骨髓根除性治疗恶性血液病临床研究

目前恶性血液病的治疗,化疗完全缓解率（ＣＲ）已达６０％～９０％。同基因或自体骨髓移值５年生存率４０％～５０％,治疗水准已达平台期,控制恶性血液病复发是血液学学者急需探索的主要课题。为探讨恶性血液病低复发,提高无病生存率（ＤＦＳ）、长期生存率（ＬＦＳ）及生存质量。我们设计了骨髓根除性治疗（ＭｅｇｌｏａｂｌａｔｉｒｅＴｈｅｒａｐｙＭＡＴ）方案。即在超大剂量化疗杀灭体内残留恶性细胞,动员大量干细胞增殖、分化迁移基础上,进行交替ＨＢＩ治疗,进一步清除恶性克隆细胞,再以过继免疫疗法目的性攻击超微量残留恶性…     

净化及非净化自体骨髓移植治疗白血病39例临床研究

报告自体骨髓移植治疗白血病３９例，其中非净化自体骨髓移植（ＡＢＭＴ）１４例，净化自体骨髓移植（ＰＡＢＭＴ）２５例。中位年龄２８岁（１０～４３岁）。ＡＭＬ２７例，ＡＬＬ１０例，ＣＭＬ２例。ＣＲ１３１例，ＣＲ２７例，ＮＲ１例。ＣＲ至移植时间中位数６．７个月（２～１９个月）。预处理方案：ＴＢＩ加Ａｒａ－ｃ、ＤＮＲ或ＶＰ１６。ＡＢＭＴ组及ＰＡＢＭＴ组３年无病生存（ＤＦＳ）率分别为６８．３２％及６７．５７％，复发率为３０．７６％及２６．８０％。但ＰＡＢＭＴ组ＡＭＬ患者３年ＤＦＳ率为８２．３５％及ＣＲ２期移７５％３年ＤＦＳ率为７５％，明显高于ＣＲ。期移植未净化者５０％。化疗组３年ＤＦＳ率为７．３８％及复发率７６．４％，两移植组疗效优于化疗组。     

自体造血干细胞移植治疗恶性血液病、肺癌临床观察

用自体造血干细胞移植（ＡＨＳＣＴ）治疗３例急性非淋巴细胞性白血病（ＡＮＬＬ）、１例霍奇金病（ＨＤ）和１例晚期肺癌（ＡＬＣ）。其中４例接受自体外周血干细胞移植（ＡＰＢＳＣＴ），１例接受自体骨髓移植（ＡＢＭＴ）。ＡＮＬＬ、ＨＤ、ＡＬＣ分别用ＭＡＣ、ＳＥＡＭ、ＳＥＥＣ方案预处理。５例患者移植后均获造血重建。ＡＮＬＬ和ＨＤ已分别持续完全缓解４８９天、３７２天、３３５天、２３０天；１例ＡＬＣ患者在移植后完全缓解１１５天后出现颅内复发。初步结果提示ＡＨＳＣＴ能延长ＡＮＬＬ、ＨＤ和ＡＬＣ患者的无病存活期     

自体骨髓干细胞移植治疗慢加急性乙型肝炎肝衰竭患者疗效初步研究

目的 探讨血浆透析滤过联合自体骨髓干细胞移植治疗慢加急性乙型肝炎肝衰竭患者的疗效。方法 入组120例慢加急性乙型肝炎肝衰竭早中期患者,均接受内科综合治疗和血浆透析滤过（PDF）治疗,其中58例接受PDF联合自体骨髓干细胞移植治疗,观察患者症状、体征、生存率、活动状态评分（ECOG）、终末期肝病模型（MELD）评分、CTP分级和肝功能的变化。结果 在治疗24 w和48 w,干细胞移植组患者生存率分别为70.7%和55.2%,显著高于血浆透析滤过组的51.6%和32.2%（P<0.05）,干细胞移植组患者ECOG评分≥2级者分别为27.5%和12.5%,显著低于血浆透析滤过组的56.3%和40.0%（P<0.05）;在治疗24 w,干细胞移植患者MELD评分和吲哚菁绿15分钟存留率（ICGR15）分别为（18.6±4.1）和（20.6±8.1）%,显著低于血浆透析滤过患者【分别为（20.4±5.2）和（28.7±10.3）%,P<0.05】;58例行自体骨髓干细胞移植治疗患者术中未出现严重不良反应。结论 自体骨髓干细胞移植治疗经血浆透析滤过术后的早中期患者可明显提高患者生存率,并且有良好的安全性。     

