胶原海绵复合新生大鼠原代心肌细胞构建工程化心肌组织

目的:探索以胶原海绵为支架、新生大鼠原代心肌细胞为种子细胞,于体外构建工程化心肌组织的方法。方法:实验于2005-12/2006-11在解放军第四军医大学西京医院心内科实验室完成。Ⅰ型胶原海绵剪切成方形片状(2.0cm×1.4cm×0.2cm),经60Co照射消毒,于DMEM培养液中水化1h左右。另取1d龄SD大鼠心脏,剪成小碎块,然后用2.5g/L胰蛋白酶于37℃中消化,吸取上清至含胎牛血清的DMEM中,重复消化四五次,用差速贴壁法除去大部分成纤维细胞,将细胞沉淀用DMEM培养液以2×109L-1的密度悬浮备用。将上述的心肌细胞悬液1mL缓慢滴注于玻璃模型中的胶原海绵上,然后置于细胞培养中培养。肉眼及显微镜主要观察工程化心肌组织在培养期间的自发收缩情况,包括收缩的部位、强度、频率、一致性以及收缩随时间变化的情况。苏木精-伊红染色观察工程化心肌组织内胶原纤维的变化,细胞形态,胞核的形状及细胞之间的连接。免疫组织化学染色和透射电镜观察工程化心肌组织片的形态和功能。结果:①细胞接种于胶原海绵上1d后,细胞/胶原复合物的凝胶化过程基本完毕,体积保持恒定,维持至培养结束,第3天细胞/胶原复合物局部出现点片状自发收缩,第5天整个细胞/胶原复合物出现同步化自发收缩,收缩频率61～199次/min。2周后37.5%的工程化心肌组织的自发收缩活动减弱,但75%的工程化心肌组织的自发收缩活动持续至培养结束。②苏木精-伊红染色、免疫组织化学染色和透射电子显微镜显示,工程化心肌组织内细胞间连接广泛存在,细胞多呈纵向分布,胞核呈长圆形,胞浆内α-肌节肌动蛋白阳性,胞内肌原纤维排列整齐,可见到心肌特异性的肌小节结构和Z线,多数细胞具有分化的心肌细胞表型。结论:用新生大鼠原代心肌细胞为种子细胞、以Ⅰ型胶原海绵为支架材料,构建出的工程化心肌组织,于体外可长时间持续自发收缩,该细胞/胶原复合物的形态结构与生理功能均类似于成熟大鼠心肌组织。     

A fuzzy logic model for differential diagnosis of lower urinary tract dysfunctions

Lower urinary tract dysfunctions (LUTD) restrict quality of life, resulting in decreased work productivity and emotional well‐being. However, most people are not diagnosed because they do not seek medical treatment. In addition, some facilities do not adequately train health professionals in the evaluation, diagnosis and treatment of these conditions. The study's objective was to develop a decision support system modelled on fuzzy logic that defines LUTD using the terminology of the International Continence Society. This methodological study aimed to develop a model that uses the maximum–minimum composition (max–min) of fuzzy relations that can perform differential diagnoses of LUTD. The model was tested in 100 cases (50 men and 50 women), and the data were obtained from medical records containing the clinical data and results of urodynamic studies. All medical records were reviewed by a specialist in urology. The model was capable of determining a diagnosis in full (62%) or partial (36%) agreement with the medical report. Agreement between the model and the medical report was excellent (kappa = 0·98, p ? 0·001, CI = 0·88–1) or substantial (kappa = 0·53, p ? 0·001, CI = 0·45–0·60), considering overestimative accordance (where accordance is assumed when at least one diagnosis is equal) and underestimative accordance (where accordance is assumed when all diagnoses are equal), respectively. The proposed model based on the max–min composition of fuzzy relationships is very simple and performed well. However, more tests are recommended before the model is used as a decision support system.     

