依那西普治疗难治性成人斯蒂尔病:附4例病例报告并文献复习

目的探讨依那西普对难治性成人斯蒂尔病(AOSD)的疗效,为生物制剂治疗难治性AOSD的可行性提供证据。方法 4例明确诊断的AOSD患者,经大剂量激素治疗及甲泼尼龙冲击治疗、静脉丙种球蛋白和环磷酰胺冲击(或甲氨蝶呤)治疗效果不佳,选择激素、环磷酰胺(或甲氨蝶呤)联合依那西普(益赛普)治疗,观察疗效。结果患者经应用甲泼尼龙、改变病情抗风湿药(DMARDs)及静脉丙种球蛋白冲击治疗病情仍未控制,加用依那西普37.5～50 mg/周,1～2周后体温均得到控制,2个月内炎性指标恢复正常,5个月内甲泼尼龙减至8 mg/d,随访6个月病情稳定,且不良反应轻微。结论依那西普可用于治疗难治性AOSD,与激素及DMARDs合用,既有利于疾病的控制,又有助于激素顺利减量。     

非清髓性环磷酰胺治疗难治性狼疮肾炎的初步研究

目的 探讨非清髓性环磷酰胺(CTX)冲击治疗难治性狼疮肾炎(LN)的疗效及安全性.方法 对6例难治性LN患者进行非清髓性CTX 20～40 mg/kg冲击治疗,比较CTX治疗前后2周血、尿检测指标、肾小球滤过率(GFR)、尿蛋白定量(24 h)、系统性红斑狼疮活动指数(SLEDA1)评分的变化.结果 治疗后2周尿蛋白定量(24 h)显著降低[(1904±904)和(319±97)mg,P＜0.05],尿白细胞计数[(2.7±2.8)和(0.5±1.0)个/μP＜0.05]和SLEDAI评分[(17±5)和(6±5)]治疗前后差异均有统计学意义(P＜0.05),而血清补体C3水平显著升高[(0.60±0.17)和(0.94±0.78)g/L,P=0.017],差异均有统计学意义.白细胞达谷值距CTX末次冲击时间平均为11.2 d.1例出现鼻窦炎,1例脱发,2例胃肠道反应.结论 非清髓性CTX冲击治疗难治性LN安全有效.这一初步研究结果有待大样本的临床双盲试验证实.     

继发性甲状旁腺功能亢进患者甲状旁腺切除术后短期钙磷变化的观察与分析

目的 探讨继发性甲状旁腺功能亢进(SHPT)患者行甲状旁腺切除术(PTX)后短期钙磷变化情况并分析其相关因素。方法 回顾性分析于我院行PTX的难治性SHPT患者18例，收集所有患者术前的基线资料和术后第1天、第3天及第7天的血全段甲状旁腺激素(iPTH)、血碱性磷酸酶（ALP）、血钙、血磷等生化指标并进行比较，统计所有患者术后1周的补钙量。采用Pearson和Spearman相关分析研究患者术前血iPTH、血钙、血磷、血ALP水平及术后1周补钙总量的相关性。结果 术后第1天、第3天和第7天患者血iPTH和血磷与术前比较均明显下降(P均＜0.05)；术后第1天血ALP与术前比较明显下降(P＜0.05)；术后第7天血钙与术前比较明显下降（P＜0.05）。术前血iPTH水平与术前血ALP水平呈正相关(r=0.773,P＜0.001)，术后1周补钙量与术前血iPTH水平(r=0.855,P＜0.001)、术前血ALP水平(r=0.925,P＜0.001)均呈正相关。结论PTX治疗难治性SHPT安全有效，能在短期内快速纠正血钙、血磷的代谢紊乱。     

难治性成人斯蒂尔病的临床相关因素分析

目的 探讨难治性成人斯蒂尔病(AOSD)的临床特点及相关因素,为其诊断和治疗提供临床经验.方法 对15例难治性AOSD和60例轻症AOSD进行回顾性分析.先将研究变量做单因素分析,再将有意义的计数资料型变量进行多因素非条件Logistic回归分析,对有意义的计量资料型变量绘制受试者工作特征曲线(ROC).结果 临床症状中,难治性AOSD组浆膜炎和心肺受累发生频率和外周血白细胞计数和C反应蛋门(CRP)值显著高于轻症AOSD组.Logistic回归分析提示,心肺受累的患者更倾向于难治性AOSD.根据ROC曲线分析得出:CRP≥182.5 mg/L(特异性98.3%,敏感性86.7%)或白细胞计数＞23.4×10~9/L(特异性93.3%,敏感性80.0%)时,难治性AOSD的可能性较大.结论 伴有心肺受累,白细胞≥23.4×10~9/L或CRP≥182.5 mg/L的AOSD患者可能是难治性AOSD.     

