/103 to 147/89 mm Hg (P less than 0.05, n = 10), and mean night-time blood pressure was reduced from 137/79 to 121/69 mm Hg (P less than 0.05, n = 10).(ABSTRACT TRUNCATED AT 250 WORDS)

Measurement of absolute left ventricular volume by radionuclide angiography: a technical review.

Absolute left ventricular volumes have important clinical implications in the evaluation of cardiac performance. Several invasive and noninvasive techniques have been reported, none of which can be considered ideal for this purpose. Contrast angiography, echocardiography and radionuclide ventriculography are open to criticism. Different radioisotopic approaches are described with emphasis on the importance of accurate separation of left ventricular activity, the selection of background activity, and the correction for photon attenuation by body tissues. Improper use of statistics and validation techniques have obscured the value of these techniques. In the absence of a 'gold standard' there should be a 'radioisotopic' left ventricular volume with established independent characteristics, repeatability and reproducibility by which new approaches can be judged.

Radionuclide measurements of diastolic function for assessing early left ventricular abnormalities in the hypertensive patient.

Three measurements of diastolic filling were compared in 29 patients with essential hypertension and 27 age matched normotensive controls. Systolic function was normal in all but one of the patients. The mean (1SD) first one third filling fraction (a measurement of early diastolic filling) was significantly lower in the hypertensive groups (0.27 (0.24] than in the control group (0.45 (0.16)). The hypertensive group was subdivided into those with electrocardiographic abnormalities and those without. In the subgroup with a normal electrocardiogram the mean (1SD) first one third filling fraction measurement (0.28 (0.16)) was significantly lower than in the control group. In the subgroup with an abnormal electrocardiogram, the first one third filling fraction was even lower (0.24 (0.9)). In addition, the time to peak filling rate (213 (56) ms) was significantly longer in the subgroup with the abnormal electrocardiogram than in the control group (164 (45) ms). However, the interobserver reproducibility of the time to peak filling measurement was poor. The peak filling rate was low in the subgroup with an abnormal electrocardiogram, but not significantly different from the normal controls. The discriminatory value of the three diastolic measurements did not improve with exercise. These results showed an early diastolic filling abnormality in essential hypertension that did not appear to be caused by disease of the large coronary vessels as it was present in patients with normal wall motion and a normal exercise electrocardiogram. The occurrence of diastolic abnormalities when systolic function is still normal may mark an early stage in the development of hypertensive heart failure, at a time when the process is still potentially reversible.

Effects of a new vasodilating beta-blocking drug, carvedilol, on left ventricular function in stable angina pectoris.

The effects of a new vasodilating beta-blocking drug, carvedilol, were studied in 20 patients with chronic stable angina using a single-blind, placebo-controlled protocol. Two doses of carvedilol, 25 mg twice daily and 50 mg twice daily, were compared with placebo using analysis of variance. The study design consisted of 2 weekly phases of initial placebo followed by carvedilol, 25 mg twice daily and then 50 mg twice daily, and a second placebo period. Supine rest and exercise radionuclide ventriculography was performed at the end of each phase. Carvedilol produced a significant dose-related reduction in rest and exercise heart rate and blood pressure (p less than 0.01 to less than 0.0001). Ejection fraction at rest increased significantly, from a mean (+/- standard error) of 53 +/- 3% with placebo to 58 +/- 3% with carvedilol, 50 mg twice daily, but no improvement was noted in ejection fraction on exercise. Relative, counts-based end-systolic and end-diastolic volumes were significantly reduced at rest (p less than 0.001). Rest peak filling rate index, first-third filling fraction and ejection rate index increased significantly with carvedilol. A dose-related change was observed with rest ejection fraction, peak filling rate index and ejection rate index. Exercise-induced ST-segment depression improved significantly with both doses of carvedilol compared with placebo. Carvedilol was well tolerated and produced significant hemodynamic improvement. This salutary effect on left ventricular function may confer advantages in long-term treatment of patients with chronic stable angina.