Multifocal pyomyositis: report of two cases

Pyomyositis is a primary infection of the striated muscles. We describe the clinical and imaging features of pyomyositis in two patients, one diabetic and the other immunocompetent. Treatment with incision, drainage and antibiotics was successful and resulted in full recovery. Increased awareness, especially in immuno‐competent patients, should lead to earlier diagnosis, correct treatment and a better outcome.     

Trauma exposure and posttraumatic stress disorder in adults with severe mental illness: a critical review

There is a great deal of research on the prevalence, correlates, and treatment of PTSD in the general population. However, we know very little about the manifestation and consequences of PTSD in more complicated patient populations. The purpose of the current paper is to provide a comprehensive review of PTSD within the context of severe mental illness (SMI; i.e., schizophrenia spectrum disorders, mood disorders). Extant data suggest that trauma and PTSD are highly prevalent among individuals with SMI relative to the general population, and both are associated with adverse clinical functioning and increased healthcare burden. However, trauma and PTSD remain overlooked in this population, with low recognition rates in public-sector settings. Additionally, there are few data on the clinical course and treatment of PTSD among individuals with SMI. Particularly lacking are longitudinal studies, randomized controlled treatment trials, and studies using ethno-racially diverse samples. Furthermore, there is a need to better understand the interplay between trauma, PTSD, and severe forms of mental illness and to further develop and disseminate evidence-based PTSD treatments in this population. The current state of the literature and future directions for practice are discussed.     

Contribution of the Vertebral Posterior Elements in Anterior–Posterior DXA Spine Scans in Young Subjects

Because DXA is a projection technique, anterior–posterior (AP) measurements of the spine include the posterior elements and the vertebral body. This may be a disadvantage because the posterior elements likely contribute little to vertebral fracture resistance. This study used QCT to quantify the impact of the posterior elements in DXA AP spine measures. We examined 574 subjects (294 females and 280 males), age 6–25 yr, with DXA and QCT. QCT measures were calculated for the cancellous bone region and for the vertebral body including and excluding the posterior elements. DXA data were analyzed for the entire L₃ vertebra and for a 10‐mm slice corresponding to the QCT scan region. BMC and BMD were determined and compared using Pearson's correlation. The posterior elements accounted for 51.4 ± 4.2% of the total BMC, with a significant difference between males (49.9 ± 4.0%) and females (52.8 ± 3.9%, p < 0.001). This percentage increased with age in younger subjects of both sexes (p < 0.001) but was relatively consistent after age 17 for males and 16 for females (p > 0.10). DXA areal BMD and QCT volumetric BMD correlated strongly for the whole vertebra including the posterior elements (R = 0.83), with BMC measures showing a stronger relationship (R = 0.93). Relationships were weaker when excluding the posterior elements. We conclude that DXA BMC provides a measure of bone that is most consistent with QCT and that the contribution of the posterior elements is consistent in young subjects after sexual maturity.     

Posttraumatic Growth in Treatment-seeking Female Assault Victims

The importance of measuring growth outcomes following a traumatic event has been highlighted in recent literature (e.g., Linley, Joseph: Journal of Traumatic Stress 17:11–21, 2004). Although reports of growth are abundant, the relationship between growth outcomes and post-trauma distress remains unclear, with studies yielding conflicting results regarding this relationship. The purpose of the present study was to explore the interrelationships among growth outcomes and measures of depression and posttraumatic stress disorder (PTSD) among 100 female treatment-seeking physical and sexual assault victims. Although the majority of women reported some degree of growth in this study, and growth scores were comparable to those from other samples, measures of depression and PTSD were not significantly related to growth scores. The implication of these findings and future direction for research are discussed.     