鬼臼噻吩苷、地塞米松和持续静脉输注环磷酰胺治疗进展性难治性骨髓瘤

作者报告用环磷酰胺(CTX)持续输注,联合鬼臼噻吩甙(VM-26)及地塞米松治疗进展性难治性多发性骨髓瘤(MM)。病人与方法 21例进展性难治性 MM 患者,男13例,女8例,中数年龄57(43～81)岁,其中Ⅲ_(A)期18例,Ⅲ(B)期3例。M 蛋白成份类型,IgG 型16例,IgA 型4例,本周蛋白型1例。21例中对 MP 方案原发性耐药者9例,用其它方案药物治疗后复发并耐药者12例。治疗方法:每个月使用 VM-2630mg/M~2静注第1～2天;地塞米松40mg 静注第1～7天;CTX200mg/M~2持续静脉输注(用轻便泵)第1～7天。为了避免影响 CTX 的烷化活性,将每     

儿童难治性自身免疫性疾病自体外周血干细胞动员采集和分选的临床研究

目的 探讨儿童难治性自身免疫性疾病进行自体外周血干细胞动员采集的安全性和CD34+细胞分选纯化的可行性及其临床意义.方法 8例儿童难治性自身免疫性疾病,包括4例系统性红斑狼疮、2例皮肌炎,1例幼年型类风湿关节炎和1例多发性硬化,予行CD34+细胞纯化的自体外周血干细胞移植.首先采用环磷酰胺(CTX)联合粒细胞集落刺激因子(G-CSF)方案动员外周血干细胞,然后采用CS-3000血细胞分离机采集外周血,通过CliniMACS细胞分选仪分选自体外周血CD34+细胞,将其用保养液配置冻存于-80℃冰箱.采用非清髓内去除T的预处理方案,即卡氮芥+足叶乙苷+阿糖胞苷+马法兰+抗胸腺球蛋白(ATG)或CTX+ATG或CTX+马法兰+ATG,于第0天回输自体外周血CD34+细胞.结果 儿童能够耐受自体外周血干细胞动员采集过程,无动员相关死亡,动员后获得的单个核细胞数和CD34+细胞数的平均值分别为8.35×108/kg和7.92×106/kg,纯化后的白体外周血CD34+和CD3+细胞数的平均值分别为6.28×106/kg和0.71×105/kg.回输后中性粒细胞和血小板的植入中位时间分别为+11d和+15 d.结论 经CTX联合G-CSF方案可动员出足量的外周血干细胞,经CS-3000血细胞分离机采集可获得足够的单个核细胞,在动员过程中原发病无明显进展恶化,患儿能耐受动员方案,采集过程顺利安全;经CliniMACS细胞分选仪分选的自体外周血CD34+细胞纯度高,移植后造血恢复;采用CD34+细胞纯化的自体外周血移植治疗是常规治疗无效的儿童难治性自身免疫性疾病的可选择治疗措施之一.     

经自然腔道软式内镜治疗重症急性胰腺炎的价值探讨

目的 探讨经自然腔道软式内镜对重症急性胰腺炎(SAP)早期腹腔病变的治疗价值.方法 SAP患者随机分成内镜组(69例)和对照组(65例).内镜组患者在常规治疗基础上,入院8h内实施经自然腔道腹腔内镜治疗,对照组患者采用常规治疗.结果 内镜组患者入院第2天出现肠蠕动,第8天肠蠕动恢复正常;对照组患者入院第8天出现肠蠕动(P＜0.01),第14天肠蠕动恢复正常(P＜0.01).内镜组人院第2、4、8、10、14天腹腔内压力显著低于对照组(P＜0.01),入院第4、8、10、14天外周血TNF-α、IL-6、IL-8浓度显著低于对照组(P＜0.01),入院第2～14天APACHEⅡ评分显著优于对照组(P＜0.05).内镜组治愈65例(94.20％),好转2例(2.90％),死亡2例(2.90％),平均住院(15.98±7.88)d;对照组治愈32例(49.23％),好转22例(33.85％),死亡11例(16.92％),平均住院(56.85±20.54)d.两组治愈率、好转率及死亡率差异有统计学意义(P＜0.01).结论 经自然腔道软式内镜治疗和腹腔置管灌洗透析能清除SAP患者早期腹腔内炎性渗液,解除腹腔内高压,置管引流和腹膜透析微创、有效,值得推广.     

