以国产rHuG-CSF为动员剂作外周血造血干细胞移植治疗恶性血液病的临床观察

为了进一步探讨外周血造血干细胞移植 (PB SCT)的动员方法 ,我们分别采用国产重组人粒细胞集落刺激因子 (rHuG CSF ,商品名特尔津 )和进口rHuG CSF(商品名惠尔血 )动员后作异基因外周血造血干细胞移植 (Allo PBSCT)和自体外周血造血干细胞移植 (APBSCT)治疗恶性血液病患者各2 4例和 2 7例 ,结果特尔津作为动员剂在APBSCT中安全、有效 ,现报告如下。1　资料与方法1 .1 　 分组与动员方法Allo PBSCT分组及动员方法 :特尔津组正常供者 1 3例 ,男 8例 ,女 5例 ,中位年龄 2 8(1 8～ 5 2 )岁 ,中位体重 6 5 (46～ 85 )kg。惠尔血…     

G-CSF动员后异基因骨髓联合外周血干细胞移植治疗血液病

目的 探讨粒细胞集落刺激因子(G-CSF)动员的异基因骨髓与外周血干细胞混合移植后造血重建、移植物抗宿主病(GVHD)、复发及生存情况.方法 45例血液病患者进行了动员后的异基因骨髓联合外周血干细胞混合移植,人白细胞抗原(HLA)全合37例,1～3个位点不合8例.38例恶性病中32例采用清髓性预处理,6例为减低强度预处理;7例重型再生障碍性贫血(SAA)均采用环磷酰胺联合兔抗人胸腺细胞球蛋白(ATG)及甲泼尼龙预处理.采用环孢素联合霉酚酸酯预防移植物抗宿主病,HLA不全相合患者加用ATG.供者给予G-CSF连续5天皮下注射,注射后第5天采集外周血干细胞,第7天采取骨髓血.结果 45例患者均获得快速造血重建,中性粒细胞绝对计数≥0.5×109/L,血小板≥20×109/L的中位时间分别为移植后的12(8～18)天和16(10～28)天.10例发生了急性GVHD(22%),Ⅱ度以上1例.可评估的42例患者中16例出现了慢性GVHD,7例为广泛型(16%).复发9例,死亡11例,其余34例中位随访时间16月(10～46月),可评估的2年无病生存率为75%.结论 G-CSF动员后的异基因骨髓联合外周血干细胞移植治疗血液病可获快速造血重建,移植相关死亡率及重度急、慢性GVHD的发生率低,复发率不增高.     

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.     

血液病患者异基因外周血造血干细胞移植术后高血糖发生危险因素分析

目的探讨血液病患者异基因外周血造血干细胞移植术（allo-PBSCT）后高血糖的发生情况及危险因素。方法选择接受allo-PBSCT至今仍无病生存的血液病患者62例,根据术后是否发生高血糖分为高血糖组15例和对照组47例,对患者的临床资料进行回顾性分析。结果①将移植后糖尿病和糖耐量受损（IGT）、空腹血糖受损（IFG）均做为移植后高血糖,结果移植后高血糖15例（24．19％）。②单因素分析显示,移植后高血糖的发生与移植年龄、回访时年龄、移植前体质量、服用环孢菌素A时间、服用糖皮质激素时间及用量、移植前吸烟史及移植后高血压密切相关（P均〈0．05）。③Logistic多因素分析表明,糖皮质激素累积使用剂量、环孢素A使用时间、移植后高血压的发生是引起高血糖的独立危险因紊（P均〈0．05）。结论高血糖是血液病患者allo-PBSCT后常见的并发症,糖皮质激素累积使用剂量、环孢素A使用时间以及移植后高血压的发生是引起移植后高血糖发生的独立危险因素。     

