格列卫联合异基因造血干细胞移植治疗慢性粒细胞白血病

目的:为了考察格列卫联合异基因造血干细胞移植治疗慢性粒细胞白血病(CML)对移植及造血重建的影响。方法:对6例CML患者于移植前6周开始口服格列卫600~800mg/d至移植当日,预处理方案是福达拉宾、白消安、环磷酰胺,人类白细胞抗原(HLA)不相合者加用抗胸腺细胞球蛋白。移植物抗宿主病防治采用环孢素A加短程甲氨喋呤加霉酚酸酯。结果:6例全部成功植入,WBC>0.5×109·L-1平均为14.2d,PLT>20×109·L-1平均为15.6d。结论:CML患者移植前给予大剂量格列卫治疗不影响干细胞植入和骨髓造血的恢复。     

非清髓异基因外周血造血干细胞移植治疗慢性粒细胞白血病

目的：探索非清髓异基因外周血干细胞移植(NST)治疗不能耐受清髓性异基因造血干细胞移植的慢性粒细胞白血病(CML)患者的疗效。方法：将5例CML患者中的4例以全身放疗加氟达拉宾，1例以马利兰、氟达拉宾加抗人胸腺细胞免疫球蛋白为预处理方案，联合环孢霉素A、霉酚酸酯和(或)短程氨甲蝶呤预防移植物抗宿主病。结果：5例均造血重建，3例完全供者型植入，2例混合型植入，其中1例植入率持续低于50％，经2次清髓性异基因造血干细胞移植后达到完全供者型植入。2例发生Ⅰ度急性移植物抗宿主病，1例发生Ⅳ度急性移植物抗宿主病，无慢性移植物抗宿主病发生。中位随访时间5(3～37)个月，无病生存3例，死亡2例。结论：对不能耐受清髓性异基因造血干细胞移植的CML患者，NST是可行而有效的。     

非清髓异基因造血干细胞移植治疗慢性粒细胞白血病

目的　探讨非清髓异基因造血干细胞移植 (NST)治疗慢性粒细胞白血病 (CML)的临床效果。方法　对 4例慢性粒细胞白血病患者进行了非清髓异基因造血干细胞移植 ,均采用以氟达拉宾为基础的非清髓预处理方案。回输CD+ 3 4 细胞分别为 9.78× 10 6/Kg、16.5 6× 10 6/Kg、2 .5 6×10 6/Kg和 2 .0 6× 10 6/Kg。结果　 4例均顺利渡过造血抑制期。 4例患者移植后WBC >1.0× 10 9/L ,中性粒细胞 >0 .5× 10 9/L ,时间分别为 +19天、+16天、+13天和 +14天 ;血小板 >2 0× 10 9/L时间分别为 +8天、+12天、+18天和 +2 2天。 2例骨髓细胞混合嵌合体形成 +15～ +2 3天 ,完全嵌合体形成 +2 3～ +4 3天 ;另 2例均于 +17天形成完全嵌合体。 4例均未发生急性移植物抗宿主病 ,例 1于第 5次供者淋巴细胞输注后发生皮肤慢性移植物抗宿主病 ,例 3于第 7次供者淋巴细胞输注后发生慢性移植物抗宿主病。 3例于非清髓异基因造血干细胞移植后 6～ 12个月出现移植物抗白血病。 4例均未发生肝静脉阻塞病、出血性膀胱炎及间质性肺炎。随诊 2～ 2 4个月 ,仍全部存活。结论　非清髓异基因造血干细胞移植治疗慢性粒细胞白血病简便、安全、并发症及支持治疗少、疗效较好。     

非清髓性干细胞移植患者供体细胞嵌合率的动态定量研究

目的　对非清髓性干细胞移植 (NST)后供受嵌合体形成动力学 ,嵌合体的转归 ,以及供体细胞嵌合率 (DC)对评价植入、复发、移植物抗宿主病 (GVHD)和长期生存的作用进行研究。方法　18例接受HLA全相合NST的患者进行DC的定量分析。术前采集供者和受者外周血 ,术后不同时间段采集受者外周血或骨髓。用QIAamp全血DNA抽提试剂盒提取样本DNA ,用AmpF/STRprofilerplus试剂盒进行 9个STR位点复合扩增后 ,产物用ABI 310遗传分析仪进行毛细管电泳 ,由Genescane和Genotype软件确定基因位点及峰面积 ,根据供受体基因型的差异计算供体细胞嵌合率。结果　 (1)移植早期植入表明 ,移植后 8d供体细胞开始占优势 (DC >6 0 % ) ,比造血重建提早 4d ;此外 ,由于移植前免疫状态不同 ,慢性髓细胞性白血病 (CML)患者供体细胞植入滞后于急性白血病和其他非恶性血液病患者 ;(2 )NST后嵌合状态有一个由混合嵌合 (MC)向完全供体细胞嵌合 (FDC)状态转化的过程 ;(3)FDC组GVHD的发生率高于MC组 (90 0 %、6 2 5 % ) ,而且从FDC状态的建立到急性GVHD发生的中位时间仅为 9d ;(4)移植后能获得无白血病生存的患者均有FDC或供体细胞高比例MC稳定嵌合的特点 ,而复发或排斥患者均在发生临床症状之前 ,出现供体细胞嵌合率的进行性下降。结论　DC     

