低肌病性皮肌炎的临床和肌肉病理特点六例分析

目的 了解低肌病性皮肌炎的临床表现和肌肉病理改变特点.方法 收集我院2008年1月至2010年6月行肌肉活检的62例皮肌炎患者,按照低肌病性皮肌炎的诊断标准筛选6例,其中4例患者肌电图呈肌源性损害.同时对6例患者进行肱二头肌活检,标本进行组织学、酶组织化学染色和免疫组织化学染色,后者的第一抗体分别为CD8、CD20和CD68鼠抗人单克隆抗体以及标记主要组织相容性复合物Ⅰ型抗原(MHC-Ⅰ)的鼠抗人单克隆抗体.结果 6例患者的肌纤维内脂肪滴均有轻至中度增多,肌束衣出现个别巨噬细胞浸润和B淋巴细胞浸润.3例患者出现个别小圆状萎缩肌纤维呈束周分布的特点,伴随个别肌纤维的坏死再生.所有患者束周分布的肌纤维膜存在MHC-Ⅰ深染,束周分布的肌间毛细血管非特异性酯酶深染.结论 部分低肌病性皮肌炎患者的骨骼肌病理改变类似经典皮肌炎,提示此病可能是单纯无肌病皮肌炎和经典皮肌炎的中间型.     

他汀相关免疫介导性坏死性肌病2例临床病理及文献复习

目的分析他汀相关免疫介导性坏死性肌病(immune-mediated necrotising myopathy,IMNM)患者的临床表现、实验室检查、电生理和肌肉病理学特点。方法回顾性分析中国人民解放军总医院2014年9月至11月2例他汀相关IMNM患者临床表现、实验室检查、电生理和肌肉活检病理特点,以及治疗、随访情况。结果 2例患者均为女性、急性或亚急性起病,发病年龄分别为55和63岁,病程分别为5和3个月。2例患者既往体健,服用他汀类药物半年后出现四肢乏力、抬头困难等不适,1例合并呼吸系统受累,1例患者可见较多肌纤维空泡和凝固性坏死,伴吞噬现象。另1例可见少量肌纤维变性、坏死,伴有少数核内移纤维。1例患者经糖皮质激素激素、另1例经糖皮质激素联合免疫抑制剂治疗有效。结论他汀相关IMNM是一种复杂的异质性疾病,呈亚急性或隐匿性起病,病情轻重不一;主要表现为肢带肌乏力,可合并有不同肌群受累;肌肉病理改变主要为形态多样的肌纤维变性坏死;激素及免疫抑制剂治疗有效。     

结蛋白基因突变相关性心肌病五家系临床和遗传特点

目的 研究中国人群结蛋白病的临床表现、肌肉病理改变和基因突变规律.方法 5个家系共36例患者,男18例,女18例.其中心肌病伴骨骼肌病19例,单纯心肌病13例,单纯骨骼肌病1例,3例死于心脏病变但生前临床不详.23例心电图检查中20例伴随多种类型的心脏传导阻滞.23例心脏超声检查发现限制型心肌病2例,扩张型心肌病和肥厚型心肌病各1例.对7例患者行骨骼肌活检,标本行常规组织学、酶组织化学、免疫组织化学和电镜检查.对21例患者、17例无症状家系成员和50名正常中国人行结蛋白基因测序.结果 肌肉活检均提示肌纤维内出现小球形或无定形的嗜酸性物质沉积,免疫组织化学染色显示存在结蛋白沉积,伴随个别肌纤维出现肌营养不良素、分层蛋白和α-辅肌动蛋白的异常聚集.电镜显示肌纤维膜下和肌原纤维之间出现大量颗粒细丝物质.在5个家系发现结蛋白存在5种新的杂合突变.所有突变只出现在患病成员,而正常家系成员及50名正常中国人中没有检测到相同突变.结论 在我国结蛋白基因多种新突变导致的结蛋白病多以不同形式的心肌病为主,特别是心律紊乱相关的心肌病,可以伴随不同程度的骨骼肌损害.     

