Community stroke rehabilitation teams: providing home-based stroke rehabilitation in Ontario, Canada.

BACKGROUND: Community stroke rehabilitation teams (CSRTs) provide a community-based, interdisciplinary approach to stroke rehabilitation. Our objective was to assess the effectiveness of these teams with respect to client outcomes. METHODS: Functional, psychosocial, and caregiver outcome data. were available at intake, discharge from the program, and six-month follow-up. Repeated measures analysis of covariance was performed to assess patient changes between time points for each outcome measure. RESULTS: A total of 794 clients met the inclusion criteria for analysis (54.4% male, mean age 68.5±13.0 years). Significant changes were found between intake and discharge on the Hospital Anxiety and Depression Scale total score (p=0.017), Hospital Anxiety and Depression Scale Anxiety subscale (p<0.001), Functional Independence Measure (p<0.001), Reintegration to Normal Living Index (p=0.01), Bakas Caregiver Outcomes Scale (p<0.001), and Caregiver Assistance and Confidence Scale assistance subscale (p=0.005). Significant gains were observed on the strength, communication, activities of daily living, social participation, memory, and physical domains of the Stroke Impact Scale (all p<0.001). These improvements were maintained at the 6-month follow-up. No significant improvements were observed upon discharge on the memory and thinking domain of the Stroke Impact Scale; however, there was a significant improvement between admission and follow-up (p=0.002). All significant improvements were maintained at the 6-month follow-up. CONCLUSIONS: Results indicate that the community stroke rehabilitation teams were effective at improving the functional and psychosocial recovery of patients after stroke. Importantly, these gains were maintained at 6 months postdischarge from the program. A home-based, stroke-specific multidisciplinary rehabilitation program should be considered when accessibility to outpatient services is limited.

Outcome using a conservative tracheostomy strategy in intensive care.

BACKGROUND AND AIMS: We have a conservative approach to tracheostomy in intensive care, in that every patient considered for tracheostomy in our unit is discussed at a clinical meeting to evaluate potential benefit and harm from the procedure. This study examined tracheostomy numbers, complications and outcome of patients who had tracheostomy in comparison to our general intensive care population and to Scottish national data. METHODS: We collected prospective data on all patients having a tracheostomy over a three year period. Data included included time to tracheostomy, type of procedure (open or percutaneous), ventilator settings immediately before tracheostomy, peri- and post-operative complications and mortality. RESULTS: The number of tracheostomies was low (27 of 692 patients, 4%) and time to tracheostomy high (mean, 18 days) in comparison to published data. Patients who had a tracheostomy had a hospital mortality that was greater than predicted by the APACHE II scoring system (55% actual mortality vs. 44% predicted). Standardised mortality ratio (SMR) was 1.29 for tracheostomy patients and 0.89 for patients who did not have a tracheostomy. Length of stay and mortality were similar to national figures. One patient in the tracheostomy group developed tracheal stenosis that needed surgical intervention. There were no cases of symptomatic tracheal stenosis in the much larger group managed with orotracheal intubation alone. CONCLUSIONS: We found that a conservative approach to performing tracheostomy reduced the number of procedures performed without affecting overall unit outcomes.

Reciprocal regulation of choline acetyltransferase and choline kinase in sympathetic neurons during cholinergic differentiation.

The regulation of the synthesis of acetylcholine and phosphatidylcholine in rat sympathetic neurons was examined in the context of cholinergic differentiation. We demonstrate that the activities of choline acetyltransferase (ChAT) and choline kinase (CK) are inversely affected by treatment of sympathetic neurons with retinoic acid, utilized as an agent that induces cholinergic differentiation. Whereas ChAT specific activity increased 2- to 4-fold after 12 days of treatment with 5 microM retinoic acid, CK specific activity decreased by 25-30%. These changes in enzyme activities were essentially reflected in the incorporation of [methyl-3H]choline into ACh and the metabolites of the CDP-choline pathway for phosphatidylcholine synthesis. When sympathetic neurons were treated under high potassium conditions (50 mM) for 12 days, the specific activity of CK increased 1.3-fold whereas the activity of ChAT decreased by up to 90%. Furthermore, experiments in which the incorporation of [methyl-3H]choline into ACh and the metabolites of the CDP-choline pathway was measured in the absence of Na+ or in the presence of hemicholinium-3 (HC-3), demonstrate that CK has access to the same pool of choline utilized by ChAT. These results provide evidence that the activities of ChAT and CK may be inversely regulated during the process of cholinergic differentiation.

Extensive injury of descending neurons demonstrated by retrograde labeling in a virus-induced murine model of chronic inflammatory demyelination.

