Electrical stimulation for voiding dysfunction after spinal cord injury.

Incontinence and frequency of voiding were present after spinal cord injuries in 18 patients. A hyperreflexic bladder and/or pelvic floor weakness was found in these patients. Functional electrical stimulation resulted in relief or improvement of symptoms in 9 of the 11 patients in whom this procedure was used. An increase in anal sphincter pressure with functional electrical stimulation was a more reliable criterion than an increase in maximum urethral pressure in the selection of patients for the procedure.     

Different lymphocyte compartments respond differently to mitogenic stimulation after thermal injury.

Because of the association between the development of an immunocompromised state and an increased risk of infection, increasing attention has been focused on describing and characterizing the immune consequences of thermal injury. Results of human studies are largely based on the in vitro responsiveness of peripheral blood leukocytes, while splenocytes are generally used in the animal studies. Because the response of lymphocytes from different lymphocyte compartments may vary, we compared the responses of murine peripheral blood, splenic, Peyer's patch, and mesenteric lymph node lymphocytes to a battery of mitogens after thermal injury. Burn-induced immunosuppression was maximal in the splenic lymphocyte compartment, where the responses to all three test mitogens were depressed throughout the 28-day postburn study period. Although the PHA-induced mitogen response of lymphocytes from the other three lymphoid compartments remained suppressed throughout the study period, the response to the mitogens Con-A and PWM generally returned to normal or supranormal levels by the seventh postburn day, Therefore it appears that the effect of a thermal injury on lymphocyte function varies according to the lymphocyte compartment examined and the mitogen tested. These results raise the question of whether animal studies using splenic lymphocytes can be correlated with human studies performed on circulating blood lymphocytes.     

The role of differential class II antigen expression in stimulation of allogeneic mixed lymphocyte reactions by human monocyte hybridomas.

The recognition of foreign class II antigens on accessory cells is the crux of an alloreactive immune response. This phenomenon is clearly demonstrated in the primary mixed lymphocyte reaction, which correlates with the type and density of expressed gene products of the HLA-D region. We have generated a series of human monocyte hybridomas by fusing monocytes with the hypoxanthine guanine phosphoribosyl transferase (HGPRT)-deficient, HLA-D antigen-negative U937 histiocytic cell line. Clones bearing combination of HLA-DQ, -DP with or without HLA-DR have been isolated, allowing for the functional assessment of these molecules. In contrast to the U937 cells, the HLA-DR+DQ+DP+ clone 16.1 was capable of stimulating a primary allogeneic MLR. Interestingly, the DR- but DP+DQ+ clones 13 and 15 were also capable of stimulating alloreactive T cells, and the addition of anti-DQ or -DP but not -DR was associated with significant inhibition of the MLR response. Furthermore, gamma-IFN was found to have diverse effects on class II antigen expression in the U937 cells and the hybrids. gamma-IFN down-regulated the expression of HLA-DQ, -DP without altering -DR on clone 16.1, and this was associated with a significant reduction in its MLR stimulatory capacity. The MLR generated by this gamma-IFN-stimulated hybridoma (HLA-DR+DQ-DP-) was now unaffected by the addition of anti-DQ or -DP mAbs. In contrast, up-regulation of DQ and DP antigens on the U937 cells by gamma-IFN now rendered these cells stimulatory in MLR. These data are consistent with the concept that DQ and DP are both important allostimulatory determinants. Our results stress the potential importance of all D-region molecules in acute allograft rejection or successful engraftment.     

Electrical stimulation for the treatment of lower urinary tract dysfunction after spinal cord injury

Electrical stimulation for bladder control is an alternative to traditional methods of treating neurogenic lower urinary tract dysfunction (NLUTD) resulting from spinal cord injury (SCI). In this review, we systematically discuss the neurophysiology of bladder dysfunction following SCI and the applications of electrical stimulation for bladder control following SCI, spanning from historic clinical approaches to recent pre-clinical studies that offer promising new strategies that may improve the feasibility and success of electrical stimulation therapy in patients with SCI. Electrical stimulation provides a unique opportunity to control bladder function by exploiting neural control mechanisms. Our understanding of the applications and limitations of electrical stimulation for bladder control has improved due to many pre-clinical studies performed in animals and translational clinical studies. Techniques that have emerged as possible opportunities to control bladder function include pudendal nerve stimulation and novel methods of stimulation, such as high frequency nerve block. Further development of novel applications of electrical stimulation will drive progress towards effective therapy for SCI. The optimal solution for restoration of bladder control may encompass a combination of efficient, targeted electrical stimulation, possibly at multiple locations, and pharmacological treatment to enhance symptom control.     

