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Understanding the degree of motor paralysis in stroke patients is important for assessing the severity of functional impairment and predicting functional prognosis. Fugl-MeyerAssessment for the lower extremities (FMA-LE)is a commonly used measure with high reliability and validity, but there is no official translated Japanese version of FMA-LE.This study aimed to develop Japanese FMA-LE and verify its reliability and validity in patients with acute stroke.The Japanese FMA-LE was developed following a standardized translation process. The reliability and validity were evaluated in 50 stroke patients at an acute care hospital. Validity was examined by determining the correlation between FMA-LEand Brunnstrom Recovery Stage (BRS), as well as Short Physical Performance Battery (SPPB). Intra-raterand inter-raterrelative reliabilities were evaluated by calculating intra-classcorrelation coefficients (ICCs). Absolute reliability was assessed by determining the standard error of the measurement and minimum detectible change (MDC). Systematic error was also assessed.FMA-LEtotal score was high correlated with BRS (ρ = 0.73,p .01) and moderately correlated with SPPB (ρ = 0.69,p .01). For intra-raterreliability, ICC was 0.98 (p .01), only fixed systematic error was observed (p .01), and MDC of the FMA-LEtotal score was 1.24. For inter-raterreliability, ICC was 0.98 (p .01), no systematic error was observed, and MDC of the FMA-LEtotal score was 3.23.The Japanese FMA-LE was reliable, valid, and useful for evaluating lower extremity function of acute stroke patients.

BACKGROUND: Gait analysis, such as portable gait rhythmogram (PGR), provides objective information that helps in the quantitative evaluation of human locomotion. OBJECTIVE: The purpose of this study was to assess the reliability of PGR in post-stroke patients. METHODS: Two raters (A and B) examined 48 post-stroke patients. To assess intra-rater reliability, rater A tested subjects on three separate occasions (Days 1, 2, and 3). To assess inter-rater reliability, raters A and B independently tested participants on the same occasion (Day 3). RESULTS: There was no significant systematic bias between test occasions or raters. Intraclass correlation coefficient values were 0.93–0.97 for intra-rater reliability at both the comfortable speed and maximum speed, and 0.97–0.98 (comfortable speed) and 0.97–0.99 (maximum speed) for inter-rater reliability. The standard error was 1.25–1.49 (comfortable speed) and 1.62–1.77 (maximum speed) for intra-rater investigation, and 1.04–1.32 (comfortable speed) and 0.91–1.26 (maximum speed) for inter-rater investigation. At the 90% confidence level, the minimum detectable change ranged from 2.9–4.1%, and the error of an individual’s score at a given time point ranged from ±2.1–2.9%. CONCLUSIONS: Based on this excellent reliability of the PGR in post-stroke patients, it can be recommended as a simple test of gait analysis in this population.

Background: A recent study revealed that whole-body vibration (WBV) tends to decrease spasticity in stroke-related hemiplegic legs. However, acute changes in cortical activation after WBV a...

Background and Aim In recent years, interest in the quality of medical care has rapidly increased worldwide. However, quality indicators that contribute to establishing standard treatment in stroke medicine, especially rehabilitation, are not well-developed in Japan. Japan has established Kaifukuki (convalescent) rehabilitation wards, and the development of quality indicators for stroke rehabilitation in the convalescent phase is an urgent issue. Methods We first reviewed the literature regarding quality indicators for stroke rehabilitation. Next, we extracted candidate indicators from identified reports and guidelines and surveyed educational hospitals certified by the Japanese Association of Rehabilitation Medicine. On the basis of the survey results, we reevaluated the suitability of the proposed indicators in discussions with an expert panel. Results The questionnaire survey highlighted several important items that revealed there is room for improvement in adherence. For stroke rehabilitation in the convalescent phase, we adopted 15 indicators that were feasible as indicators to be used for comparisons between facilities, based on scoring by and opinions of the expert panel. These indicators measured structure (2 indicators), process (5 indicators), and outcome (8 indicators). Conclusion This is the first study to establish quality indicators to standardize stroke rehabilitation in Japan. We developed this set of 15 indicators using an evidence-based approach. However, many tasks remain for continuous quality improvement.

Periodontal ligament (PDL) possesses a stem/progenitor population to maintain the homeostasis of periodontal tissue. However, transcription factors that regulate this population have not yet been identified. Thus, we aimed to identify a molecule related to the osteogenic differentiation of PDL progenitors using a single cell-based strategy in this study. We first devised a new protocol to isolate PDL cells from the surface of adult murine molars and established 35 new single cell-derived clones from the PDL explant. Among these clones, six clones with high (high clones, n = 3) and low (low clones, n = 3) osteogenic potential were selected. Despite a clear difference in the osteogenic potential of these clones, no significant differences in their cell morphology, progenitor cell marker expression, alkaline phosphatase activity, proliferation rate, and differentiation-related gene and protein expression were observed. RNA-seq analysis of these clones revealed that Z-DNA binding protein-1 (Zbp1) was significantly expressed in the high osteogenic clones, indicating that Zbp1 could be a possible marker and regulator of the osteogenic differentiation of PDL progenitor cells. Zbp1-positive cells were distributed sparsely throughout the PDL. In vitro Zbp1 expression in the PDL clones remained at a high level during osteogenic differentiation. The CRISPR/Cas9 mediated Zbp1 knockout in the high clones resulted in a delay in cell differentiation. On the other hand, Zbp1 overexpression in the low clones promoted cell differentiation. These findings suggested that Zbp1 marked the PDL progenitors with high osteogenic potential and promoted their osteogenic differentiation. Clarifying the mechanism of differentiation of PDL cells by Zbp1 and other factors in future studies will facilitate a better understanding of periodontal tissue homeostasis and repair, possibly leading to the development of novel therapeutic measures.

