非清髓性自体外周血造血干细胞移植治疗系统性红斑狼疮的临床观察

目的采用非清髓性自体外周血造血干细胞移植(NAST)治疗系统性红斑狼疮(SLE),旨在用低于常规清髓性造血干细胞移植(HSCT)时的药物剂量和强度,达到既能重建SLE患者的免疫功能,又能避免因骨髓严重受抑而导致的严重并发症和高病死率。方法严格选择适合行NAST的4例SLE患者。造血干细胞的动员采用异环磷酰胺2000 mg/m2粒细胞集落刺激因子(G-CSF)。采集的干细胞量:单个核细胞(MNC)平均3.05×108/kg,CD34+细胞平均O.88×106/kg。非清髓性预处理方案:阿糖胞苷(200 mg·kg-1·d-1, -2～-1 d)及环磷酰胺(40 mg·kg-1·d-1,-2～-l d),均为静脉滴注。评价患者移植前后的相关症状、体征的改变．免疫指标的变化．造血重建的情况及并发症。结果4例患者均成功植入,外周血白细胞>1.0×109/L的平均时间为7.2 d,中性粒细胞>0.5×109/L的平均时间为8.O d,白细胞总数恢复正常的平均时间12 d,血小板>100×109/L的平均时间为IO d,血红蛋白>120 g/L的平均时间为22 d。NAST后4例患者临床症状和体征均消失,红细胞沉降率,C反应蛋白,补体C3、C4均恢复正常,尿蛋白转阴、24 h尿蛋白定量恢复正常．自身抗体大部分转阴,术前及术后淋巴细胞亚群检测显示:CD4+及CD4+/CD8+比值均有变化。并发症中1例出现败血症。随访时间为5个月～3.6年。结论与经典的清髓性HSCT治疗SLE比较,NAST造血重建快,外周血象受抑程度低,治疗安全、有效。但由于例数较少及时间有限,远期疗效尚需进一步观察。     

非清髓性自体外周血造血干细胞移植治疗系统性红斑狼疮远期疗效分析

目的探讨非清髓性自体外周血造血干细胞移植(NAST)治疗系统性红斑狼疮(SLE)的远期疗效。方法总结中山大学附属第五医院2002年11月至2005年10月4例成功接受NAST的SLE患者移植后的随访情况。非清髓性预处理移植前1～2 d静脉滴注阿糖胞苷200 mg/(kg.d)及环磷酰胺40 mg/(kg.d)。评价患者移植前后的相关症状体征、远期并发症及免疫功能的变化。结果白细胞总数恢复正常的中位时间12 d,血小板>100×109/L的中位时间为10 d,血红蛋白>120 g/L的中位时间为22 d。随访中,NAST后4例患者临床症状和体症均消失,淋巴细胞亚群检测显示:CD4+及CD4+/CD8+均恢复正常。1例男性患者移植4年后妻子正常受孕并产下一健康女婴。3例女性均恢复正常工作与生活。结论 NAST造血重建快,远期疗效确切。SLE患者NAST治疗后生活质量较好。     

不同预处理方案自体非清髓性造血干细胞移植治疗系统性红斑狼疮的临床观察

目的 比较2种不同预处理方案行非清髓性自体外周血造血干细胞移植(NAST)治疗系统性红斑狼疮(SLE)的疗效及安全性.方法 组一为阿糖胞苷(200 mg· kg-1· d-1,-2～-1 d)+环磷酰胺(40 mg·kg-1·d-1,-2～-1 d).组二为抗胸腺细胞球蛋白(30 mg· kg-1·d-1,-5～-3 d)+环磷酰胺(40 mg·kg 1·d-1,-2～-1 d).评价患者移植前后免疫指标的变化、造血重建的情况及并发症.应用配对t检验,比较2组的白细胞、中性粒细胞、血小板恢复的时间.结果 8例患者均成功植入.组一和组二各4例外周血白细胞＞1.0×109/L、中性粒细胞＞0.5×109/L、血小板＞100×109/L及血红蛋白＞120 g/L的平均时间分别为[(7.2±1.3)、(8.0±1.5)、(10.5±1.4)、(22.1±2.3)d]和[(10.4±2.1)、(12.0±1.9)、(19.3±2.1)、(28.1±2.4)d],差异有统计学意义(P＜0.01).6例抗核抗体、抗双链DNA(dsDNA)抗体于移植后30～90 d转阴,余2例分别于15个月和18个月后转阴.移植前明显降低的CD4+及CD4+/CD8+比值移植后逐渐恢复正常,2组差异无统计学意义.结论 从免疫重建来看,是否使用ATG并没有明显差别.从安全性及造血重建考虑,我们推荐用阿糖胞苷+环磷酰胺替代含有ATG的方案进行预处理.     

