甲磺酸伊马替尼治疗43例慢性粒细胞白血病进展期患者的疗效观察

目的:探讨甲磺酸伊马替尼(STI571,格列卫)治疗慢性粒细胞白血病(CML)进展期(即加速期、急变期)患者的临床疗效。方法:43例疾病进展期CML患者口服格列卫治疗,评价其血液学、细胞遗传学及分子遗传学疗效。结果:43例患者的完全血液学反应(CHR)率、完全细胞遗传学反应(CCyR)率和完全分子遗传学反应(CMR)率分别为44.2%、30.0%和21.9%,观察期内总病死率为25.6%,均于12个月内死亡,不同年龄(≤25岁,>25岁)患者之间病死率有统计学意义(P<0.05)。结论:格列卫对慢性粒细胞白血病进展期患者有一定的疗效,但耐药现象较普遍,年轻患者的预后可能较差。     

大剂量伊马替尼治疗慢性髓细胞白血病的临床观察

目的:评价大剂量(600mg/d以上)甲磺酸伊马替尼治疗慢性髓系白血病(CML)的疗效及安全性。方法:筛选28例接受大剂量格列卫治疗(600～800mg/d)的CML患者,疗程0.25～30.00个月,观察其疗效及毒副作用,并与之前接受常规剂量(300～400mg/d)格列卫时的情况比较。结果:10例(35.7%)患者达到并保持血液学完全缓解,13例(46.4%)患者达到血液学部分缓解,5例患者格列卫加量后病情仍进展;发生主要细胞遗传学反应5例(17.9%),次要细胞遗传学反应12例(42.9%);3例初始格列卫剂量为600mg/d的患者出现Ⅳ度不良反应,2例为血液学毒性,1例为剥脱性皮炎,其余25例患者中,9例发生Ⅲ度以下血液学毒性,1例发生Ⅳ度血液学毒性;非血液学不良反应均为Ⅲ度以下,主要有软组织水肿(7/28)、浆膜腔积液(5/28)、关节疼痛(2/28)以及消化道反应(3/28)。结论:大剂量格列卫对初治的、经羟基脲或IFN-α治疗失败的以及常规剂量格列卫疗效欠佳的各阶段CML均有较好疗效;对于曾接受常规剂量格列卫治疗的患者,大剂量格列卫不良反应轻微、多可耐受。     

格列卫联合化疗治疗31例慢性粒细胞白血病的临床观察

格列卫是慢性粒细胞白血病(CML)分子靶向治疗药物,目前国外多用格列卫单药治疗慢性粒细胞白血病,与化疗药物联合治疗的报告很少,特别是单药治疗CML加速期(AP)、急变期(BP)患者的疗效较低.     

厄洛替尼一线对老年中晚期非小细胞肺癌的疗效分析

目的探讨厄洛替尼一线化疗方案对于老年中晚期非小细胞肺癌患者的临床疗效及安全性。方法对收治78例老年中晚期非小细胞肺癌患者,随机分为实验组和对照组。实验组患者给予厄洛替尼化疗,对照组给予紫杉醇化疗。比较两组患者治疗的有效率、疾病控制率、无进展生存期、总生存期以及不良反应的发生情况。结果实验组患者有效率、疾病控制率、无进展生存期、总生存期分别为28.2%、76.9%、(168.3±21.4)d、(287.7±39.3)d,对照组患者为20.5%、74.4%(149.23±19.7)d、(243.7±12.6)d,实验组有效率、无进展生存期、总生存期显著高于对照组(P<0.05),两组疾病控制率无显著差别(P>0.05)。结论厄洛替尼一线化疗方案对于不愿接受传统化疗的老年中晚期非小细胞肺癌患者疗效显著,且不良反应可以耐受。     

格列卫治疗慢性髓细胞白血病的临床研究进展

格列卫(STI-571)是人类历史上第一个分子耙向治疗药物,它以前所未有的高完全血液学缓解率(CHR)和细胞遗传学缓解率彻底改变了慢性髓细胞白血病(CML)的治疗格局。随着格列卫Ⅲ期临床试验以及与α干扰素或小剂量阿糖胞苷联合应用等临床试验的相继完成,对格列卫联合用药的疗效及相关问题有了初步的了解。同时对格列卫耐药机制的研究也在不断深入,联合用药和新的酪氨酸激酶抑制剂等新药的出现为进一步提高格列卫的疗效提供了可能。本文将就格列卫的临床研究结果、当前存在的问题及其解决方法作一综述。     

尼洛替尼治疗伊马替尼耐药的慢性髓系白血病的临床观察

目的:探讨尼洛替尼在伊马替尼耐药的慢性髓系白血病( CML)患者中的疗效及不良反应.方法:9例伊马替尼耐药的CML患者,其中慢性期6例,进展期3例,持续口服尼洛替尼400 mg 2次/d,观察其疗效及不良反应.结果:6例CML慢性期患者,5例获得完全血液学反应,2例获得主要细胞遗传学反应；3例CML进展期患者均获得血液...     