Balneotherapy is a treatment with healing waters, which includes bathing and physiotherapy in thermal water, therapeutic drinks, medical massage, and water jet massage. It is based on the buoyancy, physical properties, temperature, and chemical effects of mineral water. Throughout European and Japanese medical institutions, balneology and hot spring therapy is very much a part of routine medical treatment. The mechanism of balneotherapy is not yet completely understood. Balneotherapeutic procedures are mainly performed for the prevention, treatment, and rehabilitation of musculoskeletal diseases, but they have also proven useful for various other indications such as for the treatment or rehabilitation of dermatological diseases, immuno-inflammatory diseases, chronic pain syndromes, chronic cardiac diseases, and metabolic syndromes or neurological diseases as well as in the rehabilitation of patients with psychiatric conditions. Balneotherapy works well in the case of muscle tension, as it is relieving and relaxing, and it may be associated with improvement of various diseases. However, further investigations are necessary to determine the effectiveness, safety, standard procedures, and potential side effects of balneotherapy.

IntroductionIncreasing evidence supports the utilisation of functional electrical stimulation (FES) to improve gait following stroke; however, few studies have focused exclusively on its use in the convalescent phase. In addition, its efficacy in patients with a non-Western life style has not been evaluated.Methods and analysisThis is a randomised, controlled, open-label multicentre study, comparing rehabilitation with and without FES. The purpose of our study is to test the hypothesis that the FES system improves walking ability in Japanese patients with hemiplegia during the convalescent phase. Two hundred patients aged 20–85 years who had an initial stroke ≤6 months prior to the enrolment, are in a convalescent phase (after the end of acute phase treatment, within 6 months after the onset of stroke) with functional ambulation classification 3 or 4 and have a hemiplegic gait disorder (drop foot) due to stroke have been recruited from 21 institutions in Japan. The patients are randomised in 1:1 fashion to usual gait rehabilitation or rehabilitation using FES (Walkaide). The trial duration is 8 weeks, and the primary outcome measured will be the change in maximum distance from baseline to the end of the trial, as measured with the 6 min walk test (6-MWT). The 6-MWT is performed barefoot, and the two treatment groups are compared using the analysis of covariance.Ethics and disseminationThis study is conducted in accordance with the principles of the Declaration of Helsinki and the Ethical Guidelines for Medical and Health Research Involving Human Subjects and is approved by the ethics committee of all participating institutions. The published results will be disseminated to all the participants by the study physicians.Trial registration numberThe University Hospital Medical Information Network-Clinical Studies Registry (UMIN000020604).

To investigate whether a footbath inhibits spasticity in the hemiplegic lower limbs of post-stroke patients.Randomized, controlled study.Rehabilitation education and research hospital.Twenty-two post-stroke patients were randomly allocated to control or experimental groups. After relaxing in a supine posture for 30min, the experimental group subject's legs were immersed in 41°C water below the knee joint for 15min, while the control group remained in a resting posture.Modified Ashworth Scale (MAS) scores of the affected triceps surae muscle and F-wave parameters (i.e., F-wave amplitude, F/M ratio, and F-wave persistence) were recorded before, immediately after, and 30min after each intervention. Physiological parameters were simultaneously monitored to determine the thermo-therapeutic mechanisms and side effects of footbath usage.At the time immediately after the intervention, F-wave amplitudes decreased significantly in the experimental group, compared to the control group (p0.01, difference: -106.8; 95% CI; -181.58 to -32.09). F-wave amplitudes decreased significantly after 30-min intervention in the experimental group, with a total reduction of 161.2μV being recorded compared to 8.8μV increase in the control group (p0.01, difference: -170.0; 95% CI; -252.73 to -87.33). There were also significant differences between the experimental and control group for both F/M ratio and F-wave persistence, immediately after and 30min after the intervention. Further, there were significant differences between the experimental and control group for the MAS scores immediately after the intervention (p0.05, difference: -0.72; 95% CI; -1.262 to -0.193), and 30min after the intervention (p0.05, difference: -0.73; 95% CI; -1.162 to -0.293).These findings demonstrate that the use of footbaths is an effective non-pharmacological anti-spastic treatment for use in stroke rehabilitation.

Functional electrical stimulation (FES) for patients with stroke and foot drop is an alternative to ankle foot orthoses. Characteristics of FES responders and nonresponders have not been clarified.(1) To investigate the effects of treatment with FES on patients with stroke and foot drop and (2) to determine which factors may relate to responders and nonresponders.Multicenter, nonrandomized, prospective study.Multicenter clinical trial.Participants included those who experienced foot drop resulting from stroke, were older than 20 years, and could provide consent to participate; they were enrolled from hospitals between January 2013 and September 2015 and performed rehabilitation with FES.Stroke Impairment Assessment Set Foot-Pat Test (SIAS-FP), Fugl-Meyer Assessment for Lower Extremity (FMA-LE), Modified Ashworth scale (MAS) for ankle joint dorsiflexion and plantar flexion muscles, range of motion (ROM) for ankle joint, 10-m walking test (10mWT), Timed UpGo test (TUG), and 6-minute walking test (6MWT) were evaluated pre- and postintervention. Age, gender, type of stroke, onset times of stroke, paretic side, Brunnstrom stage of the lower extremity (Br. stage-LE), Functional Independence Measure (FIM), Functional Ambulation Category (FAC), poststroke months, number of interventions, total hours of interventions, and whether a brace was used were extracted from patients' medical records and collected on the physiological examination day.The authors examined 10mWT and age, gender, type of stroke, onset times of stroke, paretic side, Br. stage-LE, FIM, FAC, poststroke months, number of interventions, total hours of interventions, whether a brace was used, SIAS-FP, FMA-LE, MAS, ROM, TUG, and 6MWT before intervention. Participants were divided into nonresponders and responders with a change in 10mWT of0.1 and ≥0.1 m/s, respectively. Single and multiple regression analyses were used for data analysis. Additionally, the changes between groups were compared.Fifty-eight responders and 43 nonresponders were enrolled. The between-group differences, compared for changes between pre- and postintervention, were significant in terms of changes in SIAS-FP (P = .02), 10mWT (P.001), 10-m gait steps (P .001), TUG (P = .04), and 6MWT (P = .006). In the adjusted regression model, gender (odds ratio [OR], 3.92; 95% confidence interval [CI], 1.426-12.25; P = .007), number of interventions (OR, 1.028; 95% CI, 1.003-1.070; P = .03), and active ankle joint dorsiflexion ROM (OR, 1.047; 95% CI, 1.014-1.088; P = .005) remained significant.The factors related to 10mWT showing changes beyond the minimal clinically important difference were found to be patient gender, number of interventions, and active ankle joint dorsiflexion ROM before intervention. When patients with stroke who have greater active ankle joint ROM, and are female, use FES positively, they may benefit more from using FES.II.

