Muscle strength, including leg strength and respiratory muscle strength, are relatively independently associated with mobility disability in elders. However, the factors linking muscle strength with ...mobility disability are unknown. To test the hypothesis that pulmonary function mediates the association of muscle strength with the development of mobility disability in elders, we used data from a longitudinal cohort study of 844 ambulatory elders without dementia participating in the Rush Memory and Aging Project with a mean follow-up of 4.0 years (SD = 1.39). A composite measure of pulmonary function was based on spirometric measures of forced vital capacity, forced expiratory volume, and peak expiratory flow. Respiratory muscle strength was based on maximal inspiratory pressure and expiratory pressure and leg strength based on hand-held dynamometry. Mobility disability was defined as a gait speed less than or equal to 0.55 m/s based on annual assessment of timed walk. Secondary analyses considered time to loss of the ability to ambulate. In separate proportional hazards models which controlled for age, sex, and education, composite measures of pulmonary function, respiratory muscle strength, and leg strength were each associated with incident mobility disability (all P values < 0.001). Further, all three were related to the development of incident mobility disability when considered together in a single model (pulmonary function: hazard ratio HR, 0.721; 95% confidence interval CI, 0.577, 0.902; respiratory muscle strength: HR, 0.732; 95% CI, 0.593, 0.905; leg strength: HR, 0.791; 95% CI, 0.640, 0.976). Secondary analyses examining incident loss of the ability to ambulate revealed similar findings. Overall, these findings suggest that lower levels of pulmonary function and muscle strength are relatively independently associated with the development of mobility disability in the elderly.
Twelve patients with cervical dystonia (CD) and predominant rotation were studied to determine the effects of changes in head posture on the specific patterns of cervical muscle activity. Turns ...analysis was used to quantify muscle activity underlying head rotation, recorded simultaneously from the agonist and antagonist muscle pairs bilaterally (sternocleidomastoid SCM and splenius SPL). Muscle activity was compared between the uncompensated dystonic posture and during the maintenance of midposition. In addition, patients were separated into two groups (geste = 6; no geste = 6) based on whether they had a clinically efficacious geste to determine the effect of geste on patterns of cervical muscle activity. Muscle activity was measured during the maintenance of midposition with and without a clinical or simulated geste. Differences in muscle activity between the groups and postures were compared using repeated measure analysis of variance (ANOVA) analyses. The four muscles tested showed a significant difference in muscle activity in the uncompensated dystonic posture as a result of the increased activity in the agonist muscle pair (SCM and SPL responsible for the dystonic posture) (EMG amplitude: F1,11 = 18.81, p = 0.0012; EMG frequency: F1,11 = 32.07, p = 0.0001). Maintaining the head in the midposition was associated with a significant reduction in muscle activity compared with the uncompensated dystonic posture (EMG amplitude: F1,9 = 6.36, p < 0.033; EMG frequency: F1,9 = 10.96, p < 0.0091). This reduction in midposition muscle activity was significantly greater in the agonist muscle pair (EMG amplitude: F1,10 = 19.70, p = 0.0013; EMG frequency: F1,10 = 44.67, p < 0.0001). In the patients with clinically effective geste, there was no additional reduction in muscle activity observed in the midposition when they performed their geste (EMG amplitude: F1,9 = 4.63, p = 0.060; EMG frequency: F1,9 = 1.22, p = 0.298). These findings suggest that CD with rotation is characterized by predominantly increased agonist muscle activation. Patients with CD retain the ability to modulate this involuntary agonist muscle activity to maintain the head in the midposition. The maintenance of the midposition does not seem to be facilitated by geste.
