44Sacral extracorporeal magnetic stimulation is an effective treatment for pelvic floor dyssynergia; Comparative study with biofeedback therapy

Background: Recent development of extracorporeal magnetic stimulation (ECMS) which uses current‐changing magnetic fields allows the induction of electrical stimulation in the desired deep tissue. Recent study showed the sacral nerve stimulation reduces corticoanal excitability that may play a functional role in anal continence mechanisms. Preliminary study shows that ECMS of sacral nerve can modify pelvic floor function and expel rectal balloon in patients with pelvic floor dyssynergia (PFD). Aims: To evaluate the effect of ECMS compared with biofeedback therapy (BF) in patients with PFD. Methods and Materials: Thirty‐eight patients who fulfilled Rome II criteria for PFD by colon transit time and anorectal function tests, were randomly treated with 8 sessions of ECMS (2/weeks; n = 19) at prone position or BF (2/weeks; n = 19) at sitting position. Stimulation parameters were set at 50–80% of maximum intensity, 10 and 50 Hz frequency, 3 s burst length with 3 and 6 s off using arm‐typed stimulator (BioCom‐1000, Mcube Co., Korea). Symptom scores for constipation with/without anorectal function test were repeatedly measured after each treatment. Response was defined as 50% or more decreased symptom score after treatment (partial response: 30–50%, poor: <30%). Results: Fifteen patients (age 49.1 ± 13.4 years, mean ± SD; 4 men) completed 8 session of BF and 14 patients (54.5 ± 17.6 years, 3 men) completed 8 session of ECMS. Four patients of BF group discontinued treatment due to unsatisfactory therapeutic effect (n = 1) and withdrew consent (n = 3) and 5 patients of ECMS group discontinued treatment because of same reasons (n = 1, 4). Total symptom scores were significantly decreased after treatment of 8 session in both treatment groups (13.4 ± 6.6 vs. 4.3 ± 4.0 for BF, p = 0.009; 14.9 ± 5.6 vs. 3.4 ± 4.0 for ECMS, p < 0.001). Bowel movements per week were also significantly increased after treatment in both groups (median 2 vs. 7 for BF, p = 0.035; median 2 vs. 7 for ECMS, p = 0.008). Thirteen out of 15 patients showed response in BF group and 12 out of 14 showed good response in ECMS group. No adverse effects in both groups. Conclusions: ECMS is as effective as BF for the treatment of PFD. Long‐term effect of ECMS for the patients with pelvic floor dyssynergia need to be evaluated in the near future.     

薄层色谱溶剂系统的最优化方法——Ⅵ.均匀设计法的再探讨

就第Ⅱ报及第Ⅴ报提出的用于选取薄层色谱最佳溶剂系统的均匀设计法进行了进一步的改进及实验验证,使其更趋完善。结果表明,该法不仅适用于已知混合物,而且适用于未知混合物,是一种比较简捷、快速且行之有效的方法。     

Efficiency of cross presentation of vaccinia virus-derived antigens by human dendritic cells.

Dendritic cells (DC) utilize at least two pathways to process viral antigens onto MHC class I molecules. The conventional endogenous route is used to acquire antigens from both infectious and non-replicating virions. Exogenous pathways are used by DC to acquire and "cross-present" antigens derived from virus-infected donor cells that by themselves lack the ability to activate T cells directly. We analyzed the role of this pathway for antigens derived from vaccinia, a virus which inhibits DC maturation and causes extensive apoptosis of infected cells, yet is highly immunogenic. Using recombinant vaccinia virus encoding the influenza matrix protein as model vector, DC were shown to cross-present vaccinia-derived antigens from both apoptotic and necrotic infected cells to antigen-specific CD8(+) T cells. Efficient cross presentation required uptake of dead cells by immature DC and exposure to maturation stimuli, especially CD40 ligand. The responding CD8(+) T cells secreted IL-2 and IFN-gamma, proliferated and developed into cytotoxic effectors. Quantification of the cross presentation of vaccinia-derived antigens showed this pathway to be highly efficient, corresponding to a peptide pulse of 10-100 nM. While monocytes also phagocytosed apoptotic and necrotic cells, they were far less efficient at cross-presenting vaccinia-derived antigens to CD8(+) T cells. The ability of DC to cross-present vaccinia-derived antigens from infected apoptotic cells or necrotic cell lysates, bypasses the deleterious effects of direct infection of DC and provides one explanation for this pathogen's immunogenicity.     

Laparoscopic resection for a left adrenal black adenoma

Adrenal black adenoma (pigmented adenoma) is quite rare. Recently, we performed a laparoscopic resection for a functioning adrenal black adenoma. We report the case here.     

