The systemic inflammatory response after spinal cord injury in the rat is decreased by α4β1 integrin blockade

Abstract The systemic inflammatory response syndrome (SIRS) follows spinal cord injury (SCI) and causes damage to the lungs, kidney, and liver due to an influx of inflammatory cells from the circulation. After SCI in rats, the SIRS develops within 12?h and is sustained for at least 3 days. We have previously shown that blockade of CD11d/CD18 integrin reduces inflammation-driven secondary damage to the spinal cord. This treatment reduces the SIRS after SCI. In another study we found that blockade of α4β1 integrin limited secondary cord damage more effectively than blockade of CD11d/CD18. Therefore we considered it important to assess the effects of anti-α4β1 treatment on the SIRS in the lung, kidney, and liver after SCI. An anti-α4 antibody was given IV at 2 h after SCI at the fourth thoracic segment and the effects on the organs were evaluated at 24 h post-injury. The migration of neutrophils into the lungs and liver was markedly reduced and all three organs contained fewer macrophages. In the lungs and liver, the activation of the oxidative enzymes myeloperoxidase (MPO), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and gp91(phox), the production of free radicals, lipid peroxidation, and cell death were substantially and similarly reduced. Treatment effects were less robust in the kidney. Overall, the efficacy of the anti-α4β1 treatment did not differ greatly from that of the anti-CD11d antibody, although details of the results differed. The SIRS after SCI impedes recovery, and attenuation of the SIRS with an anti-integrin treatment is an important, clinically-relevant finding.     

A CD11d Monoclonal Antibody Treatment Reduces Tissue Injury and Improves Neurological Outcome after Fluid Percussion Brain Injury in Rats

Abstract Traumatic brain injury (TBI) is an international health concern often resulting in chronic neurological abnormalities, including cognitive deficits, emotional disturbances, and motor impairments. An anti-CD11d monoclonal antibody that blocks the CD11d/CD18 integrin and vascular cell adhesion molecule (VCAM)-1 interaction following experimental spinal cord injury improves functional recovery, while reducing the intraspinal number of neutrophils and macrophages, oxidative activity, and tissue damage. Since the mechanisms of secondary injury in the brain and spinal cord are similar, we designed a study to evaluate fully the effects of anti-CD11d treatment after a moderate lateral fluid percussion TBI in the rat. Rats were treated at 2?h after TBI with either the anti-CD11d antibody or an isotype-matched control antibody 1B7, and both short (24- to 72-h) and long (4-week) recovery periods were examined. The anti-CD11d integrin treatment reduced neutrophil and macrophage levels in the injured brain, with concomitant reductions in lipid peroxidation, astrocyte activation, amyloid precursor protein accumulation, and neuronal loss. The reduced neuroinflammation seen in anti-CD11d-treated rats correlated with improved performance on a number of behavioral tests. At 24?h, the anti-CD11d group performed significantly better than the 1B7 controls on several water maze measures of spatial cognition. At 4 weeks post-injury the anti-CD11d-treated rats had better sensorimotor function as assessed by the beam task, and reduced anxiety-like behaviors, as evidenced by elevated-plus maze testing, compared to 1B7 controls. These findings suggest that neuroinflammation is associated with behavioral deficits after TBI, and that anti-CD11d antibody treatment is a viable strategy to improve neurological outcomes after TBI.     

International skeletal society outreach in Argentina

From June 28th to 29th, 2013, the Argentinian ISS Outreach Program took place in collaboration with the Centro de Diagnóstico Dr. Enrique Rossi in the city of Buenos Aires. A total of 690 participants attended. In the following report, we analyze the actual radiologic situation in this South American country. Outreach programs in a country such as Argentina are extremely valuable, as they provide a great opportunity for physicians that cannot travel overseas an attend international meetings such as RSNA, International Skeletal Society, or ARRS.     

Diabetic neuropathic foot ulcers and amputation

A neuropathic foot ulcer is a severe complication of diabetes that can result in a more severe complication, a lower extremity amputation. We conducted a cohort study of 24,616 individuals with a diabetic neuropathic foot ulcer treated within a multicenter wound care network. A total of 1653 (6.7%) individuals had an amputation and 46.3% of these amputations were of a toe or ray (minor amputation). In the more than 10-year follow-up period that we studied, the percentage of those who had an amputation varied between 5.6% and 8.4%. Of those who had an amputation, the percentage that had a minor amputation increased over time from 4.0% in the earliest years to more than 60% in the later years of observation. The single most important determinant of amputation was the observation of fascia, tendon, and bone at the initial assessment. In conclusion, about 7% of those with a diabetic neuropathic foot ulcer will have an amputation and in the past 10 years there has been a remarkable increase in the number of minor as compared to major amputations.     