Persistent Theiler's virus infection of SJL/J mice was used as a model to quantitatively assess the extent of descending neuron injury by chronic inflammatory demyelination of the spinal cord. By 9 months postinfection, inflammatory demyelinating lesions were present throughout the spinal cord, affecting up to 31% of the cross-sectional area of the ventrolateral columns. Axon dropout was evident in the lesions by electron microscopy and by quantitation of axons in normal-appearing white matter. Axon number in the ventrolateral columns at L1/L2 was reduced by 23% and total axon area was reduced by 37%, compared with uninfected mice. The most informative data on descending neuron injury, however, was a reduction in retrograde. Fluoro-Gold labeling. Labeling from T11/T12 of rubrospinal, reticulospinal/raphespinal, and vestibulospinal neurons was reduced by 60%, 70%, and 93%, respectively. Retrograde responses to axonal injury were observed, consisting of atrophied cell bodies, indented nuclei, and abundant lipofuscin, but cell body dropout was minimal. The number of cell bodies of vestibulospinal neurons was reduced by only 35%, whereas the number of cell bodies of rubrospinal neurons was unchanged. These results demonstrate that chronic inflammatory demyelination can severely injure axons and emphasize the need to design neuroprotective therapies in human multiple sclerosis.

Preservation of neurologic function during inflammatory demyelination correlates with axon sparing in a mouse model of multiple sclerosis.

Axonal injury has been proposed as the basis of permanent deficits in the inflammatory, demyelinating disease, multiple sclerosis. However, reports on the degree of injury are highly variable, and the responsible mechanisms are poorly understood. We examined the relationships among long-term demyelination, inflammation, axonal injury, and motor function in a model of multiple sclerosis, in which mice develop chronic, immune-mediated demyelination of the spinal cord resulting from persistent infection with Theiler's virus. We studied two strains of mice, inbred SJL/J and C57BL/6x129 mice deficient in beta(2)-microglobulin and therefore CD8 lymphocytes. After 8 months of disease, SJL mice had considerably worse motor function than beta(2)-microglobulin-deficient mice. Motor dysfunction correlated linearly with the extent of demyelinated lesions in the spinal cord (lesion load) within each strain, but no difference in lesion load was present between strains. Also, the extent of remyelination did not differ between strains. Instead, the disparity in motor deficits reflected differences in the integrity of descending neurons. That is, retrograde labeling of reticulospinal, vestibulospinal, and rubrospinal neurons, although reduced in all chronically diseased mice, was two to seven times higher in beta(2)-microglobulin-deficient mice. The labeling was superior in beta(2)-microglobulin-deficient mice despite the fact that lesion expanse and therefore the number of axons traversing lesions were similar in both strains. Thus, by all criteria axons were equivalently demyelinated in SJL and beta(2)-microglobulin-deficient mice, but the extent of axonal injury differed significantly. These results indicate that mechanisms of demyelination and axonal injury are at least partly separable, and are consistent with the hypothesis that cytotoxic CD8 lymphocytes may selectively injure demyelinated axons. Additionally, the data suggest that axonal injury obligatorily results from chronic inflammatory demyelination and significantly contributes to neurological deficits.

An observational study of practice during transfer of patients from anaesthetic room to operating theatre.

We observed practice during transfer of 80 patients from anaesthetic room to operating theatre, to determine the duration of apnoea and the time without monitoring during the transfer process. Median (IQR [range]) time from disconnection of the breathing system in the anaesthetic room to the first breath in theatre was 54 (44-65 [27-196]) s, and from disconnection of the pulse oximetry probe to the first reading in theatre was 90 (74-103 [44-182]) s. In four patients (5%) arterial oxygen saturation fell to 94%, with the greatest desaturation observed 11%. The transfer process may represent a window of opportunity for the occurrence of harm or the first step in a chain of events leading to harm, and is difficult to justify on patient safety grounds.

Leukemia inhibitory factor and nerve growth factor are retrogradely transported and processed by cultured rat sympathetic neurons.

How neurons convert the presence of factors at their axon terminals into signals that affect mechanisms in their cell bodies is unknown, but retrograde axonal transport of the factors themselves may be involved. Nerve growth factor (NGF) and leukemia inhibitory factor (LIF) have previously been shown to produce changes in cell bodies of sympathetic neurons when applied to their peripheral neurites, and it is well established that NGF is retrogradely transported along sympathetic axons. In this study we show that 125I-LIF applied to terminal neurites of rat sympathetic neurons in compartmented cultures is retrogradely transported, but at a much lower level compared to the retrograde transport of 125I-NGF. Transport of 125I-LIF was competed by cotreatment with unlabeled LIF and was blocked by cotreatment with dinitrophenol. The rate of 125I-LIF transport was independent of NGF concentration. However, both 125I-LIF and 125I-NGF transport was reduced by pretreating neurons with LIF. SDS-PAGE analysis showed that retrogradely transported radiolabel which accumulated in cell body-containing extracts following transport of both 125I-LIF and 125I-NGF consisted of intact as well as partially processed species. Radiolabel also accumulated in the medium bathing the cell bodies and migrated near the dye front on SDS-PAGE, implying that both factors were extensively degraded and released by the neurons. These results are consistent with the suggestion that the retrograde transport of LIF, as thought for NGF, may be important for retrograde signaling mechanisms.

Retrograde transport and steady-state distribution of 125I-nerve growth factor in rat sympathetic neurons in compartmented cultures.

