Differential gene expression in cultured osteoblasts and bone marrow stromal cells from patients with Paget's disease of bone.

Paget's disease is a focal condition of bone. To study changes in cells within pagetic lesions, we cultured osteoblasts and stromal cells from 22 patients and compared gene expression in these cells to cells from healthy bone. We identified several differentially regulated genes, and we suggest that these changes could lead to the formation of the lesions. INTRODUCTION: Paget's disease is a focal condition of bone of unknown cause. Although it is regarded as primarily an osteoclast disorder, the tight coupling of the activity of osteoclasts and osteoblasts suggests that the osteoblast could play a key role in its pathogenesis. The aim of the study was to identify possible changes in pagetic osteoblasts and stromal cells that might contribute to the development of pagetic lesions. MATERIALS AND METHODS: Candidate genes were identified based on known bone cell regulators, supplemented with microarray analysis. Gene expression was determined by real-time PCR in primary cultures of osteoblasts and bone marrow stromal cells from pagetic patients and control subjects. Concentrations of secreted proteins were determined by ELISA. RESULTS: Dickkopf1 mRNA and protein levels were increased in both pagetic osteoblast and stromal cell cultures, and interleukin (IL)-1 and IL-6 were overexpressed in pagetic osteoblasts. These changes parallel recent findings in myeloma bone disease, which shares some clinical similarities with Paget's disease. Alkaline phosphatase was overexpressed, and bone sialoprotein and osteocalcin were underexpressed in pagetic osteoblasts, consistent with their circulating levels in pagetic patients. It is hypothesized that overexpression of Dickkopf1, IL-1, and IL-6 would result in stimulation of osteoclast proliferation and inhibition of osteoblast growth, leading to the development of the characteristic lytic bone lesions. By stimulating osteoblast differentiation, Dickkopf1 and IL-6 may also promote mineralization, leading to the conversion of lytic lesions to sclerotic. CONCLUSIONS: These findings suggest that dysregulated gene expression in pagetic osteoblasts could cause the changes in bone cell number and function characteristic of Paget's disease.     

Cognitive and neuroimaging predictors of instrumental activities of daily living.

Impaired ability to conduct daily activities is a diagnostic criterion for dementia and a determinant of healthcare services utilization and caregiver burden. What predicts decline in instrumental activities of daily living (IADLs) is not well understood. This study examined measures of episodic memory, executive function, and MRI brain volumes in relation to baseline IADLs and as predictors of rate of IADL change. Participants were 124 elderly persons with cognitive function between normal and moderate dementia both with and without significant small vessel cerebrovascular disease. Random effects modeling showed that baseline memory and executive function (EXEC) were associated with baseline IADL scores, but only EXEC was independently associated with rate of change in IADLs. Whereas hippocampal and cortical gray matter volumes were significantly associated with baseline IADL scores, only hippocampal volume was associated with IADL change. In a model including cognitive and neuroimaging predictors, only EXEC independently predicted rate of decline in IADL scores. These findings indicate that greater executive dysfunction at initial assessment is associated with more rapid decline in IADLs. Perhaps executive function is particularly important with respect to maintaining IADLs. Alternatively, executive dysfunction may be a sentinel event indicating widespread cortical involvement and poor prognosis.     

142Effects of Low‐Frequency Ultrasound Applied In Vitro to Highly Antibiotic‐Resistant Acinetobacter Isolates Recovered From Soldiers Returning From Iraq

Abstract  Brooke Army Medical Center isolated 25 highly antibiotic‐resistant Acinetobacter ssp . (primarily A. baumannii ) from wounded soldiers returning from Iraq. Concern about effective treatment of these organisms led our institution to begin investigating low‐frequency ultrasound (LFU) as a method of increasing the effectiveness of antibiotics on A.baumannii in wound management. Studies have suggested that LFU applied in conjunction with antibiotics may increase their overall effectiveness. We hypothesize that combining antibiotics with LFU may be an effective method of wound management and that this combination may be synergistic in its overall effect. In this initial work, we wanted to determine if sonocation would have an effect on our organism of interest, A. baumannii . We selected several organisms, both gram positive and gram negative, that have been shown to be killed by sonocation ( E. coli, S. aureus , and S. pyogenes ) and added three highly resistant A. baumannii isolates. Bacterial death was measured by both colony counts after 24 hours of growth and acridine orange staining using a standard protocol.
Colony counts were significantly reduced by sonocation. Furthermore, A.'baumannii colony counts were also greatly reduced by sonocation. Actual cell destruction was also visualized using acridine orange staining. Our data support the assertion that sonocation has an antibacterial effect on some bacteria, including A. baumannii . Our next step is to add antimicrobial agents and determine if their effectiveness can be increased by sonocation.     