Influence of S3 electrical stimulation on gastrointestinal dysfunction after spinal cord injury in rabbits

Objective：To investigate the effect of electrical stimulation to sacral spinal nerve 3 （S3 stimulation） on gastrointestinal dysfunction after spinal cord injury （SCI）.Methods：Six rabbits were taken as normal controls to record their gastrointestinal multipoint biological discharge,colon pressure and rectoanal inhibitory reflex.Electrodes were implanted into S3 in another 18 rabbits.Then the model of SCI was conducted following Fehling＇s method：the rabbit S3 was clamped to induce transverse injury,which was claimed by both somatosensory evoked potential and motion evoked potential.Two hours after SCI,S3 stimulation was conducted.The 18 rabbits were subdivided into 3 groups to respectively record their gastrointestinal electric activities （n=6）,colon pressure （n=6）,and rectum pressure （n=6）.Firstly the wave frequency was fixed at 15 Hz and pulse width at 400 μs and three stimulus intensities （6 V,8 V,10 V） were tested.Then the voltage was fixed at 6 V and the pulse width changed from 200 μs,400 μs to 600 μs.The response was recorded and analyzed.The condition of defecation was also investigated.Results：After SCI,the mainly demonstrated change was dyskinesia of the single haustrum and distal colon.The rectoanal inhibitory reflex almost disappeared.S3 stimulation partly recovered the intestinal movement after denervation,promoting defecation.The proper stimulus parameters were 15 Hz,400 μs,6 V,10 s with 20 s intervals and 10 min with 10 min intervals,total 2 h.Conclusion：S3 stimulation is able to restore the intestinal movement after denervation （especially single haustrum and distal colon）,which promotes defecation.     

Temporal analysis of murine lymphocyte subpopulations by monoclonal antibodies and dual-color flow cytometry after burn and nonburn injury

The immune suppression that frequently accompanies severe injury undoubtedly contributes to subsequent infectious complications. Various lymphocyte subpopulations may be identified by surface antigen expression, and alterations in antigen expression by lymphocytes may reflect host immune competence. Using monoclonal antibodies (Moabs) and dual-color flow cytometry, we studied lymphocyte phenotypic expression in mice after either controlled burn injury or hind-limb amputation, with use of peripheral blood, lymph node, and spleen for cell preparation. Moabs were utilized specific for T cells (Lyt-1), helper/inducer cells (L3T4), suppressor/cytotoxic cells (Lyt-2), B cells (IgG), and activated T cells (Ia or IL-2 receptor). The assay techniques called for small amounts of tissue and avoided gradient procedures that might result in selective loss of some lymphocyte populations. The most consistent changes observed were depressions in percentages of L3T4+ and Lyt-2+ cells in spleens of burned mice, accompanied by depression in Ia+ (possibly activated or proliferating) subsets of L3T4+ and Lyt-2+ cells, and the appearance of increased percentages of non-B, non-T lymphocytes. Changes in lymph node cells were minimal. The major alteration seen in peripheral blood was substantial depression of Ia+ subsets, although burned mice had increased circulating Lyt-2+ cells on several late postburn days. Burned mice, unlike limb-trauma mice, had marked splenic hypertrophy with more than a 300% increase in spleen weight after the 30-day postburn period. Eschar excision/implantation experiments indicated that splenic hypertrophy and splenocyte phenotypic changes are related to the presence of burned tissue, which suggests that burned tissue may partially mediate immune changes that accompany severe burn injury.     

Surface electrical stimulation of skeletal muscle after spinal cord injury.

