Clinical experience with functional electrical stimulation-assisted gait with Parastep in spinal cord-injured patients

STUDY DESIGN: Clinical evaluation of the Parastep method, a six-channel transcutaneous functional electrical stimulation device, in spinal cord-injured patients. OBJECTIVES: To investigate the motor performances of this new technique regarding energy expenditure and to evaluate its advantages and limitations, especially in social activities involving ambulation. METHODS: This study was conducted in 15 thoracic spine-injured patients. The lesion was complete except in two patients. The gait ability and the functional use were judged clinically. Energy cost was evaluated from heart rate, peak oxygen uptake, and lactatemia. RESULTS: Thirteen patients completed the training (mean: 20 sessions) and achieved independent ambulation with a walker. The mean walking distance, without rest, was 52.8 +/- 69 m, and the mean speed was 0.15 +/- 0.14 m/sec. One patient with incomplete lesion, who had been nonambulatory for 8 months after the injury, became able to walk without functional electrical stimulation after five sessions. The follow-up was 40 +/- 11 months. Five patients pursued using functional electrical stimulation-assisted gait as a means of physical exercise but not for ambulation in social activities. The patients experienced marked psychological benefits, with positive changes in their way of life. In three subjects, a comparison of physiologic responses to exercise between a progressive arm ergometer test and a walking test with the Parastep (Sigmedics, Inc., Northfield, IL) at a speed of 0.1 m/sec was performed, showing that the heart rate, the peak oxygen uptake, and lactatemia during gait were close to those obtained at the end of the maximal test on the ergometer. CONCLUSIONS: In spite of its ease of operation and good cosmetic acceptance, the Parastep approach has very limited applications for mobility in daily life, because of its modest performance associated with high metabolic cost and cardiovascular strain. However, it can be proposed as a resource to keep physical and psychological fitness in patients with spinal cord injury.     

Attenuation of natural killer cell activity during 2-h exercise in individuals with spinal cord injuries

DESIGN: Non-randomized study. OBJECTIVE: To determine natural killer cell cytotoxic activity (NKCA) to 2-h arm ergometer exercise in persons with spinal cord injuries (SCI) and the underlying mechanism of such response. SETTING: University of Occupational and Environmental Health, Japan. METHODS: We examined NKCA response to 2-h arm crank ergometer exercise at 60% of maximum oxygen consumption (VO(2max)) in SCI and able-bodied persons. NKCA and plasma concentrations of prostaglandin E(2) (PGE(2)), adrenaline and cortisol were measured before, during and immediately after the exercise. The study included seven subjects with SCI between Th11 and L4 and six able-bodied persons. RESULTS: NKCA in able-bodied subjects increased (P<0.05) at 60 min of exercise and immediately after the exercise, and remained elevated up to 2 h after exercise. However, NKCA in SCI decreased (P<0.05) immediately after exercise but recovered at 2 h after exercise. Plasma adrenaline in both groups increased significantly (P<0.05) immediately after exercise and returned to baseline level 2 h after the exercise. Plasma cortisol in both groups remained constant throughout the study. In SCI, PGE(2) significantly increased immediately after 2 h exercise and returned to the baseline level 2 h after exercise; however, it remained unchanged during the test in able-bodied subjects. CONCLUSION: Our results suggested that increase of PGE(2) in SCI partially contributes to NKCA.     

Bacteriological investigation of infected pressure ulcers in spinal cord-injured patients and impact on antibiotic therapy

STUDY DESIGN: Retrospective. OBJECTIVES: To improve the use of bacteriological results for treating spinal cord-injured patients with infected pressure ulcers. SETTING: Microbiology and Orthopaedics Department, Ambroise Paré University Hospital, Boulogne-Billancourt, France. METHODS: Tissue specimens, sampled at the end of the surgical intervention from unbridled and cleaned ulcers were analysed. Drainage liquids were cultured at day 1 (D1) and day 5 (D5) postsurgery. For part of the patients, a presurgery superficial sample was analysed and compared with the surgical and postsurgical samples. RESULTS: In all, 168 surgical samples from 101 patients, 183 D1 and 104 D5 wound drainage liquids were included in this study. Out of the 168 surgical samples 17 (10%) had a negative culture, whereas 151 (90%) had a positive culture. For drainage liquids, the culture was negative in 48% and 56% of the samples at D1 and D5, respectively. The most frequently isolated species were enterobacteria, followed by staphylococci and streptococci. CONCLUSION: Culturing deep tissue specimens sampled from the surgically cleaned and unbridled ulcers allows for the isolation of the bacterial species that are really involved in the ulcer infection. As the identification of these bacteria and their antibiotic susceptibility are available, when the culture results of the D1 postsurgical drainage liquid is also available, it is easier to choose targeted antibiotic treatment.     