奥利司他对肥胖青少年体重和机体组分的影响——随机对照试验

背景：儿童和青少年超重和肥胖正迅速增加。在该人群，单纯行为疗法减肥及维持体重下降的效果有限，但是对药物治疗尚未进行广泛的研究。 目的：确定奥利州他（Orlistat）在青少年体重治疗方面的效果及其安个性。 设计、地点和病例：于美国和加拿大32个中心、539例肥胖青少年（12—16岁；体重指数[body mass index，BMI]在第95百分化之上≥2单位）进行的多ln0、54剧（2000年8月至2002年10月）随机双盲研究。 干预：给予奥利司他（n=357）或安慰剂（n=182）120mg，每口3次，持续1年；加适度低热卡饮食（脂肪占30％）、运动和行为治疗。 主要观察指标：BMI变化；二级指标包括腰围和髋用、体重下降、脂质测量以及机体对口服葡萄糖的血糖和胰岛素反心。 结果：至12周时，两组BMI均有下降；此后，奥利司他组体重维持稳定而安慰剂组则超过基线。研究结束时，奥利司他组BMI下降0．55。而安慰剂组则增加0．31（P=0．001）。与安慰剂组的15．7％相比，奥利司他组26．5％的病例BMI下降≥5％（P=0．005）；BMI下降≥10％者分别为4．5％和13．3％（P=0．002）。在研究结束时，奥利司他组体重增加0．53kg，安慰剂组增加3．14kg（P〈0．001）。双能X线吸收测量娃示，这种差异可用脂肪体再的变化解释。奥利司他组腰围下降，安慰剂组腰围上升（-1．33cm比＋0．12cm；P〈0．05）。奥利司他组发生轻至中度胃肠道不良事件者为9％-50％，安慰剂组为1％～13％。 结论：与安慰剂比较，奥利司他与饮食、运动和行为改善联合可显著改善肥胖青少年体重的治疗。在这个青少年人群，连续使用奥利司他1年并无重要安全问题，尽管奥利司他组胃肠道不良事件较为常见。     

Models of Parkinson's disease.

Parkinson's disease (PD) is a heterogenous disease likely to be caused by more than one specific aetiological factor. In rare familial cases of PD with similar clinical features to the idiopathic form of the disease, the underlying genetic cause has been identified. These PD-associated genes have been manipulated to create animal and cell culture models of the disease that have helped to further our understanding of the pathogenesis of PD, particularly concerning causes of the selective loss of dopaminergic neurons at the molecular level. In addition, these models will aid the future development of rational therapeutic strategies. This study briefly reviews toxin-induced models and the genetics of PD. It focuses on recently developed animal models of PD, as well as in vitro approaches to model the disease.     

Outcome Following Bariatric Surgery in Super versus Morbidly Obese Patients: Does Weight Matter?

Background: Numerous investigators have attempted to identify prognostic indicators for successful outcome following bariatric surgery. The purpose of this study was to determine whether degree of obesity affects outcome in super obese [>225% ideal body weight (IBW)] versus morbidly obese patients (160-225% IBW) undergoing gastric restrictive/bypass procedures. Methods: Since 1984, 157 patients underwent either gastric bypass or vertical banded gastroplasty. Super obese (78) and morbidly obese (79) patients were followed prospectively, documenting outcome and complications. Results: Super obese patients reached maximum weight loss 3 years following bariatric surgery, exhibiting a decrease in body mass index (BMI) from 61 to 39 kg/m² and an average loss of 42% excess body weight (EBW). Morbidly obese patients had a decrease in BMI from 44 to 31 kg/m² and carried 39% EBW at 1 year. After their respective nadirs, each group began to regain the lost weight with the super obese exhibiting a current BMI of 45 kg/m² (61% EBW) versus 34 kg/m² (52% EBW) in the morbidly obese at 72 months cumulative follow-up. Currently, loss of 50% or more of EBW occurred in 53% of super obese patients versus 72% of morbidly obese (P < 0.01). Twenty-six percent of super obese patients returned to within 50% of ideal body weight (IBW) while 71% of morbidly obese were able to reach this goal (P < 0.01). Co-morbidities and complications related to surgery were similar in each group. Conclusions: Super obese patients have a greater absolute weight loss after bariatric surgery than do morbidly obese patients. Using commonly utilized measures of success based on weight, morbidly obese patients tend to have better outcomes following bariatric surgery.     

Treatment approaches for clients with a stroke‐affected upper limb: Are we following evidence‐based practice?

Stroke rehabilitation is an area of practice that many occupational therapists encounter during their career. The literature promotes a wide range of management techniques and support devices for people who have a stroke-affected upper limb, but little is known about the validity of those that occupational therapists actually use in practice. A questionnaire was sent to occupational therapists working in Queensland and northern New South Wales facilities (n = 35), in which adults with a stroke were likely to be treated. Eighteen respondents answered questions about the management techniques and support devices used in their facility, and their perception of the benefit of these devices in the reduction of hemiplegic shoulder pain. Results are discussed with reference to evidence-based practice and indicate an urgent need for the collation and dissemination of the best current evidence available for the management techniques and support devices used in this area, as well as further research to extend this evidence.