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A series of analogues of the indole-2-carboxylate GV150526, currently in clinical trials as a potential neuroprotective agent for the control of the cerebral damage after stroke onset, was designed based on previous studies dealing with the electronic features of the north-east region of the glycine binding site associated with the NMDA receptor. In particular, the substitution of the para position of the terminal phenyl ring of GV150526 with suitable hydrophilic groups resulted in the identification of a new class of glycine antagonists. These compounds exhibited nanomolar in vitro affinity to the glycine binding site, high receptor selectivity, and outstanding in vivo potency. In particular, 3-[(E)-2-[(4-ureidomethylphenyl)aminocarbonyl]ethenyl]-4, 6-dichloroindole-2-carboxylic acid was found to be highly effective in the middle cerebral artery occlusion (MCAo) model in the rat, an animal model of focal ischemia, when given both prior to and after the occlusion of the middle cerebral artery. Notably, a significant neuroprotective effect was seen in this model postischaemia, when the administration of this compound was delayed up to 6 h from the occlusion of the middle cerebral artery, further confirming the wide therapeutic window seen for GV150526A.

A novel series of indole-2-carboxylate analogues of GV150526 (1) in which the propenoic double bond was substituted with different "probes" or replaced by a isosteric cyclopropyl moiety were synthesized and evaluated for their affinity profile in order to obtain further information on the pharmacophoric model of the glycine binding site associated to the NMDA receptor.

The asymmetric synthesis of carboxyphenyl prolines was performed according to Schöllkopf methodology, to prepare possible antagonists of the metabotropic glutamate receptor mGluR1.

A novel series of indole-2-carboxylate analogues of GV 150526 (1) in which the terminal phenyl ring belonging to the side chain present in the position C-3 has been replaced with a bridged cycloalkyl group was synthesized and evaluated for its pharmacological profile. Modelling studies on this class of novel glycine antagonist allowed us to identify an asymmetric lipophilic pocket present in the "North-Eastern" region of the pharmacophoric model of the glycine binding site associated to the NMDA receptor. Among the derivatives prepared, 3-[2-(1-adamantylaminocarbonyl)ethenyl]-4,6-dichloroindole-2 -carboxylic acid 6b and 3-[2-(norbornylaminocarbonyl)ethenyl]-4,6-dichloroindole-2-c arboxylic acid 6l were found to be antagonists acting at the strychnine-insensitive glycine binding site, showing nanomolar affinity for the glycine binding site (Ki = 63 and 19 nM, respectively), coupled with high glutamate receptor selectivity (IC50 > 10(-5) M at the NMDA, AMPA, KA binding sites) and high in vivo potency after systemic administration by inhibition of convulsion induced by NMDA in mice.

A novel series of 3-carbamoylethynyl-2-carboxyindoles, antagonists acting at the strychnine-insensitive glycine binding site associated with the NMDA receptor, has been synthesised. This new versatile approach involves the introduction of a 2-chloroethenyl moiety in position C-3 with subsequent derivatisation of the terminal carboxyl group, followed by an unusual elimination of HCl to afford the ethynyl functionality. This novel series of glycine antagonists was evaluated in terms of in vitro affinity at the glycine binding site and the most potent compound was tested in vivo in the NMDA-induced convulsions model in mice.

Manipulation of the cervical spine (MCS) is used in the treatment of people with neck pain and muscle-tension headache. The purposes of this article are to review previously reported cases in which injuries were attributed to MCS, to identify cases of injury involving treatment by physical therapists, and to describe the risks and benefits of MCS. One hundred seventy-seven published cases of injury reported in 116 articles were reviewed. The cases were published between 1925 and 1997. The most frequently reported injuries involved arterial dissection or spasm, and lesions of the brain stem. Death occurred in 32 (18%) of the cases. Physical therapists were involved in less than 2% of the cases, and no deaths have been attributed to MCS provided by physical therapists. Although the risk of injury associated with MCS appears to be small, this type of therapy has the potential to expose patients to vertebral artery damage that can be avoided with the use of mobilization (nonthrust passive movements). The literature does not demonstrate that the benefits of MCS outweigh the risks. Several recommendations for future studies and for the practice of MCS are discussed.

Twenty 4,5-dimethylpyrrole-2-carboxylic acids (5a-t) with different 2-carbamoylvinyl chains in position 3 were prepared to further investigate the relationships between structure and in vitro affinity for the strychnine-insensitive glycine-binding site. None of these compounds was superior to (E)-3-(N-phenyl-2-carbamoylvinyl)-4,5-dimethylpyrrole-2-carb oxylic acid III (pKi = 6.70), which was taken as a reference standard, but overall the results obtained indicate that the N-phenyl-2-carbamoylvinyl substituent of III may be replaced with the N-(1-adamantyl)-2-carbamoylvinyl group as in 5h (pKi = 6.20) without considerable loss of affinity. This finding adds to previous knowledge.

Compounds 2 and 3 were designed in order to probe the North-East region of the strichnine-insensitive glycine binding site of the NMDA receptor. The two products were obtained readily by a tandem aldol condensation-lactonization-elimination step which affords the desired E isomer with complete regioselection.

Temporal and spatial relationships between head motion and tilt of a visual surround were evaluated in conditions 3 and 6 of the sensory organization test (SOT) to determine the validity of visual stabilization during computerized dynamic platform posturography (CDP). Seven healthy subjects participated (mean age 42.4 years, SD = 19 years, range 25-72 years). Sagittal head translation and head pitch were evaluated separately with respect to displacement of the visual surround. Overall, the mean correlation between sagittal head motion and surround tilt was r = 0.68 for C3 and r = 0.93 for C6. The average phase (aggregate findings supported with trial-by-trial analysis), however, showed that sagittal head displacement leads motion of the visual surround ( + 452 ms for C3 and + 250 ms for C6). The mean correlation between head pitch and surround tilt was r = -0.30 for C3 and r = -0.72 for C6. Head pitch also leads visual surround motion (+567 ms for C3 and +539 ms for C6), but with greater variability than sagittal head translation. The results showed that visual stabilization was not consistently achieved during SOT conditions 3 and 6. The fundamental assumption that posture behaves as an inverted pendulum, with control of equilibrium originating in the lower extremities, does not appear to be applicable to the voluntary corrections of sway required during the SOT.

