恒定磁场协同阿霉素诱导肝癌细胞凋亡的研究

目的：探讨恒定磁场联合阿霉素对诱导肝癌细胞凋亡的影响。方法：采用流式细胞仪碘化丙啶染色法和活细胞荧光染色法（Ｈｏｅｃｈｓｔ染色法），观察不同处理因素对细胞凋亡率的影响。结果：两种实验方法均显示０５ｍｇ／Ｌ的阿霉素与对照组比较没有显著差异（Ｐ＞００５），而单独用恒定磁场或１０ｍｇ／Ｌ的阿霉素与对照组比较有显著性差异（Ｐ＜００５）。应用恒定磁场后发现，０５ｍｇ／Ｌ和１０ｍｇ／Ｌ浓度的阿霉素诱导ＨｅｐＧ－２细胞凋亡的结果与对照组相比，均有显著差异（Ｐ＜００５）。结论：恒定磁场具有增强阿霉素诱导肝癌细胞凋亡的作用     

飞龙掌血水提物对垂体后叶素所致大鼠缺血心肌的保护作用

目的：观察飞龙掌血水提物（Ｆ０１）对急性缺血心肌的保护作用。方法：采用垂体后叶素所致大鼠急性心肌缺血模型观察药物的作用。结果：Ｆ０１（１７５或３００ｍｇ／ｋｇ）及维拉帕米在大部分时点上能明显缓解垂体后叶素所引起的心电图Ｔ波变化（Ｐ＜００５或Ｐ＜００１）。垂体后叶素使对照组１００％的动物发生心律失常，而在Ｆ０１组（１００、１７５或３００ｍｇ／ｋｇ）及维拉帕米组中，心律失常的发生率分别为７０％（Ｐ＞００５）、４４％（Ｐ＜００５）、２０％（Ｐ＜００１）和１１％（Ｐ＜００１）。结论：Ｆ０１对垂体后叶素所致急性缺血心肌具有保护作用，其效应与剂量呈相关性。     

内毒素大鼠休克早期血浆组织因子与组织因子途径抑制物的观察

目的：观察内毒素休克早期大鼠血浆ＴＦ、ＴＦＰＩ的变化。结果：静脉给予内毒素的大鼠ＭＡＰ呈进行性下降，至１２０ｍｉｎ时降至（５８±２５）ｋＰａ，ＴＦ含量高于对照组（Ｐ＜００５），而ＴＦＰＩ无显著改变（Ｐ＞００５）。血浆ＴＮＦ含量明显增高（Ｐ＜００１），ＡＴⅢ活性显著低于对照组（Ｐ＜００１）；ＷＢＣ计数减少（Ｐ＜００１），ＰＬ计数无明显改变（Ｐ＞００５）。结论：内毒素休克早期休克组织因子凝血途径易化因素增强，而拮抗因素不变或减弱     

高血压无左室肥厚患者舒张功能改变的观察

目的：探讨高血压无左室肥厚患者舒张功能的改变。方法：高血压无左室肥厚患者、高血压伴左室肥厚患者与正常血压者各４０例,均进行超声心动图检查和动态血压检测。结果：高血压伴左室肥厚组、高血压无左室肥厚组与正常对照组比较,二尖瓣血流Ｅ峰、Ａ峰、Ｅ／Ａ比率、等容舒张时间及舒张早期减速度均有明显差异（Ｐ＜００５,Ｐ＜００１）,而高血压左室肥厚组与高血压无左室肥厚组两组间,则无明显差异（Ｐ＞００５）。３个组的左室射血分数（ＥＦ）无明显差异（Ｐ＞００５）。动态血压监测显示,高血压左室肥厚组与高血压无左室肥厚组２４ｈ平均收缩压和舒张压、白昼平均收缩压和舒张压、血压负荷有显著差异（Ｐ＜００５,Ｐ＜０．０１）,而夜间平均收缩压、舒张压无显著差异（Ｐ＞００５）。结论：高血压患者在出现左室肥厚前可出现舒张功能异常,可能与夜间血压持续升高有关。     