Screening for PTSD in public-sector mental health settings: the diagnostic utility of the PTSD checklist

There are few available data on how to accurately screen for and assess posttraumatic stress disorder (PTSD) among severely mentally ill adults, a group with high rates of unrecognized trauma and PTSD symptoms. We examined the diagnostic utility of a widely used screening instrument, the PTSD Checklist (PCL), for diagnosing PTSD among 44 traumatized, adult, public-sector mental health patients recruited through a community mental health program. Participants completed the PCL and the Clinician-Administered PTSD Scale (CAPS), which is considered the "gold standard" for determining PTSD diagnoses. Data provide preliminary support for the use of the PCL as a screening instrument in public psychiatric settings, indicating that the optimal cut-point for adults with severe mental illness is about 54 (with slightly higher or lower recommended cut-points depending on the clinical context and purpose of the PCL). Such data are critical to ensuring that public-sector mental health patients with trauma-related difficulties are identified and referred for appropriate services.     

Enhancing patient safety in psychiatric settings

OBJECTIVE: There is growing national consensus that use of institutional measures of control, such as seclusion, restraint, enforced medications, and hand-cuffed transport, within psychiatric hospitals is all too common and is potentially counter-therapeutic. Unfortunately, little is known about how to reduce such measures of last resort. This article reviews the available literature and describes a proposed research agenda involving a behavioral effort, the Engagement Model, for reducing seclusion and restraint procedures and enhancing patient safety in psychiatric settings. METHODS: Using Medline and PsychInfo, we reviewed studies that specifically evaluated efforts to reduce seclusion and restraint on psychiatric units. Key search terms included seclusion, restraint, reduc*, psychiatric patient safety, psychiatric safety, psychiatric sanctuary, and quality of care psychiatry. RESULTS: Only very limited data are available on reducing measures of last resort and improving the safety of psychiatric settings, and virtually no controlled data are available concerning the effectiveness of specific behavioral efforts on subsequent reduction of seclusion and restraint events. In light of the paucity of data, we describe efforts to incorporate and evaluate such a model in a large academic psychiatric hospital using a multiple baseline times-series design and review principles for and obstacles to implementing this model. CONCLUSIONS: It is hoped this discussion will stimulate research on this understudied topic and provide a framework for improving patient safety in psychiatric settings.     

Statins and fenofibrate affect skeletal muscle chloride conductance in rats by differently impairing ClC-1 channel regulation and expression

Background and purpose:

Statins and fibrates can produce mild to life-threatening skeletal muscle damage. Resting chloride channel conductance (gCl), carried by the ClC-1 channel, is reduced in muscles of rats chronically treated with fluvastatin, atorvastatin or fenofibrate, along with increased resting cytosolic calcium in statin-treated rats. A high gCl, controlled by the Ca²⁺-dependent protein kinase C (PKC), maintains sarcolemma electrical stability and its reduction alters muscle function. Here, we investigated how statins and fenofibrate impaired gCl.

Experimental approach:

In rats treated with fluvastatin, atorvastatin or fenofibrate, we examined the involvement of PKC in gCl reduction by the two intracellular microelectrodes technique and ClC-1 mRNA level by quantitative real time-polymerase chain reaction. Direct drug effects were tested by patch clamp analysis on human ClC-1 channels expressed in human embryonic kidney (HEK) 293 cells.

Key results:

Chelerythrine, a PKC inhibitor, applied in vitro on muscle dissected from atorvastatin-treated rats fully restored gCl, suggesting the involvement of this enzyme in statin action. Chelerythrine partially restored gCl in muscles from fluvastatin-treated rats but not in those from fenofibrate-treated rats, implying additional mechanisms for gCl impairment. Accordingly, a decrease of ClC-1 channel mRNA was found in both fluvastatin-and fenofibrate-treated rat muscles. Fenofibric acid, the in vivo metabolite of fenofibrate, but not fluvastatin, rapidly reduced chloride currents in HEK 293 cells.

Conclusions and implications:

Our data suggest multiple mechanisms underlie the effect of statins and fenofibrate on ClC-1 channel conductance. While statins promote Ca²⁺-mediated PKC activation, fenofibrate directly inhibits ClC-1 channels and both fluvastatin and fenofibrate impair expression of mRNA for ClC-1.