Poor association between allergen-specific serum immunoglobulin E levels, skin sensitivity and basophil degranulation: a study with recombinant birch pollen allergen Bet v 1 and an immunoglobulin E detection system measuring immunoglobulin E capable of binding to FcɛRI

BACKGROUND: Results from several studies indicate that the magnitude of immediate symptoms of type I allergy caused by allergen-induced cross-linking of high-affinity Fc epsilon receptors on effector cells (mast cells and basophils) is not always associated with allergen-specific IgE levels. OBJECTIVE: To investigate the association of results from intradermal skin testing, basophil histamine release and allergen-specific IgE, IgG1-4, IgA and IgM antibody levels in a clinical study performed in birch pollen-allergic patients (n = 18). METHODS: rBet v 1-specific IgEs were measured by quantitative CAP measurements and by using purified Fc epsilon RI-derived alpha-chain to quantify IgE capable of binding to effector cells. Bet v 1-specific IgG subclasses, IgA and IgM levels were measured by ELISA, and basophil histamine release was determined in whole blood samples. Intradermal skin testing was performed with the end-point titration method. RESULTS: Our study demonstrates on the molecular level that the concentrations of allergen-specific IgE antibodies capable of binding to Fc epsilon RI and biological sensitivities are not necessarily associated. A moderate association was found between cutaneous and basophil sensitivity. CONCLUSION: Our results highlight the quantitative discrepancies and limitations of the present diagnostic tools in allergy, even when using a single allergenic molecule. The quantity of allergen-specific serum IgE is only one component of far more complex cellular systems (i.e. basophil-based tests, skin tests) used as indirect diagnostic tests for IgE-mediated allergic sensitivity.     

脂肪来源间充质干细胞对大鼠肝移植的免疫调节作用

目的探讨大鼠脂肪来源间充质干细胞(MSC)对大鼠肝移植术后急性排斥反应的作用。方法分离、培养SD大鼠MSC,体外混合淋巴细胞培养(MLC)体系中,研究MSC对Wistar大鼠T细胞增殖的抑制作用。以SD与Wistar大鼠为供受体建立肝移植模型。随机分为MSC处理组与空白对照组,术后第7天检测肝功能、血清白细胞介素(IL)-2和白细胞介素(IL)-10水平、肝组织病理形态及肝细胞凋亡。结果体外MLC中,Wistar大鼠T细胞增殖明显受抑,抑制率为48.44%。实验组血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总胆红素(TBIL)、IL-2、IL-10分别为(134.2±45.0)、(162.5±30.5)U/L、(30.6±5.4)μmol/L、(187.35±18.26)、(193.95±37.62)μg/L;对照组上述指标分别为(355.6±54.3)、(296.4±71.2)U/L、(145.7±28.6)μmoL/L、(295.73±57.15)、(75.12±11.23)μg/L,两组差异有统计学意义(P<0.05);病检提示实验组排斥反应较对照组明显减轻;脱氧脲核苷酸缺口末端标记(TUNEL)检测提示实验组肝细胞凋亡程度明显低于对照组(P<0.05)。结论供体来源MSC能明显抑制MLC体系中受体源T细胞的增殖,并能显著减轻大鼠肝移植术后急性排斥反应。     

Alemtuzumab (CAMPATH 1H) Induction Therapy in Cadaveric Kidney Transplantation—Efficacy and Safety at Five Years

Alemtuzumab is a powerful lymphocyte depleting antibody currently being evaluated in solid organ transplantation. This paper describes 5-year results of a single center study of alemtuzumab as induction in renal transplantation. Thirty-three renal transplant recipients received 20 mg alemtuzumab on day 0 and 1, followed by half-dose cyclosporin monotherapy (trough concentration 75-125 ng/mL) from day 3. They were compared in a retrospective contemporaneous-controlled manner with 66 kidney transplant recipients transplanted in the same period and center who received conventional immunosuppression with cyclosporin, azathioprine and prednisolone. In the alemtuzumab group 12% of recipients died compared to 17% in the control group (p = 0.48); likewise graft loss was similar in both groups (21% vs. 26%, respectively, p = 0.58). Incidence of acute rejection was also comparable at 5 years (31.5% vs. 33.6%), although the pattern of rejection was different with 14% patients in the alemtuzumab group experiencing rejection over 1 year post-transplant compared to none in the control group. There was no significant difference between groups in terms of infection or serious adverse events. While acknowledging the limitations of a relatively small single-center study, results suggest that alemtuzumab induction allowed satisfactory long-term patient and graft survival equivalent to that seen with standard triple immunosuppression, while avoiding steroid therapy.     