The aim of this study was to assess the feasibility of applying a novel neuromuscular electrical stimulation system, targeting shoulder flexion, elbow extension, wrist extension, and individual finger extensions, to improve motor control and function of the hemiparetic upper limbs in chronic stroke patients.Fifteen participants with chronic (1 yr after cerebrovascular accident) upper limb hemiparesis were enrolled. The subjects underwent upper limb training for 60 mins per day, 6 days per week, for 2 wks, using both a shoulder-and-elbow stimulation device and a wrist-and-finger stimulation device developed by the study investigators. Outcomes were assessed using the upper extremity component of the Fugl-Meyer assessment, the action research arm test, and the modified Ashworth scale before and after intervention.All patients completed the training successfully using the neuromuscular electrical stimulation system without any safety incidents or other complications reported. Nonparametric statistical analyses indicated significant improvements in the upper extremity component of the Fugl-Meyer assessment and action research arm test scores, both at P0.01. There were also significant reductions in modified Ashworth scale scores for the elbow and the wrist flexor, both at P0.01.The multimuscle stimulation approach and method presented in this study seem feasible, and the improvements of upper limb motor control and functional test in chronic stroke patients justify further controlled investigation.

The purpose of this study was to compare the effects of a novel neuromuscular electrical stimulation (NMES) to the effects of conventional treatment in patients with dysphagia after brain injury. In total, 26 patients were non-randomly divided into an experimental group (n = 12) and a control group (n = 14). The experimental group received NMES intervention followed by conventional treatment, including thermal-tactile stimulation with intensive repetition of a dry-swallow task. The control group received conventional treatment without NMES. NMES at a fixed pulse duration of 50 μs and a frequency of 50 Hz was delivered over the skin areas above the motor point of the target muscles, i.e., the bilateral geniohyoid, mylohyoid/anterior belly of the digastric, and thyrohyoid muscles, using a high-voltage pulsed-current device. The two groups received 40-min treatments once a day, 5 days per week, for 8 weeks. Outcome, assessed before and 8 weeks after treatment, was evaluated with regard to the videofluoroscopic dysphagia scale (VDS), the anterior and superior displacement of the hyoid bone and larynx, and the functional oral intake scale. Both groups exhibited improvement, but the experimental group exhibited more significant improvement in the displacement of the hyoid bone and larynx, VDS-total score, and VDS-pharyngeal score than the control group did. The results suggest that NMES combined with conventional treatment is superior to conventional treatment alone in patients with dysphagia following treatment for brain injury. Further investigations are necessary to examine the effects of NMES in patients with more varied types of diseases.

To examine the feasibility of adapting whole body vibration (WBV) in the hemiplegic legs of post-stroke patients and to investigate the anti-spastic effects, and the improvement of motor function and walking ability. Twenty-five post-stroke patients with lower-limb spasticity were enrolled in the study. Each subject sat with hip joint angles to approximately 90° of flexion, and with knee joint angles to 0° of extension. WBV was applied at 30 Hz (4–8 mm amplitude) for 5 min on hamstrings, gastrocnemius and soleus muscles. The modified Ashworth scale was significantly decreased, active and passive range of motion (A-ROM, P-ROM) for ankle dorsiflexion and straight leg raising increased, and walking speed and cadence both improved during the 5-min intervention. Our proposed therapeutic approach could therefore be a novel neuro-rehabilitation strategy among patients with various severities.

To investigate the impact of stroke on health status and the effects of repetitive facilitation exercises (RFEs) for convalescent patients after stroke.The study was a prospective observational study of patients enrolled in an RFE programme. Between April 2008 and March 2012, 468 patients with stroke were enrolled in an intensive, comprehensive RFE programme. Patients participated in this interdisciplinary programme for 12 weeks, for an average of 5 hours per week. Before and immediately after the programme, several measures of rehabilitation outcomes and health-related quality-of-life were evaluated.At baseline, most patients (95.4%) had modified Rankin scale scores of 3-5. Their health-related quality-of-life was significantly impaired, with physical and mental component summary scores on the Short Form 36-item questionnaire (SF-36) of 30.7 and 35.8, respectively. After the RFE programme, all outcome measures improved significantly.The results demonstrate that convalescent patients after stroke may benefit substantially from RFE programmes in stroke rehabilitation centres, even when patients have impaired health status or high levels of healthcare utilization. Thus, an RFE programme is a simple yet highly effective means to improve rehabilitation outcomes and health-related quality-of-life, with a relatively low dropout rate.