rhG-CSF未经动员与动员后供者外周血淋巴细胞与干细胞采集物的细胞构成及功能比较

目的比较重组人粒细胞集落刺激因子（rhG-CSF）动员后供者外周血干细胞（PBSC）采集物与未经动员供者外周血淋巴细胞采集物的细胞构成及功能。方法取异基因造血干细胞移植供者的rhG-CSF动员后PBSC采集物（A组）和未经动员的淋巴细胞采集物（B组）,以流式细胞术测定采集物组分、T细胞亚群、树突细胞（DC）及其亚群、CD14^＋细胞和CD19^＋细胞B7分子的表达、CD4^＋T细胞IL-4和IFNγ等细胞因子的分泌情况,四甲基偶氮唑盐法测定T淋巴细胞增殖能力。结果两组采集物的CD3^＋、CD4^＋、CD34^＋、CD14^＋细胞比例有明显差异,A组DC细胞及其亚群的比例明显高于B组,尤以DC2升高为著（P=0．000）,CD14^＋细胞上B7分子的表达A组明显低于B组,CD19^＋细胞上B7分子的表达无明显差异,分析两组CD4细胞内因子的分泌情况,A组的Ⅱ类细胞因子IL-4及IL-4／IFNγ均明显高于B组（P值分别为0．044,0．012）,经rhG—CSF动员后采集物的T淋巴细胞增殖能力明显下降。结论动员后的PBSC采集物较未经动员的淋巴细胞采集物富集了更多的CD34^＋、CD14^＋细胞,同时rhG—CSF动员后DC2比例的明显升高使得CD4细胞向Th2分化,PBSC含有更多的Ⅱ类细胞因子和其T细胞增殖能力的下降、共刺激分子的下调均提示PBSC较供者淋巴细胞输注更少地引起急性移植物抗宿主病的发生。     

异基因造血干细胞移植治疗恶性血液病临床分析

异基因造血干细胞移植（allo-HSCT）是治疗血液系统疾病的重要手段,能够使恶性血液疾病得到治愈,明显改善预后.我们自2001年5月～2010年5月对37例恶性血液病患者进行了allo-HSCT.现报道如下。     

粒细胞集落刺激因子对供者外周血干细胞动员的影响

目的：探讨外周血造血干细胞移植（PBSCT）供者应用粒细胞集落刺激因子（G-CSF）后细胞成分的变化和药物对供者身体状况的近期影响。方法：对18例健康PBSCT供者应用一定剂量G-CSF,4-5d后采集外周血单个核细胞进行检测及观察用药后出现的不良反应。结果：外周血白细胞在动员后4-5 d达峰值,动员后比动员前高7-14倍。供者单个核细胞（MNC）和CD34^＋细胞值之间差异无统计学意义。结论：对PBSCT供者应用G-CSF 5-10μg/（kg.d）,4-5 d可有效动力员MNC和CD34^＋细胞。     

腺病毒介导的hVEGF165基因治疗对骨髓移植后骨髓造血干细胞恢复的影响及其意义

目的：探讨重组腺病毒Ad—EGFP／hVEGF165介导的血管内皮细胞生长因子在骨髓移植后小鼠体内的表达效率及对骨髓造血干细胞恢复的影响。方法：利用细菌内同源重组法快速构建复制缺陷型腺病毒Ad—EGFP／hVEGF165，经尾静脉注射给同基因骨髓移植BALB／c小鼠；在移植后不同时间，通过荧光显微镜、RT—PCR、免疫组化染色和ELISA方法检测外源基因在小鼠体内的表达；取移植后30d小鼠骨髓单个核细胞并计数，随后进行脾集落形成单位试验(CFU—S)以评价VEGF基因转移组小鼠骨髓造血干细胞数量恢复情况。结果：重组腺病毒AdEGFP／hVEGF165介导的VEGF基因转移广泛分布在骨髓移植小鼠心、肺、肝、脾、肾、小肠和骨髓组织；小鼠血浆中VEGF浓度高峰出现在移植后2d；接受重组腺病毒AdEGFP／hVEGF165基因干预治疗组小鼠骨髓单个核细胞计数及其形成的脾集落数量明显高于其他对照组。结论：腺病毒成功介导了hVEGF165基因在骨髓移植小鼠体内的稳定表达，明显促进骨髓移植小鼠骨髓造血干细胞数量的恢复．是骨髓单个核细胞数量增加的根本原因。     