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     

自体骨髓干细胞移植治疗慢性肝衰竭研究

目的探索自体骨髓干细胞移植对肝衰竭患者的治疗作用,为干细胞移植的临床应用研究提供基础。方法35例慢性重症肝病患者,20例行自体骨髓干细胞移植治疗,15例作为对照。在无菌条件下,从患者髂后上棘抽取骨髓30～50ml,分离纯化骨髓干细胞。在局部麻醉下行肝动脉介入,将分离的骨髓干细胞移植于肝脏。患者在移植后1、2、4、8周进行肝功能检测。观察患者移植后不同时间症状改善情况及术后不良反应情况。结果在移植8周后,患者丙氨酸转氨酸逐渐降低,由平均181.7μmolL降至72.1μmolL;总胆红素由平均153.8μmolL降至80.2μmolL;直接胆红素由平均74.1μmolL降至40.5μmolL;白蛋白逐渐升高,由平均26.5μmolL升至31.5μmolL;与对照组相比有明显差异,表明移植后患者肝功能明显改善。干细胞移植后凝血酶原活动度逐渐上升,由术前平均28.2%上升至50.1%。进一步观察自体骨髓干细胞移植对肝衰竭患者生存率的影响,发现移植后1周生存率为100%,4周为95%(1920),8周后为90%(1820),12周后为85%(1720),较对照组生存率明显升高。移植后大多数患者有明显症状改善,移植后8周内腹水减轻10例(50%),食欲改善15例(75%),体力好转11例(55%),腹胀减轻9例(45%)。在20例移植患者中未发现严重并发症,术后有轻度恶心1例,发热1例。结论自体骨髓干细胞移植治疗后,患者肝功能和凝血机制明显改善,生存率提高,症状好转,表明骨髓干细胞移植对肝衰竭患者治疗有效,安全,不良反应少。     

经冠脉移植自体骨髓干细胞治疗扩张型心肌病的安全性及疗效

目的：探讨经冠状动脉自体骨髓干细胞移植治疗扩张型心肌病的安全性和疗效。方法：选择经超声、冠状动脉造影证实为扩张型心肌病患者52例，随机分为自体骨髓干细胞移植组（细胞移植组）和对照组，两组均予常规抗心力衰竭（心衰）药物治疗，细胞移植组自体骨髓干细胞经微导管注入左、右冠状动脉。两组术前，术后24h、48h，1、3和6个月分别检测血常规及生化指标（肝功能、肾功能、血糖、血脂、血尿酸、肌酸激酶、肌酸激酶同工酶和hs—CRP），术前，术后1、3和6个月分别行超声心动图、动态心电图、6min步行试验检查。结果：细胞移植组术后24h、48h，1、3和6个月血常规及生化指标与对照组和自身术前相比均无显著性差异（P〉0．05）。术后6个月，细胞移植组6min步行路程增加，与对照组有显著差异（P〈0．05），与术前有显著差异（P〈0．05），但超声心动图显示两组间左室舒张末容积和左室射血分数无统计学差异（P〉0．05）。围手术期及术后6个月随访中未见任何严重心律失常等不良反应发生。结论：经冠状动脉自体骨髓干细胞移植治疗扩张型心肌病安全、有效。     

