脐血移植治疗恶性血液病的临床研究

目的 :研究脐血移植 (CBT)在恶性血液病长期造血重建和移植物抗宿主病 (GVHD)及其他移植相关并发症发生情况。方法 :用CBT治疗恶性血液病 11例。供者均为患儿同胞 ,并于产前HLA配型 ,其中 9例完全相合 ,2例 4个位点相合。预处理选用Bu/Cy方案。仅用环孢素A(CsA)预防GVHD。脐血平均采集量 14 1(76～ 2 0 8)ml,输入有核细胞 (NCs)中位数 3.5 (1.5～ 10 .0 )× 10 7/kg。 结果 :9例造血重建 ,ANC >0 .5× 10 9/L的中位时间为 17(13～ 4 2 )d ,>1.0× 10 9/L中位时间为 2 1(16～ 5 0 )d ,PLT >2 0× 10 9/L中位时间为 2 6 (2 1～ 4 8)d ,>5 0× 10 9/L的中位时间为 4 5 (31～ 80 )d。DNA微卫星位点检测 ,2 8～ 90d呈现完全嵌合。其中 3例发生Ⅰ～Ⅱ度急性GVHD ,1例Ⅲ～Ⅳ度急性GVHD ,3例发生慢性局限性GVHD ,2例未植活。结论 :①同胞HLA相合脐血移植安全、有效。②CBT造血恢复时间与输入有核细胞数有关 ,最好NCs≥ 3.5× 10 7/kg。③Bu/Cy方案副作用小 ,是儿童造血干细胞移植安全有效的预处理方案。④HLA相合者仅用CsA即可预防GVHD。     

HLA不全相合无血缘关系脐血移植治疗急性白血病

目的 :探讨HLA不全相合无血缘供者脐血移植 (UCBT)治疗血液系统恶性肿瘤造血重建、移植相关并发症的发生和生存情况。方法 :对 1例 15岁女性急性非淋巴细胞白血病 (ANLL)患者进行HLA 1个位点不相合2份UCBT。预处理方案 :采用白消安、环磷酰胺 (BU/CTX)方案 ,同时应用抗胸腺细胞球蛋白 (ATG)和Daclizumab(赛尼哌 ,zenapax)。移植物抗宿主病 (GVHD)的预防采用环孢菌素A(CsA)联合短程甲氨蝶呤 (MTX)和霉酚酸酯(MMF)方案。移植有核细胞数 (NC)为 4 .9× 10 7/kg ,CD34+ 细胞为 5 .36× 10 5/kg。结果 :中性粒细胞绝对计数 >0 .5× 10 9/L的时间为移植后第 15天 ;血小板计数 >5 0× 10 9/L的时间为移植后第 37天 ;全血细胞恢复正常的时间为移植后第 4 2天。移植后第 2 1天DNA指纹图提示供者型。受者已无病生存 2 0 0d。结论 :HLA 1个位点不相合的UCBT是可行的 ,对于体重量大的受者 2份脐血移植 (CBT)是可行的。     

同基因外周血造血干细胞移植成功治疗肝炎后重型再生障碍性贫血1例报告

目的 :研究同基因外周血造血干细胞移植治疗肝炎后重型再生障碍性贫血的疗效。观察其造血重建情况及移植相关并发症。方法 :1例 17岁体重 6 2kg的肝炎后重型再生障碍性贫血患者 ,采用环磷酰胺 5 0mg·kg-1·d -1× 4d ,抗淋巴细胞球蛋白 5mg·kg-1·d -1× 4d。预处理后 ,给予HLA完全相合的孪生胞姐外周血造血干细胞移植 ,输入有核细胞 3.8× 10 8/kg ,CD34+ 细胞为 (8.7× 10 6) /kg ,移植物抗宿主病 (GVHD)预防方案选用环孢菌素A加FK 5 0 6。结果 :移植后第 10天白细胞计数 >2 .9× 10 9/L ,第 4 0天血常规基本恢复正常。随访 4 2个月 ,患者一般状况良好 ,重要脏器功能正常。结论 :本例应用同基因外周血造血干细胞移植成功治疗肝炎后重型再生障碍性贫血病例 ,本方法具有骨髓造血恢复快、相关并发症少等特点     