Radionuclide left ventricular ejection fraction: a comparison of three methods.

Three commercially available computer programs (a semiautomatic method, a manual method, and a regional method) were used to calculate left ventricular ejection fraction from the equilibrium multiple gated radionuclide ventriculograms obtained from 24 normal male subjects and 20 men with heart failure. In the normal subjects the ejection fraction values calculated by each method were significantly different (mean SD) difference between semiautomatic and manual 3.3 (5.8); between semiautomatic and regional 12.0 (6.3); and between manual and regional 8.7 (6.9]. In the patients with heart failure the ejection fraction values calculated by the semiautomatic method differed significantly from those calculated by the manual and regional methods (mean (SD) difference between semiautomatic and manual 3.4 (4.7); between semiautomatic and regional 4.9 (4.9); and between manual and regional 1.5 (6.2]. The ejection fraction values obtained by the semiautomatic method were generally higher and more consistent than those derived from the manual and regional methods. An ejection fraction of greater than or equal to 50% with the semiautomatic method would be regarded as normal but if the same normal range was applied to the regional method nine (38%) of the 24 normal subjects would appear to have an abnormal left ventricular function. Clinicians should be aware that the method used to generate a time-activity curve is an important consideration in the calculation of ejection fraction. Each centre should establish its own range and reproducibility for the method it uses to measure ejection fraction. These values should not be assumed to apply to any other method.

Once- and twice-daily bevantolol for systemic hypertension using 24-hour ambulatory intraarterial blood pressure recording.

The antihypertensive efficacy of bevantolol, a selective beta 1-adrenoreceptor antagonist, was evaluated in 17 patients with essential hypertension, using continuous ambulatory intraarterial blood pressure (BP) monitoring. The study compared a twice-daily regimen (titrated dose of 200 to 600 mg/day) with the same amount given in a single daily dose. Within-patient comparisons of mean hourly systolic and diastolic BPs and heart rate showed a highly significant effect with twice-daily therapy (p less than 0.001) for all of the 24 hours. Similar significant results were obtained with a single morning dose. There was no difference between the pattern or extent of BP reduction with the 2 regimens. The decrease in BP after bevantolol persisted during the physiologic tests (rest, tilt, isometric and dynamic exercise). Four patients developed minor side effects with the single morning dose, and only 1 patient with the twice-daily regimen. These effects included tiredness, fatigue and dizziness. Unlike pure beta-blocking agents, bevantolol controlled the early morning increase in BP, lending support to the belief that it possesses vasodilatory properties in addition to beta blockade. These results suggest that bevantolol may be useful as first-line therapy in a once-daily dosage for the treatment of essential hypertension.

Effects of tiapamil, a new calcium channel blocker, on ambulatory intraarterial blood pressure and exercise-induced changes in blood pressure.

The duration and magnitude of effect of a new calcium-channel blocker, tiapamil, given twice daily, was studied in 17 hypertensive patients using ambulatory intraarterial blood pressure recording. The drug produced moderate reductions of blood pressure throughout the 24-h cycle with slight reduction of effect before each dose. Ten patients reported side effects, and one withdrew as a result of these. Tiapamil attenuated the blood pressure rise during dynamic cycle ergometry but had no effect on the increase during isometric hand grip. We conclude that tiapamil is similar to existing calcium-channel blocking agents in lowering the blood pressure, but it does not appear to influence the response to isometric exercise in this dose.

The effects of long-acting pinacidil on intra-arterial blood pressure.

We have tested the efficacy of a new long-acting preparation of pinacidil, an arterial vasodilator, using continuous intra-arterial ambulatory blood pressure recording. An acute dose produced a measurable effect lasting for 12 h. The duration of this effect was less during chronic twice daily drug administration. Side effects were common, causing two out of nine patients to withdraw from the study. Tilt testing produced no postural hypotension and there was no evidence of rebound hypertension on the withdrawal day.