Objective: To examine in subjects with stroke using their nonparetic side how different levels of stimulus-response (S-R) compatibility, which require different levels of information processing, affect manual tracking control., Design: Descriptive study comparing finger movement tracking performance under S-R-compatible and S-R-incompatible conditions between subjects with stroke and healthy controls. Four two-factor analysis of variance tests with one independent factor (group, gender, laterality, or order) and one repeated measures factor (position) comprised the data analysis., Setting: University-based research setting., Patients: Forty subjects with chronic stroke: 20 right hemiplegia (average age, 65.2+/-2.3 yrs); 20 left hemiplegia (average age, 68.6+/-2.3 yrs). Fifty-one healthy controls: 24 using nondominant hand (average age, 68.6+/-2.1 yrs); 27 using dominant hand (average age, 68.7+/-2.0 yrs). All were right-handed., Main Outcome Measure: Tracking accuracy index (AI), based on root-mean-square error normalized to scale of each subject's tracking target., Results: In S-R-incompatible condition, AI of subjects with stroke was not significantly different from controls (F[1, 89]=1.73, p=.19). In S-R-compatible condition, AI of control subjects was significantly better than subjects with stroke (F[1, 89]=14.3, p=.0003)., Conclusion: Manual tracking is impaired in nonparetic hand of subjects with stroke, suggesting that information processing, distinctly separate from motor weakness, may be an underestimated problem impairing controlled movements in individuals with stroke.

The synthesis and preliminary biological evaluation of novel (E)-3-(2-(N-phenylcarbamoyl)-vinyl)pyrrole-2-carboxylic acids bearing alkyl, acyl, alkoxy, phenyl, and halo substituents at the 4- and 5-positions of the pyrrole ring are reported. These compounds were studied for their in vitro affinity at the strychnine-insensitive glycine-binding site of the N-methyl-D-aspartate (NMDA) receptor complex. In the [3H]glycine binding assay (E)-4,5-dibromo-3-(2-(N-phenylcarbamoyl)vinyl)pyrrole-2-carboxylic acid 6w (pKi = 7.95 +/- 0.01) and the 4-bromo-5-methyl 6j (pKi = 7.24 +/- 0.01) and 4,5-dimethyl 6g (pKi = 6.70 +/- 0.03) analogues were the most active compounds of the series. Qualitative structure-activity analysis points to a negative correlation between bulk of the C-4 and C-5 substituents and affinity which is enhanced by halo-substituents. QSAR analysis by the Hansch descriptors F, R, pi, and MR, on a subset of compounds with pKi > or = 4, indicates that electron-withdrawing groups at C-4 and C-5 enhance the affinity. Bulk and lipophilicity are also relevant for the substituents at these positions. 6g was found to be a full antagonist (alpha = 0; enhancement of the [3H]TCP binding). The in vivo potency of 6g, 6j, and 6w was evaluated by the inhibition of NMDA-induced convulsions in mice by both the i.v. and po routes; 6w was the most active compound (ED50 = 3 x 10(-3) (0.8-10) g/kg, i.v. and 30 x 10(-3) (4.5-61) g/kg, p.o.). The results of this study indicate that the 3,4-disubstitutedpyrrole-2-carboxylate represents a novel template for the design of new glycine antagonists.

The purposes of this study were to compare disabilities and health status associated with temporomandibular disorders (TMD) to other musculoskeletal disorders, to describe the types of physical therapy administered to patients with TMD, and to evaluate health-related quality of life (HRQOL) as an index of clinical change following physical therapy treatment. Outcomes for 56 patients (mean age 40 years, SD 13 years; 89% female) were evaluated from a large database generated by the Focus on Therapeutic Outcomes network. A generic assessment of HRQOL--the Medical Outcomes Study (MOS) 17--was used to evaluate the physical and mental aspects of disability associated with TMD, and the results were compared descriptively to three groups of patients with different cervical pain syndromes. The results showed that patients with TMD had limitations in social function, emotional well-being, and energy level similar to patients with cervical disorders. Physical function (i.e., walking, carrying loads, or lifting), however, was much more limited in cervical disorder patients and bodily pain interfered more with daily work. Large positive effect sizes (> 0.80) in the areas of social function and bodily pain indicated clinical improvement for patients with TMD at the completion of physical therapy. The results suggest that the MOS-17 may be useful as one measure of clinical change for patients with TMD who receive physical therapy.

Assessing both physical and mental health is necessary in clinical settings to quantify the scope of disability and to evaluate the effectiveness of treatment programs. Changes in health-related quality of life following physical therapy treatment for many patients with orthopaedic-related diagnoses is not known. The purposes of this study were to describe changes in health-related quality of life between the initial assessment and the time of discharge from physical therapy for the most common orthopaedic diagnoses and to compare the patterns of deficit among diagnostic categories. Patient outcomes in this study were evaluated from a large database generated by the Focus on Therapeutic Outcomes (FOTO) network. Health-related and employment outcomes were described for adult patients who were classified using ICD-9-CM codes. The most common orthopaedic diagnostic categories were sacroiliac sprain, back sprain, low back pain (radiating and nonradiating), neck sprain, neck pain (radiating and nonradiating), adhesive capsulitis of the shoulder, rotator cuff injury, shoulder sprain, knee dislocation, knee sprain, and knee derangement. The primary outcome measure was a 17-item questionnaire (the MOS-17) derived from the RAND 36-Item Health Survey (SF-36) and the 12-item Short Form Health Survey (SF-12). The comparison of each cohort to population norms was made by calculating a standard score on patient data adjusted for age and gender. An effect size was calculated to measure the change in health or employment status between the initial assessment and discharge from physical therapy. For all diagnostic categories, health-related quality of life with respect to norms and employment status showed a consistent pattern of improvement at the time of discharge compared with the initial assessment. There were only small changes in physical function for neck and shoulder diagnostic categories. Nearly all of the diagnostic categories had large reductions in bodily pain. The amount of clinical change in the physical components of health-related quality of life--especially the physical function and role physical domains--differed substantially across specific diagnostic categories. The largest improvements in the physical function occurred for patients with knee dislocation and knee sprain. Patients with knee dislocation also had the largest improvement in role limitations due to physical problems. The design of this study does not permit conclusions about the efficacy of physical therapy. Further study is needed to determine if the finding of different levels of health status improvement across diagnostic categories was due to the nature of the outcome measure, the type of treatments given to each patient, or other confounding variables, like depression or preinjury functional level.