非血缘异基因脐血移植治疗SAA可行性研究

目的评价非血缘脐血移植(UCBT)治疗急性重型再生障碍性贫血(SAA)的疗效。方法SAA患者6例,采用环磷酰胺和抗胸腺细胞球蛋白预处理方案;移植方式为HLA不全相合UCBT;应用环孢素A和骁悉预防移植物抗宿主病(GVHD)。随访时间为60~1358d。结果移植后l2~38d造血重建。短串联重复序列-聚合酶链反应分析显示移植后l7~150d基因型表现为完全性患者型,未发生GVHD。血常规、骨髓象检查正常。结论非血缘HLA配型不合的脐血用于治疗SAA是可行的。     

HLA半相合血缘性骨髓移植治疗慢性粒细胞白血病4例

目的:探索半相合未去除T细胞骨髓移植治疗慢性粒细胞白血病的可行性。方法:4例慢性粒细胞白血病患者接受HLA1或2个位点不相合亲缘骨髓移植。用阿糖胞苷、环磷酰胺和全身照射进行预处理,供者应用GCSF250μg/d,连用7d后采髓。移植物抗宿主病(GVHD)预防除用环孢菌素A(CsA)和甲氨蝶呤(MTX)外,在移植前第4天～第1天用抗胸腺细胞球蛋白ATG(兔抗)2.5mg/(kg·d),移植后第7天开始加用霉酚酸酯1.0g/d。结果:患者移植后均获得造血重建,中性粒细胞>0.5×109/L和血小板>20×109/L的中位时间分别是12.5(10～14d)和22d(18～25d)。4例患者发生急性Ⅰ度GVHD,其中1例2个位点不相合者进展为急性肠道和肝脏Ⅳ度GVHD,于+81d合并感染死亡。1例发生迟发性出血性膀胱炎。中位随访时间20个月(5～25个月)。无病存活3例,其中2例存活在1年以上。结论:供者应用GCSF后采髓,多种免疫抑制剂联合应用的HLA不全相合未去除T细胞骨髓移植,在治疗慢性粒细胞白血病过程中,有效地降低了急性重症GVHD发生,提高了无病生存。     

单倍体相合造血干细胞移植在难治高度恶性淋巴瘤中的应用

目的 :探讨应用单倍体相合骨髓移植对难治高度恶性非霍奇金淋巴瘤 (NHL)治疗的可行性。方法 :6例难治高度恶性NHL伴有骨髓浸润患者接受人白细胞抗原 (HLA) 2～ 3个位点不合的单倍体相合移植 ,供者用粒细胞集落刺激因子 (G CSF)促进后采髓 ,急性移植物抗宿主病 (GVHD)预防例 1采用环孢菌素A(CSA)、短程甲氨蝶呤 (MTX)、霉酚酸酯 (MMF)和抗胸腺细胞球蛋白 ,余 5例除上述药物外 ,还加用CD2 5单克隆抗体。结果 :6例移植后均获造血重建 ,粒细胞绝对数 >0 .5× 10 9/L中位天数是 17d ,血小板 >2 0× 10 9/L的中位天数是 2 2d ,骨髓植活直接证据检测证实为完全供者造血。 1例于移植后 2 0d时发生急性Ⅳ度肠道GVHD ,可评价慢性GVHD病例4例 ,均发生慢性GVHD ,其中 1例广泛性慢性GVHD ,口服泼尼松和CSA病情控制。中位随访 2 0 (7～ 4 2 )个月 ,1例重度GVHD于移植后 2个月死亡 ,1例在移植后 4个月并发真菌感染死亡 ,无病存活 4例 ,Karnofshy生存质量评价为 10 0 %。结论 :研究表明单倍体相合未经体外去T细胞骨髓移植对难治高度恶性NHL具有一定治疗价值 ,能够降低急性重症aGVHD发生和减少移植相关死亡。     

