非糜烂性胃食管反流病患者酸灌注及食管扩张脑诱发电位的研究

目的研究非糜烂性胃食管反流病(NERD)患者和正常人食管扩张刺激(OD)-脑诱发电位(CEP)的特征及食管酸灌注后 CEP 的改变,探讨 NERD 患者食管内脏高敏感性的发生机制。方法10例健康志愿者和21例 NERD 患者参与试验;采用 Synectics 内脏刺激器/电子气压泵和带有低顺应性气囊及多个灌注式压力通道的导管给食管以时相性扩张刺激和酸灌注;利用食管气囊扩张术检测受试者食管最大耐受痛阈,用75%最大疼痛耐受容积作为诱发刺激的强度(刺激频率为12次/min,连续64次);采用 OD-CEP 系列技术记录并分析食管酸灌注前后 NERD 患者和正常人 CEP 的变化。组间比较采用 t 检验,多组间比较采用单因素方差分析。结果食管时相性机械扩张刺激诱发出可识别、可重复、多峰的 CEP 波形,以 NP 型为主。正常对照者 N1、P1、N2波潜伏期分别为(246±77)、(388±84)和(502±78)ms,NERD 患者 CEP 波形变异性大,其 N1、P1、N2波潜伏期分别为(192±46)、(293±76)和(440±79)ms,较对照组明显缩短(P 值均<0.05);P1-N2峰间波幅明显增加[(6.2±1.9)μV 比(7.8±3.2)μV,P<0.05]。食管酸灌注能明显缩短 NERD 患者 N1、P1、N2波潜伏期,与酸灌注前相比差异有统计学意义(P 值均<0.05),且酸灌注后 NERD 患者 P1-N2皮层波幅值较酸灌注前显著增加(p<0.05),健康对照组除 CEP 的 N1波潜伏期较对应基线值显著降低(P=0.05)外,其余 CEP 参数均无明显改变。结论 NERD 患者存在食管对机械和酸刺激的高敏感性及食管-中枢内脏感觉传导通路失凋。     

非糜烂性反流病患者食管内脏高敏感性与食管下括约肌局部降钙素基因相关肽阳性神经纤维的关系

背景：食管内脏高敏感性是非糜烂性反流病（NERD）最重要的病理生理特征之一，但引起食管内脏感觉过敏的确切机制仍不甚清楚。目的：通过测定NERD患者食管对机械扩张刺激和对酸刺激的敏感性变化和降钙素基因相关肽（CGRP）在食管下括约肌（LES）局部组织中的表达，探讨食管感知阈值与LES局部黏膜CGRP表达之间的关系。方法：采用Synectics内脏刺激器／电子气压泵行食管气囊扩张术以检测食管对机械扩张刺激的敏感性；采用食管酸灌注试验（betastein test）检测食管对酸的敏感性；采用免疫组化法和罔像分析技术观察LES局部组织中CGRP的表达。结果：根据对酸刺激和（或）机械扩张刺激的感知过敏，NERD患者可分为感知过敏组（21例）和感知正常组（10例）。感知过敏组患者食管对气囊扩张刺激的初始感知闽值和最大耐受疼痛阈值较感知正常组和正常对照组显著降低（P〈0．05）。感觉过敏组LES黏膜中CGRP阳性纤维数和平均吸光度（A）值较感知正常组和正常对照组显著增高（P〈0．05）。LES局部组织中CGRP阳性产物A值与食管初始感知阈值和最大耐受疼痛阈值呈直线负相关（r分别为-0．68和-0．79．P〈0．03）。结论：多数NERD患者存在对食管机械扩张刺激和（或）对食管酸刺激感知过敏；感知过敏的NERD患者其LES局部黏膜中CGRP表达增加，提示LES肽能神经的改变可能与食管内脏高敏感性有关。     

非糜烂性胃食管反流病患者大脑皮质诱发电位的研究

目的通过比较食管扩张刺激-脑诱发电位(OD-CEP)的改变,探讨非糜烂性胃食管反流病(NERD)患者食管内脏高敏感性的发生机制,旨在进一步获得NERD患者食管-中枢内脏感觉传导通路失调的客观依据。方法10例正常健康自愿者和21例NERD患者参与试验;采用Synectics内脏刺激器/电子气压泵和带有低顺应性气囊的导管给食管以时相性扩张刺激;利用食管气囊扩张术检测受试者食管最大耐受痛阈,用75%最大疼痛耐受容积作为诱发刺激的强度(刺激频率为12次/分,连续64次);采用OD-CEP系列技术记录并分析NERD患者和正常人CEP的变化。结果食管气囊扩张刺激能诱发出可识别、可重复的、多峰的CEP波形,以NP型为主。与正常对照者比较,NERD患者CEP波形变异性大,其N1、P1、N2波潜伏期明显缩短(P值分别为0·016,0·003,0·031),且NERD患者CEP的P1-N2峰间波幅明显增加(P=0·03)。结论NERD患者经食管时相性扩张后产生的特征性CEP改变证实其食管内脏高敏感性及食管-中枢内脏感觉传导通路的失调。     