Effect of lesion level on the orthotic gait performance in individuals with complete paraplegia

STUDY DESIGN: Cross-sectional, experimental research. OBJECTIVES: To clarify the effect of lesion level on cardio-respiratory responses and biomechanical characteristics of walking with a reciprocating gait orthosis in complete paraplegia with spinal cord injury (SCI). SETTING: National Rehabilitation Center for Persons with Disabilities, Japan. METHODS: Ten SCI individuals (age: 20-34 years, injured level: Th5-12) who experienced orthotic gait training at least for 10 weeks participated in two experiments: (1) measurement of the cardiorespiratory responses during 20 min of orthotic gait exercise; and (2) three-dimensional motion analysis and ground reaction force measurement using the VICON system. We calculated the following parameters: pulmonary ventilation, oxygen consumption (VO(2)), heart rate (HR), gait speed, cadence, stride length, crutch force (CF), hip range of motion (ROM), and hip angular velocity (VEL). Further, energy consumption and energy cost were calculated using the steady-state value of VO(2) and gait speed. RESULTS: The steady-state value of the VO(2) (18.2 +/- 3.80 ml/kg) and HR (133.0 +/- 21.63 b/min) tended to be larger in higher thoracic SCI subjects. There were strong positive correlations between the lesion level and walking speed (r = 0.74), energy cost (r = 0.85), and hip ROM (r = 0.78). On the other hand, negative correlation between the lesion level and peak CF (r = -0.78) was clarified. CONCLUSIONS: The physiological intensity of the orthotic gait strongly depended on the level of lesion. It seems likely that a limited hip range of motion and excess upper limb load result in the low energy cost of orthotic gait for the higher thoracic level of paraplegic patients.     

The impact of donor natural killer cell alloreactivity on allogeneic hematopoietic transplantation

Although natural killer (NK) cells are triggered to kill by many activating receptors, lysis of autologous cells is blocked by inhibitory receptors (called Killer cell Ig-like receptors or KIRs) which recognize epitopes shared by certain major histocompatibility complex (MHC) class I allele groups (called KIR ligands). As these inhibitory receptors are clonally distributed, they constituted a repertoire containing different allospecificities. Thus, the NK cells in the repertoire are lytic against allogeneic targets that do not express their inhibitory KIR ligands. In hematopoietic human-leukocyte-antigen (HLA)-haplotype mismatched transplantation, donor-vs-recipient alloreactive NK cells improve engraftment, decrease the incidence of leukemia relapse and do not cause Graft-vs-Host disease (GvHD). Pre-transplant molecular high-resolution HLA of recipient and donor, KIR genotyping of the donor and direct assessment of the donor NK repertoire identify donors with the potential for donor-vs-recipient NK cell alloreactivity.     

Anesthetic requirements and stress hormone responses in spinal cord-injured patients undergoing surgery below the level of injury

Neuraxial anesthesia decreases the minimum alveolar concentration. We determined the effects of spinal cord injury (SCI) on sevoflurane requirements and stress hormone response. Twenty-two chronic SCI patients undergoing surgery below the level of the injury were enrolled in the study, and 15 patients without cord injury served as control patients. Bispectral index score was maintained at 40-50. Measurements included end-tidal sevoflurane concentrations, systolic arterial blood pressure, heart rate, and plasma catecholamine and cortisol concentrations. During surgery, systolic arterial blood pressure, heart rate, and Bispectral index were comparable between SCI and control groups. However, end-tidal sevoflurane concentration was significantly smaller in the SCI (0.81%-1.06%) versus control (1.28%-1.31%) patients. In the control group, plasma norepinephrine and cortisol concentrations were significantly increased during and 1 h after surgery compared with awake baseline values. In the SCI group, the sympathoadrenal and cortisol responses were virtually abolished. We conclude that SCI reduces the anesthetic requirement by 20%-39% during surgery below the level of injury, in association with blunted sympathoadrenal and cortisol responses.     