亲属间HLA半相合干细胞移植治疗难治复发性白血病患者30例疗效分析

目的观察亲属间HLA半相合干细胞移植(SCT)治疗难治复发性白血病(RL)的疗效。方法对自1998年8月至2004年8月期间进行HLA半相合SCT治疗30例RL的治疗结果进行分析。结果30例患者均为RL,其中急性非淋巴细胞白血病13例,急性淋巴细胞白血病10例,慢性粒细胞白血病6例,Ⅳ期淋巴瘤1例。男18例,女12例,中位年龄25(3~52)岁。30例患者均接受HLA半相合SCT。12例为父母给子女,4例为子女给父母,其余为同胞。HLA3个位点不合12例,HLA2个位点不合13例,5例HLA1个位点不合。预处理方案为氟达拉宾、马利兰、环磷酰胺方案,部分患者在此方案基础上加用抗人胸腺细胞球蛋白。平均移植单个核细胞数5·0(2·9~8·0)×108/kg,CD3+4细胞数为5·5(3·0~6·5)×106/kg。30例中24例完全供者植入,3例供、受者部分嵌合,经供者淋巴细胞输注转为完全供者型;1例移植失败,1例移植后2d死于重症霉菌感染,1例移植后28d死于重症肝静脉阻塞病;移植后WBC>1·0×109/L平均时间14(11~18)d,血小板>20×109/L时间15(11~18)d。6例发生Ⅲ~Ⅳ度重症移植物抗宿主病(GVHD),7例发生慢性GVHD,白血病缓解率90%,随访3~60个月,平均生存时间为16·9个月。7例复发,其中2例脑膜白血病复发,复发中位时间为10(3~24)个月,14例生存,10例仍无病生存。结论HLA半相合SCT能使大部分RL患者缓解,也能使部分RL患者获长期生存;HLA半相合SCT具有较强的移植物抗白血病效应,但在疾病状态下进行HLA半相合SCT,白血病仍会复发。     

异基因造血干细胞移植治疗高龄恶性血液病的疗效分析

目的探讨异基因造血干细胞移植治疗年龄较大的白血病患者安全性和疗效。方法采用HSCT治疗10例45—63岁恶性血液病患者,HLA6／6位点相合8例,5／6位点相合2例。以清髓性方案预处理4例,减低强度方案预处理6例。HLA不全相合患者加用ATG。采用环孢素联合霉酚酸酯预防移植物抗宿主病（GVHD）。结果本组10例受者均获造血重建。中性粒细胞绝对计数≥0．5×10^9／L,血小板≥20×10^9／L的中位时间分别为移植后12（9～16）天和15（12～21）天。3例发生了急性GVHD（30％）,Ⅱ度以上2例。可评估的9例患者中2例出现了慢性GVHD（22％）。复发2例,死亡3例。可评估的2年无病生存率为70％。结论造血干细胞移植对于高龄白血病患者是一种有效、安全的根治疗法。     

脐血移植治疗WAS的疗效观察

目的:分析湿疹血小板减少伴免疫缺陷综合征(WAS)患儿脐血移植后的疗效和影响因素,为供体选择和受体移植的时机提供经验。方法:5例WAS患儿接受非血缘脐血干细胞移植,分析移植前营养状态、移植时年龄、HLA相合度、移植后移植物抗宿主病(GVHD)及感染因素对移植效果的影响,随访时间截止到2016年1月。结果:5例WAS患儿成功植入。粒细胞植入时间分别为15d、12d、11d、14d、15d,血小板植入时间分别为39d、16d、16d、34d、36d,HLA高分辨检测显示供受体相合度分别为8/10、10/10、5/10、10/10、10/10;其中3例患儿移植前有巨细胞病毒血症,移植后血小板植入缓慢,1例中度营养不良的患儿移植后有皮肤及肠道重度GVHD和反复重症感染。结论:移植前患儿巨细胞病毒血症和移植前营养状态是影响血小板植入和预后的主要因素,HLA高分辨位点相合程度对粒细胞和血小板植入及GVHD没有显著影响。     

单份HLA相合无关脐血移植治疗多次复发的超体重儿童急性淋巴细胞白血病

目的:探讨单份HLA相合无关脐血移植治疗多次复发且移植前处于复发状态的超体重儿童急性白血病(AL)的可能性。方法:对1例患急性淋巴细胞白血病(ALL)的多次复发且移植前处于复发状态的超体重11岁男孩进行HLA相合UCBT。预处理方案:全身放疗加环磷酰胺加氟达拉滨。移植物抗宿主病(GVHD)的预防采用环孢素A(CsA)联合短程甲氨蝶呤(MTX)方案。移植有核细胞数为0.32×108/kg,CD34+细胞占1.71%,粒巨细胞集落形成单位为0.046×106/kg。结果:中性粒细胞绝对值>0.5×109/L的时间为+19d,血小板>50×109/L的时间为+35d。+30d骨髓象示CR3,+60d染色体检查示:46XY[15]。STR检测示供体植入。结论:对多次复发且移植前处于复发状态的超体重儿童AL,应用单份HLA相合无关脐血移植治疗是可行的。     

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.