Differentiation of ICOS+ and ICOS− recent thymic emigrant regulatory T cells (RTE Tregs) during normal pregnancy,pre‐eclampsia and HELLP syndrome

Two different subsets of naturally occurring regulatory T cells (nT_regs), defined by their expression of the inducible co‐stimulatory (ICOS) molecule, are produced by the human thymus. To examine the differentiation of ICOS⁺ and ICOS^?CD45RA⁺CD31⁺ recent thymic emigrant (RTE) T_regs during normal pregnancy and in the presence of pre‐eclampsia or haemolysis elevated liver enzymes low platelet (HELLP)‐syndrome, we used six‐colour flow cytometric analysis to determine the changes in the composition of the ICOS⁺ and ICOS^? T_reg pools with CD45RA⁺CD31⁺ RTE T_regs, CD45RA⁺CD31^? mature naive (MN) T_regs, CD45RA^?CD31⁺ and CD45RA^?CD31^? memory T_regs. With the beginning of pregnancy until term, we observed a strong differentiation of both ICOS⁺ and ICOS^?CD45RA⁺CD31⁺ RTE, but not CD45RA⁺CD31^? MN T_regs, into CD45RA^?CD31^? memory T_regs. At the end of pregnancy, the onset of spontaneous term labour was associated with a significant breakdown of ICOS⁺CD45RA^?CD31^? memory T_regs. However, in the presence of pre‐eclampsia, there was a significantly increased differentiation of ICOS⁺ and ICOS^?CD45RA⁺CD31⁺ RTE T_regs into CD45RA^?CD31⁺ memory T_regs, wherein the lacking differentiation into CD45RA^?CD31^? memory T_regs was partially replaced by the increased differentiation of ICOS⁺ and ICOS^?CD45RA⁺CD31^? MN T_regs into CD45RA^?CD31^? memory T_regs. In patients with HELLP syndrome, this alternatively increased differentiation of CD45RA^?CD31^? MN T_regs seemed to be exaggerated, and presumably restored the suppressive activity of magnetically isolated ICOS⁺ and ICOS^? T_regs, which were shown to be significantly less suppressive in pre‐eclampsia patients, but not in HELLP syndrome patients. Hence, our findings propose that the regular differentiation of both ICOS⁺ and ICOS^?CD45RA⁺CD31⁺ RTE T_regs ensures a healthy pregnancy course, while their disturbed differentiation is associated with the occurrence of pre‐eclampsia and HELLP syndrome.     

Bone marrow microenvironment facilitating dendritic cell: CD4 T cell interactions and maintenance of CD4 memory

This study shows that bone marrow (BM) stroma expresses constitutively multiple adhesion molecules (ICAM-1, VCAM-1, MadCAM-1, P-selectin) relevant for the homing and infiltration of BM by blood derived T lymphocytes, and also the co-stimulatory molecule CD80, relevant for T cell activation. T cells were capable of homing to BM but not to thymus. Homing to BM involved the integrins LFA-1alpha and alpha4 which interact with the above constitutively expressed cell adhesion molecules (CAMs). CD3 T cells were detected together with BM resident CD11c dendritic cells (DCs), often enriched in follicle-like structures in BM parenchyma. Cognate interactions between transferred antigen specific transgenic CD4 T cells and antigen laden BM-DCs led to formation of multicellular clusters in situ in BM, to generation of lymphoblasts and to clonal T cell expansion within such clusters. The great majority of BM-CD4 T cells had a memory phenotype suggesting that the BM microenvironment facilitates maintenance of CD4 memory. These results extend and corroborate our previous findings on BM-CD8 T cell mediated immune responses. Together these findings suggest that DC-T cell interactions in BM play an important role in immune responses to blood-borne antigen and in the establishment of systemic immunity and long-term memory.     

Tacrolimus dosage requirements after initiation of azole antifungal therapy in pediatric thoracic organ transplantation

Azole antifungals inhibit the metabolism of tacrolimus mediated by CYP3A4. Upon initiation of azole therapy, the required dose reduction of tacrolimus is unknown. We reviewed our experience with azole antifungals in our pediatric thoracic transplant population receiving tacrolimus. Tacrolimus levels and dosage requirements were compared before and during azole therapy. Thirty-one patients received both tacrolimus and an azole antifungal (fluconazole = 9, itraconazole = 22). The tacrolimus dose was empirically reduced by approximately one-third when azole therapy was initiated. Mean tacrolimus dose requirements decreased by 68% within the first month of therapy (pre-azole: 0.27 +/- 0.14 mg/kg/day; 30 day post-azole: 0.087 +/- 0.069 mg/kg/day; p < 0.001). Despite a mean decrease in tacrolimus dose from baseline of 33, 42, and 55% on day 1, 2, and 4 of azole therapy, respectively, there was still an unintended 38% increase in tacrolimus levels during the first month of azole therapy. A calculated dose-reduction protocol of 50% on day of azole initiation, 70% on day 3, and 75% on day 14 should result in minimal mean changes in the tacrolimus levels. There was no difference in tacrolimus dose reduction between fluconazole and itraconazole groups. Azole antifungals markedly decrease tacrolimus requirements within the first few days of therapy. An initial reduction in tacrolimus dose by one-third is insufficient, and dose reduction of at least 50% upon azole initiation seems warranted. Once azole antifungal therapy is initiated, frequent therapeutic drug monitoring is required.