非清髓性异基因造血干细胞移植后淋巴细胞重建

我们观察了 7例白血病患者行非清髓性异基因造血干细胞移植 (NAST)后淋巴细胞功能的变化报告如下。一、资料和方法1.对象 :7例均为我院 2 0 0 0年 12月～ 2 0 0 1年 10月行NAST的白血病患者 ,女 4例 ,男 3例 ,年龄 17～ 5 6岁。患者的资料 ,见表 1。 10例健康作为对照组。预处理方案 :氟拉达滨 30mg·m-2 ·d-1,移植前第 9～ 5天或环磷酰胺 30mg·kg-1·d-1,移植前 4～ 3天 ;马利兰 2mg·kg-1·d-1,移植前 8～ 5天 ;抗胸腺球蛋白 10mg·kg-1·d-1,移植前第 7～ 4天。环孢素A(CsA) 2mg·kg-1·d-1,移植前 1天开始用 ,胃肠功能恢复后改为…     

改良非清髓性异基因造血干细胞移植治疗SAA疗效观察

目的探讨非清髓性异基因造血干细胞移植(NAST)治疗重型再生障碍性贫血(SAA)的方法及疗效。方法对20例急性SAA患者进行NAST,预处理采用小剂量环磷酰胺、抗淋巴细胞球蛋白或抗胸腺细胞球蛋白;移植后采用环孢菌素、骁悉、抗CD25预防移植物抗宿主病(GVHD)。采用短串联重复序列复合扩增技术检测供者植入情况。结果10例异基因外周血造血干细胞移植患者造血功能获得快速重建;8例脐血造血干细胞移植患者均未植入,但自身造血亦获得安全重建。发生急性GVHD1例,慢性GVHD2例,严重感染性休克、间质性肺炎、败血症各1例均治愈,突发心衰死亡1例,造血重建失败并发感染死亡2例。结论改良NAST疗效肯定、植入率高、并发症少、造血功能恢复快,是治疗SAA的有效方法。     

自体外周血造血干细胞移植治疗系统性红斑狼疮的临床观察

目的 探讨自体外周血造血干细胞移植(APBSCT)治疗难治性系统性红斑狼疮(SLE)的临床疗效和安全性.方法 10例难治性SLE患者接受APBSCT治疗,应用环磷酰胺(CTX)2～4 g/m2和粒细胞集落刺激因子5～10 μg·kg-1·d-1行外周血造血干细胞动员;预处理包括CTX(50 mg·kg-1·-1,-6～-3 d)和抗胸腺细胞球蛋白(ATG,15～20 mg·kg-1·d-1,-2 d、-1 d、1 d、2 d).患者输注的CD34+细胞＞2×106/kg.评估治疗前后临床表现、SLE疾病活动指数(SLEDAI)和免疫指标的变化.结果 APBSCT后10例SLE患者的临床症状缓解,SLEDAI评分降低,均获得造血重建,中性粒细胞＞0.5×109/L的中位数时间为9.5 d,血小板＞20×109/L中位数时间是11 d;尿蛋白减少或消失,抗核抗体滴度减低或转阴,补体水平升高;移植相关的并发症有:2例败血症,2例巨细胞病毒感染,1例出现肾毒性,3例急性左心衰竭,3例心律失常,无移植相关死亡.结论 APBSCT能够改善SLE患者的疾病活动和免疫学指标,是一种有效的治疗难治性SLE的方法,但远期疗效需进一步观察.     