STUDY DESIGN: Survey. OBJECTIVE: Examine muscle contractile activity during electrical stimulation (ES) after spinal cord injury (SCI). SETTING: General community of Athens, Georgia, USA. METHODS: Eight clinically complete SCI adults (C6 to T12) 4+/-1 (mean+/-SE) years post injury and eight able-bodied adults were studied. Surface ES was applied to the left m. quadriceps femoris for three sets of 10, 1 s isometric actions (50 Hz trains, 400 micros biphasic pulses, 50 micros phase delay, 1 s: 1 s duty cycle) with 90 s of rest between sets. Current was set to evoke isometric torque that was (1) sufficient to elicit knee extension with 2.3 kg attached to the ankle (low level ES), and (2) intended to equal 30% (mid level ES) or 60% of maximal voluntary torque of able-bodied adults (high level ES, able-bodied only). The absolute and relative cross-sectional area (CSA) of m. quadriceps femoris that was stimulated as reflected by contrast shift in magnetic resonance images and torque were measured. RESULTS: Six+/-2, 20+/-2 and 38+/-4% of the average CSA of m. quadriceps was stimulated during low, mid and high level ES, respectively, for able-bodied. Corresponding values for SCI for low and mid level ES were greater (61+/-12 and 92+/-7%, P = 0.0002). Torque was related to the CSA (cm2) of stimulated muscle (Nm = 3.53 x stimulated CSA+13, r2 = 0.68, P = 0.0010), thus ES of a greater per cent of m. quadriceps femoris in SCI was attributed to their smaller muscle (24+/-3 vs 73+/-5 cm2, P = 0.0001). The decline in torque ranged from 9+/-l to 15+/-4% within and over sets for low, mid or high level ES in able-bodied. SCI showed greater (P = 0.0001) fatigue (19+/-3 to 47+/-6%). CONCLUSION: The territory of muscle activation by surface electrical stimulation varies among SCI patients. Given sufficient current, a large portion of the muscle of interest can be stimulated. The resulting torque is modest, however, compared to that attainable in able-bodied individuals due to the small size and limited fatigue resistance of skeletal muscle years after spinal cord injury.     

Effect of N-acetylcysteine treatment on the expression of leukocyte surface markers after burn injury

Oxidative stress and inflammatory processes generate edema in burns. Treatment of consequent hypovolemia is a challenge.The aim of study was to assess if glutathione pro-drug N-acetylcysteine (NAC) can influence inflammation and fluid requirement. We also aimed to compare organ functions scores and vasoactive drug requirement. This prospective randomised study involved 28 patients with burn injury affecting more than 20% of body surface area. Fourteen patients were on standard therapy, whereas for other 14 patients NAC was supplemented. Blood samples were taken on admission and on the next five consecutive mornings. Leukocyte surface marker expressions were determined, multiple organ function scores, use of vasopressor agents and fluid requirements were recorded daily.Expression of CD11a (p < 0.05), CD18 (p < 0.05) and CD97 (p < 0.01) on the granulocytes were significantly lower in the NAC treated group, similarly to lymphocyte CD 49d (p < 0.05) and monocyte CD 49d (p < 0.01) and CD 97 (p < 0.05) expression. No significant difference was found in the fluid requirement between groups but patients the NAC group required less vasopressor and inotropic drugs from day 4.NAC treatment is associated with a less pronounced inflammation reflected in lower CD marker expression and vasopressor requirement.     

Eye motility dysfunction after soft-tissue injury of the cervical spine: A controlled, prospective study of 38 patients

We investigated eye motility prospectively in 40 patients with a soft-tissue injury of the cervical spine. The initial oculomotor test, performed within 3 months, was pathologic in 8 patients. The follow-up test in 38 patients, on average 15 months after the accident, remained pathologic in the 8 patients and 5 additional patients had changed from normal to pathologic test results.

At follow-up, all the 13 patients with oculomotor dysfunction had persisting symptoms, while 5 of the 25 cases with normal test results still were symptomatic.     

