Focal spasticity therapy with botulinum toxin: effects on function, activities of daily living and pain in 100 adult patients.

OBJECTIVE: Analysis of the effects of a comprehensive focal spasticity program in adult patients. DESIGN: Retrospective study of an out-patient cohort. PATIENTS: One hundred patients were enrolled in the study (54 men and 46 women, mean age 41 years (SD 14). Cerebral palsy and stroke were equally common (80% in total). The remaining patients had miscellaneous diagnoses, including traumatic brain injury. METHODS: On average 230 units (SD 101) of botulinum toxin A Botox was given for 227 principal therapy targets chosen by the patient or the caregiver. One patient could have several targets for therapy. Administration of botulinum toxin was combined with 260 additional therapeutic interventions, most of which were forms of physical therapy. The effects were assessed after 6 weeks and compared with baseline functional abilities 1-2 weeks prior to therapy. RESULTS: Improvement was observed for 211 (93%) therapy targets, no change in 15 (7%), and impairment in 1, corresponding to an overall improvement in 90 patients (90%), 9 unchanged (9%) and worsening in 1. Spasticity assessment (Ashworth scale 0-4; 30 patients) showed a statistically significant improvement (median at baseline was 3 vs 2 after therapy, mean difference 1.2, p<0.001). CONCLUSION: Improvement was observed in >or=90% of patients and in their principal therapeutic targets in a cohort receiving their first focal spasticity treatment with botulinum toxin A and additional therapy. A strict strategy for patient selection and comprehensive management was followed.     

Balance and gait improved in patients with MS after physiotherapy based on the Bobath concept

Background and Purpose . Patients with multiple sclerosis (MS) tend to have movement difficulties, and the effect of physiotherapy for this group of patients has been subjected to limited systematic research. In the present study physiotherapy based on the Bobath concept, applied to MS patients with balance and gait problems, was evaluated. The ability of different functional tests to demonstrate change was evaluated. Method . A single‐subject experimental study design with ABAA phases was used, and two patients with relapsing–remitting MS in stable phase were treated. Tests were performed 12 times, three at each phase: A (at baseline); B (during treatment); A (immediately after treatment); and A (after two months). The key feature of treatment was facilitation of postural activity and selective control of movement. Several performance and self‐report measures and interviews were used. Results . After intervention, improved balance was shown by the Berg Balance Scale (BBS) in both patients, and improved quality of gait was indicated by the Rivermead Visual Gait Assessment (RVGA). The patients also reported improved balance and gait function in the interviews and scored their condition as ‘much improved’. Gait parameters, recorded by an electronic walkway, changed, but differently in the two patients. Among the physical performance tests the BBS and the RVGA demonstrated the highest change, while no or minimal change was demonstrated by the Rivermead Mobility Index (RMI) and Ratings of Perceived Exertion (RPE). Conclusion . The findings indicate that balance and gait can be improved after physiotherapy based on the Bobath concept, but this should be further evaluated in larger controlled trials of patients with MS. Copyright © 2006 John Wiley & Sons, Ltd.     

Possible genetic defects in regulation of glycosaminoglycans in patients with diabetic nephropathy

The hypothesis of genetic defects in glycosaminoglycan (GAG) regulation among patients with insulin-dependent diabetes mellitus (IDDM) and nephropathy was assessed by studies in tissue cultures of fibroblasts obtained from 7 patients with normal urinary albumin excretion, 11 patients with diabetic nephropathy, and 6 nondiabetic control subjects. The incorporation of [2H] glucosamine and [35S] sulfate into hyaluronic acid (HA), chondroitin sulfate and dermatan sulfate (CS + DS), and heparan sulfate (HS) was measured in cells, matrix, and medium and related to micrograms of tissue protein. Large interindividual variations were seen in all three groups, and the incorporation of [3H] glucosamine into HA, CS + DS, and HS and [35S] sulfate into CS + DS and HS were not significantly different between the three groups. However, the fractional incorporation of [3H]glucosamine into HS was significantly reduced in diabetic patients with nephropathy compared with control subjects. This was the case not only when related to the total amount of GAGs (P = 0.014) but also when related to HA (P = 0.014). No significant difference was seen between control subjects and normoalbuminuric diabetic patients. The degree of N-sulfation of HS was not significantly different between the experimental groups. The results suggest that patients with diabetic nephropathy may suffer from deficiencies of coordinate regulation in the biosynthesis of GAG in fibroblasts, which may lead to a reduced density of HS in the extracellular matrix. If these changes reflect alterations in the biosynthesis of GAG from endothelial, myomedial, and mesangial cells, this observation may be relevant for the pathogenesis of severe diabetic complications.     