HLA半相合非清髓异基因造血干细胞移植治疗难治性急性白血病1例

目的探讨HLA半相合非清髓异基因造血干细胞移植(NAST)在治疗难治性急性白血病中的作用。方法2002-06采用非清髓预处理的NAST治疗军事医学科学院附属307医院难治性急性髓性白血病患者1例。预处理方案主要由抗淋巴细胞球蛋白(ATG)、阿糖胞苷(Ara-C)、氟达拉滨(Flu)和环磷酰胺(CTX)等组成。移植物抗宿主病(GVHD)的预防采用环孢素A(CSA)、霉酚双酯(MMF)、甲氨蝶呤(MTX)和CD25单抗。结果患者移植过程顺利,于移植后第100d转为完全供者型植入。患者于移植后出现皮肤Ⅰ度GVHD,经治疗后好转。结论应用HLA半相合NAST治疗难治性急性白血病患者,简便安全,疗效好,为无HLA相合供者的白血病患者治疗开辟了新的治疗手段。     

清髓性及非清髓性干细胞移植后巨细胞病毒感染及其结果:一项配对比较研究

对不适合常规清髓性异基因造血干细胞移植(HSCT)者,非清髓性异基因HSCT逐渐成为一种治疗选择。但该方法能否降低移植相关感染率,尚不清楚。本文旨在配对比较分析各种方法移植后巨细胞病毒(CMV)感染率。 方法 1997年1月至2000年4月血液系统恶性肿瘤患者56例,进行非清髓性HSCT(第0天给予TBI 2 Gy照射;移植后给予环孢素);其中有18例于第-4天至第-2天接受氟达拉宾 30 mg·m~(-2)·d~(-1)预处理。多数供者为HLA相合或相关。每1例非清髓性HSCT患者配对2例同期常规清髓性HSCT患者作为对     

异基因造血干细胞移植治疗MDS临床研究

目的探讨HLA配型相合异基因造血干细胞移植（allo—HSCT）治疗骨髓增生异常综合征（MDS）的可行治疗方案和疗效。方法以HLA配型相合的骨髓移植治疗MDS患者6例,预处理方案为非清髓性预处理方案1例,清髓性预处理方案5例;以霉酚酸酯、环孢菌素A加短疗程的甲氨喋呤预防移植物抗宿主病（GVHD）。结果6例患者均造血重建。5例清髓性预处理方案仍然无病存活,非清髓性预处理方案1例移植后出现MDS,于移植后17个月死亡。移植后最长无病存活时间已达8a。移植期间发生Ⅰ、Ⅱ°急性移植物抗宿主病（aGVHD）4例。结论allo-HSCT治疗MDS可行、有效,清髓性预处理方案可能对于长期稳定植入有利。     

非清髓性造血干细胞移植加供者淋巴细胞输注治疗多发性骨髓瘤1例报告并文献复习

目的研究非清髓性造血干细胞移植(NST)治疗多发性骨髓瘤(MM)的疗效,观察移植相关并发症的发生.方法1例42岁MM患者,供者为其胞姐,HLA配型完全相合.动员方案粒细胞集落刺激因子(G-CSF)10 μg·kg-1·d-1×5 d.预处理方案抗胸腺细胞球蛋白(ATG)8 mg·kg-1·d-1×3 d,马法兰(MEL)120 mg/m2×1 d.移植单个核细胞数(MNC) 6.5×108/kg;CD34+细胞 4.4×106/kg.环胞菌素A(CsA)和短程甲氨蝶呤(MTX)预防移植物抗宿主病(GVHD).移植后分别于+41 d、+76 d和+112 d进行3次供者淋巴细胞输注(DLI).结果移植后15 d中性粒细胞计数> 0.5×109/L,21 d血小板计数>50×109/L,24 d性染色体和微卫星法DNA指纹图监测显示为混合嵌合体,随着DLI的进行,逐渐转为供者型完全嵌合体,骨髓瘤细胞和血清M蛋白均逐渐消失,移植后8个月达完全缓解.在+180 d(第三次DLI后68 d)发生II度急性GVHD,经甲泼尼龙和CsA治疗得以控制.现随访36个月,患者情况良好,仍处于完全缓解状态.结论非清髓性造血干细胞移植加供者淋巴细胞输注治疗MM是可行和有效的.     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.