大白鼠尾动脉吻合实验的方法与体会

报告了960次大白鼠尾动脉吻合实验,采用端端吻合法800次,即刻通畅率96.5％,套叠吻合法160次,即刻通畅率100％。作者认为利用大白鼠尾动脉作吻合训练,具有节省动物、可多次操作、无需无菌条件、操作简单易行等优点,并介绍了操作方法和注意点。     

头皮电烧伤骨外露带毛发皮瓣修复

目的：探讨头皮电烧伤骨外露用头皮扩张皮瓣移植修复的临床效果。方法：采用早期扩创,保留部分坏死骨质,用邻近头皮扩张使带毛发的头皮面积扩大后移植覆盖创面,电性失活骨质在血循环良好的皮瓣覆盖下,为周边及基底健康骨质生长起到支架作用,皮瓣扩张到一定面积后移植到裸露骨质上,使其得以修复。结果：在治疗的9例中,除1例皮瓣边缘在1．5cm×1．5cm坏死外,其余皮瓣全部成活,未发生感染坏死,创面均一次性封闭。结论：头皮电烧伤骨外露扩张后皮瓣带毛发修复,可缩短创面愈合时间,外形较好,易掌握,效果较为满意。     

Granulomatous jellyfish dermatitis

The induction of a granulomatous inflammation by jellyfish toxins is rare. More typically, acute toxic and urticarial reactions are seen. An 11-year-old boy developed a striated urticarial erythema on the left cheek after contact with a gelatinous mass while swimming in the sea in Croatia. After initial erosion, a striated induration developed in the area of contact. Histological examination revealed a granulomatous inflammation with some eosinophils. While topical steroid-based antiinflammatory and antibacterial therapy over several weeks was not effective, topical therapy with tacrolimus 0.1% for two two-week treatment periods led to healing of the skin changes with a slight scar. There was no clinical recurrence after 5 month of follow-up.     

Individualized Mycophenolate Mofetil Dosing Based on Drug Exposure Significantly Improves Patient Outcomes After Renal Transplantation

Efficacy and safety of mycophenolate mofetil (MMF) may be optimized with individualized doses based on therapeutic monitoring of its active metabolite, mycophenolic acid (MPA). In this 12-month study, 137 renal allograft recipients from 11 French centers receiving basiliximab, cyclosporine A, MMF and corticosteroids were randomized to receive either concentration-controlled doses or fixed-dose MMF. A novel Bayesian estimator of MPA AUC based on three-point sampling was used to individualize doses on posttransplant days 7 and 14 and months 1, 3 and 6. The primary endpoint was treatment failure (death, graft loss, acute rejection and MMF discontinuation). Data from 65 patients/group were analyzed. At month 12, the concentration-controlled group had fewer treatment failures (p = 0.03) and acute rejection episodes (p = 0.01) with no differences in adverse event frequency. The MMF dose was higher in the concentration-controlled group at day 14 (p < 0.0001), month 1 (p < 0.0001) and month 3 (p < 0.01), as were median AUCs on day 14 (33.7 vs. 27.1 mg*h/L; p = 0.0001) and at month 1 (45.0 vs. 30.9 mg*h/L; p < 0.0001). Therapeutic MPA monitoring using a limited sampling strategy can reduce the risk of treatment failure and acute rejection in renal allograft recipients 12 months posttransplant with no increase in adverse events.     

Usefulness of PCR Strategies For Early Diagnosis of Chagas'' Disease Reactivation and Treatment Follow-Up in Heart Transplantation

Heart transplantation (HTx) is a useful therapy for end‐stage Chaga? cardiomyopathy; however, Chagas reactivation remains a mayor complication. Parasitological methods offer poor diagnostic sensitivity, and use of more sensitive tools such as the Polymerase chain reaction (PCR) is usually necessary. In the present study, reactivation incidence and PCR usefulness for early reactivation diagnosis, as well as for treatment response evaluation during follow‐up, were analyzed using Strout parasite detection test, in 10 of 222 consecutive HTx patients suffering Chagas cardiomyopathy. PCR strategies targeted to minicircle sequences (kDNA, detection limit 1 parasite/ 10 mL blood) and miniexon genes (SL‐DNA, 200 parasite/10 mL) were performed to compare parasite burdens between samples. No patients received prophylactic antiprotozoal therapy (benznidazole). Five patients (50%) exhibited clinical reactivation within a mean period of 71.6 days; positive Strout results were observed in most cases presenting clinical manifestations. kDNA‐PCR was positive 38–85 days before reactivation, whereas SLDNA‐PCR became positive only 7–21 days later, revealing post‐HTx parasitic load enhancement present prior to clinical reactivation development. Reactivations were successfully treated with benznidazole and generated negative PCR results. Results observed in this study indicate the value of PCR testing for an early diagnosis of Chagas reactivation as well as for monitoring treatment efficacy.     

Immunosuppression Minimization in Pediatric Transplantation

The greatest benefit of immunosuppression minimization for children may lie in improving patient morbidity, by the elimination of the inherent side effects of steroid and calcineurin inhibitors (CNI). The newer generation of powerful induction and maintenance immunosuppressants offers an option for selected immunosuppression minimization strategies, some of which have been shown to also reduce graft morbidity. Steroid minimization and avoidance in single-center uncontrolled trials have shown early promise and the availability of data from an ongoing randomized, prospective, controlled trial of steroid avoidance in children will provide necessary data to support a practice change for steroid elimination in children. Calcineurin inhibitor minimization and addition of mycophenolate mofetil (MMF) or sirolimus have shown variable improvements in renal function, though suboptimal efficacy and safety with the currently proposed regimes have limited their application. Randomized, prospective studies of steroid and calcineurin inhibitor minimization and/or avoidance are warranted to clearly confirm the short and long-term safety and efficacy of alternative immunosuppression combinations. Linked pharmacokinetic and mechanistic studies within these trials will allow for optimizing drug dosing and monitoring. This article reviews published experience to date with steroid and calcineurin minimization in pediatric renal transplantation and discusses the risks and benefits of these approaches.