异基因外周血造血干细胞移植治疗急性白血病(附1例报告)

目的 :探索异基因外周血造血干细胞移植 (allo PBSCT)治疗急性白血病的疗效和移植物抗宿主病(GVHD)的防治。方法 :急性淋巴细胞白血病 (ALL )患者 1例 ,HLA配型完全相合。预处理采用白消安、环磷酰胺(BU/CTX )方案 ;GVHD的预防采用常规环胞菌素A(CsA)加短程甲氨蝶呤 (MTX)加霉酚酸酯 (MMF)方案。治疗慢性GVHD(cGVHD)采用MMF加CsA加硫唑嘌呤 (6 mp)加泼尼松加酞咪哌啶酮 (反应停 ,Thalidomide)。移植有核细胞数 (NC)为 12 .32× 10 8/kg ,CD34+ 细胞为 14 .78× 10 6/kg。结果 :移植 +13d获造血重建 ,同时DNA指纹图提示供者型。移植 +2 2d检测染色体核型为 4 6 ,XX ,10 0 %嵌合。移植 +98d血型由B型转变为A型。移植 +2 10d发生cGVHD ,随访 19个月 ,cGVHD已控制 ,患者现无病生存。结论 :异基因外周血造血干细胞移植可有效治疗急性白血病 ,本例造血重建迅速 ,cGVHD通过治疗后可有效控制     

BU／CY预处理方案的异基因外周血干细胞移植治疗急性白血病

目的 :观察 BU / CY预处理方案的异基因外周血干细胞移植 (Allo- PBSCT)治疗急性白血病的疗效。方法 :用 BU / CY预处理方案行 Allo- PBSCT治疗急性白血病 5例 ,其中急性淋巴细胞白血病 (AL L ) 4例 (CR13例 ,CR2 1例 ) ,急性非淋巴细胞白血病 (ANL L) 1例 (CR1 )。预处理方案 BU/ CY:BU4m g/ (kg· d)× 4,CTX6 0m g/ (kg· d)× 2。其中 2例 AL L 分别加米托蒽醌 40～ 5 0 m g。用 G- CSF10 μg/ (kg· d)× 5 d进行造血干细胞动员 ,分离单个核细胞 (MNC)中位数 6 .48× 10 8/ kg〔(3.5～ 7.0 )× 10 8/ kg〕。 CD34+细胞中位数 6 .6× 10 6 / kg〔(4.0～9.6 6 )× 10 6 / kg〕。结果 :全部患者移植后均重建造血 ,粒细胞 >0 .5× 10 9/ L,中位数 13d;血小板 >30× 10 9/ L,中位数为 13d;血小板 >5 0× 10 9/ L,中位数为 15 d。发生迟发性出血性膀胱炎 1例 ,白血病复发死亡 1例 ,CMV肺炎死亡 1例。其余 3例分别无病生存 11、9、7个月。结论 :Allo- PBSCT具有造血重建快 ,采集干细胞方便 ,供者易接受等优点     

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     

异基因外周血造血干细胞移植治疗难治性白血病(附1例报告)

对 1例难治性急性粒 -单细胞白血病 (AML - M4 b)患者施行异基因外周血造血干细胞移植 (allo-PBSCT ) ,以 Cy/ TBI方案预处理后 ,输注 HL A完全相合的同胞供者经 G- CSF动员的外周血单个核细胞(PBMNCs) 9.0× 10 8/ kg,其中 CD34 细胞 6 .2 5× 10 6 / kg;移植物抗宿主病 (GVHD)的预防用 Cs A MTX方案。结果 : 15天时 ,外周血中性粒细胞 >0 .5× 10 9/ L,血小板 >5 0× 10 9/ L; 30天时 ,外周血三系均完全恢复正常。仅有 度皮肤 GVHD发生。认为对于难治性白血病 ,如有 HL A相合供者 ,应及早行异基因造血干细胞移植 (allo-HSCT)特别是 allo- PBSCT,具有受者造血与免疫功能重建快等优点     

造血干细胞移植治疗重型再生障碍性贫血临床研究

对10例重型再生障碍性贫血（SAA）患者行造血干细胞移植（HSCT），骨髓移植（BMT）1例，外周血干细胞移植（PBSCT）7例，脐血移植（CBT）2例。结果1例BMT及5例PBSCT完全植入；2例PBSCT嵌合植入者分别在移植后3、12个月发生宿主排斥移植物反应，分别用再次外周血造血干细胞输注、免疫疗法后血象恢复正常；2例CBT未成功植入，但均重建造血功能。随访6～44个月，9例存活，1例死于急性心功能衰竭。     