Sildenafil in the treatment of sexual dysfunction in spinal cord-injured male patients

OBJECTIVES: The aim of this study was to evaluate the efficacy and safety of sildenafil in the treatment of erectile dysfunction (ED) in spinal cord-injury (SCI) patients. Moreover, we looked for neurological conditions permitting therapeutic success and for the ideal dose needed to achieve sufficient erections. METHODS: 41 SCI patients were prospectively examined. Sexual dysfunction was assessed by means of anamnesis, the International Index of Erectile Function (IIEF) questionnaire, and neurological examination. Psychogenic erection capacity was tested by audiovisual stimulation and reflexive erection using a vibrator device. Neurophysiological recordings and cystomanometry were performed in parallel to clinical examinations. Neurophysiological recordings included sympathetic skin responses (SSR), pudendus somatosensory evoked potentials (pSSEP), and bulbocavernous reflex (BCR). Urodynamics aimed at classifying the neurogenic bladder dysfunction (upper motoneuron lesion versus lower motoneuron lesion). Intracavernous injection tests with PGE1 were performed in all patients to exclude major organic disease. 50 mg sildenafil was first given 3 times. Thereafter, the doses were adapted according to patients' reports. RESULTS: Clinically, 28 subjects preserved either reflexive erections (24) or psychogenic erections (4), 11 had both types and only 2 presented with a complete loss of erection. 38 patients (93%) had a positive response to sildenafil and reached a penile rigidity sufficient to permit sexual intercourse. 3 patients dropped out because of non-response despite having increased the dosis up to 100 mg. 22 patients (58%) showed functional erections 1 h after 50 mg sildenafil, whereas 14 (37%) required higher doses of 75-100 mg. By comparing the IIEF questionnaire scores before and after therapy, there was a significant improvement in erectile function and intercourse satisfaction from 9.2+/-4.4 SD) and 4.5 (+/-2.5 SD) to 25.5 (+/-4.2 SD) and 10.5 (+/-2.1 SD) points, respectively (p<0.05). Nearly 10% (4/41) suffered from side effects such as headache or dizziness. Two of them stopped therapy because of the side effects. At least 36 patients (88%) continue treatment with sildenafil. Absence of both psychogenic (nonsomesthetic supraspinally elicited) and reflexive (somesthetic spinally elicited) erections, confirmed by urodynamical and electrophysiological findings (SSR perineum, BCR and pSSEP), seems to exclude a successful treatment. In contrast, SCI male patients with preserved function of at least one component of the erection phenomenon (psychogenic/reflexive) responded well to sildenafil and the dose required to achieve erections sufficient for sexual intercourse did not differ between the two groups. CONCLUSIONS: Sildenafil proves to be a valuable and safe therapeutic management in ED of SCI patients. Therefore, patient acceptance and satisfaction are high. The most common dose required to achieve a satisfying erection is 50 mg. The efficacy of sildenafil depends on sparing of either sacral (S2-S4) or thoracolumbar (T10-L2) spinal segments which, in this study, have been shown to be of relevance in mediating psychogenic erections in male SCI patients. Complete disturbance of any neurogenic impulses excludes successful treatment.     

Prognostic impact of natural killer cell recovery on minimal residual disease after autologous stem cell transplantation in multiple myeloma

IntroductionNatural killer cells are a potent effector lymphocyte subset that can induce cytotoxicity without the need for antigen sensitization or presentation. NK cells are a tempting target –for immune therapy, monoclonal antibody, or genetic engineering-to enhance immune surveillance mechanisms against myeloma cells.Materials and methodsWe hypothesized an association between natural killer cell recovery after autologous stem cell transplantation (ASCT) and disease outcomes in multiple myeloma patients.We concluded a prospective study that started enrolling patients in January 2020 to identify the association between absolute NK cell count two to three after ASCT and disease outcomes after autologous stem cell transplantation in multiple myeloma using univariate and multivariate analysis.ResultsNatural killer cell recovery was evaluated during the third month after ASCT, day +60 to +90 post-ASCT. Our patients had a mean NK cell count of 90.53, ranging from 14 to 282 Cell/μL (Std Dev 84.64 Cell/μL). The odds of having a minimal residual disease (MRD-positivity) among patients with partial remission before transplantation is four times higher than patients with very good partial response or better (95% confidence interval 0.45–35.79). Our patients were classified into two groups based on MRD status after ASCT, an MRD-negative group of eight participants and an MRD-positive group of seven participants. The mean absolute NK cell count was significantly higher in the MRD-negative cohort, 131.38 Cell/μL, versus 43.86 Cell/μL in the MRD-positive group (p = 0.049).ConclusionWe conclude that for multiple myeloma patients treated with ASCT, high absolute NK cell counts two to three months after ASCT is an independent predictor for MRD negativity.     

