The performance of primary human renal cells in hollow fiber bioreactors for bioartificial kidneys

Bioartificial kidneys (BAKs) containing human primary renal proximal tubule cells (HPTCs) have been applied in clinical trials. The results were encouraging, but also showed that more research is required. Animal cells or cell lines are not suitable for clinical applications, but have been mainly used in studies on BAK development as large numbers of such cells could be easily obtained. It is difficult to predict HPTC performance based on data obtained with other cell types. To enable more extensive studies on HPTCs, we have developed a bioreactor containing single hollow fiber membranes that requires relatively small amounts of cells. Special hollow fiber membranes with the skin layer on the outer surface and consisting of polyethersulfone/polyvinylpyrrolidone were developed. The results suggested that such hollow fiber membranes were more suitable for the bioreactor unit of BAKs than membranes with an inner skin layer. An HPTC-compatible double coating was applied to the insides of the hollow fiber membranes, which sustained the formation of functional epithelia under bioreactor conditions. Nevertheless, the state of differentiation of the primary human cells remained a critical issue and should be further addressed. The bioreactor system described here will facilitate further studies on the relevant human cell type.     

A new in vivo method to investigate antibiotic penetration and concentration in spontaneous infectious spondylodiscitis

Spontaneous discitis is unusual and typically affects children. Hematogenous delivery of an infectious organism is the likely main cause. Common treatment method including conservative and surgical treatments, which also needs prolonged antimicrobial therapy based on an effective inhibitory concentration, can be achieved on the local disc space. Intradiscal antibiotic concentration was measured after the disc was harvested after preventive administration of antibiotics in previous studies. On the one hand the disc cannot simulate the infection situation when the inflammation leads to end plate destruction, vascular invasion and increase of permeability. On the other hand antibiotic concentrations were measured in vitro which cannot tell the actual situation in vivo. It is necessary to find a reliable evaluation method to decide whether the antibiotic can penetrate and make an effective inhibitory concentration in the local disc at the beginning of the treatment in vivo. Systemic antibiotics like nutrients enter and leave the disc by the only way of passive diffusion. The postcontrast MRI has been widely used as a noninvasive method of studying transport into the disc. The enhancement following contrast administration can be measured in T1 sagittal MR images by placing suitable cursors and evaluating the signal intensity (SI) of the region. Therefore we hypothesise that serial postcontrast MRI can be used to measure antibiotic concentration in the infected intervertebral disc in vivo. If the hypothesis is verified, we can better determine the choice of antibiotics and antibiotic treatment regime at the beginning of the treatment to improve the treatment success rate.     

HLA-DR4 antigen and idiopathic dilated cardiomyopathy susceptibility: a meta-analysis involving 11,761 subjects

Idiopathic dilated cardiomyopathy (IDC) has been hypothesized as a multifactorial disorder initiated by an environment trigger in individuals with predisposing human leukocyte antigen (HLA) alleles. Published data on the association between HLA-DR4 antigen and IDC risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Studies in English-language articles were identified by a search of PubMed and Embase database (inception to June 2010). A total of 19 case-control studies including 1378 cases and 10,383 controls provided data on the association between HLA-DR4 antigen and genetic susceptibility to IDC. Overall, statistically elevated frequency of HLA-DR4 allele [OR (odds ratio), 1.58; 95% CI (confidence interval), 1.21-2.07; P = 0.0009] was found in patients with IDC compared with controls. When stratified by myocardial biopsy or non-biopsy cases, statistically increased risks were found for IDC in both subgroups. In the subgroup analysis by ethnicity, significantly increased risk was found among Europeans from 12 case-control studies (OR, 1.54; 95% CI, 1.11-2.12; P = 0.009). In conclusion, our results suggest that HLA-DR4 antigen is a low-penetrant risk factor for developing IDC in Europeans.     