Staged bilateral carotid stenting, an effective strategy in high-risk patients - insights from a prospective multicenter trial

OBJECTIVE: To prospectively evaluate outcomes of high-risk patients undergoing bilateral carotid artery stenting (CAS). METHODS: A total of 747 patients at increased risk for carotid endarterectomy (CEA) were enrolled in a prospective registry at 47 US sites of the Boston Scientific EPI: A Carotid Stenting Trial for Risk Surgical Patients (BEACH) trial. Among them, 78 (10.4%) patients underwent contralateral CAS > 30 days after the primary CAS procedure. Patients were followed at 1, 6, and 12 months, and annually thereafter for 3 years. The primary endpoint was the cumulative incidence of non Q-wave myocardial infarction within 24 hours, periprocedural (相似文献   

Varus and valgus flexion laxity of total knee alignment methods in loaded cadaveric knees.

Both total knee alignment methods, the anatomic and classic, seek to achieve stability in flexion and extension. However, posterior femoral condyle referencing (anatomic alignment) combined with perpendicular tibial resection (classic alignment) results in a 3 degree relative internal rotation of the femoral component with lateral joint opening. The current cadaver study investigated the influence of total knee alignment methods and femoral component malrotation (3 degrees and 6 degrees internal and external malrotation) on femorotibial laxity. Varus and valgus excursion tests were done at 0 degrees, 30 degrees, 60 degrees, and 90 degrees knee flexion under vertical loading conditions of 150 N. None of the alignments produced increased laxity in extension. The largest laxity was found on the varus test at 60 degrees flexion with the femoral component at 6 degrees internal rotation. A 3 degree internal rotation of the femoral component showed increased varus laxity only for the combined alignment method. This finding shows that the femoral component position of the combined alignment method is a 3 degree relative internal malrotation and that an additional internal malrotation may compromise varus stability. Posterior femoral condyle referencing did not provide proper femoral component rotation. A ligament tensor may be helpful in determining femoral component rotation after soft tissue release in extension is performed.     

Microgravity culture condition reduces immunogenicity and improves function of pancreatic islets1

BACKGROUND: The failure of pancreatic islet allotransplants observed in almost all clinical attempts is related to poor initial islet function and allograft rejection. To remedy these problems we cultured islets in microgravity conditions to improve their function and to reduce their immunogenicity. METHODS: Fresh mouse islets or mouse islets cultured in stationary dishes or microgravity bioreactors were transplanted to streptozotocin-induced diabetic mouse recipients. RESULTS: Both allogeneic dish- or bioreactor-cultured islets survived more than 100 days compared with fresh allogeneic islets, which were rejected in less than 15 days. Islet titration studies revealed that 250 fresh or dish-cultured, but only 30 to 120 bioreactor-cultured, islets were necessary to produce euglycemia. Furthermore, glucose tolerance tests showed that bioreactor-cultured islets functioned better compared with fresh and dish-cultured islets on day 30 postgrafting. Immunostaining and transmission electron microscopy (TEM) analyses showed the gradual disappearance of dendritic cells in cultured islets compared with fresh islets. TEM revealed that the ultrastructure of islets from bioreactor, but not dish, appeared healthy and closely resembled fresh islets. Interestingly, TEM and scanning electron microscopy showed that only bioreactor-cultured islets developed unique and multiple nutritional channels between arrays of islet cells. TEM with colloidal lanthanum tracer revealed that only bioreactor islet cell cultures were devoid of tight junctional complexes, which may facilitate channel formation. CONCLUSION: Microgravity condition decreases immunogenicity and significantly improves the function of secretory cells.     

Application of 2 vibrators salvages ejaculatory failures to 1 vibrator during penile vibratory stimulation in men with spinal cord injuries

PURPOSE: Penile vibratory stimulation is the treatment of first choice for anejaculation in men with spinal cord injury. Nonresponders to penile vibratory stimulation are usually referred for electroejaculation or surgical sperm retrieval. Compared to penile vibratory stimulation these methods are invasive and usually yield lower total motile sperm, potentially limiting options for assisted reproductive technologies. To avoid these less than ideal options a simple method to salvage penile vibratory stimulation failures would be of benefit to spinal cord injured patients. We investigated the recovery rate when 2 vibrators were used to salvage ejaculatory failures to 1 vibrator in men with spinal cord injury. MATERIALS AND METHODS: A retrospective chart review was performed in 297 spinal cord injured men who underwent a total of 965 trials of penile vibratory stimulation at our center between 1991 and 2006. Only trials with high amplitude vibrators were examined. All men underwent 2 or more penile vibratory stimulation trials using 1 vibrator applied to the dorsum or frenulum of the glans penis. Men failing to ejaculate with 1 vibrator received 1 or more trials in which the glans penis was then sandwiched between 2 vibrators. RESULTS: Of all men 49% and 57% of those whose level of injury was T10 or above responded to penile vibratory stimulation with 1 vibrator. Of failures with 1 vibrator 22% responded to penile vibratory stimulation with 2 vibrators. CONCLUSIONS: Application of 2 vibrators salvaged ejaculatory failures to 1 vibrator during penile vibratory stimulation procedures in men with spinal cord injury. This simple penile vibratory stimulation sandwich method is recommended before referring patients for electroejaculation or surgical sperm retrieval.