体外反搏治疗失血性休克中一氧化氮合酶的变化

目的：探讨反搏治疗失血休克中一氧化氮合酶（ＮＯＳ）的变化。方法：复制狗的失血休克模型，用同位素方法测定反搏前后各组织的ＮＯＳ活性。结果：体外反搏后平均动脉压较反搏前明显上升（Ｐ＜００１）。脑ＮＯＳ测定值假手术对照组明显高于失血休克组Ｐ＜００１）及失血休克克反搏组（Ｐ＜００１），失血休克组则明显低于失血休克反搏组（Ｐ＜００１）；心肌ＮＯＳ活性假手术对照组与失血休克反搏组均明显高于失血休克组（Ｐ＜００５，Ｐ＜００１），但假手术对照组与失血休克反搏组之间无显著差异（Ｐ＞００５）；主动脉ＮＯＳ活性假手术对照组明显高于失血休克组（Ｐ＜００１）及失血休克反搏组（Ｐ＜００５），但失血休克组与失血休克反搏组间无明显差异（Ｐ＞００５）。结论：体外反搏可以增强小血管ＮＯＳ活性，ＮＯＳ活性的恢复则可能在反搏治疗中起重要作用     

脑梗塞性痴呆脑电活动研究

将经ＣＴ证实的脑梗塞病人９０例分为痴呆组（试验组ｎ＝５０，年龄５５．８±６．９岁）与无痴呆组（对照组ｎ＝４０，年龄５７．６±５．８岁），分别作脑电图（ＥＥＧ）描记。结果发现：试验组ＥＥＧ局限异常率明显高于对照组（Ｐ＜０．０５）；试验组ＥＥＧα波低波幅者、低波率者、低指数者及有泛化者均显著高于对照组（Ｐ＜０．０５或＜０．０１）；试验组异常ＥＥＧ快波（β波）与慢波（θ、δ波）出现率均高于对照组，但以β波为著（Ｐ＜０．０５）。     

环维黄杨星D治疗心绞痛的甲襞微循环观察

对黄杨碱治疗的６２例冠心病心绞痛甲襞微循环变化进行观察。结果表明：９６．８％（６０／６２）的病例甲襞微循环有异常改变，且病情愈重其改变愈明显。用该药４．５ｍｇ／日（１．５ｍｇ，ｔｉｄ）治疗６０天结果显示：绝大多数微循环异常指标都获改善（Ｐ＜０．０５～０．０１），并认为该药有部分类似茛菪类药物的作用。对少数严重病例的异常微循环改善不明显。心绞痛缓解率及心电图（ＳＴ、Ｔ）改善率分别在７０％以上及５０％～７０％之间。面药对降高明固醇及高甘油三酯作用不明显（Ｐ＞０．０５），而对升高高密度脂蛋白具有较好疗效（Ｐ＜０．０５）。该药无明显毒副作用。     

自然流产妇女的丈夫精子染色体分析

应用人精子与去透明带金黄地鼠卵受精技术制备人精子染色体标本。对１０例有自然流产史妇女的丈夫共２３０个精子核型进行了分析,并与正常可育男性的２１０个核型对照。结果显示,流产组的精子染色体数目异常率为３９％,与正常组相比（２８％）,两者无显著性差异（Ｐ＞０．０５）;但流产组中结构异常的断裂和无着丝粒断片的比率（６０％;９５％）显著性高于对照组（２５％;２８％）。     

老年前期和老年高血压病患者动态心电图分析

分析８０例老年前期，９８例老年期高血压病患者２４小时全信息动态心电图特点。结果显示：二组患者平均心率及５次心搏最大心率均无显著差异（Ｐ＞０．０５），５次心搏最小心率及最大最小心率的差有显著差异（Ｐ＜０．０５），老年期高血压病患者心率变异性（ＨＲＶ）明显低于老年前组（Ｐ＜０．０５），其房性及室性心律失常的发生率均高于老年前组（Ｐ＜０．０５），提示老年组高血压病患者迷走神经功能受损明显，并与心律失常的发生有一定关系。     

