Glial cell line-derived neurotrophic factor-dependent recruitment of Ret into lipid rafts enhances signaling by partitioning Ret from proteasome-dependent degradation

The receptor tyrosine kinase (RTK) Ret is activated by the formation of a complex consisting of ligands such as glial cell line-derived neurotrophic factor (GDNF) and glycerophosphatidylinositol-anchored coreceptors termed GFRalphas. During activation, Ret translocates into lipid rafts, which is critical for functional responses to GDNF. We found that Ret was rapidly ubiquitinated and degraded in sympathetic neurons when activated with GDNF, but, unlike other RTKs that are trafficked to lysosomes for degradation, Ret was degraded predominantly by the proteasome. After GDNF stimulation, the majority of ubiquitinated Ret was located outside of lipid rafts and Ret was lost predominantly from nonraft membrane domains. Consistent with the predominance of Ret degradation outside of rafts, disruption of lipid rafts in neurons did not alter either the GDNF-dependent ubiquitination or degradation of Ret. GDNF-mediated survival of sympathetic neurons was inhibited by lipid raft depletion, and this inhibitory effect of raft disruption on GDNF-mediated survival was reversed if Ret degradation was blocked via proteasome inhibition. Therefore, lipid rafts sequester Ret away from the degradation machinery located in nonraft membrane domains, such as Cbl family E3 ligases, thereby sustaining Ret signaling.     

Defining the Origins of the Iliofemoral, Ischiofemoral, and Pubofemoral Ligaments of the Hip Capsuloligamentous Complex Utilizing Computer Navigation

Purpose  

To use computer navigation software to investigate the specific origins of the hip capsuloligamentous complex.     

Average 7-Year Survivorship and Clinical Results of a Newer Primary Posterior Stabilized Total Knee Arthroplasty

We evaluated the average 7-year survivorship and clinical results of a newer primary posterior stabilized total knee arthroplasty (TKA). The modifications in this design included a deeper patellar sulcus aimed at reducing contact stresses, improving patellar tracking, and achieving greater maximum flexion. A consecutive group of 137 patients (171 knees) who underwent TKAs using the Optetrak PS knee prosthesis between October 1997 and March 2004 were followed for an average of 6.8?years (range 4.0-11.5?years). Preoperative range of motion (ROM) and Knee Society scores were obtained and compared to that of the patients' most recent follow-up. Manipulation under anesthesia (MUA) and revision of the implant for any reason were considered endpoints for Kaplan-Meier survival analysis of all knees. Twenty-one knees (12.3%) underwent MUA. Three knees (1.8%) underwent revision, resulting in a 97.2% survival at a mean 10?years follow-up. Pain scores and ROM significantly improved after surgery (from preoperative average of 5.3 and 105° respectively to 44.6 and 120° postoperatively). These findings suggest that this posterior stabilized knee design is both a safe and effective option for patients undergoing primary TKA.     

Physician attitudes to the concept of ‘men''s health’ in Asia

BackgroundMen's health is an emerging medical and public health concept, but it is confronted by special challenges in the Asia-Pacific medical and cultural context.MethodsA telephone survey was conducted with physicians in Korea, Taiwan and Singapore. The interview was conducted in Korean (Korea), Mandarin (Taiwan) or English (Singapore) by trained interviewers. The physicians interviewed were drawn from a variety of medical specialties including urology, primary care, endocrinology and cardiology.ResultsIn total, 810 physicians from various medical specialities took part in the survey. There was only broad general agreement (>50%) between the physicians in the various countries on a range of questions relating to men's health, such as the conditions most associated with men's health, the predictability of illness/disability with age etc, and physician willingness to discuss problems in sexual health.ConclusionsThe data from this survey suggest that, although not as clearly defined as women's health, the treatment of men's health cuts across many different medical specialties and takes in a broad spectrum of health conditions. Therefore, there is a clear opportunity for the medical community to define, refine and improve the treatment and understanding of men's health in Asia.     

Instant Vertebral Assessment: A Noninvasive Dual X-ray Absorptiometry Technique to Avoid Misclassification and Clinical Mismanagement of Osteoporosis

The presence of a vertebral fracture significantly increases the risk of future fracture, classifies a patient with "clinical" osteoporosis, and usually results in treatment for osteoporosis. However, the majority of vertebral fractures are silent, and lateral X-rays (the standard method for identification) are not routinely obtained. Instant vertebral assessment (IVA), a technology that utilizes dual X-ray absorptiometry (DXA), provides rapid assessment of vertebral fractures and is highly correlated with vertebral fractures, as assessed on standard lateral spine X-rays. To assess the role of IVA in patient management, we examined standard bone mineral density (BMD) of the spine, total hip, and femoral neck and spine IVA by DXA in 482 participants screened for an osteoporosis study, who had no previous knowledge of vertebral fractures. Using World Health Organization (WHO) guidelines, subjects were classified using BMD at the spine, total hip, femoral neck, or any combination of these central sites. In addition, we considered subjects as osteoporotic if they had vertebral fractures independent of low bone density. We found that vertebral fractures assessed by IVA were present in 18.3% of asymptomatic postmenopausal women recruited for this study. The sensitivity of BMD alone to diagnose osteoporosis based on either a vertebral fracture or low BMD using WHO criteria ranged from 40 to 74%. This means that between 26 and 60% of osteoporotic individuals could have potentially been missed. Furthermore, 11.0-18.7% of clinically osteoporotic individuals would have been classified as normal by BMD criteria alone. We conclude that IVA is a useful adjunct in the clinical identification of osteoporosis and may prevent mismanagement of osteoporotic patients.     

