Transcanal cochlear implantation under monitored anesthesia care.

OBJECTIVE: Given the associated risk of general anesthesia in elderly patients with cardiovascular disease, the authors set out to determine the feasibility of transcanal cochlear implantation under local anesthesia with monitored anesthesia care. METHODS: A 70-year-old man with a history of coronary artery bypass grafting, diabetes mellitus, and an American Society of Anesthesiologists Class III cardiac status underwent cochlear implantation under local with monitored anesthesia care. RESULT: With the described technique and regimen of intravenous remifentanil and dexmedetomidine, the patient tolerated the 60-minute procedure without tachycardia, hyper- or hypotension, or cardiac ischemia. CONCLUSION: Cochlear implantation using the pericanal electrode technique performed under local anesthesia with monitored anesthesia care is possible in patients at risk for undergoing general anesthesia for cochlear implantation.     

Self-mutilation in adolescents.

Self-mutilation is not a new trend or phenomenon in adolescents. Self-mutilation can be divided into three categories: major, stereotypic, and moderate/superficial. Moderate/superficial self-mutilation is the most common type in adolescents and includes cutting, burning, and carving. School nurses are positioned to identify, to assist, and to educate adolescents who are self-mutilating, as well as those who may be at risk. A crucial intervention by school nurses is referral of students who are self-mutilating, because it is a gateway to treatment. Treatment, which includes therapy and medication, may be a difficult and lengthy process. The adolescent who self-mutilates may find the school environment difficult during treatment. School nurses must become educated about adolescent self-mutilation in order to care for those who engage in this behavior. Prevention of self-mutilation should focus on increasing coping mechanisms, facilitating decision-making strategies, encouraging positive relationships, and cultivating self-esteem.     

Optimal timing of a single dose of zoledronic acid to increase strength in rat fracture repair.

We hypothesized that ZA treatment would bolster fracture repair. In a rat model for closed fracture healing, a single dose of ZA at 0, 1, or 2 wk after fracture significantly increased BMC and strength of the healed fracture. Delaying the dose (1 or 2 wk after fracture) displayed superior results compared with dosing at the time of fracture. INTRODUCTION: Bisphosphonates are known to increase bone strength and thus the resistance to fracture by decreasing osteoclastic bone resorption. These properties may enable bisphosphonates to also increase the strength of fracture repair. Zoledronic acid (ZA) is a potent bisphosphonate with a high affinity for bone mineral, allowing bolus intravenous dosing in a range of indications. In this study, we examined the application of bolus dose ZA in endochondral fracture repair. MATERIALS AND METHODS: Carbon-14 labeled ZA was used in a closed rat fracture model. Rats were divided into five treatment groups (n = 25 per group): saline control, local ZA (0.01 mg/kg), and three systemic bolus ZA groups (0.1 mg/kg) with different administration times: at fracture, 1 wk after fracture, and 2 wk after fracture. Rats were killed 6 wk postoperatively. Postmortem analyses included radiography, QCT, microCT, biomechanical testing, scintillation counting, autoradiography, and histology. RESULTS: Single-dose systemic ZA administration significantly increased callus volume, callus BMC, and mechanical strength. Perioperative treatment increased mechanical strength by 30% compared with controls (p < 0.05). Administering the systemic dose at 1 or 2 wk after fracture further increased mechanical strength compared with controls by 44% and 50%, respectively (p < 0.05). No significant differences in mechanical parameters were seen with local injection at the dose studied. Autoradiographic analysis indicated that ZA binds significantly to bone that is present at the time of administration. ZA quantification indicated that delayed administration significantly increased the uptake efficiency in the callus. Histological and microCT analysis showed that ZA treated calluses had a distinctive internal structure consisting of an intricate network of retained trabecular bone. CONCLUSIONS: The timing of a single systemic dose of ZA plays an important role in the modulation of callus properties in this rat fracture model; delaying the single dose produces a larger and stronger callus.     

SI12Lymphocyte Subsets Following Autologous Transfer of CD25 Depleted Leukapheresis Products

The CXCL12/CXCR4 chemokine axis is a well characterized and important chemotactic stimulus/receptor unit that orchestrates the homing and migration of cells to the bone marrow and to ischemic tissues following tissue damage. Here, we demonstrate that the sialomucin, CD164, a regulator of haemopoietic precursor cell adhesion to stroma and entry of primitive CD34⁺CD38^lo/‐ precursor cells into cycle, modulates the migration of CD133⁺ cord blood cells to CXCL12 by associating with the CXCR4 receptor. This was demonstrated by a reduction in CD133⁺ cell migration on fibronectin to CXCL12 (i) by engaging the functional class II glycosylation‐dependent epitope on CD164 with the 103B2/9E10 class II but not the N6B6 class III antibody; and (ii) by RNAi knockdown of CD164 protein levels in CD133⁺ cells. The inhibition of migration was more pronounced in the more primitive CD34⁺CD38^lo/‐ cell subset. Similar studies using the Jurkat cell line confirmed these findings and led to further analyses using alternative chemokines. A direct association between CXCR4 and CD164 was demonstrated by the co‐localisation of CD164 with CXCR4 and VLA‐4 and VLA‐5 at the leading edge of CD133⁺ cells when CXCL12 was presented on fibronectin. This was further supported by immunoprecipitation studies that demonstrate in the absence of CXCL12, CXCR4 is associated only with VLA‐4 and VLA‐5 but on exposure to CXCL12, CD164 is rapidly recruited to the CXCR4 complex. Knock‐down of CD164 using siRNA revealed that signalling through CXCR4 via PKC‐ζ was significantly dampened. Our findings therefore support a novel association between three distinct families of cell surface receptors that regulate both cell migratory and proliferative responses and identify a CD164 as a key regulator of the CXCL12/CXCR4 axis.     

