A double‐blind,randomized trial of 0.05% betamethasone vs. topical catalase/dismutase superoxide in vitiligo

Background Among all the topical immunomodulators, vitiligo's mainstay therapy includes topical corticosteroids. Many other non‐immune theories have also been suggested for vitiligo's pathogenesis, but the role of oxidative stress has gained more importance in recent years. Objective To compare the effect of topical 0.05% betamethasone vs. catalase/dismutase superoxide (C/DSO). Study design Randomized, matched‐paired, double‐blind trial. Setting Dermatology Section, University of Antioquia, Medellín, Colombia. Subjects Patients (aged > 18 years or between 12 and 18 years) with parent's informed consent, with stable or active bilateral vitiligo. Intervention Topical 0.05% betamethasone or C/DSO. Methods Two lesions similar to each other in size were chosen. All assessments were made by two blinded investigators, and photographs were subjected to morphometry analysis. Main outcome Skin repigmentation by digital morphometry. Results Twenty‐five patients were enrolled in the study (21 women and 4 men). Mean age of participants was 40 years (range: 12–74 years). One patient on C/DSO experienced a mild local erythematous papular rash that self‐resolved. At 4 months of therapy, there was no statistical difference on the percentage of repigmentation between betamethasone and C/DSO (5.63% ± 27.9 vs. 3.22% ± 25.8, respectively, P = 0.758). After 10 months of therapy, the percentage of skin repigmentation increased to 18.5 ± 93.14% with betamethasone and to 12.4 ± 59% with C/DSO, but again, we found no statistical differences (P = 0.79). Discussion and conclusions Few studies have described objective methods to evaluate repigmentation among vitiligo patients. Digital morphometry provides an objective assessment of repigmentation in vitiligo. Objective vitiligo repigmentation with topical C/DSO at 10 months is similar to topical 0.05% betamethasone. Although a mild adverse effect was related to the use of C/DSO, such finding was not severe enough to discontinue treatment.     

Meniscus tears of the knee: prospective evaluation with CT

A total of 209 patients underwent prospective axial computed tomography (CT) examinations of the knee to evaluate the ability of this technique to identify and characterize knee menisci in patients believed to have meniscus tears. Of the 359 knees examined, 105 subsequently underwent arthrography, arthroscopy, or arthrography and arthroscopic surgery. In this group, the sensitivity of CT was 88.5%, specificity was 95.5%, and accuracy was 91.5%. Although axial CT is a sensitive and effective method for the detection and characterization of tears involving the medial and lateral menisci, purely horizontal or nondisplaced peripheral tears may be difficult to demonstrate.     

An anti-EnaTS detected in the serum of an MiI homozygote

The serum of EH reacted with all red cells (RBCs) except her own, ficin- or trypsin-treated red cells, and En(a-) red cells. This reactivity defined an anti-EnaTS specificity. The red cells of the proposita typed as M-N+S-S+, Vw+Mur-Hil-Hut-Anek-Lane-, Wr(a-b+), EnaKT+. Red cells of five relatives were Vw+ and positive with her serum. Titration studies suggest that EH is genetically an MiI homozygote and that her Vw+ relatives are MiI heterozygotes. There is no history of consanguinity. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting studies have agreed with the serologic observations. A variant sialoglycoprotein of faster mobility than normal glycoprotein A, but no normal glycoprotein A, was detected on her red cells. Treatment with N-glycanase did not alter the mobility, which indicated that there was no N-glycosylation of residue 26. These findings are in agreement with the reported properties of the Mi.I-specific glycoprotein A. The relatives' Vw+ red cells showed the variant sialoglycoprotein and normal glycoprotein A. EH appears to be the first reported MiI homozygote.     

Time-dependent loss of surface complement regulatory activity during storage of donor blood

The survival of transfused red cells (RBCs) diminishes with time of in vitro storage in blood banks, but the molecular mechanisms underlying the slow but incessant deterioration are incompletely understood. To investigate the possibility that impaired resistance to autologous complement attack could play a role in this phenomenon, packed RBCs stored for variable periods were assayed for decay-accelerating factor (DAF) and CD59, two glycoinositol-phospholipid (GPI)-anchored, membrane- associated complement regulatory proteins that function physiologically to protect blood cells from autologous complement activation on their surfaces. Immunoradiometric and flow cytometric assays employing DAF and CD59 monoclonal antibodies showed that levels of both surface proteins gradually declined over 6 weeks. Digestion analyses with phosphatidylinositol-specific phospholipase C, an enzyme that releases GPI-anchored proteins from cell surfaces, showed that DAF and CD59 molecules with GPI anchors containing unacylated inositol were preferentially lost. These findings suggest: 1) that DAF and CD59 molecules with acylated GPI anchors are more stable in RBC membranes than are molecules with unacylated GPI anchors, and 2) that DAF and CD59 loss may participate with other membrane alterations that occur during in vitro storage in compromising the survival of transfused cells.     