Background. Loss of motor function is a common consequence of aging, but little is known about the factors that predict idiopathic motor decline. Our objective was to test the hypothesis that ...late-life social activity is related to the rate of change in motor function in old age. Methods. Longitudinal cohort study with a mean follow-up of 4.9 years with 906 persons without stroke, Parkinson disease, or dementia participating in the Rush Memory and Aging Project. At baseline, participants rated the frequency of their current participation in common social activities from which a summary measure of social activity was derived. The main outcome measure was annual change in a composite measure of global motor function, based on 9 measures of muscle strength and 9 motor performances. Results. Mean (SD) social activity score at baseline was 2.6 (0.58), with higher scores indicating more frequent participation in social activities. In a generalized estimating equation model, controlling for age, sex, and education, global motor function declined by approximately 0.05 U/y (estimate, 0.016; 95% confidence interval CI, -0.057 to 0.041 p = .02). Each 1-point decrease in social activity was associated with approximately a 33% more rapid rate of decline in motor function (estimate, 0.016; 95% CI, 0.003 to 0.029 p = .02). The effect of each 1-point decrease in the social activity score at baseline on the rate of change in global motor function was the same as being approximately 5 years older at baseline (age estimate, -0.003; 95% CI, -0.004 to -0.002 p < .001). Furthermore, this amount of motor decline per year was associated with a more than 40% increased risk of death (hazard ratio, 1.44; 95% CI, 1.30 to 1.60) and a 65% increased risk of incident Katz disability (hazard ratio, 1.65; 95% CI, 1.48 to 1.83). The association of social activity with the rate of global motor decline did not vary along demographic lines and was unchanged (estimate, 0.025; 95% CI, 0.005 to 0.045 p = .01) after controlling for potential confounders including late-life physical and cognitive activity, disability, global cognition depressive symptoms, body composition, and chronic medical conditions. Conclusion. Less frequent participation in social activities is associated with a more rapid rate of motor function decline in old age.
Our objective was to assess the ability of the microcomputed tomography scanner to correctly image normal and synostosed cranial sutures at the ultrastructural level.
Two specimens of coronal sutures ...were collected from operative specimens. After appropriate preparation, histological sections were obtained and stained with toluene blue for evaluation. Representative histological sections were compared to microcomputed tomography slices.
With microcomputed tomography, we successfully imaged one normal and one synostosed human coronal suture and performed a quantitative analysis of these specimens. Microcomputed tomography scanning was found to be a highly accurate imaging device for the evaluation of cranial suture development. Microcomputed tomography offers three-dimensional imaging at the microscopic level and allows for rapid quantitative analysis of bone architecture, including several measurements unavailable through histologic analysis. We believe that microcomputed tomography can play an important role in imaging and in the quantitative analysis of the stereology of bone microarchitecture. Among its advantages, microcomputed tomography is able to image many more slices than are obtainable through histology, and the method is not prone to human error. Microcomputed tomography slices are generated without destruction of the specimen and without loss or corruption of reproducible data. Structure-oriented slices from microcomputed tomography together with cellular-oriented sections from histology are complementary in the overall quantitative analysis of cranial sutures.
Preclinical investigations indicated that recombinant human ciliary neurotrophic factor (rhCNTF) may have potential as therapy for amyotrophic lateral sclerosis (ALS). We evaluated the safety and ...efficacy of rhCNTF in a prospective, double‐blind, placebo‐controlled trial in 570 patients with US. Patients were randomized to receive 0.5, 2, or 5 μg/kg/day rhCNTF, or placebo, for 6 months. The primary efficacy end point was the change from baseline to the last on‐ treatment value of a combination megascore for limb strength (maximum voluntary isometric contraction) and pulmonary function. Secondary end points included individual arm and leg megascores, pulmonary function tests, an activities‐of‐daily‐living outcome measure, and survival. The four treatment groups were similar at baseline with respect to age, sex, disease duration, and muscle strength values. At all doses tested, rhCNTF had no beneficial effect on the primary or secondary end points. Certain adverse events, as follows, appeared to be dose related: injection site reactions, cough, asthenia, nausea, anorexia, weight loss, and increased salivation. There was an increased number of deaths at the highest dose level. rhCNTF had no benefical effect on any measure of ALS progression. There were increased adverse events in the 5 μg/kg group and increased deaths.
Neuromuscular jitter was determined in the extensor digitorum communis (EDC) of 41 healthy control subjects and 8 patients with myasthenia gravis (MG). Standard single-fiber electromyographic (SFEMG) ...techniques were used, except that a monopolar electrode (MPE) was substituted for a single-fiber electrode (SFE). In normals, mean jitter for 20 pairs was 22.4 +/- 2.8 microseconds and the mean jitter for an individual pair was 22 +/- 5.6 microseconds. In the age range tested (18 to 49 years), jitter did not change with increasing age. When MPE jitter studies were repeated in 16 normals, mean jitter usually varied by less than 10% (mean 7.4% +/- 6.2%) and remained normal. Jitter was significantly increased in MG compared to normals 73 +/- 56 microseconds versus 22 +/- 5.6 microseconds (F = 149.4, P less than 0.0001). Using an analog pain scale, the discomfort during electromyography using MPE and SFE was compared between the left and right arms in 35 normals. MPEs caused less discomfort than SFEs (P = 0.0031), and were preferred (71% versus 20%) to SFEs (chi 2 = 9.21, P = 0.01). Based on these results, we conclude that MPE determined jitter studies are reproducible, can distinguish between normals and MG, and are associated with less discomfort than SFE.