Scientific quality of clinical research an analysis of 40 research projects in pharmacology/pharmacotherapy

Objective: The scientific quality of research is an important ethical issue. To clarify the quality of research projects in pharmacotherapy/pharmacology, 40 randomly selected research projects in pharmacotherapy/pharmacology submitted to a research ethics committee were reviewed. Results: Eight of the projects would not have contributed new knowledge nor were they necessary as controls for the results of previous research. Fifteen of the research protocols were of good quality, 15 could be used after revisions, and 10 were unfit for use. Eleven of the research projects were not finished 5 years after they were started. A written report was produced from 26 of the projects. Nine were of good quality and could be accepted for publication in a medical journal, 10 of the reports were in need of revision before publication, and 7 should not be accepted for publication. Conclusion: Research in this field ought to be improved, and ways to improve the standard of clinical trials in pharmacotherapy are dicussed. Received: 1 April 1996 / Accepted in revised form: 28 June 1996     

Receptor binding of N-(methyl-11C) clozapine in the brain of rhesus monkey studied by positron emission tomography (PET)

By means of positron emission tomography the uptake and kinetics of N-(methyl-¹¹C)clozapine in different brain regions have been studied in Rhesus monkeys. ¹¹C-clozapine rapidly entered the brain and maximum radioactive uptake was seen 5–12 min after administration. Highest uptake was measured in the striatum. Other regions with an uptake higher than in the cerebellum were thalamus and mesencephalon. The radioactivity from different brain regions decreased with an elimination half-life of about 5 h and parallelled the plasma kinetics of unlabelled clozapine. The striatum/cerebellum ratio of ¹¹C-clozapine-derived radioactivity remained constant during the period studied and did not change after pretreatment with atropine. In contrast, the striatum/cerebellum ratio was somewhat lower after pretreatment with N-methylspiperone (NMSP), indicating competition for the same binding sites in the striatum. After pretreatment with increasing doses of clozapine, a dose-dependent protection of binding sites in the striatum for ¹¹C-NMSP was seen. It is concluded that clozapine is more loosely bound to dopamine receptors in the striatum than N-methylspiperone and that the kinetics of clozapine in the brain parallel that in the plasma. The binding properties of clozapine within the brain may explain some of the clinical properties of the drug.     

Interactions between serotonin and substance P in the spinal regulation of nociception

Interactions between 5-hydroxytryptamine (5-HT) and substance P (SP) in the mouse spinal cord were investigated using the tail-flick test and the behavioral response evoked by intrathecal (i.th.) SP or i.th. 5-HT. I.th. injection of 5-HT (20 μg) or the 5-HT₁ receptor agonists(+)-8-hydroxy-2-(di-n-propylamino)tetralin ((+)-8-OH-DPAT) (20 μg) or 5-methoxy-3(1,2,3,6-tetrahydropyridine-4-yl)-1H-indole (RU 24969) (20 μg) markedly inhibited the tail-flick reflex. The effect of these compounds was reduced when SP (5 μg) was given i.th. 55 min, or 55 and 45 min before the agonists. The tail-flick latencies recorded 5 min before injection of a 5-HT agonist were similar in animals treated with SP or vehicle. The changes in the tail-flick test were not due to changes in tail skin temperature since only minimal differences in the skin temperature were recorded between the groups injected with SP or vehicle. I.th. injection of SP (10 ng) or 5-HT (2 μg) produced a similar behavioral response consisting of biting, licking and scratching of the caudal part of the body, indicative of nociceptive stimulation. The responses both to i.th. SP and 5-HT were reduced after i.th. application of SP receptor antagonist [d-Arg¹,d-Trp^7,9,Leu¹¹]-SP (Spantide) (5 μg), as well as 5 min after i.th. injection of the 5-HT receptor antagonist metergoline (4 μg). The data may indicate functional interactions between SP and 5-HT in the mouse spinal cord, which may take place in neurons involved in the processing of nociception.     

Axillary recurrence in breast cancer.

AIM: To determine whether axillary recurrence reflects inadequate axillary treatment or adverse pathological features. METHODS: The case-records were reviewed of 2122 women aged under 75 years, treated for invasive breast cancer during the time-period 1/1/86-31/12/91 in a geographically defined area. Data were abstracted on operations performed, pathological features, post-operative treatments and details of axillary recurrence. The risk of axillary recurrence was examined by pathological, treatment and patient factors. RESULTS: Axillary recurrence was more than twice as likely after inadequate compared to adequate treatment of the axilla (adequate staging or axillary radiotherapy or clearance). Delayed treatment of the axilla was not as successful as adequate primary treatment: multiple axillary recurrences were twice as common, one third of which were uncontrolled at time of death. Inadequate surgical treatment was associated with increased rates of recurrence despite endocrine therapy, chemotherapy or radiotherapy. Lymphoedema was twice as common if axillary radiotherapy was combined with any axillary surgical procedure. CONCLUSIONS: Axillary recurrence is more common in tumours with adverse pathology but may also result from inadequate axillary treatment. In order to minimise axillary recurrence, optimal treatment of the axilla entails adequate staging (sampling of four or more nodes) and treatment (axillary clearance or radiotherapy and endocrine therapy) in all women.