白消安在异基因造血干细胞移植预处理方案中的研究进展

正白消安(busulfan,BU)即1,4-丁二醇二甲磺酸酯,是一个双功能烷化剂。1950年,研究发现BU对造血干细胞具有明显的毒性作用,血液系统外的毒副作用小,BU被广泛用于治疗髓系肿瘤性疾病〔1〕。1974年研究发现了BU高效的清髓性作用〔2〕,BU开始代替全身照射(TBI)成为造血干细胞移植(HSCT)预处理方案的重要组成部分〔3〕。BU联合环磷酰胺(BU/CY)是目前最常用的经典     

自体造血干细胞移植治疗难治性白血病疗效观察

目的观察自体外周血造血干细胞移植（Auto-PBSCT）对难治性白血病的疗效。方法15例难治性白血病患者均为髓性白血病,行Auto-PBSCT。预处理方案：BU／CY（马利兰＋环磷酰胺）（10例）或联合IA（去甲氧柔红霉素）（2例）或联合HD-Ara—C（大剂量阿糖胞苷）（3例）。移植后治疗：常规方案巩固化疗维持1a。结果15例患者Auto-PBSCT后全部获完全缓解,除1例移植后死于肺部真菌感染外,其余14例均好转出院,1例半年后复发,其余13例无病存活至今。结论Auto-PBSCT是治疗难治性白血病安全、有效的方法,可延长患者的生存期。     

自体外周血造血干细胞移植治疗非霍奇金淋巴瘤182例临床分析

目的　评价自体外周血造血干细胞移植 (APBSCT)治疗非霍奇金淋巴瘤 (NHL)患者的疗效。方法　全国 34家单位采用APBSCT治疗NHL 182例。其中第一次完全缓解 (CR1)移植 112例 ,部分缓解 (PR)或复发期移植 70例。外周血造血干细胞 (APBSC)动员方案分为四组 :1组为大剂量环磷酰胺 (HD CY)联合粒细胞 集落刺激因子 (G CSF) 5 5例 ;2组为大剂量阿糖胞苷 (HD Ara C)联合G CSF7例 ;3组为增大环磷酰胺剂量的针对性化疗方案联合G CSF 10 2例 ;4组为单独应用G CSF 18例。预处理方案 :移植前处于CR1状态的 112例中 ,含有全身照射 (TBI)的预处理方案 39例 ,不含TBI的 73例 ;PR或复发的 70例中 ,含有TBI的预处理方案 2 9例 ,不含TBI的 4 1例。结果　四组所采集到的APBSC均可达到临床所需数量。四组间采集的单个核细胞数与采集次数之间无统计学差别。移植后WBC≥ 1 0× 10 9/L的中位数时间为 12 (10～ 30 )d ;血小板≥ 2 0× 10 9/L的中位数时间为 12 (0～ 181)d。患者移植后平均随访时间为 2 4个月。预期 3年无病生存率 (DFS)移植前达CR1期者 6 9 7% ;PR和复发期为 4 4 9%。在移植前达CR1期患者中 ,含有TBI和不含TBI的预处理方案的 3年DFS无统计学差别 (70 1%、6 8 0 % )。而对于PR或复发期患者 ,前者优于后者 (5 7     

难治性白血病异基因骨髓移植后髓外复发的危险因素和治疗

目的：探讨难治性白血病移植后髓外复发（软组织）的危险因素、治疗方法和疗效。方法：2001～2003年间15例急性白血病患者进行了异基因造血干细胞移植（allo-HSCT），其中6例为难治性或晚期白血病。6例晚期患者中4例移植后出现髓外复发（软组织肉瘤，EMD），治疗全部采用联合化疗加放疗、供者淋巴细胞输注（DLI），2例加用免疫细胞因子，1例进行了2次移植。结果：4例患者移植到发生EMD的间隔时间分别为10、5、8、8个月，均无骨髓复发的证据。经治疗2例无病生存，1例带瘤生存，1例死亡。allo-HSCT后生存期分别为15、27＋、24＋、19＋个月。结论：①移植后出现髓外复发患者的预后较差；②EMD的发生与移植前疾病状态、有无移植物抗宿主病（GVHD）、移植后免疫抑制剂的停用时间有关。晚期患者移植后，免疫抑制剂在可能的情况下应尽早减量、停药；③髓外复发早期，化疗和DLI在部分病例中有效；而当肿瘤负荷较大时，DLI的疗效欠佳，此时降低预处理剂量的二次移植不失为一种有效的治疗选择。     