Sex differences in cytokine production and surface antigen expression of peripheral blood mononuclear cells after surgery

BACKGROUND: Several clinical and epidemiological studies have observed a better outcome after sepsis in women than in men. The purpose of this study was to determine if these sex differences are observed in cytokine responses and the surface antigen expression of monocytes. In addition, the clinical courses of male and female patients after gastrointestinal surgery were compared. METHODS: A total of 25 patients with gastric carcinoma who underwent gastrectomy were enrolled in this study. Tumor necrosis factor-alpha (TNF-alpha), interleukin-10, and interferon-gamma (IFN-gamma) production by lipopolysaccharide-stimulated peripheral blood mononuclear cells (PBMCs) as well as the expression of Toll-like receptor-4 (TLR-4), TLR-2, human leukocyte antigen-D related (HLA-DR), and CD16 on monocytes in 16 men and 9 women on the day before surgery were compared with measurements on postoperative day (POD) 1. Furthermore, postoperative infectious complications, the development of systemic inflammatory response syndrome, and serum C-reactive protein levels on POD3 were compared. RESULTS: TNF-alpha production of PBMCs and TLR-2 and CD16 expression on monocytes were significantly higher in women than in men before surgery. IFN-gamma production of PBMCs and HLA-DR expression on monocytes were significantly lower in men than in women on POD1. Furthermore, TNF-alpha production of PBMCs on POD1 was significantly increased, and both IFN-gamma production and HLA-DR expression were significantly decreased compared with that observed before surgery in men, but no corresponding significant changes were observed in women. In addition, C-reactive protein levels on POD3 were significantly higher in men than in women. CONCLUSIONS: Both TNF-alpha and interleukin-10 production of PBMCs and both TLR-2 and CD16 expression on monocytes were significantly higher in women than in men on the day before surgery. Excessive TNF-alpha and suppressive IFN-gamma production of PBMCs, as well as a decrease in HLA-DR expression on monocytes, occurred more often in men than in women after surgery, suggesting that these factors all contribute to an increased susceptibility of men to develop systemic inflammatory response syndrome or postoperative infectious complications.     

Elevated expression of cyclooxygenase-2 contributes to immune dysfunction in a murine model of trauma.

BACKGROUND: Cyclooxygenase-2 (Cox-2), the inducible form of Cox, is a rate-limiting enzyme in the synthesis of prostaglandins (PGs). Prostaglandin E2 (PGE2) and other eicosanoids possess immunosuppressive properties. Previously, traumatic injury was found to stimulate the synthesis of PGs and cause immune dysfunction. In this study a murine model was used to determine the effect of trauma on the expression of Cox-2 in macrophages and to elucidate the role of Cox-2 in trauma-induced immune dysfunction. METHODS: Mice were randomized to control or trauma (femur fracture plus 40% blood volume hemorrhage) groups. One, 4, and 7 days after injury, splenic macrophages were isolated and assayed for expression of Cox-2 and production of PGE2. In addition, the effect of pharmacologically inhibiting Cox-2 or knocking out the Cox-2 gene on trauma-induced suppression of splenocyte mitogenesis was determined. RESULTS: Trauma led to increased expression of Cox-2, enhanced synthesis of PGE2, and suppressed splenocyte mitogenesis. Both pharmacologic inhibition and genetic deletion of Cox-2 abrogated trauma-mediated suppression of splenocyte mitogenesis. CONCLUSIONS: These experiments link trauma-induced increases in Cox-2 expression and PGE2 production to reduced immune function. Cox-2 represents a potential pharmacologic target to prevent or reverse trauma-induced immunosuppression.     

脾切除对乙型肝炎肝硬化患者外周血T细胞及其活化抗原HLA-DR的影响

目的：检测乙型肝炎肝硬化脾切除患者外周血T细胞活化抗原HLA-DR的表达水平,探讨其临床意义。方法：以28例乙型肝炎肝硬化脾切除患者为实验组（肝硬化脾切除组）,同时以38例乙型肝炎肝硬化非脾切除患者和22例健康人为对照组（肝硬化非脾切除组、健康组）。采用流式细胞技术检测外周血T淋巴细胞亚群及HLA-DR抗原的表达。结果：肝硬化脾切除组患者外周血CD3＋、CD4＋和CD8＋百分含量分别为（41.59±6.79）%,（22.64±6.87）%和（19.16±7.28）%,显著低于健康组和肝硬化非脾切除组。肝硬化脾切除组患者CD4＋/CD8＋的比值显著高于健康组;HLA-DR在CD3＋、CD4＋和CD8＋上的表达水平分别为（25.42±5.51）%,（22.36±4.90）%和（28.53±8.35）%,与健康组相比差异无统计学意义,但在CD3＋和CD8＋上的表达水平显著低于肝硬化非脾切除组。结论：肝硬化脾切除患者存在细胞免疫功能缺陷,表现为T细胞数量的减少和活化功能的下降。     

Agonist of peroxisome proliferator-activated receptor-gamma, rosiglitazone, reduces renal injury and dysfunction in a murine sepsis model.

