Yen-Ho Wang

Circulating levels of markers of inflammation and endothelial activation are increased in men with chronic spinal cord injury.

BACKGROUND/PURPOSE Accelerated atherogenesis is often seen in individuals with chronic spinal cord injury (SCI). However, the mechanisms contributing to this phenomenon remain unclear. This study aimed to evaluate whether SCI per se is associated with a low-grade chronic inflammatory state and endothelial activation, both of which are well-documented prerequisites for atherogenesis. METHODS Serum levels of markers of inflammation (C-reactive protein [CRP], interleukin-6, and soluble CD40 ligand) and endothelial activation (endothelin-1, soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule-1 [sVCAM-1]) were measured in SCI patients with CRP levels < 10 mg/L and with no evidence of active infection. Sixty-two men with traumatic neurologically complete SCI (20 tetraplegics and 42 paraplegics) and 29 age-matched male controls were enrolled. RESULTS Compared with able-bodied controls, subjects with SCI had a significantly lower body mass index (BMI) (-7%) and significantly lower serum levels of albumin (-10%), creatinine (-20%), low-density lipoprotein cholesterol (-10%), and high-density lipoprotein (HDL) cholesterol (-25%), and showed a trend toward higher fasting insulin levels. Irrespective of injury level and duration, subjects with SCI had significantly higher serum levels, compared to able-bodied controls, of CRP (mean, 4.0 +/- 2.7 mg/L vs. 1.4 +/- 1.1 mg/L), interleukin-6 (median, 2.5 pg/mL vs. 0.4 pg/mL; range, 1.5-3.6 pg/mL vs. 0.2-0.5 pg/mL), endothelin-1 (mean, 1.3 +/- 0.4 pg/mL vs. 0.9 +/- 0.3 pg/mL), and sVCAM-1 (mean, 1170 +/- 318 ng/mL vs. 542 +/- 318 ng/mL). The serum levels of all four factors correlated negatively with levels of serum albumin, creatinine and HDL cholesterol, but not with BMI or fasting insulin levels. In multivariate analyses, SCI was the only factor that was independently associated with increased serum levels of CRP, interleukin-6, endothelin-1 and sVCAM-1 after adjustment for confounding factors such as serum albumin and creatinine levels and parameters of dyslipidemia and insulin resistance. CONCLUSION In this study, we have, for the first time, demonstrated that SCI per se is associated with a low-grade chronic inflammatory state and endothelial activation, which may partly explain the increased atherogenic risk in patients with long-standing SCI.

Wogonin Improves Histological and Functional Outcomes, and Reduces Activation of TLR4/NF-κB Signaling after Experimental Traumatic Brain Injury

Background Traumatic brain injury (TBI) initiates a neuroinflammatory cascade that contributes to neuronal damage and behavioral impairment. This study was undertaken to investigate the effects of wogonin, a flavonoid with potent anti-inflammatory properties, on functional and histological outcomes, brain edema, and toll-like receptor 4 (TLR4)- and nuclear factor kappa B (NF-κB)-related signaling pathways in mice following TBI. Methodology/Principal Findings Mice subjected to controlled cortical impact injury were injected with wogonin (20, 40, or 50 mg·kg−1) or vehicle 10 min after injury. Behavioral studies, histology analysis, and measurement of blood-brain barrier (BBB) permeability and brain water content were carried out to assess the effects of wogonin. Levels of TLR4/NF-κB-related inflammatory mediators were also examined. Treatment with 40 mg·kg−1 wogonin significantly improved functional recovery and reduced contusion volumes up to post-injury day 28. Wogonin also significantly reduced neuronal death, BBB permeability, and brain edema beginning at day 1. These changes were associated with a marked reduction in leukocyte infiltration, microglial activation, TLR4 expression, NF-κB translocation to nucleus and its DNA binding activity, matrix metalloproteinase-9 activity, and expression of inflammatory mediators, including interleukin-1β, interleukin-6, macrophage inflammatory protein-2, and cyclooxygenase-2. Conclusions/Significance Our results show that post-injury wogonin treatment improved long-term functional and histological outcomes, reduced brain edema, and attenuated the TLR4/NF-κB-mediated inflammatory response in mouse TBI. The neuroprotective effects of wogonin may be related to modulation of the TLR4/NF-κB signaling pathway.

