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.     

NPY hyperinnervation in Hirschsprung's disease: both adrenergic and nonadrenergic fibers contribute.

In Hirschsprung's disease, the aganglionic bowel is characterized by an absence of ganglion cells and an increased number of adrenergic and presumed cholinergic nerve fibers. In addition, a severe derangement of peptide-containing nerve fibers is encountered including a hyperinnervation of neuropeptide Y (NPY)-containing fibers. Using immunochemical and immunocytochemical methods, we examined the nature of the NPY-containing nerve fibers contributing to the hyperinnervation. The concentration of NPY was markedly increased in the aganglionic segment. Coexistence of NPY, vasoactive intestinal peptide (VIP), and the adrenergic enzyme tyrosine hydroxylase (TH) showed small populations of nerve fibers containing NPY/TH, NPY/VIP, or TH alone in ganglionic intestine. Numerous nerve fibers stored VIP but lacked NPY. These fibers did not contain TH, indicating that all VIP-containing fibers are nonadrenergic. In the aganglionic intestine there was a marked increase in the number of nerve fibers storing NPY/TH and NPY/VIP, whereas the fibers storing VIP alone were reduced in number. A small number of nerve fibers storing NPY alone occurred in the hypertrophic nerve bundles. NPY/VIP-containing nerve fibers were particularly numerous in the mucosa in aganglionic intestine, which may be of interest in the diagnosis of Hirschsprung's disease allowing the use of mucosal biopsy specimens. Thus, the proliferating NPY-containing nerve fibers in the aganglionic intestine seem to comprise three different populations, one adrenergic and two nonadrenergic, one of which contains in addition VIP.     

Neonatal reference values for ionized calcium, phosphate and magnesium. Selection of reference population by optimality criteria

Thirty-one full-term newborn babies were investigated in order to establish reference values for ionized calcium. Only children fulfilling certain optimality criteria (with best possible maternal and infant conditions and uncomplicated pregnancy and delivery) were included. All infants were breast fed. Capillary blood for analysis of ionized calcium was collected by heel puncture on day 1 (6-36 h post partum, p.p.), day 3 (60-84 h p.p.) and day 5 (108-132 h p.p.). Ionized calcium was measured with a semi-automatic electrode system ICA 1 (Radiometer A/S, Copenhagen, Denmark). The reference ranges (mean +/- 2 SD) for days 1, 3 and 5 were 1.05-1.37, 1.10-1.42 and 1.20-1.48 mmol/l, respectively. The mean ionized calcium concentration on day 1 was significantly lower than on days 3 and 5. Reference values are also given for total calcium, magnesium and phosphate. We emphasize that it is impossible to calculate ionized calcium from total calcium or vice versa.     

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.     

Distinct Pharmacologic Properties of Neuromuscular Blocking Agents on Human Neuronal Nicotinic Acetylcholine Receptors: A Possible Explanation for the Train-of-four Fade

Background: Nondepolarizing neuromuscular blocking agents (NMBAs) are extensively used in the practice of anesthesia and intensive care medicine. Their primary site of action is at the postsynaptic nicotinic acetylcholine receptor (nAChR) in the neuromuscular junction, but their action on neuronal nAChRs have not been fully evaluated. Furthermore, observed adverse effects of nondepolarizing NMBAs might originate from an interaction with neuronal nAChRs. The aim of this study was to examine the effect of clinically used nondepolarizing NMBAs on muscle and neuronal nAChR subtypes.

Methods: Xenopus laevis oocytes were injected with messenger RNA encoding for the subunits included in the human [alpha]1[beta]1[varepsilon][delta], [alpha]3[beta]2, [alpha]3[beta]4, [alpha]4[beta]2, and [alpha]7 nAChR subtypes. The interactions between each of these nAChR subtypes and atracurium, cisatracurium, d-tubocurarine, mivacurium, pancuronium, rocuronium, and vecuronium were studied using an eight-channel two-electrode voltage clamp setup. Responses were measured as peak current and net charge.

Results: All nondepolarizing NMBAs inhibited both muscle and neuronal nAChRs. The neuronal nAChRs were reversibly and concentration-dependently inhibited in the low micromolar range. The mechanism (i.e., competitive vs. noncompetitive) of the block at the neuronal nAChRs was dependent both on subtype and the NMBA tested. The authors did not observe activation of the nAChR subtypes by any of the NMBAs tested.