We have used compartmented cultures of rat sympathetic neurons to quantitatively examine the retrograde transport of 125I-nerve growth factor (NGF) supplied to distal axons and to characterize the cellular events that maintain steady-state levels of NGF in cell bodies. In cultures allowed to reach steady-state 125I-NGF transport, cell bodies contained only 5-30% of the total neuron-associated 125I-NGF, whereas 70-95% remained associated with the distal axons. This was true over an 8 pM to 1.5 nM 125I-NGF concentration range, indicating that saturation of high affinity receptors could not account for the large fraction of 125I-NGF remaining in axons. Dissociation assays indicated that 85% of 125I-NGF associated with distal axons was surface-bound. At steady-state, only 2-25% of the distal axon-associated 125I-NGF was retrogradely transported each hour, with higher transport rates associated with younger cultures and lower 125I-NGF concentrations. The velocity of 125I-NGF retrograde transport was estimated at 10-20 mm/hr. However, as in a previous report, almost no 125I-NGF transport was observed during the first hour after 125I-NGF administration, indicating a significant lag between receptor binding and loading onto the retrograde transport system. During 125I-NGF transport through axons spanning an intermediate compartment in five-compartment cultures, little or no 125I-NGF was degraded or released from the axons. After transport, 125I-NGF was degraded with a half-life of 3 hr. In summary, although some cellular events promoted NGF accumulation in cell bodies, distal axons represented by far the principal site of NGF-receptor interaction at steady-state as a result of a low retrograde transport rate.

Safe use of remifentanil in a patient treated with the monoamine oxidase inhibitor phenelzine.

We report the safe use of remifentanil as part of the anaesthetic technique in a patient undergoing major head and neck surgery who was being treated for depressive illness with the non-specific monoamine oxidase inhibitor (MAOI) phenelzine.

Cholinergic differentiation of rat sympathetic neurons in culture: effects of factors applied to distal neurites.

Cholinergic properties are induced in sympathetic neurons by several factors applied to entire neurons in culture. Evidence from work with the rat sweat gland model indicates that factors located in target tissues can induce cholinergic differentiation in vivo. We now report that when leukemia inhibitory factor (LIF), heart cell-conditioned medium (HCCM), or dermal fibroblast-conditioned medium (DFCM) is applied to only distal neurites in compartmented cultures of rat sympathetic neurons, the neurons exhibit an increase in specific choline acetyltransferase activity and a concomitant decrease in levels of tyrosine hydroxylase. LIF, HCCM, and DFCM also induce neurite fasciculation, thus suggesting an additional role of cholinergic switching factors in regulating axon-axon and/or axon-substrate adhesion. These results demonstrate that rat sympathetic neurons have the cellular machinery to respond to cholinergic differentiation cues located in peripheral targets, analogous to the response to nerve growth factor.

Quantitative ultrastructural analysis of a single spinal cord demyelinated lesion predicts total lesion load, axonal loss, and neurological dysfunction in a murine model of multiple sclerosis.

Infection of susceptible mice with Theiler's murine encephalomyelitis virus results in neurological dysfunction from progressive central nervous system demyelination that is pathologically similar to the human disease, multiple sclerosis. We hypothesized that the development of neuropathology proceeds down a final common pathway that can be accurately quantified within a single spinal cord lesion. To test this hypothesis, we conducted quantitative ultrastructural analyses of individual demyelinated spinal cord lesions from chronically infected mice to determine whether pathological variables assessed within a single lesion accurately predicted global assessments of morphological and functional disease course. Within lesions we assessed by electron microscopy the frequencies of normally myelinated, remyelinated, and demyelinated axons, as well as degenerating axons and intra-axonal mitochondria. The frequency of medium and large remyelinated fibers within a single lesion served as a powerful indicator of axonal preservation and correlated with preserved neurological function. The number of degenerating axons and increased intra-axonal mitochondria also correlated strongly with global measures of disease course, such as total lesion load, spinal cord atrophy, and neurological function. This is the first study to demonstrate that functional severity of disease course is evident within a single demyelinated lesion analyzed morphometrically at the ultrastructural level.

Glycopyrrolate reduces nausea during spinal anaesthesia for caesarean section without affecting neonatal outcome.

We have tested the hypotheses that glycopyrrolate, administered immediately before induction of subarachnoid anaesthesia for elective Caesarean section, reduces the incidence and severity of nausea, with no adverse effects on neonatal Apgar scores, in a double-blind, randomized, controlled study. Fifty women received either glycopyrrolate 200 micrograms or saline (placebo) i.v. during fluid preload, before induction of spinal anaesthesia with 2.5 ml of 0.5% isobaric bupivacaine. Patients were questioned directly regarding nausea at 3-min intervals throughout operation and asked to report symptoms as they arose. The severity of nausea was assessed using a verbal scoring system and was treated with increments of i.v. ephedrine and fluids. Patients in the group pretreated with glycopyrrolate reported a reduction in the frequency (P = 0.02) and severity (P = 0.03) of nausea. Glycopyrrolate also reduced the severity of hypotension, as evidenced by reduced ephedrine requirements (P = 0.02). There were no differences in neonatal Apgar scores between groups.