常温肝脏缺血再灌注损伤防治的实验研究

目的和方法：配制一种肝保护液，１００ｍＬ主要含有果糖７５ｇ、谷胱苷肽１５ｇ、别嘌呤醇２５ｇ、维生素Ｅ０３ｇ、地塞米松１０ｍｇ、川芎嗪０４ｇ、山莨菪碱１０ｍｇ和丹参２０ｍＬ。采用大鼠常温肝缺血６０ｍｉｎ－再灌注模型，治疗组４０只大鼠于缺血前１０ｍｉｎ和再灌注前１０ｍｉｎ，静注肝保护液１ｍＬ／ｋｇ，对照组４０只大鼠静注平衡液１ｍｌ／ｋｇ。结果：治疗组术后７ｄ存活率为６０％（１２／２０），而对照组为１５％（３／２０）；治疗组术后血清水平和再灌注后肝坏死范围明显低于对照组（Ｐ＜００５）。结论：肝保护液对大鼠肝常温缺血再灌注损伤具有明显的防治作用，这与减轻肝血窦阻力、增加肝血流，改善肝脏微循环障碍有关。     

Effect of hysterectomy on conserved ovarian function

The aim of this study was to assess the impact of premenopausal Total Abdominal Hysterectomy (TAH) on the function of the remaining ovaries by reviewing the menopausal age in TAH treated patients. We retrospectively reviewed the medical records of 510 women who had previously undergone TAH, either with or without unilateral salpingo-oophorectomy, due to benign disease at the department of Obstetrics and Gynecology, Yonsei University College of Medicine, between Jan 1989 and Dec 1992. Out of the 510 women, the 94 who were throughly followed up were included in the study, and their menopausal age based on patient symptoms was compared to that of the control group. The mean menopausal age in TAH treated patients was significantly lower than that of the control group (P < 0.001). There was a positive correlation between age at operation and menopausal age. From this study, we could conclude that TAH accelerated ovarian dysfunction, and that the younger the patient was at the time of operation, the earlier the onset of menopause. It is hence apparent that women treated with TAH are at risk of early menopause and should receive adequate hormone replacement therapy.     

Hormonal,syndromal and EEG mapping studies in menopausal syndrome patients with and without depression as compared with controls

The aim of the study was to investigate brain function in menopausal depression by EEG mapping, as compared with menopausal syndrome patients without depression and normal controls, and to correlate neurophysiological with clinical and hormonal findings in order to elucidate the pathogenesis of depression in the menopause. Methods: One hundred and twenty-nine menopausal women, aged 45–60 years, with no previous hormonal replacement therapy were investigated in regard to hormones (estradiol [E₂], follicle stimulating hormone [FSH], clinical symptomatology (Kupperman Index [KI], Hamilton depression score [HAMD]) and brain function (EEG mapping). Based on KI and DSM-III-R research criteria for major depression, 3 groups were available for statistics (after removal of protocol violators): group A had a KI of <15 and no depression (n = 29); group B had a KI of ≥ 15 and no depression (n = 29) and group C had a KI of ≥ 15 and fulfilled the criteria for major depression (n = 60). Results: EEG maps of depressed patients demonstrated less total power and absolute power in the delta, theta and beta band, more relative delta and less alpha power as well as a slower delta/theta and faster alpha and beta centroid than controls, suggesting a vigilance decrement. Group B did not differ from group A. Correlation maps showed significant relationships between estradiol levels and EEG measures (the lower the E₂, the worse the vigilance) and between the EEG measures and the Hamilton depression (HAMD) score (the worse the vigilance, the higher the depression score). There were no correlations between the hormones E₂ and FSH and the syndromes KI and HAMD. In the target variable, the asymmetry index, depressed patients showed less alpha power over the right than left frontal lobe, whereas normal controls exhibited the opposite. Group B did not differ from group A. The frontal asymmetry index was significantly correlated with the Hamilton depression score and suggests right frontal hyper- and left frontal hypoactivation in depression. Conclusion: Although hormonal findings are not directly linked to psychic changes, low estradiol levels do contribute to a decreased vigilance at the neurophysiological level, which is in turn correlated with higher depressive and menopausal symptomatology at the behavioural level. Depression is furthermore correlated to a right frontal hyper- and left frontal hypoactivation.     