以心脏症状首发的青年高肌酸肌酶血症临床病理特点分析

目的:报道10例以心脏症状首发的骨骼肌疾病,讨论该类疾病临床及肌肉病理改变特点。方法:选取2010年1月至2016年5月,以心脏症状首发的骨骼肌疾病就诊的10例患者,总结患者心脏及骨骼肌受累的临床特点,经知情同意后对患者行肌肉活检,标本进行常规组织学、酶学及免疫组织化学染色,7例患者进行基因学检查。结果:10例患者分别诊断为:脂肪沉积症3例,糖原累积病1例,强直性肌营养不良1例,Becker肌营养不良1例,肌原纤维肌病1例,混合结缔组织病合并多发性肌炎1例,Danon病1例,特发性良性肌炎1例。结论:心脏症状及心源性猝死可为骨骼肌病的首发症状或主要症状,尤其是青年不明原因的高CK血症患者。阳性家族史、肌肉病理有空泡和异常物质沉积为猝死的危险因素。     

抗信号识别颗粒抗体肌病八例临床分析

目的 总结抗信号识别颗粒抗体肌病患者的临床和骨骼肌病理改变特点.方法 选择8例患者采取免疫印迹法测定血清肌炎抗体谱并进行肌肉活检,肌肉标本进行组织学、酶组织化学和免疫组织化学染色.免疫组织化学染色的第一抗体为鼠抗人CD8、CD20、CD68单克隆抗体,分别标记T细胞、B细胞和巨噬细胞,主要组织相容性复合体(MHC)-Ⅰ单克隆抗体标记肌纤维膜,CD31单克隆抗体标记毛细血管内皮细胞.结果 8例患者血清抗信号识别颗粒抗体均为强阳性,其中3例伴随Ro-52抗体阳性.8例患者骨骼肌出现肌纤维坏死、再生以及巨噬细胞浸润,2例患者伴随肌纤维肥大和间质增生,2例伴随少数T细胞浸润.存在部分MHC-Ⅰ阳性肌纤维,毛细血管密度正常.结论 抗信号识别颗粒抗体肌病以缓慢发病的肢体无力为主要表现,可伴肺部病变.肌纤维坏死、再生为其主要病理改变,可以类似肌营养不良改变.     

风湿性多肌痛的骨骼肌病理改变特点

目的探讨风湿性多肌痛的临床和骨骼肌病理改变特点。方法13例老年和老年前期患者符合1979年Bird的风湿性多肌痛诊断标准，发病年龄49～78岁，平均60．3岁，主要临床表现为急性发病的四肢近端骨骼肌对称性持续性疼痛。其中5例伴37℃～38℃的低热，1例有轻微贫血，未发现颞浅动脉炎的改变。13例血沉均增快，其中10例血沉大于50mm／1h，8例C反应蛋白升高，1例正常，4例未查；9例行肌酶检查，其中2例轻度升高；7例行肌电图检查，2例可见肌源性损害，5例正常。对患者的肱二头肌进行活检，标本进行组织学染色和酶组织化学染色。结果13例患者均有Ⅱ型肌纤维的萎缩，8例肌纤维氧化酶活性出现虫蚀样改变，8例出现肌纤维内脂肪滴增多，3例可见个别不典型破碎样红肌纤维，2例小血管周围可见少量炎细胞浸润。患者经过激素治疗后症状迅速改善，血沉及C反应蛋白显著下降。结论本组患者的主要临床特点是出现对称性骨骼肌疼痛和血沉加快，多数患者存在C反应蛋白升高，而贫血和颞浅动脉炎发生率不高。骨骼肌常见病理改变为Ⅱ型肌纤维萎缩和虫蚀样氧化酶活性改变，肌纤维内脂肪滴增多和部分患者出现破碎样红肌纤维提示此病常伴随能量代谢异常。     

