甲基强的松龙联合丙种球蛋白治疗重症手足口病的疗效分析

目的：探讨甲基强的松龙联合丙种球蛋白治疗重症手足口病的临床疗效。方法回顾性分析重症手足口病患儿214例的临床资料,根据治疗方法分为常规治疗组与联合治疗组。联合治疗组在常规治疗的基础上给予足量、早期甲基强的松龙联合丙种球蛋白治疗。比较两组临床疗效。结果联合治疗组的临床疗效显著优于常规治疗组（P＜0.05）。联合治疗组体温恢复正常时间、皮疹消退时间、神经症状和肺炎表现消失时间、白细胞、血糖降至正常时间显著短于常规治疗组（P＜0.01）。结论早期、足量甲基强的松龙联合丙种免疫球蛋白治疗重症手足口病能够显著提高临床疗效,值得临床推广。     

RSV毛细支气管炎SP-D基因多态性与甲强龙疗效的关系

目的 探讨汉族儿童呼吸道合胞病毒（respiratory syncytial virus,RSV）毛细支气管炎肺表面活性蛋白D（surfactant protein D,SP-D）基因多态性与甲强龙治疗疗效的关系.方法 采用MGB测序法检测150例RSV毛细支气管炎和150例健康对照组SP-D-11位点、160位点基因多态性,并进行基因型、等位基因型频率分析,分析基因多态性和毛细支气管炎发病的关系,采用（x2）检验.150例患儿在常规治疗基础上加用甲强龙静脉滴注,连用3d.分析SP-D基因多态性对甲强龙治疗疗效的影响,采用方差（F）分析.结果 病例组SP-D Met11Thr位点TT、CT、CC三种基因型频率分别为7.3％、44.0％、48.7％,T、C等位基因频率分别为29.3％、70.7％.三种基因型及等位基因频率与对照组比较差异有统计学意义（x2 =6.751、5.823,P＜0.05）.SP-D Ala160Thr位点AA、GA、GG三种基因型频率分别为4.0％、29.3％、66.7％,A、G等位基因频率分别为18.7％、71.3％,两组基因型及等位基因频率与对照组比较差异无统计学意义（x2 =0.182、0.181,P＞0.05）.不同基因型在平均住院天数、临床症状改善差异均无统计学意义（P＞0.05）.结论 杭州地区汉族儿童存在SP-D基因多态性,SP-DMet1 1Thr位点与RSV毛细支气管炎疾病易感性存在关联,SP-D Met11Thr C等位基因可能易感基因;而SP-D Ala160Thr位点与RSV毛细支气管炎疾病易感性无关联.SP-DMet1 1Thr、SP-D Ala160Thr的多态性并不影响甲强龙治疗的疗效.     

甲泼尼龙治疗AECOPD临床分析

目的了解甲泼尼龙治疗AECOPD的临床效果。方法将158例AECOPD患者随机分为两组,实验组81例,对照组77例;对照组常规抗炎、平喘、祛痰、氧疗、等对症治疗,实验组在此基础上,加用甲强龙80 mg/次,2次/d静点。治疗前和治疗第5 d、第10 d分别观察症状和体征、动脉血PaO2变化、FEV1%预计值变化。结果治疗第5 d、第10 d,两组症状和体征缓解率比较、两组动脉血PaO2变化值比较、两组FEV1%预计值变化值比较,两者差异均有统计学意义。结论甲泼尼龙可快速缓解AECOPD症状、缩短病程。     

Glucocorticoid inhibition of neuropathic limb edema and cutaneous neurogenic extravasation