Objective: To determine the influence of an extended outpatient rehabilitation program on symptom frequency, fatigue, and functional status for persons with multiple sclerosis (MS)., Design: Nonequivalent pretest/posttest control-group design, with posttest 1 year after initial assessment. Multiple regression analysis and analysis of covariance were used to control for symptom severity at the initial assessment and comorbid factors including depression, cognitive function, and social interaction. Effect sizes (ES) provided a descriptive measure of the change in outcomes., Setting: Outpatient multidisciplinary rehabilitation clinic., Patients: Forty-six patients with definite chronic progressive MS; 20 received treatment and 26 were in a nontreatment comparison group ("waiting list")., Intervention: Rehabilitation services for 5 hours, 1 day per week, over 1 year., Main Outcome Measures: The MS-Related Symptom Checklist composite score, fatigue frequency, and selected items from the Rehabilitation Institute of Chicago Functional Assessment Scale., Results: Receiving treatment was a significant predictor of reduced symptom frequency (partial r2 = .26) at the 1-year follow-up. The ES adjusted for baseline values indicated substantial reductions in symptom frequency for the treatment group (EStreatment = .27 vs ESwaitlist = -.32). Fatigue was significantly reduced at the time of follow-up for the treatment group compared with the waiting list group (EStreatment = .46 vs ESwaitlist = -.20). There were no statistically significant differences among groups regarding functional status, but there appeared to be less loss of functional status in the treatment group compared with the waiting list group (EStreatment = -.07 vs ESwaitlist = -.70)., Conclusions: An extended outpatient rehabilitation program for persons with definite progressive MS appears to effectively reduce fatigue and the severity of other symptoms associated with MS.

Background and Purpose: The health-related quality of life of patients with multiple sclerosis (MS) is an important aspect of care outcome. The purpose of this study was to compare health-related quality of life between patients who received weekly comprehensive outpatient rehabilitation for 1 year and a group that did not receive rehabilitation., Subjects: Twelve patients receiving outpatient care for chronic progressive MS (mean age = 44.5 years, SD = 11.6) were compared with 19 similar patients (mean age = 49.2 years, SD = 9.2) on a waiting list who were not receiving outpatient care., Methods: A pretest-posttest longitudinal design was used to descriptively compare outcome measures. Multivariate regression analyses were used to determine which variables, controlled for baseline health status and other relevant patient characteristics, were related to the best outcomes at the time of the 1-year follow-up., Results: The treatment group showed improvements in six health status measures on the Rand 36-Item Health Survey 1.0 (SF-36) that were not improved in the wait-listed group. Outpatient treatment was the sole predictor of positive outcome for energy/fatigue (partial R2 = .43) and change in general health (partial R2 = .19). In addition, the treatment group was associated with a positive outcome (together with other independent variables) in the domains of social function and social support., Conclusion and Discussion: Patients with chronic progressive forms of MS appear to derive benefits from an ongoing comprehensive outpatient rehabilitation program. [Di Fabio RP, Choi T, Soderberg J, Hansen CR. Health-related quality of life for patients with progressive multiple sclerosis: influence of rehabilitation.

Background and Purpose: Identifying elderly community dwellers who are at risk for falling was assessed using a comprehensive screening tool referred to as the "Fast Evaluation of Mobility, Balance, and Fear" (FEMBAF). The purpose of this study was to evaluate the concurrent validity and reliability of scores on the FEMBAF., Subjects: Thirty-five elderly persons living in the community (4 men, 31 women), with a mean age 79.9 years (SD = 8.5, range = 60-92), participated., Methods: Subjects were tested using the FEMBAF and three other instruments-the balance subscale of the Tinetti Performance-Oriented Mobility Assessment (B-POMA), the Clinical Test of Sensory Interaction on Balance (CTSIB), and the Timed Up and Go Test. Scores on the FEMBAF were compared with scores on each the other instruments using Spearman rank-order correlation coefficients and analysis of covariance (with age as the covariate) for living status and diagnostic category. A comparison of the number of subjects classified as being at risk for falling was done descriptively for the FEMBAF, B-POMA, and CTSIB., Results: Associations (r > .35) were found between the FEMBAF and each of the other instruments in the areas of FEMBAF risk-factor count, task completion, mobility, and strength. The FEMBAF classified a greater number of subjects as being at risk for falling (89%) compared with the B-POMA (43%) and the CTSIB (63%). The mean chance-corrected percentage of agreement between raters on the FEMBAF was kappa = .95 (SD = .15) for assessment of risk factors and kappa = .96 (SD = .12) for task completion., Conclusion and Discussion: The FEMBAF provides valid and reliable measurements of risk factors, functional performance, and factors that hinder mobility.

The quality of sensory information that is necessary for balance and postural stability will depend to a great extent on head stability as the body moves. How older persons coordinate head and body motion for balance during volitional activities is not known. The purposes of this article are to present a basis for understanding the influence of aging on head control during voluntary motion and to discuss some data that demonstrate how elderly people might control head movement to improve gaze and the quality of vestibular inputs. A "top-down" or "head-first" control scheme is proposed as the mechanism that elderly people without disabilities use to maintain head position during self-initiated motion. This type of control ensures that the angular position of the head in space remains relatively constant--through the use of a head-stabilization-in-space (HSS) strategy--regardless of the magnitude or direction of displacements in the body's center of force. The HSS strategy is thought to reduce potential ambiguities in the interpretation of sensory inputs for balance and is derived primarily from a geocentric (orientation to the vertical) frame of reference. Egocentric (orientation of the head with respect to the body) or exocentric (orientation to objects in the environment) frames of reference, however, refine the control of head stabilization. Preliminary research suggests that elderly people use the HSS strategy to control head pitch during difficult balance tasks. These findings, if supported by more definitive studies, may be useful in the treatment of patients with balance disorders. The treatment of patients with balance dysfunction is discussed within the conceptual framework of a "head-first" organization scheme.