Early and intensive rehabilitation predicts good functional outcomes in patients admitted to the stroke intensive care unit

Purpose. Earlier and more intense rehabilitation benefit stroke patients. Yet, studies have caution intensive therapy during acute brain injury. This study examined the rehabilitation commencement time and intensity as predictors of functional outcomes in acute stroke patients admitted to the stroke intensive care unit (ICU). Method. Sociodemographic, medical, rehabilitative and functional data were collected on 154 acute stroke patients. Regression analyses were used to identify predictors for the basic activities of daily living (Barthel Index, BI) and the walking ability at discharge. Result. Rehabilitation commencement time and intensity significantly predicted the BI score at discharge after adjusting for initial severity (National Institute of Health Stroke Scale, NIHSS) and age (p < 0.05). For the walking function at discharge, only the rehabilitation intensity was a significant predictor after adjusting for initial severity and age (p < 0.05). Furthermore, with increasing rehabilitation intensity, patients with severe stroke benefited more than those with moderate stroke. Conclusion. Rehabilitation commencement time and intensity, after adjusting for admission functional status and severity of stroke, remained to be important predictors of stroke functional outcomes. This study supported the recommendation to commence rehabilitation early and intensively and provided evidence that this claim can be extended to acute stroke patients admitted to an ICU.

Hormone changes in men with spinal cord injuries.

The steady state profiles of 63 men with traumatic spinal cord injuries (24 quadriplegics and 39 paraplegics; average age of 31.2 ± 6.8 yr; 18-44 yr) were studied. The average length of post-traumatic period was 6.2 ± 5.0 yr, ranging from 8 months to 20 yr. It was found that all the subjects had normal serum thyroxine, thyrotropin, cortisol, growth hormone and plasma adrenocorticotropic hormone. Seven cases (11.1%) had low serum triiodothyronine and eight cases (12.7%) had low serum testosterone. On the other hand, 17 cases (27.0%) had hyperprolactinemia; 9 cases (14.3%) had elevated serum testosterone level; 6 cases (9.5%) had elevated serum follicle-stimulating hormone; and 4 cases (6.3%) had elevated serum luteinizing hormone. The level of spinal cord injury, injury period and patient age had no correlation with other serum hormone changes except that quadriplegic subjects had lower serum triiodothyronine than the paraplegic, with a mean of 1.42 ± 0.30 v 1.70 ± 0.36 nmol/liter (P < 0.005). Of the eight subjects who had low serum testosterone, none had elevated gonadotropin. There were also eight subjects with elevated follicle-stimulating hormone and/or luteinizing hormone, six of them had normal serum testosterone and two had elevated serum testosterone. This suggested their hypogonadism did not result primarily from classic primary gonadal failure. It could be speculated that other testicular paracrine factors and/or alteration of hypothalamus-pituitarytesticular axis are involved in the pathogenesis of hypogonadism. Further studies in this field will provide information regarding male reproductive physiology and may have impact on fertility enhancement options for men with spinal cord injuries.

Dose-Response Relation Between Neuromuscular Electrical Stimulation and Upper-Extremity Function in Patients With Stroke

Background and Purpose— The purpose of our study was to investigate the effects of different doses of neuromuscular electrical stimulation (NMES) on upper-extremity function in acute stroke patients with severe motor deficit. Methods— Sixty-six acute stroke patients were randomized to 3 groups: high NMES, low NMES, or control. The low-NMES group received 30 minutes of stimulation per day, and the high-NMES group received 60 minutes per day, for 4 weeks. The Fugl-Meyer Motor Assessment Scale, Action Research Arm Test, and Motor Activity Log were used to assess the patients at baseline, 4 weeks, and 12 weeks post baseline (follow-up). Results— Both NMES groups showed significant improvement on Fugl-Meyer Motor Assessment and Action Research Arm Test scales compared with the control group at week 4 and follow-up. The high-NMES group showed treatment effects similar to those of the low-NMES group. Conclusions— Higher and lower doses of NMES led to similar improvements in motor function. A minimum of 10 hours of NMES in combination with regular rehabilitation may improve recovery of arm function in stroke patients during the acute stage.