To date, controlled clinical trials evaluating the efficacy of underwater exercise in improving the lower-extremity function and quality of life (QOL) in post-stroke patients have yet to be conducted. The purpose of the present study was to determine whether repeated underwater exercise enhances the therapeutic effect of conventional therapy for post-stroke patients.This was a pilot controlled clinical trial.The study took place in a research facility attached to a rehabilitation hospital.This prospective trial included 120 consecutive post-stroke inpatients with hemiplegic lower limbs (Brunnstrom stage 3-6). Patients were assigned to either an experimental or a control group. Patients in the experimental group received both repeated underwater exercise and conventional rehabilitation therapy.The underwater exercise consisted of 30-min training sessions in a pool with a water temperature of 30-31°C in which patients followed the directions and movements of trained staff. Training sessions were conducted once a day on 2 days of the week for a total of 24 times. Patients in the control group received only the conventional therapy.The 10-Minute Walk Test (10MWT), the Modified Ashworth Scale, and the 36-Item Short Form Health Survey were the outcome measures used. Lower-extremity function and QOL were assessed before and upon completion of the 12-week program.Improvements in 10MWT results and spasticity parameters were greater in the experimental group than they were in the control group (p 0.01). Significant differences between the groups were observed in magnitudes of changes of all QOL parameters (p 0.01).Combining conventional therapy with repeated underwater exercise may improve both lower-extremity function and QOL in post-stroke patients.

To preliminarily assess the acute effects of a single warm-water bath (WWB) on serum adipokine activity, we measured serum adiponectin, leptin and other metabolic profiles before, immediately after and 30 minutes after WWB in seven healthy male volunteers (mean age, 39.7 ± 6.0 years; mean body mass index, 21.6 ± 1.8 kg/m2). The subjects were immersed in tap water at 41°C for 10 minutes. Two weeks later, the same subjects underwent a single WWB with a bath additive that included inorganic salts and carbon dioxide (WWB with ISCO2) by the same protocol as for the first WWB. Leptin levels significantly increased immediately after WWB with tap water and ISCO2 (both P

Fibromyalgia syndrome (FMS) is a chronic disorder that is characterized by widespread pain with localized tenderness. We aimed to investigate whether thermal therapy combining sauna therapy and underwater exercise improved pain, symptoms, and quality of life (QOL) in FMS patients. Forty-four female FMS patients who fulfilled the American College of Rheumatology (ACR) criteria received 12-week thermal therapy program comprising sauna therapy once daily for 3 days/week and underwater exercise once daily for 2 days/week. Pain, symptoms, and QOL were assessed using a pain visual analog scale (VAS), a fibromyalgia impact questionnaire (FIQ), and a short form 36-item questionnaire (SF-36), respectively. All of the patients reported significant reductions in pain and symptoms of 31-77% after the 12-week thermal therapy program, which remained relatively stable (28-68%) during the 6-month follow-up period (that is, the thermal therapy program improved both the short-term and the long-term VAS and FIQ scores). Improvements were also observed in the SF-36 score. Thermal therapy combining sauna therapy and underwater exercise improved the QOL as well as the pain and symptoms of FMS patients.

We aimed to determine the effects of angiotensin II receptor blocker on cerebral hemodynamics and rehabilitative outcome. Sixteen hypertensive patients with a history of stroke received 10–20 mg olmesartan daily for eight weeks. Blood pressure decreased after treatment compared with the baseline, whereas cerebral blood flow (CBF) values of the affected and nonaffected sides increased. The results of the cerebrovascular reserve capacity were also statistically increased in the affected side. Improvements were observed in three rehabilitative outcome parameters. These findings suggest that olmesartan has beneficial effects in hypertensive patients with stroke and impaired CBF autoregulation, and might improve cerebral circulation and rehabilitative outcome.

A stroke patient with right hemiplegia and mirror movement underwent transcranial magnetic stimulation (TMS) and somatosensory-evoked potential (SEP) testing. The motor-evoked potentials (MEPs) of both abductor pollicis brevis muscles after stimulating the unaffected right hemisphere showed similar latencies, and were potentially produced by corticospinal tracts from the same motor cortex. N(20) responses of SEPs were recorded at C(4)' after contralateral stimulation of the unaffected left median nerve, but not stimulation of the affected right median nerve. The mirror movements and motor recovery might have utilized an ipsilateral motor pathway between the unaffected hemisphere and the affected hand.

Footbaths are considered to provide beneficial thermal therapy for post-stroke patients with spasticity, but their anti-spastic effects have not been investigated comprehensively. The present study aimed to evaluate alterations in motor-neuron excitability using F-wave parameters in post-stroke patients with spastic hemiplegia. Subjects' legs below the knee joint were immersed in water at 41 degrees C and F-wave recordings were made over the abductor hallucis muscle before, immediately after, and 30 min after thermal treatment. Antidromic stimulation was performed on the tibial nerve at the ankle. Measurements included F-wave amplitude, F-wave/M-response ratio, changes in modified Ashworth scale (MAS), body temperature and surface-skin temperature. The mean values of both F-wave parameters were higher on the affected side before footbath treatment. In post-stroke patients, the mean values of F-wave parameters were significantly reduced after footbath treatment (P < 0.01). The anti-spastic effects of footbath treatment were indicated by decreased F-wave parameters, in parallel with decreases in MAS. Body temperature was significantly increased both immediately after, and 30 min following footbath treatment in both groups, which appeared to play an important role in decreased spasticity. Surface-skin temperature increased immediately after footbath treatment in both groups and returned to baseline 30 min later. These findings demonstrate that the use of footbaths is an effective nonpharmacological anti-spastic treatment that might facilitate stroke rehabilitation.

The purpose of this study was to assess the relative benefits of angiotensin II receptor blockers (ARBs) and calcium channel blockers (CCBs) on cerebral hemodynamics and rehabilitation outcome in hypertensive stroke patients. We randomly assigned 35 patients to either the olmesartan (n=18) or amlodipine (n=17) treatment groups for 8 weeks. Changes in cerebral blood flow (CBF) and cerebrovascular reserve capacity (CRC) were quantified using xenon-CT and rehabilitation parameters were also measured. Over 24 h, olmesartan and amlodipine both reduced blood pressure (BP) to similar levels (systolic BP, -16.1+/-2.7 mm Hg vs. -15.7+/-3.1; diastolic BP, -9.2+/-2.9 vs. -8.6+/-3.3 mm Hg, respectively). In olmesartan-treated patients, CBF significantly increased in the affected and unaffected hemispheres, and CRC increased significantly in the affected hemisphere. No increases in CBF and CRC were observed in amlodipine-treated patients. Patients treated with olmesartan showed effective rates of improvement in hand (30.0%), upper extremities (40.0%) and lower extremities (100.0%), measured by Brunnstrom stage; these improvements were significantly different from those in amlodipine-treated patients for the total (P0.02) and lower extremity (P0.05) scores. There were no significant differences in Barthel indices and Mini-Mental State Examination (MMSE) scores. Olmesartan, but not amlodipine, had beneficial effects on CBF, CRC and rehabilitation outcomes in hypertensive stroke patients, by a mechanism independent of BP reduction and possibly by normalizing CBF autoregulation. Our results suggest that olmesartan may improve cerebral circulation and rehabilitation in hypertensive stroke patients in whom CBF autoregulation is impaired.