A series of indole-2-carboxylates bearing suitable chains at the C-3 position of the indole nucleus was synthesized and evaluated in terms of in vitro affinity using [3H]glycine binding assay and in vivo potency by inhibition of convulsions induced by N-methyl-D-aspartate (NMDA) in mice. 3-[2-[(Phenylamino)carbonyl]ethenyl]-4,6-dichloroindole-2-carboxyl ic acid (8) was an antagonist at the strychnine-insensitive glycine binding site (noncompetitive inhibition of the binding of [3H]TCP, pA2 = 8.1) displaying nanomolar affinity for the glycine binding site (pKi = 8.5), coupled with high glutamate receptor selectivity (> 1000-fold relative to the affinity at the NMDA, AMPA, and kainate binding sites). This indole derivative inhibited convulsions induced by NMDA in mice, when administered by both iv and po routes (ED50 = 0.06 and 6 mg/kg, respectively). The effect of the substituents on the terminal phenyl ring of the C-3 side chain was investigated. QSAR analysis suggested that the pKi value decreases with lipophilicity and steric bulk of substituents and increases with the electron donor resonance effect of the groups present in the para position of the terminal phenyl ring. According to these results the terminal phenyl ring of the C-3 side chain should lie in a nonhydrophobic pocket of limited size, refining the proposed pharmacophore model of the glycine binding site associated with the NMDA receptor.

Activities of daily living require both anticipatory and reactive postural adjustments. The influence of stroke on anticipatory and reactive balance behaviors is addressed in this article. Two primary deficits appear to underlie postural instability following stroke. The first deficit type is characterized by a loss of postural muscle recruitment in both lower extremities (not hyperactive stretch reflexes). The second deficit type is related specifically to the lack of limb stabilization on the paretic side of the body. These two categories of deficit might result from the disruption of geocentric and egocentric references for postural stability with cerebrovascular disease. Context-dependent postural responses are either relearned or retained following stroke, but deficits in the sequencing and timing of stabilizing neuromuscular responses appear to be resistant to adaptation. Prior knowledge of an impending balance disturbance improves the initiation of reactive postural adjustments in subjects with stroke but has no effect on the initiation of stabilizing responses associated with voluntary motion. The results suggest that reactive and anticipatory postural adjustments are controlled by different neural mechanisms and may require separate attention in a rehabilitation program.

Outcome of physical therapy for patients receiving workers' compensation may be related to a variety of factors, including the presence or absence of herniated lumbar intervertebral disc. The purpose of this study was to determine the level of disability, physical impairment, and rate of return-to-work for patients with disc disease and for those with mechanical low back pain syndrome without evidence of disc lesion. Twenty patients with disc disease and 22 patients with mechanical low back pain syndrome participated in this study. Physical therapy consisted of multiple interventions, including manual therapy based on the pattern of motion-provoked symptoms. The Oswestry disability questionnaire, fingertip-to-floor distance, and maximum pain-free isometric static lift were measured at the initial evaluation, 1 month following the initial assessment, and at discharge from the clinic. Patients with disc disease did not show significant improvement in the mean Oswestry score or in forward bending, but did show increased static lift capacity. In contrast, patients with mechanical low back pain syndrome had a significant reduction in disability and significant improvements in fingertip-to-floor distance and maximum pain-free isometric static lift. At the time of discharge, 90% of the patients followed with mechanical low back pain syndrome returned to work in some capacity compared with 45% of the patients followed with disc disease. A physical therapy program with multiple interventions that includes treatment based on the pattern of motion-provoked symptoms appears to have the greatest benefit for patients with mechanical low back pain syndrome.

Objective: To compare the sensitivity and specificity of platform posturography with other vestibular tests for patients with peripheral vestibular deficits (PVD), Meniere's disease, benign paroxysmal positional vertigo (BPPV), and central nervous system-vestibular impairment (CNS)., Data Sources: A computed search was conducted using the Index Medicus database (1966-1994) and Current Contents Science Editions., Study Selection: Studies were selected for analysis if the article addressed the sensitivity and/or specificity of platform posturography, compared posturography with another objective test of vestibular function, identified the basis for abnormal test results, and reported the data with sufficient detail to calculate an effect size from a 2 x 2 contingency table., Data Extraction: A count of the normal and abnormal test results for posturography and the criterion standard were retrieved from each article, analyzed using a chi 2 statistic, and converted to an effect size. A positive effect size indicated that posturography identified abnormalities in patients who had normal tests on the criterion standard., Data Synthesis: Sensitivity and specificity of posturography were about 50%. The overall effect size was small (0.13) but positive. The diagnostic category had a significant influence on the predictive value of abnormal results (73% for Meniere's disease and BPPV, compared with 41% for PVD, and 44% for mixed CNS and PVD (F2,12 = 5.26, P = .02) and on the magnitude of the effect size (0.41 for mixed CNS and PVD compared with 0.22 for Meniere's disease and BPPV, and -0.10 for PVD (F2,12 = 13.95, P = .001)., Conclusions: Platform posturography provides a measurable supplement to the standard vestibular examination. The enhancement was most notable when the target population included patients with CNS deficits.

Various motor patterns or 'strategies' can be used to maintain balance. The purpose of this study was to determine the responsiveness of a pediatric strategy score (PED-SS) compared to a standard strategy score (SS) as a measure of age-related changes in the force patterns used to maintain stance. Eighty-one healthy children between 3-6 years of age were tested during stance on a force platform while facing a visual surround. The platform, visual surround (or both) moved simultaneously with the child's body sway. Four sensory conditions that altered visual and somatosensory (support surface) inputs were presented. The PED-SS was found to be more responsive to age-related changes in balance behavior compared to the SS. The oldest children (aged 5 and 6 years) showed the greatest ability to utilize horizontal A/P shear force to maintain stance and this finding was reflected only in the PED-SS. The implications of evaluating force strategy as one component of balance in healthy children is discussed with respect to the early developmental assessment of vestibular and developmental coordination disorders.

