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。     

Cancers of the prostate, penis, and testicles: epidemiology, prevention, and treatment

Cancer is a disease that most people fear. Nurses are required to provide information on how to avoid cancer, and, once the diagnosis is made, how to cope with it. Prevention and early detection of the cancers described in this article are in the very early stages of knowledge development, but general health promotion guidance can be offered on how to avoid most cancers (ie, no tobacco use, a high-fiber and low fat diet, exercise, and maintaining a normal weight). Nurses also can advise patients to be screened for colorectal cancer at the appropriate ages and time intervals and to be aware as new developments occur in the scientific base for screenings in the areas of prostate, penile, and testicular cancer. Finally, coping with these forms of cancer often requires the patient to make major lifestyle and psychological changes, especially if surgery in the genital area occurs. Decreased libido, incontinence, and impotence are major complications that can occur with these illnesses. The male cancers described vary tremendously in their prevalence, incidence, mortality, treatment, and survival rates. Within this group, there are remarkably positive outcomes and outcomes much in need of improvement. Penile and testicular cancers are the bright spots in this picture; both are uncommon, and both are eminently treatable. Prostate cancer, on the other hand, is quite common, difficult to screen, difficult to treat without major sexual problems, and yet receives relatively little funding from the NIH. Although as many men die from prostate cancer as women die from breast cancer, NIH funds breast cancer research at much higher levels than prostate cancer. According to the latest data available at the NIH Web site, during the 1990s, the amount of NIH funding varied from four times more for breast cancer (1993) to 2.9 times more in 1999. For fiscal year 2002, NIH is providing $522 million in funding for breast cancer and $278 million for prostate cancer. Private foundation funds for prostate cancer are much smaller than those available for breast cancer. Both types of cancer are extremely important to address, and both should receive adequate research attention. Nurses can advocate for more funding for prostate cancer, from basic science approaches to behavioral science strategies.     

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.     

A Stage I pilot study of acceptance and commitment therapy for methadone detoxification

Background

While agonist replacement therapies are effective for managing opioid dependence, community treatment programs are increasingly choosing detoxification. Unfortunately, success rates for opioid detoxification are very low, in part, due to physical and psychological symptoms associated with opioid withdrawal. Few behavior therapies specifically address the distressing experiences specific to opioid withdrawal. A novel behavioral treatment, acceptance and commitment therapy (ACT), works from the premise that the avoidance of unpleasant private experiences (thoughts, feelings, bodily sensations) is ubiquitous yet may be pathogenic, resulting in treatment drop-out and further drug use.

Methods

This Stage I pilot study developed and tested an ACT-based opioid detoxification behavioral therapy. Opioid dependent patients (N = 56) who were attending a licensed methadone clinic were randomized to receive either 24 individual therapy sessions of ACT or drug counseling (DC) in the context of a 6-month methadone dose reduction program.

Results

While no difference was found on opioid use during treatment, 37% of participants in the ACT condition were successfully detoxified at the end of treatment compared to 19% of those who received DC. Fear of detoxification was also reduced across time in the ACT condition relative to DC.

Conclusion

This first study of ACT to assist opioid detoxification indicates promise. Research is needed to refine specific treatment strategies for this population to further strengthen effects.     

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.     

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.     

A word of caution: Early failure of Magmaris® bioresorbable stent after pulmonary artery stenting

Bioresorbable scaffolds (BRS) have been advocated as the fourth revolution in interventional cardiology medical devices with promising technology to improve the treatment of coronary artery disease with an event-free future. We describe the first reported use and early collapse of the Magmaris® Resorbable Magnesium Scaffold (RMS) stent (BIOTRONIK AG, Switzerland) to relieve left pulmonary artery severe stenosis in a newborn after the Norwood procedure. The stent collapse was detected 2 weeks after implantation and urgently treated with a balloon-expandable stent. This complication raises the alarm about the need to keep implanted RMS under scrutiny. The possibility of faster scaffold resorption in small babies or lack of sufficient radial force of RMS to resist acute vessel recoil has led to ineffective relief of branch pulmonary artery stenosis and failure to enable a safe short-term bridge to Stage II palliation.