柴竹石膏汤对29例反复发热结核病并发其他感染患者的疗效分析

目的 初步分析柴竹石膏汤治疗反复发热结核病并发其他感染患者的临床疗效。方法 搜集2016年3月至2018年3月解放军总医院第八医学中心结核科收治的确诊为继发性结核病并发其他非结核性感染(均有明确细菌学感染证据),且经不同时间常规抗结核和抗感染治疗仍持续或反复发热的29例患者。所有患者均在知情同意的情况下停用抗其他细菌感染的抗生素后,采用柴竹石膏汤(自拟方)进行治疗,观察柴竹石膏汤治疗7d后的退热效果和出院后2个月的远期疗效。其中抗结核药物治疗与抗感染治疗的时间以及热程分别为1~6个月,平均(2.0±1.8)个月;7~180d,平均(43.3±36.6)d;10d至6个月,平均(20.0±4.0)d。结果 29例患者经柴竹石膏汤治疗7d后,完全控制20例(69.0%),部分控制6例(20.7%),有效2例(6.9%),无效1例(3.4%),总有效率为96.6%(28/29)。其中26例(89.7%)完全控制及部分控制患者中,12例(46.2%)3d内体温恢复正常,8例(30.8%)患者3~5d内体温恢复正常,6例(23.1%)患者5~7d内体温恢复正常,停药1个月后体温均无反复;2例有效患者中,1例在服药第9天体温降至正常,1例第10天内体温降至正常,经观察体温有反复,体温波动于37.5℃左右,继续加用中药汤剂治疗,1个月后体温恢复正常;1例无效患者重新加用抗真菌药物治疗后,2个月后体温逐渐恢复至正常。结论 柴竹石膏汤治疗反复发热结核病并发其他感染患者具有较好临床疗效,其退热机理有待在临床实践中进一步研究。     

自体外周血干细胞移植治疗难治性系统性红斑狼疮的临床研究

目的探讨自体外周血干细胞移植(APBSCT)治疗难治性系统性红斑狼疮(SLE)的临床疗效。方法对难治性SLE患者进行APBSCT治疗。采用环磷酰胺(CTX) 粒细胞集落刺激因子(G-CSF)方案动员,CS-3000血细胞分离机采集外周血干细胞并保存于-80℃冰箱;用CTX50mg/(kg.d)×3～4d方案预处理后,解冻后回输冻存的干细胞的治疗方法。观察APBSCT前后临床表现及免疫学指标的变化。结果动员后获得单个核细胞数(MNC)(3.383～3.704)×108/kg;CD34 细胞数(4.4～11.12)×106/kg。3例均获得造血重建,中性粒细胞>0.5×109/L、血小板>20×109/L的中位数时间分别是8.3d、10d。移植后患者临床症状消失,1例并肾功能不全、难治性高血压和重度贫血的患者移植后恢复正常。3例患者自身抗体转阴或滴度减低,尿蛋白定性消失,SLE疾病活动指数(SLE-DAI)由移植前的平均15分下降为移植后6个月的平均4分。结论APBSCT治疗难治性SLE安全有效,近期疗效好,远期疗效有待进一步观察。     

急诊十二指肠镜联合早期肠内营养治疗老年急性胆源性胰腺炎的临床疗效

目的探讨急诊十二指肠镜联合早期肠内营养治疗老年急性胆源性胰腺炎(ABP)的效果及并发症。方法选择该院2010年1月至2014年1月治疗的ABP老年患者180例,随机分为急诊行十二脂肠镜治疗(肠镜组)60例、急诊十二指肠镜联合早期肠内营养治疗(联合组)60例,保守治疗(保守组)60例。比较治疗前、治疗后1、5、10 d血淀粉酶、白细胞、血肿瘤坏死因子(TNF)-α、C反应蛋白(CRP)水平及体温恢复正常所需时间、腹部压痛消失所需时间、并发症等指标。结果联合组较保守组、肠镜组治疗后第5、10天血淀粉酶、TNF-α、CRP水平差异有统计学意义(P0.05);白细胞恢复正常时间联合组与保守组比较差异有统计学意义(P0.05),与肠镜组比较差异无统计学意义(P0.05),联合组、肠镜组腹痛缓解时间、体温恢复正常时间比较有显著性差异(P0.05);三组并发症,联合组、肠镜组与保守组差异有统计学意义(P0.05),联合组与肠镜组比较差异无统计学意义(P0.05)。结论急诊十二指肠镜联合早期肠内营养治疗老年ABP安全、可靠、有效,值得临床推广。     

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.     

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.     

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.     

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.