造血干细胞移植治疗恶性血液病151例

造血干细胞移植（ＨＳＣＴ）是近２０多年来治疗恶性血液病的重要方法，使恶性血液病根治率提高到５０％以上，使某些恶性肿瘤疗效大为提高，现介绍我们近年来所进行的１５１例ＨＳＣＴ治疗恶性血液病的经验，并对有关问题进行讨论。一、资料与方法（一）病例选择１９８７...     

化疗联合粒细胞集落刺激因子动员外周血干细胞效果观察

2000年3月以来，我院应用化疗联合粒细胞集落刺激因子(G-CSF)动员外周血干细胞，取得良好效果。现报告如下。     

Seven cardinal questions for the patient with ear,nose or throat complaints: Review

The incidence of otolaryngological problems in general medicine practice is highly seasonal and approaches 25% in some months of the year. Accurate diagnosis in the otolaryngology office often requires the use of binocular microscopy, nasal endoscopy, and flexible laryngoscopy, none of which are available in a general medicine office. Therefore, history taking and physical examination techniques available in the non-otolaryngology office are of utmost importance. Using evidence-based history taking for ear, nose, and throat (ENT) problems facilitates dealing with patients who present with otolaryngologic complaints. In this paper, I present 7 cardinal questions to be asked when taking the history of a patient with ENT complaints.     

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.     

MUTATION FREQUENCY IN NURSES AND PHARMACISTS WORKING WITH CYTOTOXIC DRUGS

Individuals occupationally exposed to cytotoxic drugs may be at risk owing to the effects of these agents on DNA. As an index of DNA damage, in vivo mutations were measured in lymphocytes from 24 oncology nurses or pharmacists and 24 matched controls. Mutation frequency was significantly increased in exposed individuals and appeared to be related to duration of exposure. However, the overall magnitude of the increase was small and its biological significance remains to be determined.     

A single injection of adrenergic agonists enhances pineal melatonin production in Turkish hamsters

Abstract: The purpose of this study was to determine whether the pineal gland of Turkish hamsters (Mesocricetus brandti) responds to adrenergic agonists with an increase in melatonin production, and, if it does, whether the sensitivity of the pineal gland to agonists would differ throughout the dark phase. Adult Turkish hamsters weighing 110–210 g received a subcutaneous injection of isoproterenol (ISO, 1 mg/kg B.W.) or norepinephrine (NE, 1 mg/kg B.W.) at different times of night. Animals exposed to LD 16:8 responded to ISO or NE with increased pineal melatonin content only when injected at dawn, when endogenous melatonin is at basal or near-basal levels. When the 8 hr scotophase was entirely replaced with light, the responsiveness to ISO injections at dawn disappeared. In animals exposed to light from 30 min prior to injection to the time of sacrifice, ISO injections increased pineal melatonin content (P < 0.005, three-way ANOVA), which varied, depending on the specific time of injection (effect of time of night, P < 0.05, three-way ANOVA). These results demonstrate that (1) adrenergic agonists enhance the production of pineal melatonin in Turkish hamsters, (2) this stimulatory effect takes place late, but not early in the 8 hr scotophase, and (3) the adrenergic induction of pineal melatonin production in Turkish hamsters requires priming by darkness during the appropriate circadian phase.     

