ProMACE/CytaBOM方案治疗难治性或复发性非霍奇金淋巴瘤的疗效观察

目的：探讨ProMACE/CytaBOM方案治疗难治性和(或)复发性非霍奇金淋巴瘤(NHL)的疗效。方法：采用ProMACE／CytaBOM方案治疗18例难治性和(或)复发性NHL患者，其中难治性NHL患者8例，复发性NHL患者10例。结果：5例难治性和(或)复发性NHL患者达到完全缓解(CR率为27．8％)，4例达部分缓解(PR率为22．2％)，总有效率为50．0％；目前12例仍生存，其中生存最长者26个月(2例)，仍处于CR期。毒副作用主要为消化道症状、轻度肝功能异常以及骨髓抑制。结论：ProMACE／CytaBOM方案对部分难治性和(或)复发性NHL患者仍有效，毒副作用较轻，可用于治疗对其他化疗方案无效的难治性和(或)复发性NHL。     

Membrane-bound Steel factor induces more persistent tyrosine kinase activation and longer life span of c-kit gene-encoded protein than its soluble form

Alternative splicing of exon 6 results in the production of two isoforms of Steel factor (SLF): the membrane-bound and soluble forms. To investigate differences in the kinetics of c-kit tyrosine kinase activated by these two isoforms, we used a stromal cell line (SI/SI4) established from SI/SI homozygous murine embryo fetal liver and its stable transfectants containing either hSCF248 cDNA (including exon 6; secreted form) or hSCF220 cDNA (lacking exon 6; membrane-bound form) as the source of each isoform. Interaction of factor dependent myeloid cell line MO7e with stromal cells producing either isoform resulted in activated c-kit tyrosine kinase and induction of the same series of tyrosine phosphorylated cellular proteins in MO7e cells. However, SI4- h220 (membrane-bound form) induced more persistent activation of c-kit kinase than SI4-h248 (soluble form) did. Flow cytometric analysis and pulse-chase studies using [35S]methionine showed that SI4-h248 induced rapid downmodulation of cell-surface c-kit expression and its protein degradation in MO7e cells, whereas SI4-h220 induced more prolonged life span of c-kit protein. Addition of soluble recombinant human SLF to SI4- h220 cultures enhanced reduction of cell-surface c-kit expression and its protein degradation. Because the kinetics of c-kit inactivation strikingly fits with the protein degradation rates of c-kit under the conditions described above, rapid proteolysis of c-kit protein induced by soluble SLF stimulation may function as a "turn-off switch" for activated c-kit kinase.     

Therapy for ongoing graft-versus-host disease induced across the major or minor histocompatibility barrier in mice with anti-CD3F(ab')2-ricin toxin A chain immunotoxin

A new pharmacologic agent, anti-CD3F(ab')2-ricin toxin A chain (RTA), was synthesized for the purpose of targeting T cells and as a means of treating established graft-versus-host disease (GVHD). The Fc region of anti-CD3 monoclonal antibody (MoAb) was removed to prevent its ability to activate T cells. The resulting F(ab')2 fragments were conjugated to deglycosylated RTA (dgRTA), a catalytic and potent phytotoxin. The resulting immunotoxin (IT) was potent (greater than 95% inhibition) and selective in inhibiting T-cell mitogenesis in vitro. In vivo, the IT depleted 80% of T cells in mice receiving bone marrow (BM) transplants. Transplantation in an aggressive acute GVHD model using C57BL/6 donor cells and H-2 disparate B10.BR recipients resulted in an infiltration of CD3-expressing cells and a median survival time (MST) of 20 to 30 days. A 5-day course of anti-CD3F(ab')2-RTA (30 micrograms/d intraperitoneally) beginning 7 days after GVHD induction was beneficial in treating established GVHD in these mice, as evidenced by significantly prolonged survival (MST, greater than 80 days), superior mean weight values, and improved clinical appearance. Neither intact anti-CD3, unconjugated anti-CD3 F(ab')2 fragments, nor a mixture of anti-CD4 and anti-CD8 MoAbs (which are highly effective in prophylactic models) were as effective. F(ab')2 fragments made from anti-Lyt-1 (the murine homologue of human anti-CD5) linked to RTA were also not effective, despite the fact that both anti-CD3F(ab')2-RTA and anti-Lyt- 1F(ab')2-RTA had similar half-lives of about 9 hours. The IT also increased MST in two aggressive models of GVHD across non-H-2 minor histocompatibility barriers, indicating that the usefulness of anti- CD3F(ab')2-dgRTA is not limited to a single-strain combination. This agent should be further investigated as an alternative to current strategies for treating steroid refractory GVHD.     