自体骨髓单个核细胞移植治疗肝硬化的临床评价

目的探讨肝动脉插管自体骨髓单个核细胞（BM—MNCs）移植治疗肝硬化的安全性、可行性及疗效。方法201例肝硬化患者,其中131例进行自体骨髓单个核细胞移植,70例作为对照组。骨穿采集自体骨髓体外分离纯化骨髓单个核细胞。经肝动脉插管将其移植入肝脏。分别于移植后4、8、12、24周观察血清白蛋白（ALB）、胆碱酯酶（CHE）、凝血酶原活动度（PTA）及总胆红素（TBil）变化情况,观察患者并发症及预后。结果移植组患者移植前血清ALB、CHE及PTA分别为29．33g／L、2387．4U／L和46．4％。移植后4周分别升至32．37g／L、2875．9U／L和53．54％,12周分别为32．95g／L、3190．6U／L和57．24％,24周则分别为32．22g／L、3066．5U／L和56．02％。患者移植后24、周内血清ALB、CHE和PTA水平较治疗前均显著升高,而对照组则无明显升高,两组比较差异有统计学意义。而血清TBil在移植后24周内改善情况与对照组相比差异无统计学意义。两组患者24周内主要并发症发生率及预后情况差异无统计学意义。移植后无严重不良事件发生。结论自体骨髓单个核细胞移植能改善肝硬化患者肝脏合成能力,并有良好的安全性。     

自体造血干细胞移植的临床应用进展：急性白血病

自体造血干细胞移植（ASCT）是指采集患者骨髓或外周血干细胞低温保存,并于其接收大剂量化疗或放疗（预处理）后回输,以重建造血和免疫功能。ASCT包括自体外周血造血干细胞移植（APBSCT）及自体骨髓造血干细胞移植（ABMT）,以往多用于治疗血液系统恶性疾病（如白血病、淋巴瘤）,近年来逐渐用于实体瘤（如乳腺癌、卵巢癌）、自身免疫性疾病、缺血性疾病（如糖尿病足、心肌梗死）及中枢神经系统疾病等领域。现将其在临床的应用进展分述如下。     

自体骨髓移植治疗急性白血病临床研究

报道３８例急性白血病微波净化后自体骨髓移植结果。移植时中位年龄２６岁，均为初次缓解。经强烈放疗、化疗预处理后移植。移植后中位持续缓解时间２１个月，中位无病生存期３５个月。４例移植后于３～８个月复发死亡，２例分别于１２、１５个月出现中枢神经系统白血病，治疗后仍存活。全组患者５年无病生存率及复发率分别为６７．８％及１６．８％。     

Three layer functional model and energy exchange concept of aging process

Relying on a certain degree of abstraction, we can propose that no particular distinction exists between animate or living matter and inanimate matter. While focusing attention on some specifics, the dividing line between the two can be drawn. The most apparent distinction is in the level of structural and functional organization with the dissimilar streams of ‘energy flow’ between the observed entity and the surrounding environment. In essence, living matter is created from inanimate matter which is organized to contain internal intense energy processes and maintain lower intensity energy exchange processes with the environment. Taking internal and external energy processes into account, we contend in this paper that living matter can be referred to as matter of dissipative structure, with this structure assumed to be a common quality of all living creatures and living matter in general. Interruption of internal energy conversion processes and terminating the controlled energy exchange with the environment leads to degeneration of dissipative structure and reduction of the same to inanimate matter, (gas, liquid and/or solid inanimate substances), and ultimately what can be called ‘death.’ This concept of what we call dissipative nature can be extended from living organisms to social groups of animals, to mankind. An analogy based on the organization of matter provides a basis for a functional model of living entities. The models relies on the parallels among the three central structures of any cell (nucleus, cytoplasm and outer membrane) and the human body (central organs, body fluids along with the connective tissues, and external skin integument). This three-part structural organization may be observed almost universally in nature. It can be observed from the atomic structure to the planetary and intergalactic organizations. This similarity is corroborated by the membrane theory applied to living organisms. According to the energy nature of living matter and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions.     