Impaired Hypothalamus-pituitary-adrenal Axis In Men With Spinal Cord Injuries

Huang T-S, Wang Y-H, Lee S-H, Lai J-S: Impaired hypothalamus-pitutary-adrenal axis in men with spinal cord injuries. Am J Phys Med Rehabil 1998; 77:108–112 Twenty-five men with spinal cord injuries were studied for evaluation of the hypothalamus-pituitary-adrenal axis, using corticotropin-releasing hormone and insulin-induced hypoglycemia. Twenty-five age-matched healthy male volunteers served as controls. Three spinal cord-injured subjects had hyperprolactinemia, three had elevated basal follicle-stimulating hormone levels, one had an elevated basal luteinizing hormone level, and four had hypotestosteronemia. The mean plasma adrenocorticotropin response to corticotropin-releasing hormone of spinal cordinjured subjects was smaller than that of the healthy controls but did not reach a statistical significance. The cortisol response to corticotropin-releasing hormone of the spinal cord-injured subjects was significantly lower than that of healthy controls. However, the difference disappeared if a correction was made for baseline values. Six spinal cord-injured subjects did not have a cortisol response to insulin-induced hypoglycemia, and they had either a minimal or no adrenocorticotropin response. Another 11 spinal cord-injured subjects had a maximal cortisol response to insulin-induced hypoglycemia below the lowest limit of normal, i.e., 0.5 μmol/1. Among these spinal cord-injured subjects, three had a less than 50% increase of plasma adrenocorticotropin after insulin-induced hypoglycemia. These findings are consistent with the notion that spinal cord-injured subjects have an altered central neurotransmitter tone and substantiate the hypothesis that an afferent neural pathway exists between the adrenal and hypothalamus and may modulate stressinduced secretion of adrenocorticotropin. Long-term abnormal adrenocorticotropin secretion may cause mild adrenocortical atrophy and, thereby, a reduced cortisol response.

ASSOCIATION OF DEPRESSION AND PAIN INTERFERENCE WITH DISEASE-MANAGEMENT SELF-EFFICACY IN COMMUNITY-DWELLING INDIVIDUALS WITH SPINAL CORD INJURY

OBJECTIVE To determine factors influencing disease-management self-efficacy in individuals with spinal cord injury. DESIGN A cross-sectional study. SUBJECTS/PATIENTS Forty-nine community-dwelling individuals with chronic spinal cord injury (mean age 44 years) participated in the study. METHODS Each subject was evaluated for disease-management self-efficacy (Self-efficacy for Managing Chronic Disease), depression (10-item Center for Epidemiologic Studies Depression Scale), pain interference (Pain Interference Scale), and availability of support (Interpersonal Support Evaluation List short form). Multiple regression analysis was performed to determine the relative contributions of these factors to disease-management self-efficacy. RESULTS The mean disease-management self-efficacy score was 6.5 out of 10 (standard deviation 1.6). Bivariate correlation analysis showed that higher self-efficacy was significantly correlated with longer time since injury (r = 0.367, p = 0.010), better social support (r = 0.434, p = 0.002), lower pain interference (r = -0.589, p <0.001), and less severe depressive symptoms (r=-0.463, p=0.001). In multiple regression analysis, only lower pain interference and less severe depressive symptoms were significantly associated with higher disease-management self-efficacy (F 4,44=10.249, R2=0.482, p<0.001). CONCLUSION Disease-management self-efficacy is suboptimal in many community-living people with spinal cord injury. This research suggests that rehabilitation of patients with spinal cord injury should include self-efficacy-enhancing strategies. Alleviation of depressive symptoms and pain self-management may be important for improving disease-management self-efficacy in this population, but this requires further study.