Long-term follow-up of autoantibody profiles in black female lupus patients and clinical comparison with Caucasian and Asian patients

The aim was to determine whether the autoantibody profile in Black female lupus patients is associated with clinical subsets, fluctuates over time and/or reflects disease activity. A clinical comparison with Caucasian and Asian patients matched for age of onset and disease duration was also undertaken. Up to seven serial bleeds from Black female lupus patients who had been followed up for periods of 3.15 yr were tested for antibodies to Ro/SSA, La SSB. Sm, RNP and ribosomal P using ELISA research assays. Significant differences in both clinical and serological profiles between the ethnic groups were found. Varying aspects of disease activity were linked to anti-DNA (renal, cardiovascular, global score), anti-ribosomal P (musculoskeletal, haematology) and anti-Sm (general) antibodies. There are differences in clinical and serological profiles amongst systemic lupus erythematosus patients of different ethnic origin. However, using the BILAG system, relatively few antibodies were found to reflect disease activity accurately in serial measurements.      

Predictors of outcome in Cryptococcus neoformans var. gattii meningitis

In Papua New Guinea, <it>Cryptococcus neoformans</it> var. <it>gattii</it> meningitis has a high fatality rate even in immunocompetent patients. Our retrospective study attempted to identify marker of poor prognosis. Of 88 immunocompetent patients, 30 (34.1%) died, usually soon after admission, and mortality was higher in men (<it>p</it> = 0.025) and older patients (<it>p</it> = 0.039). Death was associated with altered consciousness (<it>p</it>&lt;0.001), a history of convulsions prior to treatment (<it>p</it> = 0.002) and a maximum systolic blood pressure of &gt;150 mmHg (<it>p</it> = 0.017). These data suggest that death results from raised intracranial pressure and subsequent tentorial herniation. However, CSF opening pressure measured on admission was raised in 29/36 (81%) patients and did not predict outcome. In survivors, relapse was uncommon and was not predicted by discharge serum cryptococcal antigen titres, which were frequently raised on completion of therapy in asymptomatic patients. Mortality may be reduced if efforts are made to lower intracranial pressure in those patients who present with markers of poor prognosis.      

Blood donation-related neurologic needle injury: evaluation of 2 years' worth of data from a large blood center

BACKGROUND: There is little information in the medical literature on t he clinical spectrum of blood donation-related neurologic needle injury and on its frequency in a blood donor population. STUDY DESIGN AND METHODS: Sixty-six cases of blood donation-related neurologic needle injury were identified from nursing reports made during a 2-year collection period involving 419,000 whole blood donations. Telephone follow-up was completed on 56 of the 66 cases to better define clinical symptoms, the donor's desire for physician consultation, recovery times, and residual effects. RESULTS: Symptoms in 66 donors included numbness or tingling (n = 54), excessive or radiating pain (n = 43), and loss of arm or hand strength (n = 8). Of the 56 donors with complete follow-up, 17 (30%) consulted a physician one or more times. Recovery times in these 56 donors were <3 days (n = 22), 4 to 29 days (n = 17), 1 to 3 months (n = 13) 3 to 6 months (n = 2), and >6 months (n = 2). Fifty-two of 56 donors achieved a full recovery, and 4 other donors had only a mild, localized, residual numbness. The incidence of blood donation-related neurologic needle injury was 1 of every 6300 donations. CONCLUSION: While donor recovery may in some cases require a great deal of time and/or physician consultation(s), total recovery appears to be the rule. The incidence of blood donation-related neurologic needle injury is relatively low.     