Background and Purpose: The use of back school as a treatment for low back pain is widespread, but determining the efficacy of this approach is complicated by variations in back schools and study methods across clinical trials. The purpose of this study was to conduct a meta-analysis to synthesize existing evidence on the efficacy of back school as either a primary intervention or a part of a comprehensive rehabilitation program for patients with low back pain., Methods: The results of 19 prospective randomized controlled trials were evaluated. Quantitative reviewing procedures were used to calculate the effect sizes that compared patients receiving back school with those in a control or comparison group. Effect sizes were computed for 206 hypothesis tests involving 2,373 patients., Results: The average effect size for comprehensive rehabilitation programs that included back school (d = 0.28) was larger than the average effect size for programs that offered back school as the primary intervention (d = -0.14). When effect sizes were stratified by program type and outcome, the comprehensive programs were superior to primary back school programs with respect to pain reduction, increased spinal mobility, and increased strength. Both types of programs showed reasonable success with education/compliance outcomes (d = 0.27-0.28). Lower effect sizes were found among the types of programs for disability and work/vocational outcomes (d < or = 0.20)., Conclusions and Discussion: Back schools were most efficacious when coupled with a comprehensive rehabilitation program. Efficacy was supported for the treatment of pain and physical impairments and for education/compliance outcomes. Work/vocational and disability outcomes, however, were not improved substantially beyond control levels in comprehensive or primary back school programs. [Di Fabio RP. Efficacy of comprehensive rehabilitation programs and back school for patients with low back pain: a meta-analysis.

Sensitive and specific measures are needed to identify patients with vestibular impairments. The purpose of this clinical perspective is to describe the sensitivity and specificity of dynamic and static platform posturography for detecting vestibular disorders. The sensory organization test (SOT) of dynamic posturography (EquiTest), the motor "perturbation" test, and Romberg's tests on a static (fixed) force platform each had over 90% specificity. This finding means that nearly all of the subjects who should have tested negative, did test negative on each type of assessment. The sensitivity of the SOT was evaluated across five studies involving a total of 836 patients with peripheral vestibular deficits (PVDs). Abnormalities in the SOT were detected in only 40% (n = 338) of the cases. Static platform posturography sensitivity was evaluated across six studies involving a total of 571 patients with PVDs, and abnormalities were detected in 53% (n = 302) of these cases. Tests of spontaneous and positional nystagmus and the horizontal component of the vestibuloocular reflex (VOR), by comparison, detected PVDs in 48% of 798 patients with suspected vestibular impairment. For patients with vestibular deficits associated with central nervous system disease, a total of 389 cases were identified in five studies and SOT abnormalities were found in 54% (n = 209) of these cases. The motor perturbation test was abnormal in 35% (n = 41) of 119 patients with central vestibular disease. In conclusion, the sensitivity of static posturography appeared to be slightly better than that of dynamic posturography for detecting PVDs, but the level of sensitivity for each posturography test, as well as for tests of horizontal VOR function, was considered to be low. Combining either type of posturography with other tests of vestibular function, however, increased the overall sensitivity of detecting vestibular deficits to 61% to 89%. It was concluded that dynamic and static platform posturography as well as tests of VOR function lack adequate sensitivity to detect vestibular impairment when applied in isolation. Posturography appears to detect vestibular deficits in some patients who had normal VOR assessments and, therefore, provides supplemental rather than redundant information about vestibular dysfunction.

Background and Purpose: The efficacy of a physical therapy outpatient program with multiple interventions to treat low back pain in subjects receiving workers' compensation was examined. The primary purpose of the study was to describe the level of disability, physical impairment, and rate of return to work for compensated patients., Subjects: One hundred thirty-eight patients (84 male, 54 female), aged 17 to 63 years (mean = 38, SD = 10), were evaluated prospectively., Methods: Subjects were assessed initially (INA) and were reevaluated 1 month later (1MO) and again at the time of discharge (DC). The Oswestry disability score, fingertip-to-floor distance during forward bending, maximal isometric lift, and work status were described as outcomes. Subjects were grouped based on compliance, chronicity, and leg symptoms. Each disability/impairment outcome was analyzed with paired t tests (INA versus 1MO and INA versus DC). The frequency of subjects returning to work across groups was evaluated with a chi-square analysis corrected for unequal group sizes., Results: Overall, there was improvement in each dependent measure at 1MO and DC compared with the INA. Subjects with high compliance had a 10% reduction in mean disability at 1MO and a 12% reduction in mean disability at DC compared with the INA. The low-compliance group, in contrast, showed less than a 5% reduction in mean disability at both the 1MO and DC assessments compared with the INA. The magnitude of improvement in disability status, forward bending, and maximal lift was approximately two to three times greater for subjects with acute symptoms compared with those with chronic symptoms. The increase in mean forward bending for subjects without leg symptoms was over twice as large as the increase in forward bending for subjects with leg symptoms. Seventy-five percent of the subjects followed at DC (30 out of 40) were released to work in some capacity. There was no association between compliance or presence of leg symptoms and work status at DC. Eighty percent of the subjects with acute symptoms, however, were working at the time of DC compared with 44% of those with chronic symptoms., Conclusion and Discussion: Compliance, chronicity, and leg symptoms are all factors that can affect the outcome of physical therapy. The positive outcomes for subjects who complied with therapy suggest that a physical therapy program with multiple interventions may decrease disability and impairment.

Vestibular impairments have not been routinely identified in patients with multiple sclerosis (MS), because of the confounding effects of deficits in other neural systems. In this study, 35 patients with MS were evaluated by means of a systematic alteration of the sensory environment (dynamic posturography) in order to identify those patients who became unstable when vestibular inputs were needed to maintain stance. Subjects were assigned to either a high-function (HF) or a low-function (LF) group on the basis of a functional status assessment score obtained prior to the posturography test. For the HF group, 30% (7/23) had abnormal posturography scores. Of those subjects, 3 had a vestibular dysfunction pattern or a somatosensory-vestibular impairment. In contrast, 58% of the LF group (7/12) had abnormal posturography scores. Nearly all of these LF patients (6/7) had a vestibular dysfunction pattern or a combined visual-vestibular or somatosensory-vestibular impairment. Posturography might serve as one method to evaluate the functional consequences of a vestibular deficit in patients with MS.