Wheelchair-Related Accidents: Relationship With Wheelchair-Using Behavior in Active Community Wheelchair Users

OBJECTIVE To report the prevalence, mechanisms, self-perceived causes, consequences, and wheelchair-using behaviors associated with wheelchair-related accidents. DESIGN A case-control study. SETTING Community. PARTICIPANTS A sample of experienced, community-dwelling, active manual and powered wheelchair users (N=95) recruited from a hospital assistive technology service center. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Wheelchair-using behaviors, wheelchair-related accidents over a 3-year period, and the mechanisms and consequences of the accidents. RESULTS Among the 95 participants, 52 (54.7%) reported at least 1 accident and 16 (16.8%) reported 2 or more accidents during the 3 years prior to the interview. A total of 74 accidents, were categorized into tips and falls (87.8%), accidental contact (6.8%), and dangerous operations (5.4%). A logistic regression found individuals who failed to maintain their wheelchairs regularly (odds ratio [OR]=11.28; 95% confidence interval [CI], 2.62-48.61) and used a wheelchair not prescribed by professionals (OR=4.31; 95% CI, 1.10-16.82) had significantly greater risks of accidents. In addition to the risk factor, lack of regular wheelchair maintenance, the Poisson regression corroborated the other risk factor, seat belts not used (incident rate ratio=2.14; 95% CI, 1.08-4.14), for wheelchair-related accidents. CONCLUSIONS Wheelchair-related accidents are closely related to their wheelchair-using behaviors. Services including professional evaluation, repair, maintenance, and an educational program on proper wheelchair use may decrease the risks of wheelchair accidents.

Pituitary-testicular and pituitary-thyroid axes in spinal cord-injured males

Thirty spinal cord-injured (SCI) males were studied for evaluation of their pituitary-testicular and pituitary-thyroid axes using combined luteinizing hormone-releasing hormone (LHRH) and thyrotropin-releasing hormone (TRH) tests and electroejaculated semen analyses. Thirty age-matched normal male volunteers served as controls. There were four subjects with low serum triiodothyronine (T3) levels, one with elevated serum follicle-stimulating hormone (FSH) level, eight with elevated serum testosterone levels, and 11 with elevated serum prolactin levels. There were significantly elevated luteinizing hormone (LH) responses to LHRH in SCI subjects when compared with normal controls. There were 16 (53.3%) SCI subjects who had exaggerated and/or prolonged LH responses. Among them, six subjects also had elevated FSH responses. There were eight and four subjects whose thyrotropin (TSH) and prolactin responses to TRH were exaggerated, respectively. Marked impaired motility was observed in 56 electroejaculated semen samples from 16 SCI subjects. There was a significant correlation between LH and total sperm count. Our data suggest that there is a reduced central dopaminergic tone in SCI subjects.

Increased risk of ischemic heart disease in young patients with newly diagnosed ankylosing spondylitis--a population-based longitudinal follow-up study.

Background Prospective data is sparse on the association between ischemic heart disease (IHD) and ankylosing spondylitis (AS) in the young. The purpose of this population-based, age- and sex- matched follow-up study was to investigate the risk of IHD in young patients with newly diagnosed AS. Methods A total of 4794 persons aged 18 to 45 years with at least two ambulatory visits in 2001 with the principal diagnosis of AS were enrolled in the AS group. The non-AS group consisted of 23970 age- and sex-matched, randomly sampled subjects without AS. The three-year IHD-free survival rate and cumulative incidence of IHD were calculated using the Kaplan-Meier method. The Cox proportional hazards regression model was used to estimate the hazard ratio of IHD after controlling for demographic and cardiovascular co-morbidities. Results During follow-up, 70 patients in the AS group and 253 subjects in the non-AS group developed IHD. The cumulative incidence rate of IHD over time was higher in the AS group than the non-AS group. The crude hazard ratio of IHD for the AS group was 1.47 (95% CI, 1.13 to 1.92; p = 0.0043) and the adjusted hazard ratio after controlling for demographic characteristics and comorbid medical disorders was 1.47 (95% CI, 1.13 to 1.92; p = 0.0045). Conclusions This study showed an increased risk of developing IHD in young patients with newly diagnosed AS.