This study determined the influence of serum neutralizing antibody titers on infection rate, symptom manifestations, and provoked signs and pathophysiologies in adults experimentally exposed to ...rhinovirus type 39 (RV-39). Antibody status was determined for 151 healthy volunteers who were then cloistered in a hotel for 6 days. At the end of the first cloister day, the volunteers were challenged with RV-39 in a median tissue culture infective dose of 100. On each of the 6 days, a nasal examination was performed, symptoms were scored, and objective tests of nasal mucociliary function, nasal airway patency, secretion production, and middle ear pressures were completed. Both subjects and investigators were blinded to the prechallenge serum homotypic antibody titers of the subjects. Four subjects presented with a wild virus and were excluded from the analysis. Of the 147 included subjects, prechallenge serum antibody titers to RV-39 were low (under 2) in 56 subjects, intermediate (2 to 8) in 51 subjects, and high (above 16) in 40 subjects. The high-titer group was significantly different from the low-titer group with respect to viral shedding, symptom load, subjective extent of illness, and secretion production, as well as in the frequency of subjects with abnormal nasal mucociliary clearance and positive middle ear pressures. The study results document that for experimental RV-39 exposure, high levels of homotypic serum neutralizing antibody titers are associated with protection from infection and a lessened degree of disease expression, but not with a reduction of otologic complications.
Using case-control methodology, we assessed prevalence and duration of exposure to putative risk factors for rapid progression of Parkinson's disease (PD) in patients not taking levodopa or direct ...dopamine agonists. We identified 31 patients termed "rapidly progressive" who were stage I or II (Hoehn and Yahr) on their first visit to our center and who progressed to stage III during the study period; we pair-matched this group with 31 "slowly progressive" patients who had the same symptom duration and the same Hoehn and Yahr stage at study entry, but whose parkinsonism did not progress to stage III during the study. Only age of PD onset was associated with different rates of PD progression; older patients at PD onset progressed more rapidly than younger patients.
A study of choline pharmacokinetics was undertaken in four patients receiving long‐term total parenteral nutrition. On consecutive days, 7, 14, 28, and 56 mmol choline chloride were intravenously ...infused over a 12‐hour period in each subject. The choline concentration was determined in plasma at baseline, ¼, 1, 3, 6, and 12 hours, and 3 and 12 hours after the infusion ended, and in daily 24‐hour urine collections. Analysis of variance showed the data fit a two‐compartment model in which elimination from the central compartment was saturable significantly better than a one‐compartment model in all four subjects (p < 10 −8 in all cases), and significantly better than a nonsaturating model in three of the four subjects (p = 1.0 × 10−9, 7.5 × 10−6, 9.4 × 10−11, respectively). The model allowed estimates of the rate constant for choline elimination at ambient levels, first‐order rate constants for transfer between central and peripheral compartments, the dissociation constant for the saturable elimination process, the apparent volume of distribution in the central compartment, the steady‐state volume of distribution, and the quantities of choline in the central compartment and in the readily exchangeable pool.
Clinical Pharmacology and Therapeutics (1994) 55, 277–283; doi:10.1038/clpt.1994.28
Reports of efficacy of botulinum toxin for cervical dystonia have relied on subjective reports of improvement or various clinical rating scales. We studied 19 patients with cervical dystonia using ...Turns analysis to determine if quantitative EMG measures of muscle activity changed following botulinum toxin injections. Before and after botulinum toxin injections, six muscles were evaluated bilaterally. Quantitative EMG analysis of active muscles injected with botulinum toxin showed a significant decline in muscle activity after botulinum toxin (F = 1,41 55.0; p < 0.001). Significant reductions in quantitative EMG parameters were also noted in noninjected active muscles after botulinum toxin treatment (F = 1,51 59.15; p < 0.001). The sum of EMG activity for all active muscles was calculated for each subject and showed a significant reduction after botulinum toxin injection MANOVA: (F = 1,5 5.69; p < 0.05. Quantitative EMG assessment provides an objective measure of response to botulinum toxin. Decreased muscle activity in noninjected muscles may result from toxin diffusion or reflect relaxation of muscles only secondarily involved in cervical dystonia.
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