Transcranial magnetic stimulation in different current directions activates separate cortical circuits

Transcranial magnetic stimulation (TMS) to the primary motor cortex (M1) produces a series of corticospinal descending waves, with a direct (D) wave followed by several indirect (I) waves. TMS inducing posterior-anterior (PA) current in the brain predominantly recruits the early I1-wave, whereas anterior-posterior (AP) directed current preferentially recruits the late I3-wave. However, it is not known whether I-waves elicited by different current directions are mediated by the same neuronal populations. We studied the neuronal mechanisms mediating I-waves by examining the influence of short-latency afferent inhibition (SAI) on various I-waves. SAI was tested with electrical median nerve stimulation at the wrist followed by TMS to the contralateral M1 at different current directions. Surface electromyograms and single motor units were recorded from the first dorsal interosseous muscle. SAI was weaker for the AP compared with that for the PA current direction. With increasing median nerve stimulation intensities, SAI increased for the PA direction but showed a U-shaped relationship for the AP direction. SAI produced more inhibition of late I-waves generated by PA than those generated by AP current direction. We conclude that late I-waves generated by PA and AP current directions are mediated by different neuronal mechanisms.     

肺错构瘤33例临床分析

肺部良性肿瘤不多见,肺错构瘤在肺部良性肿瘤中居第1位^[1]。肺错构瘤多在影像学检查中发现,文献报道在其发现的直径〈2cm的孤立性肺结节（GGO）中,约40％一45％为错构瘤^[2]。作者归纳1990—2007年间手术治疗的肺错构瘤33例,现将其诊断、治疗经验总结如下。     

Interpreting Clinical Reaction Time Change and Recovery After Concussion: A Baseline Versus Norm-Based Cutoff Score Comparison

ContextPreseason testing can be time intensive and cost prohibitive. Therefore, using normative data for postconcussion interpretation in lieu of preseason testing is desirable.ObjectiveTo establish the recovery trajectory for clinical reaction time (RT_clin) and assess the usefulness of changes from baseline (comparison of postconcussion scores with individual baseline scores) and norm-based cutoff scores (comparison of postconcussion scores with a normative mean) for identifying impairments postconcussion.DesignCase-control study.SettingMultisite clinical setting.Patients or Other ParticipantsAn overlapping sample of 99 participants (age = 19.0 ± 1.1 years) evaluated within 6 hours postconcussion, 176 participants (age = 18.9 ± 1.1 years) evaluated at 24 to 48 hours postconcussion, and 214 participants (age = 18.9 ± 1.1 years) evaluated once they were cleared to begin a return-to-play progression were included. Participants with concussion were compared with 942 control participants (age = 19.0 ± 1.0 years) who did not sustain a concussion during the study period but completed preseason baseline testing at 2 points separated by 1 year (years 1 and 2).Main Outcome Measure(s)At each time point, follow-up RT_clin (ie, postconcussion or year 2) was compared with the individual year 1 preseason baseline RT_clin and normative baseline data (ie, sex and sport specific). Receiver operating characteristic curves were calculated to compare the sensitivity and specificity of RT_clin change from baseline and norm-based cutoff scores.ResultsClinical reaction time performance declined within 6 hours (18 milliseconds, 9.2% slower than baseline). The decline persisted at 24 to 48 hours (15 milliseconds, 7.6% slower than baseline), but performance recovered by the time of return-to-play initiation. Within 6 hours, a change from baseline of 16 milliseconds maximized combined sensitivity (52%) and specificity (79%, area under the curve [AUC] = 0.702), whereas a norm-based cutoff score of 19 milliseconds maximized combined sensitivity (46%) and specificity (86%, AUC = 0.700). At 24 to 48 hours, a change from baseline of 2 milliseconds maximized combined sensitivity (64%) and specificity (61%, AUC = 0.666), whereas a norm-based cutoff score of 0 milliseconds maximized combined sensitivity (63%) and specificity (62%, AUC = 0.647).ConclusionsNorm-based cutoff scores can be used for interpreting RT_clin scores postconcussion in collegiate athletes when individual baseline data are not available, although low sensitivity and specificity limit the use of RT_clin as a stand-alone test.     

认知疗法辅助治疗产后抑郁症疗效观察

目的探讨认知疗法对产后抑郁症患者的辅助治疗效果。方法将60例产后抑郁症患者随机分为舍曲林联合认知治疗组及单用舍曲林治疗组各30例进行对照研究,疗程8周。在治疗前及治疗后、出院后第3个月和第6个月进行随访时各做1次汉密尔顿抑郁量表（HAMD）、Zung氏抑郁自评量表（SDS）评定疗效,其评定结果采用t检验。结果两组在治疗后第8周末,疗效未见统计学差异;在出院后第3个月和第6个月进行随访时,两组疗效有显著性统计学差异,研究组远期效果优于对照组。结论认知疗法辅助治疗产后抑郁症可使治疗效果更持久。