B‐Cell‐Dependent Memory T Cells Impede Nonmyeloablative Mixed Chimerism Induction in Presensitized Mice

Presensitization to HLA antigens limits the success of organ transplantation. The achievement of donor‐specific tolerance via mixed chimerism could improve outcomes of transplantation in presensitized patients. In presensitized B‐cell‐deficient μMT B6 mice, we developed nonmyeloablative bone marrow transplantation (BMT) regimens that successfully tolerized presensitized T cells, achieving long‐term (LT) multilineage chimerism and tolerance to donor‐type skin. To apply these regimens in wild‐type (WT) animals while avoiding antibody‐mediated destruction of donor bone marrow cells, presensitized WT B6 mice were rested >2 years to allow alloantibody clearance. However, chimerism and tolerance were not reliably achieved in LT presensitized WT B6 mice in which alloantibody had declined to minimal or undetectable levels before BMT. Strong antidonor memory T‐cell responses were detected in LT presensitized WT B6 mice after rejection of donor bone marrow (BM) occurred, whereas levels of alloantibody remained consistently low. In contrast, presensitized μMT B6 mice had diminished memory T‐cell responses compared to WT B6 mice. These data implicate T‐cell memory, but not alloantibody, in rejection of donor BM in LT presensitized WT mice.     

Chronic hepatitis C infection and sex hormone levels: effect of disease severity and recombinant interferon-alpha therapy

Background: We aimed to investigate the associations between androgen status and markers of liver disease severity and to determine the effect of interferon‐α (IFN‐α) treatment on sex hormone levels in the context of hepatitis C infection. Methods: We audited liver biopsy and sex hormone data from 35 men with chronic hepatitis C and a separate group of 11 men with hepatitis C who received IFN‐α treatment at Fremantle Hospital. Results: We found that men with low fibrosis scores (0–2) on the modified Knodell histological activity index were more likely to have lower sex hormone–binding globulin (SHBG) levels (38.2 ± 13.2 vs 66.6 ± 43.3 nmol/L, P < 0.001) and higher free testosterone levels (380.4 ± 102.0 vs 255.9 ±83.0 pmol/L, P = 0.01) than those with higher fibrosis scores (3–6). SHBG directly correlated with fibrosis scores (r = 0.37, P = 0.032). Free testosterone levels inversely correlated with liver fibrosis scores (r = ?0.43, P = 0.011). A transient reduction in total testosterone of 5.7 ± 4.2 nmol/L (P = 0.014) occurred within the first 6 months of IFN‐α therapy although free testosterone was unaffected. Conclusion: More severe liver disease was associated with lower free testosterone and higher SHBG. IFN‐α therapy reduced total testosterone but not to hypogonadal levels, with no decline in free testosterone. These data suggest that liver disease in hepatitis C infection modulates androgen status indirectly via increased SHBG. Screening for androgen deficiency in the context of hepatitis C infection should selectively target men with more severe liver disease or documented higher grade fibrosis.     

女性缩阴术30例临床分析

1 临床资料 2000-03/2004-06阴道松弛症女性30例,年龄24～44岁,其中24～30岁12例,占40%;31～40岁10例,占33.3%;41～44岁8例,占26.7%.术前检查阴道容三指以上,自诉因阴道松弛性生活时快感不足,均排除子宫脱垂、阴道炎及阴道肿瘤等疾病.手术在月经完全干净3 d后,采用硬膜外麻醉或局部麻醉下进行.患者取膀胱截石位,于阴道口外6点处设计出一弧形切口,左右宽度3～7 cm具体视阴道松弛程度而定,沿设计线在阴道黏膜下注射盐酸肾上腺素盐水以利止血和分离,切开并剥离阴道后壁黏膜,暴露黏膜下肌肉,以可吸收缝线拉拢缝合阴道黏膜下左右侧阴道括约肌及肛提肌等,从阴道深处开始缝合,缝到阴道口附近处.缝合后阴道容二指松.阴道后壁黏膜不切除,阴道黏膜下肌肉左右对叠缝合后阴道黏膜自然向上膨隆形成一皱襞.阴道外的横弧形切口因黏膜下肌肉左右拉拢缝合,变成竖形切口以丝线间断缝合.术后静滴抗生素3 d,每天以碘伏清洗切口1次,7 d拆线,2 mo内禁止性生活.术后随访3～6 mo,自诉性快感明显增强22例,改善8例.     

Induction of neuronal phenotypes from NG2+ glial progenitors by inhibiting epidermal growth factor receptor in mouse spinal cord injury

Besides neural stem cells, some glial cells, such as GFAP+ cells, radial glia, and oligodendrocyte progenitor cells can produce neuronal cells. Attractively, NG2+ glial progenitors exhibit lineage plasticity, and they rapidly proliferate and differentiate in response to central nervous system (CNS) injuries. These attributes of NG2+ glial progenitors make them a promising source of neurons. However, the potential of neuronal regeneration from NG2+ glial progenitors in CNS pathologies remains to be investigated. In this study, we showed that antagonizing epidermal growth factor receptor (EGFR) function with EGFR inhibitor caused a significant number of proliferative NG2+ glial progenitors to acquire neuronal phenotypes in contusive spinal cord injury (SCI), which presumably led to an accumulation of newly generated neurons and contributed to the improved neural behavioral performance of animals. In addition, the neuronal differentiation of glial progenitors induced by EGFR inhibitor was further confirmed with two different cell lines either in vitro or through ex vivo transplantation experiment. The inhibition of EGFR signaling pathway under the gliogenic conditions could induce these cells to acquire neuronal phenotypes. Furthermore, we find that the Ras‐ERK axis played a key role in neuronal differentiation of NG2+ glial progenitors upon EGFR inhibition. Taken together, our studies suggest that the EGFR inhibitor could promote neurogenesis post SCI, mainly from the NG2+ glial progenitors. These findings support the possibility of evoking endogenous neuronal replacement from NG2+ glial progenitors and suggest that EGFR inhibition may be beneficial to CNS trauma. © 2012 Wiley Periodicals, Inc.     

Diagnostic accuracy of anorectal manometry for fecal incontinence: a meta-analysis

Background: Anorectal manometry (ARM) is conventionally used to assess patients with fecal incontinence (FI). This review aims to establish the diagnostic accuracy of ARM for FI.

Method: A search of MEDLINE, EMBASE, Science Citation Index Expanded and Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library was performed. Studies examining the sensitivity and specificity of ARM measures, either individually or combined, in the diagnosis of FI, were included. Data analysis was conducted using the bivariate statistical method.

Results: Seven studies were included out of an initial search of 1499 studies. The summary sensitivity and specificity for ARM as an overall test were 0.80 (95% confidence interval (CI): 0.69–0.88) and 0.80 (95% CI: 0.65–0.90), respectively. The diagnostic odds ratio (DOR) for ARM was found to be 16.61 (95% CI: 5.52–50.03). The positive likelihood ratio (PLR) and negative likelihood ratio (NLR) for ARM were found to be 4.09 (95% CI: 2.11–7.94) and 0.25 (95% CI: 0.14–0.42), respectively. Subgroup analysis based on four studies reporting on maximum resting pressure (MRP) demonstrated a sensitivity, specificity, DOR, PLR and NLR of 0.60 (95% CI: 0.38–0.79), 0.93 (95% CI: 0.80–0.97), 20.0 (95% CI: 4.00–91.00), 8.60 (95% CI: 3.00–24.30) and 0.43 (95% CI: 0.24–0.76), respectively.

Conclusion: ARM has been shown to be an accurate test for diagnosing FI. Further studies are required to establish the diagnostic accuracy of individual ARM measures.