Sciatic nerve section in rats evokes chronic limb edema, pain behavior, and hindpaw hyperalgesia, a syndrome resembling the complex regional pain syndrome type II (CRPS II or causalgia) in man. Glucocorticoids such as methylprednisolone (MP) have been used as analgesic and anti-edematous agents in patients suffering from CRPS, and interestingly these therapeutic effects appear to persist in some patients after stopping the medication. Similar to the CRPS clinical response to glucocorticoids, we now demonstrate that chronic hindpaw edema in the sciatic transection CRPS model is reversed by a continuous infusion of MP (3 mg/kg/day over 21 days), and this anti-edematous effect persists for at least 1 week after discontinuing MP. Furthermore, there is a chronic increase in spontaneous protein extravasation in the hindpaw skin of rats after sciatic transection, similar to the increased protein extravasation observed in the edematous hands of CRPS patients. A 2-week infusion of MP (3 mg/kg/day) reduced spontaneous protein extravasation in the hindpaw skin by 80%. We postulated that increased spontaneous neurogenic extravasation resulted in development of limb edema in both the animal model and the CRPS patient, and that the anti-edematous effects of MP are due to an inhibition of spontaneous extravasation. Additional experiments examined the inhibitory effects of MP infusion on electrically-evoked neurogenic extravasation in the hindpaw skin of normal rats. MP inhibition was dose- and time-dependent, with an ED₅₀ of 1.2 mg/kg/day for a 14-day continuous infusion of MP, and a maximum inhibitory effect requiring 17 days of MP infusion (3 mg/kg/day). MP (3 mg/kg/day for 14 days) also blocked both capsaicin- and SP-evoked neurogenic extravasation, indicating a post-junctional inhibitory effect. Our interpretation is that increased spontaneous neurogenic extravasation in this CRPS model contributed to the development and maintenance of hindpaw edema, and that chronic MP administration dose- and time-dependently blocked neurogenic extravasation at a post-junctional level, thus reversing spontaneous extravasation and limb edema in this model.     

Serum cystatin C, a potent inhibitor of cysteine proteinases, is elevated in asthmatic patients

The effect of asthma pathogenesis on serum cystatin C, a potent inhibitor of cysteine proteinases and a newly proposed marker of the renal function, has not been yet determined. The objectives were to determine the 24-h pattern of cystatin C and creatinine concentrations in sera of asthmatic patients in order to test whether their concentrations might reflect circadian rhythms, the disease severity and the effect of therapy. Serum concentrations of cystatin C and creatinine were determined in steroid-independent and steroid-dependent asthmatics before and after 1 week of treatment with methylprednisolone and cyclosporin A, respectively. Samples were collected every 4 h during a 24-h period. Little or no significant effects of time on cystatin C and creatinine concentrations over a 24-h period were observed in healthy and asthmatic sera. However, significantly higher cystatin C concentrations were found in asthmatic patients compared to controls which suggests its role in the pathogenesis of asthma. Methylprednisolone increased and cyclosporin A decreased serum cystatin C concentrations after 1 week of therapy. Additionally these results support the need for the evaluation of cystatin C as a marker of glomerular filtration rate determination in asthma.     

甲基泼尼松龙联合肝素治疗儿童重型腹型紫癜的临床观察

目的 观察甲基泼尼松龙联合小剂量肝素治疗腹型过敏性紫癜的疗效.方法 选择2006年1月至2007年12月收住的83例腹型过敏性紫癜患儿随机分为氢化可的松治疗组(A组)、甲基泼尼松龙治疗组(B组)、甲基泼尼松龙联合肝素治疗组(C组).A组应用氢化可的松4～8 mg/kg,加入5%葡萄糖盐水100 ml中静脉点滴,每天1次.7～14 d后改为泼尼松口服并逐渐减量;B组应用甲基泼尼松龙2～4 mg/kg,加入5%葡萄糖盐水100ml中静脉点滴,7～14 d后改为泼尼松口服;C组在B组的基础上给予肝素钠按0.25～0.75 mg/(kg·d)加入5%葡萄糖盐水100 ml中静脉点滴7～10 d,治疗过程中和治疗后观察皮疹、腹痛、消化道出血等临床症状的改变,记录疾病反复率、合并肾损害病例尿常规恢复时间以及水钠潴留、电解质紊乱、出血等不良反应.结果 甲基泼尼松龙联合肝素治疗组在皮疹消退、腹痛缓解及消化道出血停止时间、尿检恢复正常时间均优于氢化可的松组及单纯甲基泼尼松龙组,疾病反复率也低于上述两组.结论 甲基泼尼松龙联合肝素治疗腹型过敏性紫癜在控制症状、降低反复率等方面疗效优于氢化可的松组及甲基泼尼松龙组,无明显不良反应,为治疗重型腹型过敏性紫癜的理想方案.     

