非清髓单倍体造血干细胞移植联合格列卫治疗慢性粒细胞白血病

目的:探讨格列卫联合非清髓性单倍体造血干细胞移植在治疗慢性粒细胞白血病(CML)中的作用。方法:4例CML患者,采用移植前、后口服格列卫,以环磷酰胺、阿糖胞苷、抗胸腺细胞球蛋白、赛尼派、环胞素A等作非清髓性预处理的单倍体异基因外周血造血干细胞移植。结果:移植过程顺利,4例患者均植入成功,嵌合性植入。中性粒细胞>0.5×109/L天数,16(10~21)d;血小板>20×109/L天数,10(4~15)d。3例发生Ⅰ~Ⅱ度皮肤急性移植物抗宿主病(GVHD),1例发生Ⅳ度皮肤慢性GVHD。1例+27d死于肺部感染并多脏器功能衰竭,1例死于Ⅳ度皮肤慢性GVHD并发感染。2例无病存活(随访16个月仍健在),且Ph+染色体,bcr-abl融合基因转阴。结论:非清髓单倍体造血干细胞移植联合格列卫治疗CML,具有降低移植前白血病细胞负荷,抑制残留白血病细胞增殖,促进供者完全嵌合状态的转变,增强抗移植物白血病(GVL)效应的作用,是一种有效的治疗方法,值得进一步临床研究。     

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     

非清髓性外周血干细胞移植治疗慢性粒细胞性白血病慢性期及加速期的疗效观察

目的:观察非清髓造血干细胞移植对慢性粒细胞白血病慢性期(CMLCP)、加速期(CMLAP)的疗效。方法:用福达华30mg/m2×6d,白消安4mg/kg×2d,环磷酰胺600mg/d×2d,部分患者加阿糖胞苷0.5g,q12h×4次,对12例人类白细胞抗原(HLA)全相合者进行预处理,并对其造血恢复等指标动态观察。结果:12例患者造血顺利恢复,中性粒细胞(ANC)>0.5×109/L平均为13d,血小板计数(PLT)>20×109/L平均为11.5d。+30d时经短串重复系列(STRPCR)检测12例植活患者中9例为完全嵌合状态(CDC),3例为混合嵌合体。+90d时又有1例患者转为CDC。中位随访8(2～20)个月,11例患者无病生存,1例患者死于严重移植性抗宿主疾病。结论:非清髓造血干细胞移植是CMLCP、CMLAP的有效治疗手段,对于年龄较大患者亦有良好耐受性。     

自体外周血造血干细胞移植治疗系统性红斑狼疮的初步观察

目的探讨自体外周血造血干细胞移植(APBSCT)治疗系统性红斑狼疮(SLE)的可行性及临床效果。方法对8例女性难治性SLE病人进行APBSCT。采集的干细胞的单个核细胞计数平均为1.6×108/kg[(0.07～2.6)×108/kg]。预处理方案为环磷酰胺(50mg·kg-1·d-1,-5～-2d)静脉滴注及兔抗人淋巴细胞免疫球蛋白(10mg·kg-1·d-1,-3～-1d)静脉滴注。从移植前后皮肤红斑的变化,尿的改变,SLE相关的免疫指标的变化,移植后造血重建情况,移植的并发症等方面进行评价。结果8例病人均获得成功植入,外周血白细胞总数>1.0×109/L的平均时间为9.5d,中性粒细胞计数>0.5×109/L的平均时间为10d,白细胞总数恢复正常的平均时间为14d,血小板计数>50×109/L的平均时间为30d,血红蛋白含量平均在移植后第28天升至100g/L。移植后SLE临床症状均消失,尿蛋白转阴,自身抗体大部分转阴。移植相关并发症中,均出现血清病样预处理反应,2例出现严重的低血压;4例有出血性膀胱炎;2例出现败血症;4例发生霉菌感染;2例发生间质性肺炎。随访时间2个月～2.5年。结论APBSCT治疗SLE有较好的近期疗效,但观察病例及时间有限,远期疗效还需更长时间的观察。对药物治疗难以奏效的SLE病例,该法不失为一种更佳的选择。     

甲磺酸伊马替尼在慢性粒细胞白血病异基因造血干细胞移植治疗前的应用

目的:动态观察甲磺酸伊马替尼(商品名:格列卫)在2例加速期BCRABL阳性的慢性粒细胞白血病(CML)患者异基因外周血造血干细胞移植(AlloPBSCT)前的应用。方法:应用PCR技术,对接受甲磺酸伊马替尼的BCRABL阳性的CML患者选择不同时间定性检测bcr/abl基因,同时进行骨髓形态学及染色体分析。结果:①甲磺酸伊马替尼治疗1个月后2例均达到血液学完全缓解,病例2达到细胞遗传学完全缓解;②移植后中性粒细胞>0.5×109/L,血小板>20×109/L病例1为13d,病例2为20d;③病例1于+32d血型转为供者型,病例2于+40d供受细胞稳定嵌合,目前2例患者血液学持续完全缓解。结论:化疗可以动员G0期bcr/abl阳性克隆进入增殖周期,表现对甲磺酸伊马替尼敏感,在CML尤其是进入加速期、急变期的患者行PBSCT前应用甲磺酸伊马替尼,有助于体内的bcr/abl白血病细胞清除,达到肿瘤净化作用。     

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.     

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。     

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。     

用低强度Bu/Cy预处理方案进行异基因造血干细胞移植治疗恶性血液病的疗效观察

目的探讨使用低强度Bu/Cy预处理方案进行异基因造血干细胞移植治疗恶性血液病的疗效。方法在哈尔滨医科大学附属第二医院采用低强度的Bu/Cy方案,进行异基因造血干细胞移植,治疗5例恶性血液病,预处理方案是:马利兰3~4mg/(kg·d)×3,环磷酰胺50mg/(kg·d)×2,阿糖胞苷2g/(m2·d)×1~2d,移植前7d开始环孢素A(CsA)3mg/(kg·d),霉酚酸酯(MMF)1g/d。结果5例病人均重建造血,未发生预处理相关严重并发症,5例病人已无病存活3~22个月(中位时间10·5个月)。结论低强度的Bu/Cy预处理方案,移植相关毒性减小,该方法治疗恶性血液病是安全可行的。     

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.