甲状腺再手术的时机及入路方式探讨

目的探讨甲状腺再手术的时机及手术入路方式。方法对我院2000年1月至2006年1月收治的94例甲状腺再手术患者的临床资料进行回顾性分析,主要分析再手术的时机及手术入路方式与操作难易程度的关系。结果本组病例行双侧甲状腺全切除术16例,一侧甲状腺切除并峡部切除术27例,一侧甲状腺切除术并对侧大部切除45例,单侧残余甲状腺切除加部分颈前肌群切除5例,单侧全切加同侧颈淋巴结清扫1例,再手术时间与初次手术相距4d～28年。手术入路:正中入路34例,胸锁乳突肌内侧入路23例,经胸骨舌骨肌、胸骨甲状肌间侧入路25例,正中入路加侧入路12例。手术时间1.5～2.5h,平均2.0h。结论甲状腺包块切除术后病理诊断甲状腺癌的再手术患者尽早手术。结节性甲状腺肿复发再手术的患者应作好充分术前准备,合并呼吸困难的甲状腺再手术患者采用正中入路易于松解气管前瘢痕粘连,缓解气管压迫症状;无呼吸困难症状者采用侧入路或正中入路与侧入路结合,简化手术操作、减少手术并发症。     

db/db mice exhibit severe wound-healing impairments compared with other murine diabetic strains in a silicone-splinted excisional wound model

The pathophysiology of diabetic wound healing and the identification of new agents to improve clinical outcomes continue to be areas of intense research. There currently exist more than 10 different murine models of diabetes. The degree to which wound healing is impaired in these different mouse models has never been directly compared. We determined whether differences in wound impairment exist between diabetic models in order to elucidate which model would be the best to evaluate new treatment strategies. Three well-accepted mouse models of diabetes were used in this study: db/db, Akita, and streptozocin (STZ)-induced C57BL/6J. Using an excisional model of wound healing, we demonstrated that db/db mice exhibit severe impairments in wound healing compared with STZ and Akita mice. Excisional wounds in db/db mice show a statistically significant delay in wound closure, decreased granulation tissue formation, decreased wound bed vascularity, and markedly diminished proliferation compared with STZ, Akita, and control mice. There was no difference in the rate of epithelialization of the full-thickness wounds between the diabetic or control mice. Our results suggest that splinted db/db mice may be the most appropriate model for studying diabetic wound-healing interventions as they demonstrate the most significant impairment in wound healing. This study utilized a novel model of wound healing developed in our laboratory that stents wounds open using silicone splints to minimize the effects of wound contraction. As such, it was not possible to directly compare the results of this study with other studies that did not use this wound model.     

A Clinical Pathway for Total Shoulder Arthroplasty—A Pilot Study

Background

Appropriate pain management after total shoulder arthroplasty (TSA) facilitates rehabilitation and may improve clinical outcomes.

Questions/purposes

This prospective, observational study evaluated a multimodal analgesia clinical pathway for TSA.

Methods

Ten TSA patients received an interscalene nerve block (25 cm³ 0.375% ropivacaine) with intraoperative general anesthesia. Postoperative analgesia included regularly scheduled non-opioid analgesics (meloxicam, acetaminophen, and pregabalin) and opioids on demand (oral oxycodone and intravenous patient-controlled hydromorphone). Patients were evaluated twice daily to assess pain, anterior deltoid strength, handgrip strength, and sensory function.

Results

The nerve block lasted an average of 18 h. Patients had minimal pain after surgery; 0 (median score on a 0–10 scale) in the Post-Anesthesia Care Unit (PACU) but increased on postoperative day (POD) 1 to 2.3 (0.0, 3.8; median (25%, 75%)) at rest and 3.8 (2.1, 6.1) with movement. Half of the patients activated the patient-controlled analgesia four or fewer times in the first 24 h after surgery. Operative anterior deltoid strength was 0 in the PACU but returned to 68% by POD 1. Operative hand strength was 0 (median) in the PACU, but the third quartile (75%) had normalized strength 49% of preoperative value.

Conclusions

Patients did well with this multimodal analgesic protocol. Pain scores were low, half of the patients used little or no intravenous opiate, and some patients had good handgrip strength. Future research can focus on increasing duration of analgesia from the nerve block, minimizing motor block, lowering pain scores, and avoiding intravenous opioids.     

Clinical Outcomes in Patients with Pulmonary Hypertension Undergoing Total Hip Arthroplasty

Background

Pulmonary hypertension (PH) is regarded as a risk factor for perioperative complications in patients undergoing noncardiac surgery.

Questions/Purposes

The objective of this retrospective case–control study was to evaluate the adverse outcomes of pulmonary hypertension patients undergoing elective unilateral hip replacements.

Methods

We performed a retrospective case–control study of total hip replacement patients with pulmonary hypertension (cases) and without pulmonary hypertension (control). From the years 2003 to 2008, we identified a total of 132 patients undergoing primary total hip replacements with a diagnosis of pulmonary hypertension (right ventricular systolic pressure >35). The primary outcome assessed was the incidence of adverse events that occurred during the postoperative hospital stay. Secondary outcomes studied included length of hospital stay, mortality, and ability to reach certain physical therapy milestones.

Results

The PH group had significantly more adverse events than the control group. Nonlethal cardiac dysrhythmias comprised the most common adverse outcome among the PH group. Overall, the PH group had a morbidity rate of 34.7% while the control had a rate of 21%. The PH group had longer hospital stay (6.7 days vs. 5.9). Both groups had zero mortality during the hospital stay. The PH group had comparable rehabilitation recovery times than the control group.

Conclusion

This retrospective case–control study demonstrates that pulmonary hypertension patients undergoing total hip arthroplasty are more prone to adverse outcomes, especially cardiac dysrhythmias, and longer hospital stays.