BACKGROUND: Agonists of the peroxisome proliferator-activated receptor-gamma may help to regulate inflammation by modulating the production of inflammatory mediators and adhesion molecules. The purpose of this study was to determine the protective effects of rosiglitazone on renal injury in a sepsis model and to explore the mechanism. METHODS: In lipopolysaccharide (LPS)-induced mouse sepsis, we examined the effect of rosiglitazone on LPS-induced overproduction of inflammatory mediators, on the expression of adhesion molecules in renal tubular epithelial cells and on renal function. The mechanism of the protective effect was investigated in vitro using human renal tubular epithelial cells. RESULTS: Rosiglitazone significantly decreased serum tumour necrosis factor (TNF)-alpha and interleukin (IL)-1beta levels during sepsis. The levels of blood urea nitrogen and creatinine were significantly lower in mice pre-treated with rosiglitazone than that in LPS-treated mice. Rosiglitazone reduced the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in tubular epithelial cells and interstitium of LPS-treated mice. Pre-treatment with rosiglitazone reduced the infiltration of macrophages/monocytes in renal tissue. In cultured tubular epithelial cells, rosiglitazone significantly decreased the expression of ICAM-1 and VCAM-1 induced by TNF-alpha or IL-1beta, inhibited the degradation of inhibitor kappaBalpha (IkappaBalpha) and blocked the activation of the p65 subunit of nuclear factor (NF)-kappaB. CONCLUSIONS: These results indicate that pre-treatment with rosiglitazone attenuated the production of TNF-alpha and IL-1beta and reduced adhesion molecule expression in renal tubular epithelial cells of LPS-treated mice. Rosiglitazone has an anti-inflammatory effect in renal tubular epithelial cells through the inhibition of NF-kappaB activation.     

Expression of HLA antigens on renal tubular cells in culture. II. Effect of increased HLA antigen expression on tubular cell stimulation of lymphocyte activation and on their vulnerability to cell-mediated lysis

Episodes of renal allograft rejection are characterized by an infiltrate of mononuclear leukocytes into the graft and increased HLA antigen expression by graft tubular cells. As HLA antigens are important immune-recognition molecules, we examined whether their increased expression during rejection might contribute to the rejection process. Interferon gamma (IFN-gamma)-treatment of cultured human kidney (HK) cells induced them to increase HLA antigen expression and caused a slight, but nonsignificant increase in their capacity to stimulate proliferation of allogeneic lymphocytes in primary mixed lymphocyte kidney culture (MLKC) (maximum of 8110 +/- 5015 vs. 3966 +/- 4050 counts/min on day 8), which was further increased by addition of IL-1. This proliferation never approached that induced by peripheral blood mononuclear stimulator cells (maximum of 40,325 +/- 10,694 counts/min on day 5), and addition of HK cells to mixed lymphocyte culture inhibited proliferation. There was no difference in lysis of IFN-gamma-treated or untreated HK-cell targets by "specific" cytotoxic effector cells produced in mixed lymphocyte culture using stimulator lymphocytes from the kidney cell donor (49.4 +/- 20% vs. 50.4 +/- 26% specific release in CML). Lysis by 3rd-party cytotoxic effectors produced in MLC using stimulator lymphocytes unrelated to the kidney-cell donor was greater for untreated HK cells (27.4 +/- 20%) than for IFN-gamma-treated HK targets (7.6 +/- 6%, P less than 0.001). IFN-gamma-activated naive mononuclear leukocytes lysed untreated HK targets but not IFN-gamma-pretreated targets, and this nonspecific cytotoxicity was mediated by lymphocyte- but not monocyte-enriched cell populations. HK cells are therefore poor stimulators of alloproliferation even when they express increased HLA antigen. They are lysed by both specific and nonspecific effector cells, and exposure to IFN-gamma makes them less vulnerable to nonspecific cytotoxicity and by inference, more vulnerable to specific cytotoxicity.     