Hyperhidrosis treatment with bornaprine in the acute phase of spinal cord-injured patients

STUDY DESIGN: Original article. OBJECTIVE: To test the use of bornaprine in the hyperhidrosis treatment in the acute phase of spinal cord-injured patients. SETTING: Patients with acute spinal cord lesions in the Spinal Unit of Pietra Ligure, Savona, Italy. METHOD: In 4 years, 12 patients have been treated, for a maximum period of 75 days, with dosages ranging from 2 to 4 mg day(-1). RESULTS: All of them reported long-lasting subjective benefits, without side effects, even after the interruption of the therapy. CONCLUSION: The bornaprine treatment, at 2 or 4 mg day(-1) dosage, has been effective and safe to contrast hyperhidrosis, in the acute phase of spinal cord-injured patients. This positive experience would require additional trials and a larger number of cases to gain a more solid support.     

Reassuring effect of pravastatin on natural killer cell activity in stable renal transplant patients

BACKGROUND: Administration of pravastatin soon after transplantation successfully lowers cholesterol levels, whereas a reduced number of acute rejection episodes is accompanied by a decrease in natural killer (NK) cell activity. As a consistent low NK cell activity caused by pravastatin might impair tumor surveillance leading to cancer, we studied the effect of pravastatin on NK cell activity in stable renal transplant patients. METHODS: From 14 cyclosporine (CsA)-treated and 11 azathioprine (AZA)-treated patients with hypercholesterolemia, more than 1 year after kidney transplantation, we determined NK cell number and cytotoxic activity before, and at 6 and 12 weeks after, initiating pravastatin treatment. Additionally, cholesterol levels and liver and kidney function parameters were assessed. RESULTS: During pravastatin treatment, total cholesterol and low-density lipoprotein-cholesterol levels decreased significantly in both patient groups. In the CsA group, the number and cytotoxic activity of the NK cells at 12 weeks after institution of pravastatin was in the same range as before pravastatin. Additionally, in the AZA group, pravastatin did not influence the number of NK cells. However, in the AZA group, both the number of NK cells and their cytotoxic activity were significantly (<0.002) lower compared to the values in the CsA group. CONCLUSIONS: In contrast to previous reports on decreased NK cell cytotoxicity caused by pravastatin treatment early after transplantation, we cannot confirm these results in stable kidney recipients. In our hands, NK cell cytotoxicity during pravastatin treatment was within the same range as in the absence of pravastatin. Thus, in view of the potential role of NK cells in tumor surveillance, these data are reassuring.     

The impact of stressful life events on natural killer cells

A study was carried out among members of a kibbutz to determine to what extent their capacity to cope with stressors affected natural killer (NK) cells and how this capacity was regulated by personal, family and social resources. The NK activity and NK cell markers were analysed among 92 kibbutz residents. A number of psychosocial parameters (including family function, social support, and demoralization) were assessed in parallel. A significant correlation was found between the capacity of individuals to cope with daily life stress and their cytotoxic NK activity. Individuals who were diagnosed as having anxiety neurosis had a significantly weaker NK activity and their population of Leu-11 positive cells was significantly lower than among those without such symptoms. No significant association could be determined between either NK cell activity or proportion of Leu-11 positive lymphocytes and any of the psychosocial parameters tested. Thus, while coping with stress has a significant effect on the NK system, further studies are required to elucidate the psychosocial mechanisms involved.     

Increased natural killer cell activity in patients with an abdominal aortic aneurysm

BACKGROUND: Natural killer (NK) cells have an emerging role in the development of chronic disease and in the direction and maintenance of inflammatory responses. Abdominal aortic aneurysms (AAA) is a chronic inflammatory disorder of unknown aetiology. The aim was to investigate whether NK cells showed altered function in patients with an AAA. METHODS: The presence, phenotype and function of peripheral blood and tissue NK cells from patients with an AAA, peripheral vascular disease (PVD) and healthy age-sex-matched controls were assessed before and after surgery. RESULTS: Patients with an AAA had significantly higher (P < 0.010) percentages of peripheral blood NK cells (mean (95 per cent c.i.) 23.8 (2.6) per cent) than patients with PVD (17.4 (2.9) per cent) and control subjects (16.2 (2.8) per cent). The NK cells from patients with an AAA had increased cytotoxicity on a per cell basis towards both an NK-sensitive target cell line and human aortic smooth muscle cells. Increased NK cell proportions (22.7 (3.5) per cent) and cytotoxic activity, together with higher C-reactive protein values, persisted after successful AAA repair. CONCLUSION: These data support the hypothesis that increased NK cytotoxicity could be a contributing factor in the generation or potentiation of inflammation in patients with an AAA.     