The purposes of this study were to (1) evaluate the effects of sway-referenced visual and ankle somatosensory inputs on head movement and body sway during stance and (2) determine how sway-referenced sensory inputs might influence the selection of postural patterns. Seventeen healthy adult subjects were evaluated while attempting to maintain standing balance. Ankle somatosensory inputs were altered during stance by creating support surface rotations which were continuously adjusted ("referenced") to the center of force. In selected trials, ankle somatosensory or visual inputs were distorted further by increasing the platform/body sway gain or by increasing the sway-referenced gain of a rotating visual enclosure. The results showed that spontaneous body sway in a given direction was generally associated with head displacement in the opposite direction. The slope of the sway vs. sagittal head position linear regression line was statistically greater at a sway-referenced gain of 1.5 compared to a gain of 1.0. This finding was observed specifically when mechanical compliance of the support surface was increased and occurred whether the eyes were open or closed. Horizontal shear force was generated in the same direction as head displacement and the linear regression slope was greatest with eyes open and at a sway gain of 1.5. These findings indicate that (1) destabilization of the ankles altered displacement of the head independently from visual input, and (2) visual information was necessary to produce specific postural patterns utilizing horizontal shear forces to maintain stance on a mechanically compliant surface. The results provide evidence for a neural mechanism linking ankle somatosensory inputs and head control.

The purpose of this preliminary study was to examine the intratester and intertester reliability of a functional mobility assessment tool (FMAT). Seven licensed physical therapists with varying amounts of clinical experience served as raters. Twelve patients with neurological deficits were subjects for this study. Raters were asked to provide eight possible ratings for each of eight critical mobility functions. Average weighted kappa coefficients ranged from .82 to .97. Intraclass correlation coefficients ranged from .73 to .97 for the first assessment and from .52 to .97 for the second (retest) assessment. A high degree of agreement between and within seven raters indicated that this tool may provide an effective assessment of stroke, brain injury, and spinal cord injury. Preliminary findings indicate the functional mobility assessment tool is reliable, thereby increasing the usefulness of this method for clinical assessment. The high resolution of the FMAT makes this tool ideally suited for use in future studies focusing on the prediction of mobility function following neurological insult.

The effect of altered sensory environments on balance was studied in 82 healthy children between 3 and 6 years of age. The purpose was to obtain normative measurements of postural stability during early stages of development for use in clinical posturography. Subjects were tested in three visual conditions (eyes open, blind-folded, and sway-referenced visual enclosure) during stance on either a fixed or sway-referenced force platform (EquiTest). During sway-referenced conditions, spontaneous changes in the subject's center of force (COF) drove rotational displacements of the platform and/or visual surround. The gain of platform/COF or surround/COF displacement was altered from 0.00 to 1.5. An equilibrium score (ES) was calculated based on the amount of postural sway compared to the maximum sway possible without falling. A higher ES reflected greater postural stability. An improvement in postural stability was observed between 4 and 5 years of development when the sensory environment was fixed (sway referenced gain = 0.0). In a dynamic sensory environment, however, age-related improvements in postural stability were not uniform and depended upon the specific sensory condition. For example, while 6 year olds generally showed the greatest postural stability of any age group, all ages showed statistically equivalent equilibrium scores during stance on a compliant surface with eyes closed, at all sway gains. The ability to ignore misleading sensory inputs to maintain balance was observed at 3 years of age; 76% of the 3 year olds (n = 16) were able to maintain stance in altered sensory environments at the 1.0 sway gain. In addition, postural stability was greater when visual inputs were sway-referenced compared to conditions that manipulated the support surface compliance. These data suggest that the predominance of visual-vestibular control of balance gives way to a somatosensory-vestibular dependence by age 3, but that the transition to adult-like balance responses is not complete for all sensory conditions even by age 6. The use of posturography to enhance the assessment of pediatric vestibular and sensory integration deficits is discussed.

The use of manual therapy to treat somatic pain syndromes and associated disabilities is widespread. Yet, the efficacy of manual therapy has not been previously established because equivocal findings in the literature prevent definitive conclusions. The purposes of this article are (1) to establish objective criteria for judging the validity of manual therapy research, (2) to identify and discuss the results of those trials that were determined to be valid demonstrations of treatment efficacy or valid demonstrations of nonuseful therapy, and (3) to determine whether patients who benefit from manual therapy have common characteristics. The abstracts or full reports of 146 titles with appropriate key words were reviewed. Of these, 105 studies were not primary studies of manual therapy and were thus eliminated from review. In the 41 remaining studies, 18 did not utilize statistical comparisons or report blinded assessment of outcome measures. Nine controlled studies yielded negative results, but the statistical power or minimum sample size required to detect potential differences between manual therapy and control groups was not described. The 14 studies that met the efficacy criteria were categorized by the following factors: (1) the anatomical region of intervention, (2) pragmatic versus explanatory goals, and (3) primary intervention (manipulation, mobilization, combination). There was a paucity of valid explanatory research in all areas and a particular absence of controlled trials involving manual therapy applied to the peripheral joints. Manual therapy for low back pain, however, was studied extensively. The analysis of valid trials provided clear evidence that manual therapy, particularly manipulation, can be an effective modality when used to treat patients who have low back pain. A preliminary "profile" of the patient with low back pain who would likely benefit from manual therapy included acute symptom onset with less than a 1-month duration of symptoms, central or paravertebral pain distribution, no previous exposure to spinal manipulation, and no pending litigation or workers' compensation. Suggestions for future manual therapy research are discussed.