应用功能性磁共振成像技术研究非糜烂性反流病患者食管酸灌注时大脑功能活动模式的变化

背景：血氧水平依赖性功能性磁共振成像（BOLD-fMRI）技术近来被广泛应用于人体内脏感觉的研究，而非糜烂性反流病（NERD）的发生与内脏感觉高敏有密切关系。目的：应用BOLD-fmRI技术，通过研究食管酸灌注时NERD患者大脑功能活动模式的改变，探讨NERD患者食管内脏高敏感的中枢机制。方法：对31例NERD、13例反流性食管炎（RE）和12名健康志愿者在食管酸灌注时行fMRI；根据食管内球囊扩张和酸灌注试验结果将NERD患者分为两组：感觉高敏（NERD-H）组和感觉正常（NERD-N）组；对三组受试者大脑的兴奋情况进行统计学分析。结果：食管酸灌注刺激在NERD内脏高敏的患者中激活范围较广泛，包括单侧或双侧第Ⅱ躯体感觉皮质（SⅡ）、第Ⅰ躯体感觉皮质（SI）、前额叶皮质（右侧为主）、眶额回皮质、岛叶皮质、运动区、辅助运动区、前扣带回、后扣带回、楔前叶、杏仁体、腹侧纹状体、丘脑、小脑等，其中双侧SⅡ、右前额叶皮质、运动区、辅助运动区、岛叶皮质、杏仁体、腹侧纹状体和小脑的最大信号增加幅度显著高于NERD-N组和对照组（P〈0．01）。内脏高敏的NERD患者fMRI功能初始信号呈现时间、达峰值时间较NERD-N组和对照组显著缩短（P〈0．01）。结论：食管酸灌注时产生的fMRI参数改变为揭示NERD患者中枢神经系统整合、处理食管感觉传入信息功能异常提供了依据。     

非糜烂性胃食管反流病内脏高敏感机制研究

非糜烂性胃食管反流病(NERD)是指有典型胃食管反流症状而无内镜下食管黏膜损伤的疾病，又称“内镜阴性胃食管反流病”，约占胃食管反流病(GERD)的70％。其临床症状的严重程度与GERD相似，抑酸治疗效果不佳，往往对患者的生活质量产生严重的影响。其发病机制复杂，主要包括酸反流，内脏高敏感，非酸相关性刺激，中枢及外周水平调控失衡等机制。     

神经肽参与NERD内脏高敏感外周机制的研究进展

内脏高敏感是胃食管反流病(gastroesophageal reflux disease,GERD)重要发病机制,尤其在非糜烂性反流病(non-erosive reflux disase,NERD)患者中。某些神经肽类物质如P物质(substance P,SP)和降钙素基因相关肽(calcitonin gene-related peptide,CGRP)在介导伤害性或非伤害性刺激致痛觉过敏的发生和调控中发挥关键作用,是参与痛觉信息传递过程中的重要神经递质。新近研究显示,SP和CGRP在NERD患者食管黏膜中的表达明显增加,且与疼痛感觉阈值呈明显负相关,推测某些神经肽类物质可能共同参与NERD内脏高敏感的外周机制。     

非糜烂性反流病食管黏膜超微结构研究

目的探讨非糜烂性反流病(NERD)病理性酸反流组及生理性酸反流组,其食管黏膜细胞间隙及桥粒数目等超微结构的变化情况。方法对10例健康志愿者(对照组)、39例NERD患者及10例反流性食管炎(RE)患者进行内镜检查并作食管黏膜活检,透射电镜观察标本。图像分析仪测量食管黏膜细胞间隙宽度,同时统计相应间隙中的桥粒数目。结果RE组及NERD组的细胞间隙宽度分别为(2.39±0.42)μm及(2.21±0.68)μm,两组间差异无统计学意义(P〉0.05)。对照组细胞间隙宽度为(0.63±0.21)μm,明显小于RE组及NERD组(P〈0.05)。NERD病理性酸反流组及生理性酸反流组的细胞间隙宽度分别为(2.45±0.67)μm及(1.91±0.67)μm,两组间差异有统计学意义(P〈0.05)。RE组及NERD组的桥粒数目均数分别为(0.124±0.044)个/μm2及(0.141±0.043)个/μm2,两组间差异无统计学意义(P〉0.05),但均少于对照组[(0.221±0.031)个/μm2],P〈0.05。NERD病理性酸反流组的桥粒数目[(0.110±0.032)个/μm2]明显少于生理性酸反流组[(0.171±0.028)个/μm2]。结论NERD组的细胞间隙明显宽于正常对照组,但与RE组无明显差别。NERD病理性酸反流组的细胞间隙明显宽于生理性酸反流组;细胞间隙间的桥粒数目也可能是酸诱导的细胞损伤标志。     