Immune effector mechanisms in malaria: An update focusing on human immunity

The past decade has witnessed dramatic decreases in malaria‐associated mortality and morbidity around the world. This progress has largely been due to intensified malaria control measures, implementation of rapid diagnostics and establishing a network to anticipate and mitigate antimalarial drug resistance. However, the ultimate tool for malaria prevention is the development and implementation of an effective vaccine. To date, malaria vaccine efforts have focused on determining which of the thousands of antigens expressed by Plasmodium falciparum are instrumental targets of protective immunity. The antigenic variation and antigenic polymorphisms arising in parasite genes under immune selection present a daunting challenge for target antigen selection and prioritization, and is a given caveat when interpreting immune recall responses or results from monovalent vaccine trials. Other immune evasion strategies executed by the parasite highlight the myriad of ways in which it can become a recurrent infection. This review provides an update on immune effector mechanisms in malaria and focuses on our improved ability to interrogate the complexity of human immune system, accelerated by recent methodological advances. Appreciating how the human immune landscape influences the effectiveness and longevity of antimalarial immunity will help explain which conditions are necessary for immune effector mechanisms to prevail.     

Secondary aortoduodenal fistula

Aorto-duodenal fistulae （ADF） are the most frequent aorto-enteric fistulae （80%）, presenting with upper gastrointestinal bleeding. We report the first case of a man with a secondary aorto-duodenal fistula presenting with a history of persistent occlusive syndrome. A 59-year old man who underwent an aortic-bi-femoral bypass 5 years ago, presented with dyspepsia and biliary vomiting. Computed tomography scan showed in the third duodenal segment the presence of inflammatory tissue with air bubbles between the duodenum and prosthesis, adherent to the duodenum. The patient was submitted to surgery, during which the prosthesis was detached from the duodenum, the intestine failed to close and a gastro-jejunal anastomosis was performed. The post-operative course was simple, secondary ADF was a complication （0.3%-2%） of aortic surgery. Mechanical erosion of the prosthetic material into the bowel was due to the lack of interposed retroperitoneal tissue or the excessive pulsation of redundantly placed grafts or septic procedures. The third or fourth duodenal segment was most frequently involved. Diagnosis of ADF was difficult. Surgical treatment is always recommended by explorative laparotomy. ADF must be suspected whenever a patient with aortic prosthesis has digestive bleeding or unexplained obstructive syndrome. Rarely the clinical picture of ADF is subtle presenting as an obstructive syndrome and in these cases the principal goal is to effectively relieve the mechanical bowel obstruction.     

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.     

Married to M. tuberculosis: risk of infection and disease in spouses of smear-positive tuberculosis patients

Objectives To quantify the risk of infection and disease in spouses of tuberculosis patients and the extent to which intervention could reduce the risk in this highly exposed group. Methods We compared HIV prevalence, TB prevalence and incidence and tuberculin skin test (TST) results in spouses of TB patients and community controls. HIV‐positive spouses were offered isoniazid preventive therapy (IPT), and TST was repeated at 6, 12 and 24 months. Results We recruited 148 spouses of smear‐positive patients ascertained prospectively and 3% had active TB. We identified 203 spouses of previously diagnosed smear‐positive patients, 11 had already had TB, and the rate of TB was 2.4 per 100 person years(py) over 2 years (95% CI 1.15–5.09). 116 were found alive and recruited. HIV prevalence was 37% and 39% in the prospective and retrospective spouse groups and 17% in controls. TST was ≥10 mm in 80% of HIV negative and in 57% of HIV‐positive spouses ascertained retrospectively; 74% HIV negative and 62% HIV‐positive spouses ascertained prospectively, and 48% HIV negative and 26% HIV‐positive community controls. Of 54 HIV‐positive spouses, 18 completed 6‐month IPT. At 2 year follow‐up, 87% of surviving spouses had TST ≥10 mm and the rate of TB was 1.1 per 100 py (95% CI 0.34–3.29). Conclusions Spouses are a high‐risk group who should be screened for HIV and active TB. TST prevalence was already high by the time the spouses were approached but further infections were seen to occur. Uptake and adherence to IPT was disappointing, lessening the impact of short‐duration therapy.