Vision and/or ankle somatosensory inputs often do not correlate with the position of the center of gravity. In this case, visual or somatosensory information may be in conflict with other sensory systems that convey a true sense of body orientation. The purpose of this study was to determine how conflicting visual and ankle somatosensory inputs influenced standing balance in elders with a history of falls. Forty-seven community-dwelling elders (8 male, 39 female), between 65 and 96 years of age (mean = 80.5, SD = 9.0), participated in this project. Subjects with two or more falls in the 6 months prior to study were assigned to a fall group (n = 16), whereas those with no history of falling during the same time interval were assigned to a no-fall group (n = 31). In order to remove any bias in the testing procedure, the tester was not aware of group assignments. Subjects were evaluated using a sensory organization test (SOT) for standing balance and a "Get Up and Go" test (GUGT) for general mobility. Analysis of covariance was used to evaluate the SOT scores (by group, vision, and surface condition) and the GUGT scores. Body sway is known to increase with the normal aging process, and for this reason, age was selected as a covariate. The association between the SOT total score and the GUGT score was evaluated using Spearman rank-order correlation coefficients. The results showed a significant interaction between group and surface conditions, which indicated a decreased stance duration for fallers on a compliant surface compared with the stance duration for nonfallers (adjusted mean faller stance duration = 53 seconds, SD = 42; mean nonfaller stance duration = 67 seconds, SD = 32). Subjects in the fall group also had significantly higher GUGT scores (which indicated poor mobility function) than did subjects in the nonfall group (adjusted mean faller GUGT score = 2.65, SD = 1.48; mean nonfaller GUGT score = 1.47, SD = 0.77). The Spearman correlation between total SOT scores and the GUGT scores was greater for fallers (r = -.67) than for nonfallers (r = -.44). Orientation input from the ankle appears to have greater importance for preventing falls compared with a visual reference. The SOT and GUGT may be useful in the field to establish criteria for screening elders in a fall-prevention program.

Standing balance was evaluated in ten subjects with hemiplegia using a sensory organization balance test (SOT). The SOT is a timed balance test which evaluates somatosensory, visual, and vestibular function for maintenance of upright posture. The duration of bilateral stance was assessed using combinations of three visual and two support surface conditions. Stance time was measured with eyes open, eyes closed, and with each patient wearing a visual dome to produce inaccurate visual information. The support surface conditions involved stance on a hard flat floor followed by attempted stance on a compliant foam surface. Visual deprivation or visual conflict conditions did not cause a loss of balance when stance was performed on a stable surface. However, a lower stance duration was found when patients stood on a compliant surface (p less than .05). Visual compensation was evident during the compliant-surface condition because stance duration showed the greatest reductions with eyes closed and with the visual dome. These findings suggest that the ability to integrate somatosensory information from the lower extremities for balance is compromised after cerebrovascular disease. The implications for diagnosing the specific cause of balance dysfunction and for developing sensory-specific therapeutic interventions are discussed.

Standing balance and dynamic weight shifting were evaluated in 10 subjects with hemiplegia using a sensory organization balance test (SOT) and the Fugl-Meyer sensorimotor assessment (FMSA). The SOT is a timed balance test that evaluates somatosensory, visual, and vestibular function for maintenance of upright posture. In contrast, the FMSA is a functional status assessment that indicates the amount of assistance needed during various balance tasks and the tolerated duration of the task. The results of both clinical tests were compared to determine whether the SOT correlated with functional ability. The SOT scores were significantly correlated with the FMSA balance subscores and the FMSA total lower extremity scores. Based on the results of this preliminary study, the authors concluded that the SOT may be useful for evaluating a patient's functional status. Further implications for the evaluation and treatment of balance dysfunction in persons with hemiplegia are discussed.

The locus of postural stability during dynamic, visually cued weight redistribution was studied in six hemiplegic and five able-bodied subjects. After a verbal warning with a variable foreperiod, a visual trace appeared on an oscilloscope to indicate a sway magnitude equaling half the subject's maximal voluntary sway. Body movement was cued in three directions--forward, and toward the paretic and nonparetic lower extremities. In order to assess extraneous postural patterns, all three directions of sway were analyzed for each trial. The results showed that with cued lateral sway (right or left) there was a tendency for hemiplegic subjects to reduce the dispersion (or variability) of the sway path. Clustering of the active lateral postural response near the geometric center of the sway path indicated a restricted balance response in this plane of motion. During cued forward sway the variability of the sway path was not statistically different from the able-bodied, but three-dimensional visualization of the sway pattern illustrated a qualitatively different postural response with extraneous, nonfocused balance activity biased toward the nonparetic lower extremity. Short-term practice did not alter the dispersion of the sway path for hemiplegic or able-bodied subjects in any direction. Hemiplegic extraneous movement in one case (forward sway) and restricted movement in another (lateral sway) emphasize the level of specificity which needs to be addressed during rehabilitation of balance.

The temporal and spatial characteristics of rapid voluntary body sway following unilateral cerebrovascular accident were assessed in single and combined planes of motion during a visually cued non-choice reaction time movement. Three distinct directions of intentional body sway were assessed: forward, toward the paretic, and toward the non-paretic lower extremity. Fluctuations in the center of foot pressure served as the basis for calculating body displacement and velocity by combining frontal and sagittal movement in an X-Y coordinate system (a bi-planar analysis). A linear regression analysis was used on individual force output channels to reduce the sway motion into separate component parts. The velocity profile in each direction of intended sway was calculated from the slope of the regression line (a single-plane analysis). Bi-planar velocity analysis showed that hemiplegics swayed as fast as normal subjects in any sway direction. In contrast, single plane analysis revealed a decrease in the velocity of hemiplegic sway when weight shifts were directed toward the paretic extremity. Response velocity in the non-paretic direction was similar to a comparison group of normal individuals. The apparent contradiction between single and bi-planar analyses was attributed to hemiplegic sway in extraneous planes of motion surrounding the intended sway path. During the course of body sway, hemiplegics showed a statistically larger range of extraneous movement away from the plane of intended movement. The directional deficits in sway velocity and excursion are compared to previously reported sway pathology associated with lesions of the human central nervous system.

The purpose of this study was to analyze the effects of a quadriceps femoris muscle eccentric training program on strength gain in patients with patellar tendinitis. The effect of an eight-week eccentric exercise program on quadriceps femoris muscle work was evaluated in four groups of subjects--two groups of "normal" (healthy) subjects and two groups of patients with patellar tendinitis. All four groups participated in a home muscle stretching exercise program, but only two groups--one group of normal subjects (N-A) and one group of subjects with tendinitis (T-A)--received additional eccentric training on an eccentric isokinetic dynamometer. The eccentric quadriceps femoris muscle work ratio (involved limb/uninvolved limb x 100) was used to quantify strength in the N-A and T-A Groups. Pain ratings were recorded for subjects with tendinitis before and after the eight-week experiment and were correlated with the dependent variable using a Spearman rank-order correlation coefficient. The N-A Group performed significantly better than all subjects with tendinitis (p less than .05). Subjects in the T-A Group, however, showed a trend toward increasing eccentric quadriceps femoris muscle work capacity over the eight-week training period. As pain ratings in the T-A Group increased, work ratios decreased. We concluded that eccentric exercise may be an effective treatment for patellar tendinitis, but that knee pain may limit optimal gains in strength.