Reversal of neuromotor and cognitive dysfunction in an enriched environment combined with multimodal early onset stimulation after traumatic brain injury in rats

This study was designed to investigate the additional benefits of a multimodal early onset stimulation (MEOS) paradigm when combined with enriched environment (EE) versus EE only and standard housing (SH) on the recovery after experimental traumatic brain injury (TBI). Male Sprague- Dawley rats were subjected to moderate lateral fluid percussion (LFP) brain injury (n = 40) or sham operation (n = 6). Thereafter, the injured and sham/EE + MEOS and EE only groups were placed into a complex EE consisting of tunnel-connected wide-bodied cages with various beddings, inclining platforms, and toys. Along with group living and environmental complexity, injured and sham/EE + MEOS animals were additionally exposed to a standardized paradigm of multimodal stimulation including auditory, visual, olfactory, and motor stimuli. In contrast, injured and sham/SH groups were housed individually without stimulation. A standardized composite neuroscore (NS) test was used to assess acute post-traumatic neuromotor deficits (24 h after injury) and recovery on days 7 and 15; recovery of cognitive function was assessed on days 11-15 using the Barnes maze. Neuromotor impairment was comparable in all injured animals at 24 h post-injury, but braininjured EE + MEOS rats performed significantly better than both brain-injured SH and EE groups when tested on post-injury days 7 and 15 (p = 0.004). Similarly, latencies to locate the hidden box under the Barnes maze platform were significantly shortened in EE + MEOS animals at day 15 (p = 0.003). These results indicate that the reversal of neuromotor and cognitive dysfunction after TBI can be substantially enhanced when MEOS is added to EE.     

An electromyographic study of detrusor sphincter dyssynergia in neurogenic vesical dysfunction. Part 2. Changes after radical transurethral resection of prostate and response to alpha-adrenergic stimulation

The relevance of the type of detrusor sphincter dyssynergia (DSD) and motor unit analysis as examined by simultaneous recordings of electromyography (EMG) of the external urethral sphincter (EUS) and bladder pressure was discussed in the first report. In this report, they were analysed similarly before and after radical transurethral resection of the prostate (TUR-P) to see how it was effective in relieving DSD. Furthermore, the response of the EUS to alpha-adrenergic stimulation was examined by analyzing its motor unit activity. Radical TUR-P was performed in 18 cases. After radical TUR-P, there was an improvement in the type of DSD (3 cases) or in its sub-types (8 cases), associated with decrease in residual urine rate in 16 cases. EUS responded to alpha-adrenergic stimulation with an increase in the frequency of pre-existing motor units and recruitment of new motor units. After radical TUR-P,EUS was similarly activated when stimulated with alpha-adrenergics. These data indicated that radical TUR-P was effective in relieving DSD by suppressing or abolishing abnormal continence reflex. Moreover, alpha-adrenergic activation of EUS also seemed to suggest a possible sympathetic role in the genesis of DSD, although exact mode of its involvement in the somatomotor innervation of the EUS remains to be settled.     

Hydroureteronephrosis after spinal cord injury. Effects of lower urinary tract dysfunction on upper tract anatomy

The hypothesis that upper tract changes in the absence of vesicoureteral reflux are a function of chronically elevated intravesical pressure has had increasing impact on the management of the lower urinary tract in patients with lower tract dysfunction secondary to neurogenic bladder disease. The application of our growing ability to measure bladder and bladder outlet function objectively and in a more physiologic manner through expanding urodynamic techniques will continue to provide information that can be applied to the diagnosis and treatment of lower urinary tract dysfunction and hydroureteronephrosis after spinal cord injury. Current methods of classifying lower urinary tract behavior have not provided the ability to identify accurately those patients at greatest risk for upper tract deterioration. The application of new techniques and the use of new measures may increase our ability to identify these patients.