Does reducing spasticity translate into functional benefit? An exploratory meta-analysis.

BACKGROUND: Spasticity and loss of function in an affected arm are common after stroke. Although botulinum toxin is used to reduce spasticity, its functional benefits are less easily demonstrated. This paper reports an exploratory meta-analysis to investigate the relationship between reduced arm spasticity and improved arm function. METHOD: Individual data from stroke patients in two randomised controlled trials of intra-muscular botulinum toxin were pooled. The Modified Ashworth Scale (elbow, wrist, fingers) was used to calculate a "Composite Spasticity Index". Data from the arm section of the Barthel Activities of Daily Living Index (dressing, grooming, and feeding) and three subjective measures (putting arm through sleeve, cleaning palm, cutting fingernails) were summed to give a "Composite Functional Index". Change scores and the time of maximum change were also calculated. RESULTS: Maximum changes in both composite measures occurred concurrently in 47 patients. In 26 patients the improvement in spasticity preceded the improvement in function with 18 showing the reverse. There was a definite relationship between the maximum change in spasticity and the maximum change in arm function, independent of treatment (rho = -0.2822, p = 0.0008, n = 137). There was a clear relationship between the changes in spasticity and in arm function in patients treated with botulinum toxin (Dysport) at 500 or 1000 units (rho = -0.5679, p = 0.0090, n = 22; rho = -0.4430, p = 0.0018, n = 47), but not in those treated with placebo or 1500 units. CONCLUSIONS: Using a targeted meta-analytic approach, it is possible to demonstrate that reducing spasticity in the arm is associated with a significant improvement in arm function.

Postcardiac surgery low cardiac output syndrome: dopexamine or dopamine?

OBJECTIVE: To compare the efficacy and safety of dopexamine with dopamine in the treatment of low cardiac output syndrome after cardiac surgery. DESIGN: This was a multicentre, double-blind, randomised, parallel-group study conducted in intensive care units at centres in Holland and Belgium. Patients were randomised to receive dopexamine (up to 2.0 micrograms/ kg per min) or dopamine (up to 6.0 micrograms/kg per min) for 6 h after low cardiac output syndrome was confirmed. RESULTS: 70 patients were enrolled (35/group) and there was no significant differences in the operative procedures or haemodynamics at entry into the study. Clinical efficacy, defined as a cardiac index > 2.5 l/min per m2 with urine production > 0.5 ml/kg per h and stable haemodynamics for two consecutive readings 1 h apart, was achieved by 90 and 87% of patients in the dopexamine and dopamine groups, respectively. However, more patients maintained clinical efficacy over the 6-h period in the dopexamine group, which was statistically significant at 1-2 h and approached significance at all other time points. Safety was assessed by comparing the adverse events and concomitant medication. Fewer patients on dopexamine had cardiac events compared with dopamine-treated patients (25 vs 38 events), although there was no difference in the pattern of rhythm disturbance. Fewer patients in the dopexamine group required concomitant vasodilating drugs (18 vs 30). CONCLUSION: Taking the proportion of patients achieving clinical efficacy, the time to achieve it and the maintenance of it along with the adverse event profile, dopexamine was shown to be an effective and safe drug to use in the management of low cardiac output syndrome after coronary artery bypass graft surgery and may be superior to dopamine.

Clinical studies with granisetron, a new 5-HT3 receptor antagonist for the treatment of cancer chemotherapy-induced emesis. The Granisetron Study Group.

Granisetron (BRL 43694A) is a novel, selective 5-hydroxytryptamine-3 (5-HT3) receptor antagonist developed for the prophylaxis and treatment of cytostatic drug-induced emesis. After a brief review of the preclinical evaluation of granisetron the clinical findings with this novel compound are summarised. From the data of large randomised trials one can conclude that granisetron is an active antiemetic, both as a prophylactic and an intervention agent, to an extent which is superior or at least equal to the best available antiemetic combination regimens, having a major efficacy ranging from 74 to 92%. Granisetron may be given as a single, 5-min infusion before chemotherapy and is thus more convenient to administer than many antiemetic regimens. The adverse event profile of granisetron is favourable with a wide therapeutic margin. The only consistent side-effects attributable to granisetron are headache in about 14% of the patients and constipation in about 4% of the patients. Headache induced by granisetron was generally mild and resolved spontaneously or was promptly relieved with standard analgesics. No extrapyramidal side-effects were observed with granisetron.

Can genetic polymorphism of alpha-2-macroglobulin be detected by immunoelectrophoresis? A study using sera, plasma and joint fluids from patients with rheumatoid arthritis and controls.

The technique of immunoelectrophoresis (IEP) was used to examine polymorphism of the endopeptidase inhibitor alpha-2-macroglobulin (alpha 2M) by measuring its electrophoretic mobility. Examination of the variability of the method showed that a large intra- and inter-plate variation occurred (3.3 and 11.6%, respectively). It was also shown that alpha 2M from plasma moves significantly slower than that from serum and that the mobility of alpha 2M from plasma can be increased to that of serum by treatment with trypsin. Upon comparing sera, plasma and synovial fluids from a control group (normal subjects and patients with osteoarthritis) with a group of patients with rheumatoid arthritis, no difference in alpha 2M mobility could be demonstrated. It is concluded that genetic polymorphism of alpha 2M cannot be detected by the technique of IEP.

The visualization and characterization of two immunological forms of alpha 2 macroglobulin by immunoelectrophoretic methods.

Two peaks of alpha 2 macroglobulin (alpha 2M) were demonstrated in serum or plasma treated with trypsin using crossed immunoelectro-phoresis (CIEP). Both peaks moved the same distance in the first dimension and separated only when electrophoresed into antibody containing gel. The double peak phenomenon was shown not to be an artefact of the antiserum used and that the sample had to be fresh for both peaks to be visualised. Using the methods of staggered well CIEP and crossed thin layer gel chromatography (CTLGC) both peaks were shown to be of very similar antigenicity and molecular size. The technique of line immunoelectrophoresis (LIEP) demonstrated that the newly described lower peak was the alpha 2M/protease complex. The lowest concentration of alpha 2M/protease complexes that could be detected was 0.03 g/l. The two peaks of alpha 2M do not follow the theory of rocket immunoelectrophoresis (RIEP) and this is discussed.