不同类型造血干细胞移植后巨细胞病毒感染的监测

目的观察在不同类型造血干细胞移植中巨细胞病毒感染状况。方法应用半巢式PCR技术定期检测了2001-03~2003-07苏州大学附属第一医院住院病人55例移植病人外周血标本,比较不同类型移植CMV-DNA阳性率的差别。结果在检测的462份标本中,有285份为阳性,33/55(60%)患者CMV-DNA阳性,非清髓性造血干细胞移植(NST)的阳性检出率为15/17(88·2%),亲缘间外周血造血干细胞移植(PBSCT)的阳性检出率为3/7(42·9%),非亲缘性骨髓移植(UR-BMT)的阳性检出率为7/11(63·6%),亲缘性骨髓移植(R-BMT)的阳性检出率为8/20(40·0%)。NST与PBSCT、R-BMT的巨细胞病毒感染率差别显著(χ~2=5·44,P<0·05;χ~2=9·14,P<0·05),NST与UR-BMT(χ~2=2·39,P>0·05)间的差别无统计学意义。结论巨细胞病毒感染在不同的造血干细胞移植方式可能存在差异。     

HLA表型对异基因造血干细胞移植后急性移植物抗宿主病影响的研究

目的　探讨 HL A表型对 HL A相合同胞供者异基因造血干细胞移植后急性移植物抗宿主病(a GVHD)的影响。方法　对 116例患者进行 HL A相合同胞供者的异基因造血干细胞移植 ,其中异基因骨髓移植(Allo- BMT) 37例 ,异基因外周血干细胞移植 (Allo- PBSCT) 79例 ,根据患者皮肤、肝脏及肠道的不同表现 a GVHD分为 ～ 度 ,在 111例可评估的患者中观察其 HL A表型与 a GVHD的关系。结果　表达 HL A- A2 位点患者的a GVHD发生率 (6 2 .7% )明显高于无 A2 位点患者 (4 2 .3% ) (P<0 .0 5 ) ,但 度 a GVHD的发生率 (16 .9%、13.4 % )和 ～ 度 a GVHD的发生率 (13.6 %、13.5 % )均无明显差异 (P>0 .0 5 )。其他影响 a GVHD发生率的因素为移植类型、GVHD预防方案和免疫抑制剂早期减量。结论　有 HL A- A2 位点表达者 a GVHD的发生率增加 ,但可通过选择移植方式、预防移植物抗宿主病 (GVHD)方案以及免疫抑制剂的减量时间控制 a GVHD的发生。     

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。     

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。     

HLA单倍相合造血干细胞移植治疗恶性血液病的临床研究

目的 探讨人类白细胞抗原(HLA)单倍相合造血干细胞移植(HSCT)治疗恶性血液病的疗效和主要并发症.方法 对2004年7月至2006年12月第三军医大学附属新桥医院收治的35例恶性血液病患者进行HLA单倍相合亲缘供者HSCT.采用延长、强化联合免疫抑制促进植入、抗胸腺细胞球蛋白(ATG)加强预防移植物抗宿主病(GVHD)、粒细胞集落刺激因子(G-CSF)动员的骨髓(BM)加外周血干细胞(PBSC)混合移植方案.结果 所有患者均重建供者造血.18例(51.4%)发生急性GVHD(aGVHD),其中Ⅰ度8例,Ⅱ度5例,Ⅲ度3例,Ⅳ度2例,Ⅱ～Ⅳ度aGVHD累积发生率为28.6%.12例(34.3%)发生慢性CVHD(cGVHD),均为局限性.23例患者存活,总存活率为65.7%,2年无病存活率(DFS)为62.9%.12例患者死亡,7例死于复发,5例死于移植相关合并症,其中肺部感染2例,Ⅳ度GVHD 2例,巨细胞病毒(CMV)感染1例.结论 随着预处理方案、GVHD预防方案及移植物成分的优化,HLA单倍相合造血干细胞移植的疗效明显改善,已成为治疗恶性血液病的重要方法.     

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.     

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.     

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.     

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.