无血缘关系供者造血干细胞移植治疗恶性血液病的临床研究

目的 探讨无血缘关系供者造血干细胞移植(UHSCT)治疗恶性血液病的疗效.方法 对2003年3月至2006年12月军事医学科学院附属医院45例恶性血液病患者行UHSCT后无病存活率、移植相关病死率、移植后复发率、移植物抗宿主病(GVHD)的发生率、GVHD的严重程度及转归进行分析.结果 45例患者中,3例于造血恢复前死亡.可评价的42例中,30例(71.4%)发生急性GVHD,其中Ⅱ度以上的急性GVHD 9例(21.4%).移植后复发死亡5例,感染死亡5例,GVHD相关死亡5例,现27例(64.3%)无病存活.Kaplan-Meier显示,无病存活率(58.5±13.2)%,复发率11.9%,Ⅱ度以上急性GVHD发生率21.4%.结论 UHSCT治疗恶性血液病疗效肯定,为解决供者来源提供一个可选择的途径.     

自体外周血造血干细胞移植治疗恶性淋巴瘤的护理

恶性淋巴瘤是对化疗、放疗较敏感的恶性血液病,常规治疗可使部分患者获得较好的生存,而复发、中高度恶性淋巴瘤化疗、放疗治疗效果及预后不佳。自体外周血造血干细胞移植(APBSCT)已被广泛用于对化疗敏感的恶性淋巴瘤的治疗,并取得了显著疗效。APBSCT不受供者来源和     

自体造血干细胞移植治疗恶性血液病的临床研究

应用自体造血干细胞移植(ASCT)治疗恶性血液病11例,并随机选择病种、年龄及性别相似的13例应用常规化疗的恶性血液病作为对照.结果显示所有患者均造血重建,白细胞降至0的中位时间为6(3～10)天,持续5(1～14)天,中性粒细胞恢复至＞0.5×109/L的时间为18(13～24)天.在不输血小板情况下,维持血小板计数＞20×109/L中位时间为23(17～42)天.中位持续完全缓解时间(CCR)667.7(83～1885)天.3年无病生存率46%,而对照组3年无病生存率仅为18%,P＝0.035.提示自体造血干细胞移植可提高生存质量,明显提高无病生存率.     

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。     

时辰高剂量化疗联合自体骨髓移植治疗非霍奇金淋巴瘤的长期随访

目的　探讨在自体骨髓 (造血干细胞 )移植技术支持下应用时辰高剂量的环磷酰胺、足叶乙甙、阿糖胞苷和表阿霉素等组成 COAE预处理化疗方案治疗预后差的中高度恶性非霍奇金淋巴瘤 (NHL )的疗效。方法　观察 11例 NHL患者应用该项治疗后造血与免疫功能重建、长期无病生存率、毒副作用及移植相关死亡等 ,选用COX回归模型分析性别、年龄、预处理方案、分期、移植时状态等对无病生存时间的影响。结果　所有患者均获得造血与免疫功能重建。随访 1、3、5年 ,无病生存率分别为 81.8%、6 3.6 %、5 4 .5 % ,最长存活 9年。 5例复发(4 5 .4 % )。无移植相关死亡。结论　该法在给药时间上进行了创新 ,提高了疗效 ,减低了高剂量化疗的毒副作用。该法作为有不良预后因素的中高度恶性 NHL患者诱导化疗达完全缓解后强化治疗手段的远期疗效显著 ,优于常规化疗 ,能够改善生存率     

外周血造血干细胞移植治疗恶性血液病疗效观察

目的:观察外周血干细胞移植治疗恶性血液病的疗效、探讨移植相关并发症的预防及处理.方法:回顾分析了我院自2005年5月～2006年3月,其中2例采用HLA相合的同胞异基因外周血干细胞移植(AlloPBSCT),9例采用自体外周血造血干细胞移植(Auto-PBSCT).结果:全部病例均成功获得造血重建,中性粒细胞≥0.5×109/L,平均时间为11.3 d,血小板≥20×109/L平均时间为16.3 d;无严重并发症发生,无严重GVHD发生,中位随访时间11(2～24)个月,无复发及死亡病例.结论:外周血干细胞移植是治疗恶性血液病安全、有效的方法.     

APBSCT治疗淋巴系统恶性血液病临床研究

采用自体外周血造血干细胞移植(APBSCT)治疗5例恶性淋巴瘤和2例急性淋巴细胞白血病(ALL).干细胞动员采用大剂量VP16或MOEP方案 G-CSF;经过CVB或CVBA方案预处理后行APBSCT治疗.结果 全部病例均成功获得造血重建,移植后外周血中性粒细胞达到绝对数(ANC)≥0.5×109/L平均时间为11 d,Plt达到≥20×109/L平均时间为16 d.随访1～8个月,无复发及死亡病例.提示APBSCT是治疗淋巴系统恶性血液病安全、有效的方法.     

单倍体相合造血干细胞移植治疗48例恶性血液病患者的临床分析

目的:探究恶性血液病患者行单倍体相合造血干细胞移植(haplo-HSCT)的临床疗效。方法:本研究共纳入48例患者,均采用粒细胞集落刺激因子动员外周血干细胞作为移植物的非体外去T细胞移植模式。结果:48例患者均获粒系及巨核系重建,中性粒细胞植活的中位时间为14(9～38)d,血小板植活的中位时间为16.5(9～49)d。移植后第100天时急性移植物抗宿主病(aGVHD)累积发生率为16.5%,其中Ⅲ～Ⅳ度aGVHD累积发生率为6.7%。43例患者移植后存活时间超过100d,慢性移植物抗宿主病(cGVHD)的2年累积发生率为28.6%,其中广泛型cGVHD为12.6%。2年累积复发率及累积非复发死亡率分别为23.7%、30.2%。2年及3年累积总体生存率和累积无病生存率分别为52.6%和44.5%、37.5%和33.8%。结论:非体外去T细胞的haplo-HSCT对恶性血液病患者的治疗有效,且仅用外周血干细胞与骨髓+外周血干细胞做移植物在haploHSCT中的效果无明显差异。     

自体造血干细胞移植后感染降阶梯治疗的疗效分析

自体外周血干细胞移植技术已成熟应用于临床急性白血病、非霍奇金淋巴瘤、多发性骨髓瘤等恶性血液病患者的治疗,但移植后感染的预防、控制,仍然是治疗成败的关键。现将我院53例自体造血干细胞移植患者临床资料报道如下。     

大剂量化疗自体外周血干细胞移植生物治疗序贯疗法对67例非霍奇金淋巴瘤的疗效观察

目的评价大剂量化疗、自体外周血干细胞移植、生物治疗序贯疗法对非霍奇金淋巴瘤的疗效。方法2003年6月至2007年3月在第三军医大学新桥医院对67例中、高度恶性非霍奇金淋巴瘤(NHL)患者采用大剂量化疗、自体外周血干细胞移植、白介素-2(IL-2)生物治疗序贯治疗,观察其治疗效果和相关并发症。结果67例患者中,41例完全缓解期患者(NHL-CR),经上述序贯治疗,36例持续CR(87.8%),5例复发(RE,12.2%),其中1例死亡(2.4%);26例部分缓解患者(NHL-PR),达CR15例(57.7%),RE11例(42.3%),其中死亡5例(19.2%)。结论该序贯疗法治疗非霍奇金淋巴瘤安全有效,治疗前达到CR患者疗效更好。     

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.