Serum interferon levels and natural killer cell activity in patients with asbestosis

Natural killer cell activity and serum interferon levels were measured in 30 patients with asbestosis. The chest radiographs showed type 1 changes (ILO pneumoconiosis classification) in nine, type 2 changes in 19, and type 3 changes in two. Thirty control subjects matched for age, sex, and smoking habit were also studied. Patients with asbestosis had significantly higher serum interferon levels than the controls. There was no significant difference in natural killer cell activity between patients with asbestosis and normal controls.     

Effect of long-term orthotic treatment on gait biomechanics in adolescent idiopathic scoliosis

Background contextA previous study showed subtle biomechanical changes in the gait of unbraced adolescent idiopathic scoliosis (AIS) patients such as a reduction of pelvic, hip, knee, and ankle displacements. However, lumbopelvic muscles' timing activity was bilaterally increased during gait and correlated to excessive oxygen consumption as compared with healthy subjects. Usually, a brace, when indicated, is worn strictly for 22 hours every day in skeletally immature idiopathic scoliotic girls. To our knowledge, no study has assessed the long-term brace effect (6 months) on functional activities such as level walking.PurposeTo assess the stiffening effects of 6 months' brace wearing on instrumented gait analysis in girls with thoracolumbar/lumbar adolescent idiopathic scoliosis.Study design/settingClinical prospective study.Patient sampleThirteen girls diagnosed as progressive adolescent idiopathic scoliosis with left thoracolumbar/lumbar curves (curves ranging 25°–40°).Outcome measuresAll patients underwent a radiographic and instrumented gait analysis, including assessment of kinematics, mechanics, electromyography (EMG), and energetics of walking.MethodsThe scoliotic girls were prospectively studied at S1 (before bracing) and 6 months later at S2 (out-brace: treatment effect). The gait parameters were compared with those of 13 matched healthy girls. A t paired test was conducted to evaluate the effect of the 6-month orthotic treatment in AIS girls. Student t test was performed to compare the scoliotic group at S2 and the healthy subjects to identify if the observed changes in gait parameters meant improvement or worsening of gait.ResultsAfter 6 months of orthotic treatment in AIS, thoracolumbar/lumbar curves and apical rotation remained reduced by 25% and 61%, respectively. During gait, frontal pelvis and hip motions were significantly increased. Muscular mechanical work increased becoming closer but still different as compared with healthy subjects. Bilateral lumbopelvic muscles were almost 40% more active in AIS at S1 compared with healthy subjects and did not change at S2 except for the erector spinae muscles EMG activity, which decreased significantly. Energy cost exceeded by 30% in AIS at S1 compared with healthy subjects and did not change at 6 months' follow-up.ConclusionsAfter 6 months of orthotic treatment, in an out-brace situation, the main structural thoracolumbar/lumbar curve remained partly corrected. Frontal pelvis and hip motion increased, contributing to an improvement of muscular mechanical work during walking. EMG activity duration of lumbopelvic muscles did not change except for the erector spinae muscles, which was decreased but without any beneficial change in the energy cost of walking. In summary, brace treatment, after 6 months, did not significantly influence the gait variables in AIS girls deleteriously, but did not reduce the excessive energy cost, which was 30% above the values of normal adolescents.     

自然杀伤细胞在感染中的研究进展

自然杀伤细胞（NK细胞）是人体内一类天然免疫细胞,无需提前刺激即可杀伤靶细胞和肿瘤细胞,在抗感染及抗肿瘤过程中发挥重要作用。NK细胞的发育、分化及功能等均不同于T细胞和B细胞。感染过程中NK细胞主要通过活化信号和抑制信号的共同调节来发挥杀伤作用,而在病原体感染早期发挥免疫杀伤功能。此外,NK细胞还可释放细胞因子进行免疫调节,并作为连接天然免疫和适应性免疫的桥梁。NK细胞还具有记忆性,也可特异性对抗病毒感染。总之,NK细胞在感染过程中发挥不可替代的作用。本综述对于NK细胞亚群分类、受体及其在抗感染过程中的研究进展作详细介绍。     

Influence of extirpative surgery on the natural killer cell activity in peripheral blood in cancer patients

In this study, Natural Killer Cell Activity (NKCA) in the peripheral blood was tested by 125I-udR release assay in 34 cancer patients before and one, two, and four weeks after radical surgery. Results were compared with that obtained from normal blood donors. It was found that NKCA was significantly decreased in cancer patients especially in those with lymphatic node and remote metastasis. It was also found that NKCA underwent a transient, statistically significant depression immediatly after the surgery which may have some implication in cancer metastasis sometimes seen during this critical period. The authors believe that better understanding of the kinetics of perioperative NKCA could provide information necessary on how to protect NKCA and prevent cancer dissemination.