Influence of pattern of menopausal transition on the amount of trabecular bone loss. Results from a 6-year prospective longitudinal study

INTRODUCTION: Bone density is lower in postmenopausal than in premenopausal women. Recent findings have suggested that accelerated bone loss already begins before menopause. Despite numerous cross-sectional studies on menopause-related bone density, longitudinal data on perimenopausal bone density changes are scarce. This study sought to characterize the dynamics of changes leading to postmenopausal osteopenia and to possibly find the time point at which accelerated bone loss begins. METHODS: We prospectively followed 34 pre-, peri- and early postmenopausal women without prior external hormone use, measuring their lumbar spine trabecular bone density with quantitative computer tomography at 0, 2 and 6 years. The analysis of the changes over time was done in a tri-parted fashion, since menopausal status changed variably for individual subjects: we grouped the participants according to their currently valid menopausal classification for prospective (baseline classification), interim (2 years) and retrospective (6-year classification) analysis. RESULTS: Six different patterns of menopausal transition were identified in our sample. Bone loss in the groups not reaching postmenopause during 6 years of observation was >50% of the maximum bone loss observed during the study period. Invariably for all analyses, the perimenopausal phase with estrogen levels still adequate was associated with the greatest reduction of trabecular bone mineral density, reaching 6.3% loss annually in the lumbar spine. By comparison, the average rate of loss was slower in the early postmenopause; total bone loss differed by pattern of menopausal transition (one-way ANOVA p<0.05). CONCLUSION: The presented data for the first time show the perimenopausal course of trabecular bone loss (as measured by QCT of the lumbar spine). Acceleration of bone loss during perimenopause reached half-maximal values of the total bone loss measured around menopause, despite adequate serum estradiol levels.     

Skin changes in menopause

Skin signs and symptoms were examined in 46 menopausal women prior to estrogen replacement therapy. Several symptoms such as pruritus, bruising, dryness and thinning were seen more frequently in sun-exposed skin emphasizing the contribution of photoaging. At the end of a 6-mth treatment period, no significant difference was observed in the prevalance or severity of the cutaneous signs and symptoms when patients receiving transdermal 17β-estradiol (Estraderm) were compared with controls (the only exception was cutaneous flushing). Elastic fibers from sun-protected (buttock) skin of menopausal women were studied by light and electron microscopy. In 3 women (ages 30–37) with a history of premature menopause, the elastic fibers had several degenerative changes including coalescence of cystic spaces into lacunae, peripheral fragmentation, granular degeneration and splitting of the fibers into strands. Similar age-related ultrastructural changes are normally found in individuals that are at least 20 yrs older than these patients. These findings are suggestive of a relationship between premature aging of the dermal elastic fibers and estrogen deprivation.     

Drops in estrogen levels affect brain,body and behavior: reported relationship between attitudes and menopausal symptoms

Bloch found that women who had more menopausal symptoms had a more negative view of menopause than women who had fewer symptoms. Bloch's conclusion that a negative view of menopause will lead to more symptoms implies a cause and effect assumption that is not warranted and is also counter-intuitive. Current research on the neural effects of estrogen suggest that the observed relationship is more likely to be due to the fact that some women experience negative symptoms during menopause as a result of diminished levels of estrogen. This, in turn leads these same women to adopt a more negative view of menopause, at least compared with women who have relatively less severe symptoms.     