We used a computerized delayed-reaching task with a simple reaction time (RT) to investigate the visuo-motor and spatio-temporal performance of right brain-damaged (RBD) patients with unilateral spatial neglect (USN). Fifty-three RBD patients (22 with and 31 without USN) and 25 controls performed the tasks. We recorded the following data: the first RT (RT-1), which is thought to reflect the detection of the target position (the perceptual factor); the second RT (RT-2), which represents the initiation of reaching (the motor initiation aspect of premotor factors); the movement time (MT), which is hypothesized to reflect the "pure" motor component of the task. RBD patients with both USN and hemianopia demonstrated significantly longer RTs towards the left than towards the right for both the RT-1 and the RT-2. Among the RBD patients without hemianopia, the laterality index (left side/right side) of the RT-1 in those with USN was significantly greater than in those without USN or the controls. Among the three groups, there were no significant differences between the laterality indices of either the RT-2s or the MTs. These results suggest that the impairment of leftward movement in RBD patients with USN might be caused primarily by a perceptual impairment rather than an impairment in motor initiation, and is certainly not a "pure" motor impairment.

To investigate the effectiveness of repetitive facilitative exercise (RFE) under surface neuromuscular electrical stimulation (NMES) in patients with post-stroke hemiplegia.This randomized, controlled, observer-blinded, pilot trial randomized 27 adults with severe arm impairment [Fugl-Meyer Arm scale (FMA) ≤ 20] due to stroke of 3-13 weeks duration into three groups and provided treatment on a 4-week, 40 minutes/day, 5 days/week schedule. The RFE-under-NMES group were given 100-150 repetitions of standardized movements of shoulder, elbow and wrist joints of their affected arm with concurrent low-amplitude NMES for each corresponding musculature. The RFE group was given the same exercise regimen but without NMES. The control group was treated with a conventional arm rehabilitation programme without NMES. FMA was assessed at baseline and 4 weeks.All 27 participants (nine in each group) completed the trial. At 4 weeks, the RFE-under-NMES group evidenced significantly greater improvement compared with the control group on the FMA (p = 0.003), but not with the RFE group (p = 0.092). The RFE group showed improvement compared with the control group, but it was not significant (p = 0.199).RFE under NMES is feasible in clinical settings and may be more effective than conventional rehabilitation in lessening arm impairment after sub-acute stroke.

Summary This article reviews the evolution of functional testing of the pancreas in Japan for the diagnosis and treatment of chronic pancreatitis (CP), contrasting the pre- with the post-secretin test (S test) era. In the pre-S test era, the diagnosis was based on symptoms, clinical findings, fasting serum diastase levels, and the vagostigmin- and ether-stimulation test unless morphologic evidence was available. The S test and CCK-pancreozymin (PZ) test (PS test) were introduced into Japan around 1963 and have been used as the gold standard of the exocrine pancreatic-function test. Through a series of attempts at standardization in 1971, 1985, and 1987, the method was standardized to collect duodenal juice for 60 min through a double- or triple-lumen tube after a bolus or during a continu-ous i.v. injection of secretin (100 U). The S test, however, is an invasive and cumbersome procedure. As a result, N-benzoyl-L-tyrosal-paminobenzoic acid (BT-PABA) testing and fecal chymotrypsin testing were introduced into Japan in the middle and late 1970s, respectively. Although simple and noninvasive, these two methods were found have lower sensitivity and specificity than the conventional S test. These two methods, therefore, are presently used more often for monitoring the course of disease and therapeutic effects. Additionally, the glucose tolerance test can be performed to detect endocrine pancreatic insufficiency.

Objective: To investigate whether multiple sessions of 1-Hz repetitive transcranial magnetic stimulation (rTMS) facilitates the effect of repetitive facilitation exercises on hemiplegic upper-limb function in chronic stroke patients. Design: Randomized double-blinded crossover study. Patients: Eighteen patients with hemiplegia of the upper limb. Methods: Patients were assigned to 2 groups: a motor-beforesham rTMS group, which performed motor rTMS sessions for 2 weeks followed by sham rTMS sessions for 2 weeks; or a motor-following-sham rTMS group, which performed sham rTMS sessions for 2 weeks followed by motor rTMS sessions for 2 weeks. Patients received 1-Hz rTMS to the unaffected motor cortex for 4 min and performed repetitive facilitation exercises for 40 min during motor rTMS sessions. The Fugl-Meyer Assessment, Action Research Arm Test (ARAT) and Simple Test for Evaluating Hand Function were used to evaluate upper-limb function. The Modified Ashworth Scale and F-wave were measured to evaluate spasticity. Results: Motor function improved significantly during the motor, but not sham, rTMS sessions. ARAT score gains were 1.5 (0–4.0) (median, interquartile range) during the motor rTMS session, and 0 (–0.8–1.8) during the sham rTMS session (p = 0.04). Spasticity did not significantly change during either session. Conclusion: Multiple sessions of 1-Hz rTMS facilitated the effects of repetitive facilitation exercises in improving motor function of the affected upper limb, but did not change spasticity.