吉西他滨联合奈达铂序贯化放疗治疗肺鳞癌74例临床分析

目的：探讨吉西他滨联合奈达铂序贯化放疗治疗肺鳞癌的临床应用。方法74例入选肺鳞癌患者随机分为实验组(n =37)和对照组(n =37)。对照组采用吉西他滨联合奈达铂化疗;实验组在化疗基础上采用三维适形放疗,化疗方案以21 d 为1个周期,接受4个周期化疗,化疗的第1周期同期对原发病灶进行三维适形放疗。观察患者近期临床疗效、生活质量改善情况及不良反应。结果2组患者全部完成治疗计划,实验组有效率为54.1%,疾病控制率为81.1%,疗效优于对照组(P <0.05)。实验组、对照组生活质量改善有效率为分别为73.0%、64.9%,组间比较差异无统计学意义(P >0.05)。2组主要不良反应为白细胞、血小板、血红蛋白下降及恶心呕吐,实验组患者放射性肺炎、放射性食管炎程度较轻,经对症处理后均可耐受。结论吉西他滨联合奈达铂序贯化放疗治疗肺鳞癌临床疗效显著,不良反应较轻,值得临床深入研究及推广应用。     

格列卫治疗Ph染色体阳性慢性粒细胞白血病疗效分析

目的　研究格列卫 (STI 5 71)治疗慢性粒细胞白血病的疗效 ,探讨STI 5 71联合小剂量高三尖杉酯碱 (HHT)和阿糖胞苷 (Ara C)治疗时的疗效及其副作用的耐受性。方法　选自 2 0 0 1- 0 2 2 0 0 3- 0 8第一军医大学南方医院住院37例成年人患者的骨髓细胞Ph染色体阳性或FISH双标双融合bcr/abl基因异位探针 (FISH bcr/abl)阳性率均 >90 %。其中慢性粒细胞白血病慢性期 (CML CP) 14例 ,加速期 (CML AP) 5例 ,急变期 (CML BP) 18例 ,全部接受STI5 7每天 0 3～ 0 6g ,早晨空腹顿服 ,4例CML AP和全部CML BP患者联合HHT每天 12mg和Ara C每天 30 5 0mg静脉滴注 (VD) ,714d为 1疗程 ,疗程中位数 1 5个 ,STI 5 71治疗时间的中位数 2 5个月 ,治疗满 3个月者全部复查染色体和FISH bcr/abl。结果　CML CP和AP患者的HCR 10 0 % ,主要细胞遗传学反应率 84 3% ;18例CML BP患者的HCR 38 8% ,HPR 2 7 7% ,总有效率 6 6 5 % ,主要细胞遗传学反应率 10 5 % ,骨髓抑制 90 %。CML CP、AP患者的HCR和细胞遗传学主要反应率明显高于CML BP患者 ,P <0 0 1。结论　STI5 71治疗CML显示较高的HCR和细胞遗传学反应率 ,CML CP早期效果最好 ,CML BP患者疗效最差 ,与HA联合的毒性可以耐受     

031大剂量STI571治疗对干扰素-α治疗失败的Ph+慢性粒细胞白血病患者的结果

ST1571(Imatinib mesylate，格列卫)是一有效的酪氨酸激酶抑制剂，可选择性抑制c-abl及bcr／abl基因，近来用于干扰素(IFN)-α治疗失败的慢性期慢性粒细胞白血病(CML)患者，400mg／d绝大部分(90％以上)可获得完全血液学反应，但只有少部分(40％)获得主要细胞     

原研伊马替尼转用仿制伊马替尼治疗慢性髓性白血病慢性期的疗效与安全性分析

目的:探讨原研伊马替尼(格列卫)转用仿制伊马替尼(格尼可)治疗慢性髓性白血病慢性期(CMLCP)患者的疗效与安全性。方法:回顾性分析13例格列卫转用格尼可治疗CML-CP患者的临床资料,比较分析2个用药时期的疗效和不良反应。结果:13例CML-CP患者中,11例服用格列卫期间(平均用药时间58个月)获得主要分子学反应(MMR),1例服用格列卫期间(用药时间46个月)未获得MMR,1例因服用格列卫仅1个月尚无法评估疗效。11例获得MMR的患者中,2例停用格列卫复发,转用格尼可后,均在监测时间点获得最佳反应;9例直接由格列卫转为格尼可,并维持获得MMR。1例未获得MMR的患者转用格尼可后,BCR-ABLIS值不断降低。1例服用格列卫仅1个月尚无法评估疗效的患者,因呕吐不能耐受转用格尼可,9个月达MMR。格列卫和格尼可的血液学不良反应发生率相似,主要有贫血(38.5%vs 30.8%)、白细胞减少(23.1%vs 15.4%)和血小板减少(23.1%vs 15.4%);常见的非血液学不良反应为恶心呕吐(38.5%vs 7.7%),皮疹、关节疼痛、四肢麻木、肝酶异常、手指脚趾脱屑等不良反应在服用格列卫与格尼可期间无明显差异。结论:格列卫转用格尼可治疗CML-CP患者过程中,格尼可有较好的疗效和安全性,且格尼可价格便宜,可作为CML-CP患者的用药选择,但本次研究样本量少,可能存在误差,仍需大样本研究证实。     

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.     

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.     

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.     

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.     

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.