Unusual responses of nocturnal pineal melatonin synthesis and secretion to swimming: Attempts to define mechanisms

Abstract: The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650μW/cm²) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin. These data suggest that the disparity in pineal NAT activity (which was high) and pineal melatonin (which was low), in animals swum at night, may not be caused by ANP which is released during strenuous exercise such as swimming.     

Melatonin and photoperiodic time measurement: Seasonal breeding in the sheep

Abstract: Well-established circadian physiology supports the view that photoperiodic time measurement utilizes the coincidence between the presence of light and a photosensitive phase of a 'biological clock' to alter reproductive status—the so-called external coincidence model of seasonal breeding. In this review, we examine the mechanism whereby photoperiod interacts with presumed suprachiasmatic nuclei activity to allow endogenous melatonin to normally synchronize reproductive activity to the optimal time of year. The Romney Marsh sheep is particularly explored as an experimental model. It is suggested that the on/off activity of seasonal reproduction may be a robust mechanism able to be predictably manipulated by the judicious use of the light/dark cycle and exogenous melatonin, but firmly based on circadian principles.     

Serological survey of HIV and syphilis in pregnant women in Madagascar

Objectives Peripartal transmission of human immunodeficiency virus (HIV) and Treponema pallidum, the causative agent of syphilis, leads to severe consequences for newborns. Preventive measures require awareness of the maternal infection. Although HIV and syphilis testing in Madagascar could be theoretically carried out within the framework of the national pregnancy follow‐up scheme, the required test kits are rarely available at peripheral health centres. In this study, we screened blood samples of pregnant Madagascan women for HIV and syphilis seroprevalence to estimate the demand for systemic screening in pregnancy. Methods Retrospective anonymous serological analysis for HIV and syphilis was performed in plasma samples from 1232 pregnant women that were taken between May and July 2010 in Ambositra, Ifanadiana, Manakara, Mananjary, Moramanga and Tsiroanomandidy (Madagascar) during pregnancy follow‐up. Screening was based on Treponema pallidum haemagglutination tests for syphilis and rapid tests for HIV, with confirmation of positive screening results on line assays. Results Out of 1232 pregnant women, none were seropositive for HIV and 37 (3%) were seropositive for Treponema pallidum. Conclusions Our findings are in line with previous studies that describe considerable syphilis prevalence in the rural Madagascan population. The results suggest a need for screening to prevent peripartal Treponema pallidum transmission, while HIV is still rare. If they are known, Treponema pallidum infections can be easily, safely and inexpensively treated even in pregnancy to reduce the risk of transmission.     

Variabilité des concentrations plasmatiques de l’angiotensinogène et risque d’hypertension artérielle chez le rat transgénique

Aim

Genetic polymorphisms of the human angiotensinogen gene are frequent and may induce up to 30% increase of plasma angiotensinogen concentrations with a blood pressure increase of up to 5 mmHg. Their role for the pathogenesis of human arterial hypertension remains unclear. High plasma angiotensinogen levels could increase the sensitivity to other blood pressure stressors.

Methods

Male transgenic rats with a 9-fold increase of plasma angiotensinogen concentrations and male non-transgenic rats aged 10 weeks were treated or not with NG-Nitro-L-arginine-methyl ester for 3 weeks in their drinking water (n = 3/group). Systolic blood pressure and body weight were measured at baseline and at the end of the study when left ventricular weight and ventricular expression of angiotensin I-converting enzyme and procollagen Iα1 were determined (polymerase chain reaction).