非糜烂性反流病患者食管黏膜SP和CGRP的表达

目的 观察非糜烂性反流病(NERD)和反流性食管炎(RE)患者食管黏膜内P物质(SP)和降钙素基因相关肽(CGRP)免疫反应阳性产物的表达,探讨其在NERD发病中的作用.方法 选择有典型胃食管反流症状并经反流性疾病诊断问卷(RDQ)调查、PPI试验、胃镜检查及食管24h pH检测诊断为GERD患者51例,其中RE组21例,NERD酸反流阳性组(NERD+组)12例,NERD酸反流阴性组(NERD-组)18例,采用免疫组化方法 在显微镜下观察NERD、RE患者食管黏膜内SP、CGRP的表达,应用彩色病理图像分析软件,分析计算SP、CGRP免疫反应的阳性指数(PI),并与正常对照组10例比较.结果 NERD-组食管黏膜内SP、CGRP的Pl值为96.77±31.74和24.76±29.15,明显高于NERD+组(73.64±31.38、9.78±10.30)、RE组(67.56±34.62、9.61±6.20)及正常对照组(59.82±46.15、8.64±12.12)(P均<0.05).结论 SP、CGRP在NERD-的患者食管黏膜内有明显表达,可能在食管内脏感觉中发挥着重要的作用.     

非糜烂性胃食管反流病食管酸暴露和雷贝拉唑对其诊断价值研究

目的 研究非糜烂性胃食管反流病（NERD）各亚型食管酸暴露特点,探讨雷贝拉唑对其诊断价值。方法 32例NERD患者分成3组,异常酸反流组14例,食管对酸高敏组11例,功能性烧心组7例,并以雷贝拉唑10mg,2次／d治疗2周。结果 （1）各组酸暴露：异常酸反流组酸反流总次数、长反流次数、pH〈4时间及其百分比较其他两组明显增加;食管对酸高敏组症状指数显著高于功能性烧心组[（81．0±22．5）％比（8．6±14．8）％,P〈0．01]。（2）症状比较：各组间治疗前典型症状积分和总积分相比差异均无统计学意义;食管对酸高敏组患者食管外症状积分显著高于异常酸反流组患者（4．0±3．8比0．9±2．2,P〈0．05）。（3）疗效：异常酸反流组、食管对酸高敏组患者在雷贝拉唑治疗1、2周后均有食管外症状积分、总积分的显著下降;而功能性烧心组患者仅有下降趋势,与治疗前比较差异无统计学意义;异常酸反流组与其他两组治疗后2周比较,症状积分差异有统计学意义。（4）雷贝拉唑对NERD患者1、2周治疗后总体有效率分别为56．3％、68．8％;雷贝拉唑诊断试验对异常酸反流和食管酸高敏的敏感性和特异性,在1周时分别为64．0％、71．4％,在2周时分别为80．0％、71．4％。结论 （1）异常酸反流组酸暴露主要表现在酸反流的总次数、长反流次数增多,pH〈4时间延长。（2）食管对酸高敏患者可能更易发生食管外症状。（3）雷贝拉唑诊断试验对NERD有较好的诊断和分型价值。     

问询表诊断老年人胃食管反流病的临床评价

目的探讨问询表调查在我国诊断老年胃食管反流病( GERD)的临床价值. 方法选取有烧心,反酸,胸痛等症状,且连续发作一周以上的老年患者.进行胃镜检查,胃镜阳性者归入反流性食管炎组( RE组),胃镜阴性者进一步行食道测压及 24小时胃食管 pH监测,根据结果分为非糜烂性胃食管反流病组( NERD组)和正常对照组( Normal组).所有患者均填写 Carlsson- Dent自我症状问询表并给予 PPI试验一周,以胃镜及 24小时胃食管 pH监测阳性为 GERD确诊标准,统计问询表诊断胃食管反流病的敏感性、特异性和准确率. 结果共 78例老年患者入选,经检查分为 RE组 21例、 NERD组 31例和正常对照组 26例.三组的问询表得分分别为 5.86± 2.90、 5.00± 3.14和 3.69± 1.57, RE组和 NERD组得分与 Normal组比较有显著差异( P< 0.05); RE组和 NERD组比较无明显差异.以 4分为临界值, Carlsson- Dent问卷诊断胃食管反流病的敏感性为 69.23%、特异性为 38.46%、准确率为 58.97%; PPI抑制试验结合 Carlsson- Dent问卷诊断胃食管反流病的敏感性为 88.46%、特异性为 26.92%、准确率为 67.94%. 结论 Carlsson- Dent问卷可用于筛选老年 GERD,结合 PPI试验可提高诊断的敏感性.     

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.     

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.