Background. Repetitive facilitative exercise (RFE), a combination of high repetition rate and neurofacilitation, is a recently developed approach to the rehabilitation of stroke-related limb impairment. Preliminary investigations have been encouraging, but a randomized controlled evaluation has yet to be performed. Objectives. To compare the efficacy of RFE with that of conventional rehabilitation in adults with subacute stroke. Methods. A total of 52 adults with stroke-related upper-limb impairment (Brunnstrom stage ≥III) of 3 to 13 weeks’ duration participated in this randomized, controlled, observer-blinded trial. Participants were randomized into 2 groups and received treatment on a 4-week, 40 min/d, 5 d/wk schedule. Those assigned to RFE received 100 standardized movements of at least 5 joints of their affected upper extremity, whereas those in the control group participated in a conventional upper-extremity rehabilitation program. Primary and secondary outcomes (improvement in group Action Research Arm Test [ARAT] and Fugl-Meyer Arm [FMA] scores, respectively) were assessed at the end of training. Results. In all, 49 participants (26 receiving RFE) completed the trial. ARAT and FMA scores at baseline were 19 ± 21 and 39 ± 21 (mean ± standard deviation). Evaluation at the trial’s completion revealed significantly larger improvements in the RFE group than in the control group in both ARAT ( F = 7.52; P = .009) and FMA ( F = 5.98; P = .019) scores. Conclusions. These findings suggest that RFE may be more effective than conventional rehabilitation in lessening impairment and improving upper-limb motor function during the subacute phase of stroke.

Objective To investigate whether the direct application of vibratory stimuli inhibits spasticity in the hemiplegic upper limbs of post-stroke patients. Design A randomized controlled study. Subjects Thirty-six post-stroke patients. Methods Patients were randomly allocated to the "Rest group", "Stretch group", or "Direct application of vibratory stimuli group". After relaxing in a supine posture for 30 min, subjects received the interventions for 5 min. The Modified Ashworth Scale scores and F-wave parameters were recorded before, immediately after and 30 min after each intervention. Results The Rest group showed no significant changes in F-wave parameters and Modified Ashworth Scale scores. The Stretch group showed a tendency to decrease in F-wave amplitude and F/M ratio immediately after the intervention, but not 30 min later. The Direct application of vibratory stimuli group showed significant improvements in F-wave parameters and Modified Ashworth Scale scores immediately after the intervention, which remained 30 minutes later. The changes in F-wave parameters and Modified Ashworth Scale scores observed in the Direct application of vibratory stimuli group significantly differed from those in the Rest group and the Stretch group. Conclusion The direct application of vibratory stimuli has anti-spastic effects in the hemiplegic upper limbs of post-stroke patients.

The purpose of this study was to report the first case (to our knowlege) of primary laryngeal aspergillosis in a patient with underlying CD4+ T lymphocytopenia. Laryngeal involvement of Aspergillus is more commonly seen as a part of a wider infection involving the respiratory system in an immunocompromised host. However, primary infection of the larynx is extremely rare. Although there were 12 cases of primary laryngeal aspergillosis previously reported in healthy subjects, there is no known study describing immunological findings in detail. We report a case of primary laryngeal aspergillosis in a healthy 79-year-old male. The examination of his immunity subsequently revealed that there was a marked decline in the number of CD4+ T lymphocytes and a decrease in the ratio of CD4+ to CD8+. It is suggested that it is essential to examine the defence mechanisms, specifically cell-mediated immunity in a patient showing primary laryngeal aspergillosis.

In patients with severe hypertension, chronic heart failure or history of stroke, the lower limit of cerebral blood flow (CBF) autoregulation is shifted to a higher blood pressure (BP) than in healthy subjects. This study investigated the effects of the angiotensin II receptor blocker (ARB) olmesartan on human cerebral haemodynamics and rehabilitation outcomes.Open treatment trial with pre-treatment and post-treatment evaluations.Olmesartan (10-20 mg) administered daily for 8 weeks.The 24-hour BP, clinical BP, CBF at rest, cerebrovascular reserve capacity (CRC) and rehabilitation outcomes (Brunnstrom stage, Barthel index and Mini-Mental State Examination [MMSE] score) were measured in 44 post-stroke patients with hypertension (62.2 +/- 10.7 years).The systemic BP decreased after treatment compared with baseline. The CBF increased by 11.2% on the affected side and by 8.9% on the non-affected side of the brain and the CRC also increased on both sides. Improvements were observed in the Brunnstrom stage, Barthel index and MMSE score.This study suggest that olmesartan has beneficial effects in post-stroke patients with hypertension and impaired CBF autoregulation and provides important information necessary to design future more definitive studies.

To investigate whether the direct application of vibratory stimuli inhibits spasticity and improves motor function in the hemiplegic upper limbs of post-stroke patients.Prospective pilot study.University hospital rehabilitation centre.Fourteen post-stroke patients (mean age = 57.3 years; SD = 19.1 years).A hand and forearm stimulation device and an upper-arm stimulation device, consisting of vibrators, a wooden frame and a cloth strap, applied to the upper limbs of subjects.The modified Ashworth scale (MAS) score, F-wave parameters and motor-function parameters (finger tapping, active range of motion and the simple test for evaluating hand function).Subjects showed significant and potentially durable improvements in MAS score (p0.01), F-wave parameters (p0.01) and motor-function parameters (p0.05). The MAS score, F-wave parameters and motor-function parameters dropped below the baseline values after vibratory stimulation. The MAS score and F-wave parameters remained significantly below the baseline 30 minutes after stimulation.The direct application of vibratory stimuli is an effective non-pharmacological anti-spastic treatment that could facilitate stroke rehabilitation. These results provide good evidence of potential short-term benefits of anti-spastic vibratory therapy in post-stroke patients in terms of decreased muscle tonus and improved motor function.