Rapid development of enhanced clearance after high-dose cyclophosphamide

We have studied the disposition of cyclophosphamide, its major cytotoxic metabolite phosphoramide mustard, and the synthetic glucocorticoid dexamethasone in nine patients receiving high-dose cyclophosphamide daily for 2 days before bone marrow transplantation. The total body clearance of cyclophosphamide was observed to increase from 93 +/- 27 ml/min on the first day to 178 +/- 83 ml/min on the second day. This was associated with an increase in the clearance of dexamethasone from 369 +/- 104 ml/min to 526 +/- 123 ml/min. An increased rate of formation of phosphoramide mustard with higher peak concentrations was also seen. Simulation studies show that these changes are most likely the result of an increase in the hepatic metabolism of cyclophosphamide. These results show that high-dose cyclophosphamide causes an increase in its own clearance and that of dexamethasone through an apparent induction of hepatic-metabolizing enzymes detectable 24 hours after initial exposure to cyclophosphamide.     

转脑啡肽基因移植细胞微囊化对大鼠慢性周围神经损伤的镇痛作用

目的：观察微囊化转大鼠脑啡肽原基因（pENK）细胞移植对慢性脊神经压榨性损伤大鼠的镇痛效应. 方法：实验于2006-03/2007-04在郑州大学医学重点实验室完成.①实验方法：通过反转录-聚合酶链反应技术可获得大鼠pENK基因,Hind Ⅲ,ClaⅠ双酶切后,同相应双酶切的pLNCX2载体大片段连接,构建成pENK基因反转录病毒载体pLNCX2-Enk,然后用脂质体法将该载体转染PT67细胞,G418筛选,获得携带pENK基因高滴度反转录病毒产毒细胞系.用海藻酸钠-多聚赖氨酸-海藻酸钠微囊包埋后,进行体外培养,定期检测微囊化细胞活性和pENK分泌量变化.同时,将转基因细胞移植于慢性脊神经压榨性损伤大鼠的蛛网膜下腔.②实验分组：SD大鼠60只,其中53只按照Bennett和Xie法制作大鼠慢性左侧坐骨神经压迫性损伤模型,其中42只造模成功.术后1周,将动物按随机数字表法分为3组,每组16只：微囊化转基因细胞移植组、空囊移植组和阴性对照组.微囊化转基因细胞移植组、空囊移植组分别植入微囊化细胞悬液80 μL（约300个微囊）、空微囊悬液80 μL（约300个空囊）,阴性对照组不注射任何悬液.③实验评估：术后2周和8周行甲醛实验,在大鼠一侧后爪掌侧皮下注射体积分数为0.05的甲醛50 μL,观察其注射后1 h内的痛反应.采用Abbott等所推荐的以缩腿及舔爪时间之和作为行为学反应的指标.注射甲醛后,立即记录大鼠1 h内每5 min的缩腿及舔爪时间. 结果：①术后2周甲醛实验：空囊移植组第一时相的急性痛阶段（注射后5 min）和第二时相的慢性痛阶段（注射后41～45 min）大鼠的缩腿及舔爪时间都少于微囊化转基因细胞移植组（P＜0.01）.而在静息期,3组大鼠的缩腿及舔爪时间差异无显著性意义（P＞0.05）.②术后8周甲醛实验：3组大鼠的痛觉行为都呈明显的双时相反应.除了静息期（注射后5～15 min）,微囊化转基因细胞移植组在各时间点上大鼠的缩腿及舔爪时间均低于空囊移植组（P＜0.05）.微囊化转基因细胞移植组大鼠的缩腿及舔爪时间在第一时相的急性痛阶段和第二时相的慢性痛阶段都低于空囊移植组（P＜0.05）. 结论：微囊化转pENK基因细胞移植对慢性神经痛大鼠有一定的镇痛作用,有望成为运动员慢性疼痛治疗的新方法.     

Demographic characteristics and prevalence of serologic markers among donors who use the confidential unit exclusion process: the Retrovirus Epidemiology Donor Study

BACKGROUND: Most blood centers utilize a confidential unit exclusion (CUE) process, intended to reduce the risk of transfusion-associated infectious diseases by allowing high-risk donors confidentially to exclude their blood from use for transfusion. The effectiveness of this method remains controversial. STUDY DESIGN AND METHODS: Confirmatory or supplemental test results for antibodies to human immunodeficiency virus, human T-lymphotropic virus type I, and hepatitis C virus, as well as hepatitis B surface antigen and syphilis and screening test results for antibodies to hepatitis B core (antigen) and alanine aminotransferase levels were obtained for approximately 1.8 million units donated during 1991 and 1992 at five blood centers within the United States. The prevalences of these infectious disease markers in units that the donors confidentially excluded (CUE+) and units that the donors did not exclude (CUE-) were calculated and examined within demographic subgroups. RESULTS: Units that were CUE+ were 8 to 41 times more likely to be seropositive for antibodies to human immunodeficiency virus and hepatitis C virus, hepatitis B surface antigen, and syphilis and three to four times more likely to react for antibody to hepatitis B core (antigen) or to have elevated alanine aminotransferase levels than units that were CUE- (p < 0.001). The positive predictive value of CUE (the percentage of CUE+ units that were confirmed seropositive for any marker) was 3.5 percent, and the sensitivity of CUE (the percentage of confirmed-seropositive units that were CUE+) was 2.3 percent. CONCLUSION: The current CUE process has low sensitivity and apparently low positive predictive value, and in many cases, it appeared that donors misunderstood it. Yet, CUE was not a “random process,” as CUE+ units were more likely to be seropositive for any infectious disease marker than CUE- units. This suggests that efforts to improve the CUE system may be warranted. As risk factors for transfusion-transmitted infection become more difficult to identify by history-based screening, however, such efforts may have limited effect.