多器官功能障碍评分系统:3个评分标准预测多器官功能障碍综合征结局关联性和准确性的比较与评估

目的研究高原急性呼吸窘迫综合征(HARDS)/多器官功能障碍综合征(MODS)各项诊断指标参数的变化特点,比较3个MODS评分标准预测结局的准确性。方法统一按通用的MODS诊断标准将540例ARDS/MODS患者按海拔高度分为平原对照组(CG,<430m,n=113)、中度高原1组(H1G,1517m,n=314)、中度高原2组(H2G,2261～2400m,n=78)和高原组(HG,2808～3400m,n=35)。4组分别用平原地区ARDS/MODS评分诊断标准(庐山会议评分标准和Marshall评分标准)以及兰州修订的HARDS/MODS评分标准(兰州标准),建立3个标准的数据统计模型,分别绘制受试者运行特征性曲线(ROC曲线),计算约登指数(Yoden)和最佳界值,验证3个标准在不同海拔高度预测ARDS/MODS结局的准确性;用向前逐步回归模式对影响MODS结局的多因素进行分析。结果用庐山、Marshall和兰州标准检验平原和高原不同海拔高度MODS总分的ROC曲线下面积,预测结局的敏感度、特异度及其最佳界值,结果显示,随海拔梯度上升,兰州标准明显优于庐山和Marshall标准,多元Logistic回归分析也以兰州标准的影响因素最大。结论1通用的ARDS/MODS诊断标准中某些参数界值可能不适合中度高原以上地区,建立HARDS/MODS标准是必要的,兰州标准随海拔梯度升高有进一步提高预测准确性的趋势。2海拔高度大于1500m以上地区     

急性移植物抗宿主病病人血清IL-2、IL-8、IL-10及TNF-α水平变化的研究

为了探讨细胞因子IL-2、TNF—α、IL-10、IL-8在异基因造血干细胞移植后aGVHD发病中的作用，观察33例Allo-HSCT患者aGVHD的发病情况。aGVHD的诊断主要依据临床表现，部分病例还依据皮肤、肠粘膜活检的病理学变化。移植前后定期采集患者血清，采用放射免疫法检测细胞因子IL-2、TNF—α、IL-10、IL-8的浓度的变化。结果发现，异基因造血干细胞移植后33例患者均获得造血功能重建，13例发生aGVHD，其中8例Ⅰ度aGVHD，5例Ⅱ-Ⅳ度aGVHD。IL-2、TNF—α水平在aGVHD阳性组明显高于aGVHD阴性组，而IL-10的水平在aGVHD阳性组明显低于aGVHD阴性组，IL-8水平的变化无统计学意义。结论：细胞因子IL-2、TNF—α在临床aGVHD的发病中起重要的正向调节作用，定期检测患者血清的IL-2、TNF—α水平有助于预测aGVHD的发生。     

金石穿胶囊对致石豚鼠胆汁主要成分的影响

目的 :研究金石穿对致石豚鼠胆汁中几种主要化学成分的影响 ,以确定其防治胆石症的疗效。方法 :随机将 6 0只实验豚鼠分为正常组、模型对照组、胆石通组、金石穿组 ,用致石饲料诱发豚鼠胆囊结石模型 ,喂养一段时间后处死豚鼠 ,取胆汁 ,测定其胆汁中胆红素 (Bi L)、胆固醇 (Cho)、钙离子 (Ca2 )的含量。结果 :金石穿组胆汁中Cho、Bi L、Ca2 浓度均降低。结论 :金石穿能有效降低致石豚鼠成石率 ,具有明显的防治胆石症的作用