糖原累积病Ⅳ型的临床和病理特点

目的 报道1例22岁男性糖原累积病Ⅳ型(Anderson disease)患者临床及病理特点.方法 对该患者行详细的病史询问和体格检查、心脏和腹部超声检查、头颅影像学、肌电图以及肌肉病理检查.结果患者儿童期发病,主要表现为四肢近端肌肉运动不耐受和疲劳感,偶有心悸;腹部超声示肝硬化、门脉高压和巨脾,超声心动图示心肌肥大、二尖瓣和三尖瓣轻度关闭不全;四肢骨骼肌肌电图示肌源性损害.头颅影像正常.肌肉病理HE染色示肌纤维内大量嗜碱性物质沉积,沉积物糖原染色(PAS)染色呈强阳性,淀粉酶处理后部分阳性物质被消化.电镜下嗜碱性沉积物为分支状细丝样结构以及无定型的颗粒样物质.结论 此例为国内首次报告的糖原累积病Ⅳ型,属于分支酶缺陷病,受累组织和器官以骨骼肌、肝脏、脾脏和心肌为主.     

免疫介导性坏死性肌肉病四例临床病理分析及随访

目的 总结免疫介导性坏死性肌肉病(IMNM)患者的临床、电生理和骨骼肌病理改变特点.方法 回顾性分析北京大学第三医院2011年1月—2014年1月的4例IMNM患者的临床、电生理特点及肌肉、皮肤活检的病理特点和治疗、随访情况.结果 4例患者中男女各2例,发病年龄37～58岁(平均47.5岁),病程1～60个月(平均17.8个月),急性或亚急性起病者2例,慢性起病者2例.4例患者均出现四肢近端力弱,3例颈屈肌受累,1例呼吸肌受累起病且需要呼吸机辅助呼吸,1例合并间质性肺病.4例患者信号识别颗粒(SRP)抗体强阳性;1例出现成组分布的变性坏死和再生肌纤维,3例仅出现少量散在分布的变性坏死和再生肌纤维;4例患者均可见肌纤维肥大、萎缩,伴随结缔组织轻～中度增生;部分病例可见少量炎性细胞浸润.1例患者糖皮质激素治疗及3例患者糖皮质激素联用免疫抑制剂治疗均有效.结论 IMNM临床相呈异质性,发病速度快慢不一,病情轻重不一,受累肌群分布不一;但骨骼肌病理改变相似,主要表现为:肌纤维变性、坏死、再生,无炎性细胞或很少炎性细胞浸润;糖皮质激素或联用免疫抑制剂有效.     

Duchenne型肌营养不良25例临床与病理特点分析

目的探讨Duchenne型肌营养不良(DMD)的临床及病理学特点。方法回顾性分析25例确诊的DMD患儿的临床资料和骨骼肌活检组织病理检查结果。结果 DMD均为男性,有家族史者3例,2例患儿智力偏差。独立行走后易摔跤20例,上楼梯和蹲位站立困难18例,1例有特殊的"鸭步"步态,6例患儿有双侧腓肠肌假性肥大。骨骼肌活检病理检查结果均提示肌营养不良改变,表现为肌纤维大小不等,多呈圆形,不同程度肌纤维坏死;Dystrophin单克隆抗体免疫组化染色:肌细胞膜Dystrophin蛋白表达均完全缺失。结论 DMD典型临床特点为骨盆带肌、躯干肌对称性无力,多数病人有双侧腓肠肌假性肥大。骨骼肌活检病理检查是目前确诊本病及与其他疾病鉴别的方法之一。     

运动神经元病患者骨骼肌纤维再生临床及病理研究

目的观察运动神经元病患者骨骼肌纤维再生临床及病理特点。方法选择经骨骼肌活检确诊为运动神经元病患者的临床资料及骨骼肌标本,将骨骼肌标本行HE染色、免疫组化染色,光镜观察肌纤维再生情况,部分留取电镜标本在电镜下观察骨骼肌纤维再生超微结构特点。结果活检骨骼肌标本在组化及免疫组化染色中未见明显再生肌纤维,电镜下观察到运动神经元病患者骨骼肌内可见静止、活化的肌卫星细胞。结论电镜下观察到运动神经元病患者肌肉内存在肌卫星细胞的活化、分裂及早期再生肌纤维。     

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.     

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.     

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.     

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.