P63Stem Cell and Immunotherapy Services, NHS Blood and Transplant, Birmingham, UK

Over 20 years ago, the Birmingham Blood Centre established a facility for the cryopreservation of bone marrow (BM) for patients in the West Midlands suffering from haematopoietic disorders and for whom a bone marrow transplant was indicated. Today, the use of mobilised peripheral blood (PBSC) has overtaken bone marrow as the source of stem cells for transplantation and the numbers of patients benefitting and the diversity of conditions being treated has increased enormously. Allogeneic transplants, using stem cells from healthy donors, have become increasingly successful as a result of an improving understanding of the complexities of the HLA histocompatibility system. Additionally umbilical cord blood (HUC), which in the 1980s was recognised as a source of stem cells, can now be collected and used for transplantation. As scientific knowledge and the clinical management of patients has advanced, so too have laboratory methods for manipulating cell products to enrich or deplete certain cell populations (e.g. by CD34+cell selection) in order to minimise potentially fatal graft-versus-host disease (GVHD) or to eliminate tumour cells in the case of autologous patients. Donor lymphocytes (DLI) may also be collected and used to aid a graft-versus-leukaemia (GVL) effect. The laboratory is currently developing protocols for immunotherapy using virus-specific T cells which can be prepared and infused to combat potentially fatal CMV disease post-transplant. Clinical trials of vaccines employing tumour specific dendritic cells for treating patients with hepatocellular carcinoma (HCC) and metastatic melanoma (MM), which do not respond to conventional treatments, are also underway. The advances and expansion in the Stem Cell and Immunotherapy (SCI) service in Birmingham over the last 10 year period are reflected in the table below:
 

     

Decreased Risk of Renal Allograft Thrombosis Associated With Interleukin-2 Receptor Antagonists: A Report of the NAPRTCS

Graft thrombosis is the most common cause of first year graft failure in pediatric renal transplantation. The North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) database was analyzed for cases of graft failure due to thrombosis among patients transplanted from 1998 to 2004. The impact of interleukin-2 (IL-2) receptor antagonists as induction therapy was determined. There were a total of 51 graft failures due to thrombosis among the 2750 reported renal transplants (1.85%) (95% CI (1.39%, 2.41%)). This represents the most common cause of graft loss during the first year post-transplant accounting for 35% of first year losses and 18% of all graft losses. The incidence of thrombosis among patients who received IL-2 receptor antibodies was 1.07% (12/1126) compared to 2.40% (39/1624) among patients who did not (OR 0.44, 95% CI 0.23, 0.84, p = 0.014). Use of IL-2 receptor blockade was the only significant prognostic factor in a multivariate model with previously identified risk factors. Analysis of NAPRTCS data found that the use of IL-2 receptor antibodies as induction therapy is associated with a significantly decreased risk of graft failure due to thrombosis. This provocative finding requires further investigation to determine whether thrombotic failure can be decreased by this therapeutic strategy.     

Distance-adjusted motor threshold for transcranial magnetic stimulation.

OBJECTIVE: To examine the relationship between coil-cortex distance and effective cortical stimulation using transcranial magnetic stimulation (TMS) in the left and right motor cortex. We also compare the effect of coil-cortex distance using 50 and 70 mm figure-eight stimulating coils. METHODS: Coil-cortex distance was manipulated within each participant using 5 and 10 mm acrylic separators placed between the coil and scalp surface. The effect of cortical stimulation was indexed by resting motor threshold (MT). RESULTS: Increasing distance between the coil and underlying cortex was associated with a steep linear increase in MT. For each additional millimetre separating the stimulating coil from the scalp surface, an additional approximately 2.8% of absolute stimulator output (approximately 0.062 T) was required to reach MT. The gradient of the observed distance effect did not differ between hemispheres, and no differences were observed between the 50 and 70 mm TMS coils. CONCLUSIONS: Coil-cortex distance directly influences the magnitude of cortical stimulation in TMS. The relationship between TMS efficacy and coil-cortex distance is well characterised by a linear function, providing a simple and effective method for scaling stimulator output to a distance adjusted MT. SIGNIFICANCE: MT measured at the scalp-surface is dependent on the underlying scalp-cortex distance, and therefore does not provide an accurate index of cortical excitability. Distance-adjusted MT provides a more accurate index of cortical excitability, and improves the safety and efficacy of MT-calibrated TMS.