A 55-year-old man with a chief complaint of melena had diffusely infiltrated lymphoma from the rectum to the sigmoid colon and polyclonal hypergammaglobulinemia. Biopsy specimen obtained from the rectum revealed diffuse medium-sized lymphoma cell with plasmocytosis. Histochemical analysis with monoclonal antibodies indicated that the origin of the tumor cell to be T-lymphocyte. Chemotherapy with cyclophosphamide, vincristine and prednisolone (VEP regimen) was effective for mucosal bleeding of the colonic lesion and reduction of polyclonal hypergammaglobulinemia. Five yrs later he showed recurrence of the disease and elevation of serum alphafetoprotein, and died of pulmonary infections. Autopsy finding confirmed the diagnosis of malignant lymphoma of the colon and disclosed the association of hepatocellular carcinoma.

The use of a new device consisting of a small vibrator to deliver functional vibratory stimulation (FVS) to the arm resulted in improvements of flexion of the hemiparetic shoulder in a man with thalamic bleeding. FVS delivered to the palm enabled the patient to repeat flexing his hemiparetic shoulder to manipulate objects with his hand. The functions of the patient's hemiparetic shoulder and fingers improved after treatments using FVS for 1 month. We examined whether FVS of the hemiplegic upper limb could facilitate voluntary movements of the limb by increasing the excitability of the motor cortex or the spinal motor neurons using somatosensory-evoked potentials, transcranial magnetic stimulation, F-wave, and single photon emission computed tomography. Our results did not detect an increase of excitability in the motor cortex or in spinal motor neurons by FVS.

The utility of a new computerized motor-skill analyzer for the lower limb was studied in healthy subjects and patients with stroke. The computerized motor-skill analyzer for the lower limb evaluated accuracy in a figure-tracking task with the foot. The intraclass correlation coefficients of measurements in subjects were .61 to .89 (p < .01). The trajectory errors of the unaffected lower limb in stroke patients were negatively correlated with physical ability. Trajectory errors of the patients were significantly larger than those of the healthy subjects. These results suggest that the computerized motor-skill analyzer is useful for quantitatively evaluating motor-skills of the lower limb.

Thermotherapy is generally considered appropriate for post-stroke patients with spasticity, yet its acute antispastic effects have not been comprehensively investigated. F-wave parameters have been used to demonstrate changes in motor neuron excitability in spasticity and pharmacological antispastic therapy. The present study aimed to confirm the efficacy of thermotherapy for spasticity by evaluating alterations in F-wave parameters in ten male post-stroke patients with spastic hemiparesis (mean age: 49.0+/-15.0 years) and ten healthy male controls (mean age: 48.7+/-4.4 years). The subjects were immersed in water at 41 degrees C for 10 min. Recordings were made over the abductor hallucis muscle, and antidromic stimulation was performed on the tibial nerve at the ankle. Twenty F-waves were recorded before, immediately after, and 30 min following thermotherapy for each subject. F-wave amplitude and F-wave/M-response ratio were determined. Changes in body temperature and surface-skin temperature were monitored simultaneously. The mean and maximum values of both F-wave parameters were higher on the affected side before thermotherapy. In the post-stroke patients, the mean and maximum values of both parameters were significantly reduced after thermotherapy (P0.01). Hence, the antispastic effects of thermotherapy were indicated by decreased F-wave parameters. Body temperature was significantly increased both immediately after and 30 min after thermotherapy in all subjects. This appeared to play an important role in decreased spasticity. Surface-skin temperature increased immediately after thermotherapy in both groups and returned to baseline 30 min later. These findings demonstrate that thermotherapy is an effective nonpharmacological antispastic treatment that might facilitate stroke rehabilitation.

The utility of a new device that delivers functional vibratory stimulation to the extremities was studied in 13 patients with stroke. We hypothesized that vibratory stimulation of the hemiplegic lower limb would increase gait speed in these patients. The device consisted of one battery, two small vibrators and a connecting wire. The small vibrators were stabilized on the anterior tibial muscle and gluteus medius muscle by a bandage. An analysis of the effects of functional vibratory stimulation on hemiplegic lower limb on gait speed indicated that gait speed was greater during stimulation than without. These results suggest that the new device of functional vibratory stimulation is useful for treatment in patients with stroke.

Recently, a sweet taste receptor family, the T1R family, that recognizes some carbohydrates including sucrose was identified. Although the T1R3 molecule is known to participate in heterodimers that are used as sweet- and umami-tasting receptors, there is no evidence that T1R3 alone recognizes similar ligands. We demonstrate for the first time that the candidate sweet taste receptor T1R3 is essential for the recognition and response to the disaccharide trehalose. Our system is a valuable tool not only for understanding the relationship between sweeteners and their receptors but also for exploring the diversities of their receptors, resulting in the design of new high-potency sweeteners.

Sarcoidosis affects many different organ systems. However, laryngeal involvement is rare and most cases with laryngeal involvement affect the supraglottis, occasionally secondarily extending to the vocal fold. The features of sarcoidosis in the supraglottic region have been described in several reports, but vocal fold involvement has not been presented in detail. We report an unusual case of laryngeal sarcoidosis initially involving the vocal folds in a 66-year-old man, associated with hypercalcaemia. Our report describes characteristics of the involved vocal folds. Hypercalcaemia is one of the characteristics of sarcoidosis. We concluded that laryngeal sarcoidosis should be added to the differential diagnosis of vocal fold lesions, particularly in patients with hypercalcaemia.

The chaperonin containing TCP-1 (CCT) is a eukaryotic molecular chaperone consisting of eight subunit species and assists in the folding of cytosolic proteins. We show here that all eight mouse CCT subunit genes contain sequences called heat shock elements for binding heat shock transcription factors (HSFs) by electrophoretic mobility shift assays and that these genes are transcriptionally activated by HSFs in reporter gene assays using HeLa cells transiently overexpressing HSFs. These results suggest that HSF1 and/or HSF2 play a role in Cct gene expression.