Results

At baseline, transgenic rats had +18 mmHg higher bood pressure and –8% lower body weight compared to non-transgenic rats (P < 0.05) without significant changes for the vehicle groups throughout the study (P > 0.05). NG-Nitro-L-arginine-methyl ester increased blood pressure, left ventricular weight and left ventricular weight indexed for body weight by +41%, +17.6% and +18.6% (P < 0.05) in transgenic and +25%, +5.3% and +6.7% (P > 0.05) in non-transgenic rats compared to untreated animals, respectively. Cardiac gene expression showed no differences between groups (P > 0.05).

Conclusion

Increased plasma angiotensinogen levels may sensitize to additional blood pressure stressors. Our preliminary results point towards an independent role of angiotensinogen in the pathogenesis of human hypertension and associated end-organ damage.     

Morphological and immunocytochemical heterogeneity of cultured pinealocytes from one-week-and two-month-old rats: Planimetric and densitometric investigations

Abstract: In vitro preparations of rat pinealocytes are widely used for biochemical analyses of signal transduction processes. This paper deals with morphological and immunocytochemical features of such preparations. Special attention was paid to the problems of whether pinealocytes represent a heterogeneous cell population and how such heterogeneity may develop during ontogeny. The investigations were performed with cells which were obtained from the pineal organ of one-week-and two-month-old rats, attached to synthetic peptide-coated coverslips or tissue culture chamber slides, and maintained under in vitro conditions overnight. The attached cells were then fixed with paraformaldehyde. These preparations yielded monolayers of spherical cells of different sizes; most cells were isolated, but some of them were aggregated and formed small clusters. On the average, the cells from the one-week-old animals were smaller than the cells from the two-month-old animals. Immunocytochemical demonstration of S-antigen, a pinealocyte-specific marker, showed that the majority of the cells from two-month-old animals were intensely or moderately labelled. Pinealocytes from one-week-old animals were less S-antigen immunoreactive. Only very few cells (less than 1% displayed glial fibrillary acidic protein (GFAP)-immunoreactivity. Planimetric investigations of the cell size and semiquantitative densitometric investigations of the intensity of the S-antigen immunoreaction revealed that (i) pinealocytes kept in vitro form a heterogeneous cell population, and that (ii) this heterogeneity increases during postnatal development from one-week-old to two-month-old animals. Two groups of pinealocytes can be distinguished based on their developmental fate: pinealocytes of one group grow dramatically, but show only a moderate increase in S-antigen immunoreactivity, and pinealocytes of the other group retain their size, but display a distinct increment in S-antigen immunoreacti vitv.     

Effects of pinealectomy and melatonin administration on certain indices of ovarian hyperplasia and/or hypertrophy in rats with both ovaries intact or after unilateral ovariectomy

Abstract: In earlier studies from other laboratories it was shown that melatonin decreased ovarian weight in rats and inhibited compensatory hypertrophy of the remaining ovary after unilateral ovariectomy. This study was designed to examine the influence of melatonin on certain indices of ovarian hyperplasia and/or hypertrophy in adult female rats with both ovaries preserved and with either an intact pineal gland or with the pineal gland removed (pinealectomy, PX) or, finally, in sham-PX animals. Similar studies were conducted on rats after unilateral ovariectomy, referring the examined parameters to the remaining intact ovary. The studies included mitotic activity of granulosa layer cells and corpus luteum cells, ovarian weight, ovarian cross-sectional area, cross-sectional area of the granulosa layer of all the Graafian follicles and the cross-sectional areas of the corpora lutea, visible on the ovarian cross-section. On the basis of results, we conclude that: 1) the effect of PX on the processes of ovarian hyperplasia and hypertrophy may vary; analogously, exogenous melatonin administration may influence ovarian hyperplasia and hypertrophy in different ways; 2) PX and exogenous melatonin may, under certain conditions, exert similar biological effects, even synergistic effects; 3) melatonin inhibits ovarian growth processes, while the effects of PX are variable; 4) the results indicate that in experiments performed on rats, with the use of two control groups, i.e., intact and sham-PX, melatonin effects on these two groups may differ.