异基因造血干细胞移植治疗恶性血液病临床观察

目的观察异基因造血干细胞移植(allo-SCT)治疗恶性血液病的疗效.方法选择HLA-A、B、DR位点完全相同的同胞作为供者,对13例恶性血液病患者进行allo-SCT,其中急性白血病10例,慢性白血病2例,恶性淋巴结瘤1例.采用BUCY预处理方案7例,TBI CY预处理方案4例,非清髓预移植方案2例.输入CD34细胞数(4.6～11.4)×106/kg.患者均用环孢菌素A加甲氨蝶呤预防移植物抗宿主病.结果 11例清髓性移植患者移植后9～19天外周血白细胞≥1.0×109/L,14～34天血小板≥20×109/L.移植后4例死于移植相关并发症,9例完全缓解,中位生存期26(8～73)个月.结论 allo-SCT治疗恶性血液病疗效可靠.     

大剂量美法仑预处理方案在多发性骨髓瘤自体造血干细胞移植中的疗效及安全性分析

目的 分析大剂量美法仑预处理方案在多发性骨髓瘤(MM)自体造血干细胞移植中的疗效及安全性。方法 回顾性分析2006年10月至2023年7月在广西壮族自治区人民医院血液内科行大剂量美法仑预处理方案自体造血干细胞移植的64例MM患者的临床资料。分析患者造血重建情况、移植后疾病转归及移植相关不良反应。结果 64例MM患者均获得造血重建,中性粒细胞植入中位时间为11(9～13)d,血小板植入中位时间为12(10～14)d,移植后100 d移植相关死亡率(TRM)为0。至随访结束,随访时间为4～188个月,中位随访时间为42.3(3.5～188)个月,中位生存时间未达到,总生存率为89.06%。64例MM患者中,疾病无进展46例(71.88%),疾病复发或进展18例(28.12%),死亡7例(10.94%),其中6例(9.38%)死于疾病复发或进展,1例(1.56%)死于继发急性白血病。移植后3个月达CR的患者52例(81.25%),至随访结束无疾病复发或进展41例(64.06%)。大剂量美法仑预处理方案的非血液学毒性主要为恶心呕吐、口腔黏膜炎、腹泻。64例MM患者均发生恶心呕吐,其中1～2级5...     

改良BU/CY预处理方案行异基因造血干细胞移植治疗恶性血液病的临床研究

异基因造血干细胞移植(Allo-HSCT)是目前治疗恶性血液病的有效方法,致力于提高植入率和无病存活率,降低移植相关毒性及移植相关病死率,其预处理方案的优化设计是造血干细胞移植的重点.现将我院应用改良BU/CY预处理方案治疗恶性血液病的临床及长期观察情况报道如如下.     

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。     

以静脉注射和口服白消安为预处理行HLA半相合造血干细胞移植治疗恶性血液病的比较

目的:比较以静脉注射和口服白消安(Bu)为预处理方案行亲属间HLA半相合外周血造血干细胞移植在造血重建、移植物抗宿主病(GVHD)、预处理相关毒性及并发症和疗效的差异,观察白消安注射液(ivBu)的疗效和安全性.方法:20例恶性血液病患者中,10例采用静脉注射Bu为预处理方案(ivBu组),10例采用口服Bu为预处理方案(口服Bu组),回顾性分析2组移植后造血重建、GVHD、预处理相关毒性及并发症和疗效情况.结果:ivBu组和口服Bu组移植后均获造血功能重建,2组中性粒细胞绝对值≥0.5×109/L的中位时间均为14 d(P>0.05),血小板计数≥20×109/L的中位时间分别为12和13 d(P>0.05),ivBu组急性GVHD发生率为10.0%,低于口服Bu组(50.0%)(P>0.05),慢性GVHD的发生率在2组中分别为20.0%和60.0%(P>0.05),2组在预处理相关毒性及并发症方面差异无统计学意义(P>0.05),ivBu组1例因间质性肺炎死亡,2组分别有1例和2例复发,余16例无病生存.结论:ivBu组和口服Bu组在造血重建、GVHD、预处理相关毒性及并发症等的差异均无统计学意义,以ivBu为主的预处理方案治疗血液病是安全有效的.     

自体造血干细胞移植+BEAC方案治疗预后不良非霍奇金淋巴瘤疗效观察

用自体外周血造血干细胞移植（APBSCT）＋大剂量BEAC方案治疗预后不良非霍奇金淋巴瘤（NHL）患者10例,均获快速造血功能重建,其中7例高危初治者完全缓解（CR）,3例复发者中CR2例、PR1例;无移植相关死亡。提示APBSCT＋大剂量化疗对预后不良或复发NHL安全有效,能改善患者生存率。     

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.