大剂量甲基强的松龙治疗脊髓损伤鼠的实验研究

目的 探讨大剂量泼尼松（MP）治疗脊髓损伤的可行性。方法 SD成年雌性大鼠78只，随机分成13组：即假损伤组；脊髓挫伤组（SCI组）及大剂量甲基强的松龙治疗组（MP组），再分为：1d组、3d组、7d组、14d组、21d组、28d组；用改良的Allen装置造成T12脊髓节段挫裂伤。在手术前及术后进行BBB（Basso，Beattie and Bresnahan）评分。术后立即采用大剂量冲击疗法，腹腔注射MP30mg／kg，伤后1h开始，按5．4mg／（k·h）计算23h总量，分4次腹腔注射，在不同时间点处死大鼠。取损伤节段上、下长约0．5cm脊髓连续冰冻切片，间隔取片后分别以抗神经丝蛋白、突触素抗体行免疫组化ABC染色。在光学显微镜下观察各组NF、SYP在SD大鼠脊髓的表达分布情况。结果 MP明显改善损伤脊髓的病理形态。7，14，21，28d时MP组NF染色轴突数目均明显高于SCI组。而灰度值均明显低于SCI组。MP治疗组较SCI组相同时间点神经学功能均有明显提高。结论 大剂量MP在脊髓损伤中后期明显促进其损伤后的再生，具有中远期疗效。     

The effects of immunosuppressants on FAS-mediated activation-induced cell death in human T lymphocytes

The effects of cyclosporin A (CsA) and methylprednisolone (MP) on Fas-mediated activation-induced cell death (FMAICD) of T lymphocytes were examined. T lymphocytes were activated with the immobilized anti-CD 3 and CD 28 monoclonal antibodies (MoAbs) (activation phase) and incubated further with the agonistic MoAb against Fas (death phase). Cell proliferation and DNA fragmentation were measured by XTT and diphenylamine assay. CsA in the activation phase inhibited DNA fragmentation mediated by anti-Fas MoAb but not MP. The combination of CsA and MP at the lower concentrations had little effect on FMAICD, although they had similar degrees of suppression on T lymphocyte proliferation as the maximum obtained by CsA or MP alone. In the death phase, MP induced apoptosis without 7C11 and CsA had no effects. These results indicate that the combination of CsA and MP at low concentrations could maintain FMAICD with the suppression on T lymphocyte proliferation.     

Skin atrophogenic potential of methylprednisolone aceponate (MPA)

The most prominent and most discussed local side effect of topical corticosteroids is the thinning of the skin. Therefore, the atrophogenic potential is an important indication of the quality of a new corticosteroid. Several studies have been conducted to investigate this parameter. In rats, the effect of breaking strength of the skin, the most appropriate model for evaluating atrophogenicity in animals, showed that MPA and prednicarbate (PC) reduced the breaking strengh only slightly compared to clobetasol propionate (CBP). These results indicate that MPA could be classified as a corticosteroid with low local atrophogenic potential. This was confirmed in humans by a placebo controlled double-blind study comparing intra/interindividuals MPA (cream, ointment and fatty ointment) and bethamethasone-17-valerate (BMV), CBP and PC (cream only) under occlusive dressing over 6 weeks. Three different parameters were assessed (dermal atrophy (clinical picture), surfometric measurement of the dermatoglyphic pattern, visual evaluation of telangiectasia). In all three formulations, MPA is of lower atrophogenic potential than CBP. While there is no statistical difference between BMV and MPA, the atrophogenic potential of MPA is low. In order to reflect more the clinical use of topical corticosteroids, MPA preparations (cream 0.1% and fatty ointment) has been evaluated in comparison to BMV in an 8-week non-occluded application test. MPA was applied once a day (5 days a week) and BMV twice in 20 healthy subjects according to a double-blind randomized design. Assessment of atrophogenic potential was performed weekly using clinical scores (atrophy and telangiectasia) as main criteria and skin thickness measurements (ultrasound imaging) as a second criterion. BMV cream gives higher numbers of telangiectasia than MPA preparations and vehicles. From the skin thickness measurements, MPA treatments once a day has a lower thinning potential than BMV twice a day. These findings were confirmed by clinical trials. In 1145 patients suffering from various types of eczema who used MPA in cream and ointment, mild atrophy of the skin was observed in only one patient. Moreover, clinical signs of atrophy were present in only two out of a group of 673 patients (590 adult and 83 children) treated with MPA fatty ointment. In a group of 66 patients who used this same MPA fatty ointment during 3–4 months, no signs of skin atrophy were observed. Considering animal and human studies, MPA can be classified as a corticoid with low atrophogenic potential.