Patterns of postural adjustment accompanying spontaneous single limb movement in the cat were studied to examine qualitative and quantitative variations in support strategies. A multiple plate dynamometer and electromyograph were used to measure supporting actions during consecutive trials. Weight transfer involving primarily the forelimbs was dominant. A similar tripodal stance with increased bilateral hindlimb weight-bearing characterized a secondary support strategy. Both dominant and secondary balance behavior showed transient reversals to a bipodal postural pattern. Bipodal stance exhibited increased weight-bearing in the stabilizing forelimb and in the diagonally opposite hindlimb. Selection of different postural strategies for identical phasic limb movements could possibly result from modulation of lower level reflex inhibition.

In order to study voluntary and reflexive mechanisms of postural control, young and elderly persons were given large-fast and small-slow ankle-rotation postural disturbances while standing on a movable platform capable of measuring ground reaction forces. Large-fast rotations were employed to activate long-loop reflexes, and small-slow rotations were employed to tap the higher level sensory integration aspects of postural control. Overall, the elderly persons exhibited more perturbation induced sway and showed a slowing in voluntary, as opposed to reflexive mechanisms of correcting postural disturbance. For both age groups, reflexive mechanisms were found to be relatively intact. When small perturbations were given, the elderly persons swayed more than young participants and produced sporadic reflexive activity. Moreover, elderly persons did not adapt to the small perturbations and exhibited increased postural sway to repetitive presentation of the perturbation, whereas young participants substantially decreased their postural sway. These data demonstrate that elderly persons are at some disadvantage when posture is under the control of slower, higher level sensory integrative mechanisms.

The purpose of this study was to examine the effects of a rapid length change in the elongated and shortened ankle muscles of subjects with hemiplegia during forward body sway. The onset and amplitude of electrical activity in the ankle muscles of four standing hemiplegic subjects with mild stretch reflex abnormalities and four healthy subjects were studied. Each subject stood on a platform controlled by a hydraulic servomechanism and experienced an unexpected posterior horizontal platform movement that induced a forward body sway. The activity of the gastrocnemius (agonist) and tibialis anterior (antagonist) muscles were monitored bilaterally using surface electromyography. In comparison with the healthy subjects, the hemiplegic subjects showed a greater disassociation between agonist and antagonist activation, a larger frequency of response defaults in the antagonist, and an increase in nonparetic (left) limb agonist amplitude during the 200-msec electromyographic integration period. We concluded that the sequelae of cerebrovascular disease may hamper the initiation of a passive shortening response in the tibialis anterior muscle during forward sway. This finding is functionally significant because the response deficit described seems to be exaggerated in some cases and reduced in others.

The widespread use of manual therapy techniques suggests some degree of success in their application. In this article, I review the applied clinical research on the effectiveness of using manipulation or mobilization of the lumbar spine. The literature reviewed indicates highly equivocal results when the goal of therapy was to decrease pain and increase motion. Because of a high incidence of spontaneous recovery from low back syndromes, performance measures may appear to improve significantly when proper controls are not used. Evaluation of the therapeutic effects of manual therapy is complicated by potentially confounding variables when used with other physical therapy procedures. I discuss the need for further, well-designed studies.

An EMG-force measurement system which can be placed inside a sound dampened testing chamber to study subtle postural responses in the standing quadruped is described. The dynamometer is adjustable to accommodate different foot placement strategies and to afford a more natural standing posture. A non-telemeterized method of recording EMG from an unrestrained animal is also discussed.

The purpose of this study was to analyze the effects of prior instruction on automatic postural responses and voluntary postural sways measured about the ankle joint. Ten subjects with right hemiplegia resulting from a cerebrovascular accident (mean age = 56 +/- 14 years) and 5 healthy subjects (mean age = 47 +/- 6 years) stood symmetrically on a movable force platform. During platform-induced sway, the support surface was translated horizontally to induce antero-posterior body sway about the ankle joints. Surface electromyographs were obtained from the tibialis anterior, quadriceps femoris, gastrocnemius, and hamstring muscles bilaterally. Prior knowledge appeared to have no significant influence on healthy subjects' ability to execute postural adjustments more rapidly during AP displacements. Hemiplegic subjects exhibited longer and more variable latencies in the paretic limb than in the nonparetic limb during voluntary AP weight shifts. When hemiplegic subjects had prior knowledge of the platform's movement (time and direction), latencies were significantly shorter in the paretic limb and could be as brief as those seen in the nonparetic limb. The results showed that prior knowledge may be an important treatment consideration for patients with muscle timing disorders.

The purpose of this study was to evaluate body-sway characteristics during anticipatory and reactive postural compensation. Mechanisms of postural control were studied during self-initiated rapid arm movements (RAMs) and unexpected support surface displacements (SSDs). Ten healthy subjects, 5 men and 5 women with a mean age of 28 years, were blindfolded and stood symmetrically on a moveable force platform or with weight shifted right (R) or left (L). Averaged electromyographs were obtained from L anterior deltoid, L ipsilateral biceps femoris (BFi), R contralateral biceps femoris (BFc), R quadriceps (Q), R medial gastrocnemius (G), and R tibialis anterior (TA) muscles. During SSD, the relative timing of distal-proximal synergists was altered during all biased postures. In L biased standing, functional pairs, TA-Q and G-BF, discharged at their shortest latencies. Anterior deltoid onset times during RAM were most preparatory during R weight shift. Sway latencies were shorter also in biased standing. Absolute sway latency, peak sway, and time-to-peak sway were significantly longer in SSD conditions in comparison with RAM. When disturbances in balance cannot be predicted, lower extremity preloading facilitates contralateral muscle-discharge patterns at shorter latencies. In some neurological conditions that result in incorrect body alignment, the mechanical effects of postural bias rather than the abnormal control mechanisms may at least contribute to alterations in the postural response. These results provide a basis for evaluating balance in patients with neurological deficit.