HLA半相合非清髓性造血干细胞与间充质干细胞共移植治疗重症再生障碍性贫血1例

目的:观察HLA半相合非清髓性造血干细胞与间充质干细胞(MSC)共移植治疗重症再生障碍性贫血(SAA)的疗效及安全性。方法:1例24岁男性SAA患者。应用非清髓性预处理方案,进行HLA半相合异基因外周血造血干细胞和MSC共移植。移植rhG-CSF动员的供者外周血单个核细胞9.22×108/kg,CD34 细胞8.56×106/kg,及体外扩增培养的供者骨髓MSC2.12×105/kg。结果:移植后 12d中性粒细胞数>0.5×109/L, 21d WBC4.5×109/L,Hb99g/L,PLT108×109/L。经HLA配型,红细胞亚型和VNTR检测,为供者型完全嵌合体。随访14个月,无急、慢性移植物抗宿主病(GVHD)发生。结论:HLA半相合非清髓性造血干细胞与MSC共移植治疗SAA是安全有效的方法。     

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。     

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。     

含全身照射预处理方案行HLA不相合非去T造血干细胞移植治疗白血病8例临床分析

目的探讨采用全身照射(TBI)预处理方案行人类白细胞抗原(HLA)配型不相合亲缘供者非去T异基因造血干细胞移植(allo-HSCT)治疗白血病的疗效。方法2002年4月至2007年1月北京大学血液病研究所8例采用TBI预处理方案行HLA不合非去T亲缘供者allo-HSCT的白血病患者,其中急性髓性白血病(AML)3例,急性淋巴细胞性白血病(ALL)4例,慢性粒细胞白血病1例;预处理方案采用TBI加环磷酰胺(CY)方案4例,TBI加氟达拉滨(FLU)方案4例;干细胞来源包括骨髓和外周血造血干细胞移植6例,外周血造血干细胞移植(PBSCT)2例;移植物抗宿主病(GVHD)预防采用经典的环孢素A(CsA) 霉酚酸酯(MMF) 短程甲氨蝶呤(MTX)方案。结果8例供者采集单个核细胞(MNC)中位数为7.39(6.27~12.46)×108/kg,粒细胞植入中位时间11(11~13)d,血小板植入中位时间13(11~21)d。5例发生Ⅰ~Ⅱ度急性GVHD,2例出现慢性广泛性GVHD,无严重急性GVHD或因GVHD死亡病例。中位随访时间9(3~53)个月,除1例复发存活外,其余病例无病存活。结论对于HLA不相合异基因造血干细胞移植,TBI方案是一种比较安全、有效的非去T预处理方案,对于高危和二次移植患者同样有效。     

异基因造血干细胞移植治疗慢性粒细胞白血病的疗效及预后因素分析

目的 探讨异基因造血于细胞移植（allo—HSCT）治疗慢性粒细胞白血病（CML）的疗效及预后因素分析。方法选择104例CML患者,采用Bu＋cy、改良Bu＋Cy、TBI＋CY及非清髓方案预处理后行allo—HSCT治疗。结果除1例未植活外,其余均持久性植活。3年无病生存率（DFS）为74．5％,5年累积生存率（OS）为70％。CML慢性期移植、Ⅰ-Ⅱ度急性移植物抗宿主病（GVHD）患者3年DFS分别高于CML加速期／急变期移植、Ⅲ～Ⅳ度急性GVHD患者。多因素Cox回归分析显示,疾病状态、移植类型、急性GVHD的严重程度是异基因HSCT患者长期生存的独立影响因素。结论慢性期且有HLA相合同胞供者的CML患者行allo-HSCT可获得较高长期生存率。     

静脉滴注白消安和氟达拉滨预处理方案行异基因造血干细胞移植治疗髓系血液病疗效观察

目的探讨静脉滴注白消安(Bu)和氟达拉滨(Flu)作为预处理方案,进行异基因造血干细胞移植治疗髓系血液病的疗效。方法选取2003年10月至2005年4月成都军区昆明总医院血液科髓系血液病患者9例,其中急性非淋巴细胞白血病(ANLL)3例,慢性粒细胞白血病(CML)5例,骨髓增生异常综合征(MDS)1例,均进行同胞白细胞抗原(HLA)全相合异基因造血干细胞移植。预处理方案采用移植前第6天至移植前第3天静脉滴注白消安3.2mg/(kg.d),共4d;移植前第6天至移植前第2天静脉滴注氟达拉滨30mg/(m2.d),共5d。环孢素A和霉酚酸酯(骁悉)联合应用预防移植物抗宿主病(GVHD)。结果9例患者均成功植入,中性粒细胞>0.5×109/L的平均时间为12d;血小板(PLT)>20×109/L的平均时间为14d。中位观察时间为31个月。除轻微胃肠道反应外,无严重的预处理相关毒性,移植后1个月检测证实均为供者型完全植入。发生急性GVHD2例,慢性GVHD1例。9例患者中8例无病存活。结论静脉滴注Bu/Flu预处理方案,移植相关毒性小,治疗髓系血液病安全有效。     

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.