To evaluate the value of cytology of pure pancreatic juice (PPJ) and tumor marker determination in PPJ and serum for the diagnosis of early pancreatic cancer (EPC), PPJ was obtained endoscopically from 16 patients with EPC (< 20 mm, confined to pancreas), 16 patients with chronic pancreatitis (CP), and 20 controls. Cutoff levels of CEA, CA19-9, and POA in PPJ were set from ROC curves at 40 ng/ml, 7,500 U/ml, and 1.5 U/ml, respectively. For the differentiation of EPC from CP, the sensitivity of CEA, CA19-9, and POA was 71.4, 42.9, and 50%, respectively; specificity was 93.3, 46.7, and 80%, respectively; and diagnostic accuracy was 82.8, 44.8, and 65.5%, respectively. Determination of serum tumor markers was useless. Sensitivity of cytology was 75%, specificity was 93.8%, and diagnostic accuracy was 84.4%. Combined cytology and CEA determination in PPJ increased the diagnostic accuracy to 93.1%. The combination was useful in supporting and supplementing endoscopic retrograde cholangiopancreatography (ERCP) findings for the correct diagnosis in 11 and 4 patients, respectively, with EPC; in one patient EPC was correctly diagnosed on ERCP findings alone. One of 16 patients with CP showed false-positive results. We conclude that cytology and CEA determination in PPJ with ERCP is a useful combination for the diagnosis of pancreatic cancer even in early stages.

Cytological diagnosis of pancreatic carcinoma sometimes poses difficulties in distinguishing malignant from benign cells. Recent molecular study of pancreatic carcinoma has revealed a very high incidence of a point mutation of the c-Ki-ras oncogene at codon 12 in this neoplasm. To take advantage of this technique for the diagnosis of pancreatic carcinoma, we attempted to amplify the c-Ki-ras gene from endoscopically obtained pancreatic juice by isolation of DNA and polymerase chain reaction (PCR) coupled with restriction fragment length polymorphism (RFLP). PCR was possible in approx 70% of the cases. A point mutation was nonradioisotopically detected in 4 of 6 pancreatic carcinomas and in one intraductal papillary neoplasm, whereas no mutation was detected in other cases. Thus, this method was thought to be useful for the diagnosis of pancreatic carcinoma.

The authors studied the relationship between aging and exocrine pancreatic function by the secretin test which was recently standardized by the Japanese Society of Gastroenterology. Pancreatic juice was collected at 10 min intervals for 60 minutes after a bolus intravenous injection of secretin (Secrepan, Eisai Co., Ltd., 100 U/body) through a quadruple-lumen doudenal tube equipped with double balloons. Exocrine pancreatic function was evaluated by three parameters: secretory volume, maximal bicarbonate concentration or bicarbonate output, and enzyme (amylase and lipase) output. Control subjects consisted of 65 outpatients presenting with mild vague abdominal symptoms who fulfilled the following three criteria: 1) good general condition with no known diseases; 2) no abnormality in the liver, bile duct, pancreas, kidney and metabolism judged from blood chemistry, urine and stool analysis, upper GI series, abdominal ultrasonography (US), and endoscopic retrograde cholangiopancreatography (ERCP); 3) alcohol consumption less than 25 g/day. Control subjects were divided into three groups: 15 subjects below 40 years of age (group A), 32 subjects from 40 to 65 years (group B), and 18 subjects of 65 years and above (group C). Nineteen patient with chronic pancreatitis were also studied. The group C showed significantly lower values in secretory volume, bicarbonate output, and enzyme output than group A and B. Enzyme output showed a gradual decrease with aging. However, secretory volume and bicarbonate output showed a gentle convex curve with a peak around age 40 and a rather steep down-slope after late 50s. The degree of the decrease was significantly more marked in volume and bicarbonate output than in enzyme output in group C.(ABSTRACT TRUNCATED AT 250 WORDS)

Neurofibromas of the larynx are extremely rare. They occur in association with neurofibromatosis less frequently than solitary neurofibromas. However, most laryngeal tumors in neurofibromatosis are neurofibromas. This disorder has 2 histological subtypes, which require different surgical approaches because of their biological differences. Few cross-sectional imaging studies have been performed in neurofibroma of the larynx. We describe a 44-year-old man with neurofibromatosis and nonplexiform neurofibroma of the larynx and discuss the role of preoperative computed tomography and magnetic resonance imaging in this case. The tumor was removed completely using an endolaryngeal approach without an external incision. It was possible to distinguish subtypes preoperatively on cross-sectional imaging. Magnetic resonance imaging provided more sensitive information in the diagnosis of this tumor than computed tomography. Preoperative cross-sectional imaging should be performed to help the surgeon diagnose and choose an appropriate surgical approach for this disorder.

To evaluate the effect of aging on exocrine pancreatic function, fecal chymotrypsin activity (FCA) was measured by a photometric method in 62 healthy controls (20 to 87 years old, average 51.0 years), 42 patients with non-pancreatic diseases (31 to 83 years old, average 56.1 years), 40 controls in an old-age home (63 to 92 years old, average 77.6 years), 20 patients with definite chronic pancreatitis (17 to 72 years old, average 53.5 years) and five patients with pancreatic cancer (60 to 76 years old, average 65.4 years). Exocrine pancreatic function showed a significant decrease with aging as indicated by: (a) a significant inverse correlation between aging and FCA in the 62 healthy controls (r = -0.56, p less than 0.001), in the 42 patients with non-pancreatic diseases (r = -0.59, p less than 0.001), and also in the 40 controls in an old-age home (r = -0.52, p less than 0.001); and (b) a significantly lower FCA in the 21 healthy controls aged 65 or more (designated as the B group of healthy controls) than the 41 healthy controls aged less than 65 (designed as the A group of healthy controls). The 40 controls in an old-age home showed significantly lower FCA than the B group of healthy controls. This result was ascribed to the fact that the former group consisted of significantly older subjects than the latter. No significant difference was found in FCA between patients with chronic pancreatitis, those with pancreatic cancer, the B group of healthy controls, and the controls in an old-age home.(ABSTRACT TRUNCATED AT 250 WORDS)