Postmenopausal effects of intrastriatal estrogen on catalepsy and pallidal electroencephalogram in an animal model of Parkinson's disease

The main objective was to test the preventive and treatment effects of central injection of estrogen (ES) on muscular rigidity and pallidal EEG in menopausal rats' model of Parkinson's disease (PD). We hypothesized that intrastriatal pretreatment and post-lesion treatment by estrogen improve the pallidal local EEG and muscular stiffness in animal model of menopause with PD. Forty-eight female Wistar rats (300-350 g) were ovariectomized (OVX) and divided into two main groups: Non-pretreated subgroups; sham (S), lesioned (L), post-lesion treated (LT) and pretreated subgroups; pretreated (Pt), pretreated and then lesioned (PtL), pretreated and post-lesion treated (PtLT). Pallidal local EEG was recorded by a bipolar recording electrode and muscle stiffness was scored by Dekundy's test in freely moving rats. Muscle stiffness and pallidal local EEG were indicated as main outcome measures. In pretreated group the local pallidal EEG was decreased in sham-operated rats compared with non-pretreated group (P<0.01), and SNc lesioning decreased EEG in the non-pretreated (P<0.01), while it increased the EEG in the pretreated group (P<0.01). In both groups administration of ES restore the EEG to the respective sham-operated group (P<0.01). Regarding muscle stiffness, it increased after SNc lesioning in both pretreated and non-pretreated groups and ES administration decreased the rigidity significantly (P<0.05, P<0.001 respectively). However, the lesion-induced rigidity in pretreated groups was significantly less than non-pretreated groups (P<0.05). Because of its modulatory effect estrogen may protect dopaminergic neurons from injury and may interfere with the uptake of 6-hydroxydopamine (6-OHDA) into the nigral dopaminergic neurons or alter dopamine release and uptake in remaining neurons.     

Factors associated with the age of natural menopause and menopausal symptoms in Chinese women

Objective

To investigate the factors associated with the age of natural menopause and menopausal symptoms in a large population of Chinese middle-aged women.

Study design

In this cross-sectional study, a total of 20,275 women (40–65 years) attending health screening in Jiangsu Province of China were enrolled. A structured questionnaire was used to collect data of demographics, menopausal status, chronic diseases, reproductive history, etc. Also we evaluated the severity of menopausal symptoms by Kupperman menopause index (KMI).

Main outcome measure

Menopausal age and scorings of Kupperman menopause index.

Results

The overall median age at natural menopause was 50 years. Lower educational level, poor economic status, lower body mass index (BMI), age at menarche less than 14 years, nulliparity and smoking were associated with earlier onset of natural menopause (P < 0.05). The most frequently symptoms in postmenopausal women were sexual problems (57.05%), muscle/joint pain (53.29%) and insomnia (51.02%), while fatigue, insomnia and muscle/joint pain were predominant symptoms in pre- and peri-menopausal women. After adjusting for confounding factors, logistic regression analysis revealed that women with poor educational background, low income, divorce, higher BMI, higher parity, smoking and chronic diseases presented higher KMI scores (P < 0.05).

Conclusion

The study provided an estimate of median age at natural menopause in Chinese women. The main factors contributing to earlier onset of menopause and severity of menopausal symptoms were lower educational level, poor economic status, and smoking. Thus, this study provides important insights for physicians to prevent and treat menopause related symptoms.     

Hormone replacement therapy may alleviate sleep apnea in menopausal women: a pilot study.

OBJECTIVE: The incidence of sleep apnea syndrome (SAS) in women increases after menopause. Progestins alone do not alleviate SAS in menopausal women. However, progestins may require concomitant estrogen administration and estrogen alone may stimulate breathing during sleep. To test these hypotheses, we studied the effects of estrogen alone and estrogen combined with progestin on SAS in menopausal women, using a prospective, cross-over, inception cohort study. DESIGN: In this pilot study, five women who developed SAS after menopause underwent 2 nights of polysomnography to obtain a baseline, then returned for polysomnography after 3-4 weeks of taking micronized 17 beta-estradiol (E2) and after 10-12 days of taking E2 combined with medroxyprogesterone acetate (E2 + P). Sleep stages were scored according to Rechtshaffen and Kales, frequency and length of apneas were recorded for each subject each night, and the data were analyzed by Student's t test. RESULTS: E2 and E2 + P both reduced the Respiratory Distress Index. E2 also raised the lowest oxygen desaturation associated with apneic episodes. Total minutes of rapid eye movement sleep increased, and the number of waking episodes decreased when the women were taking E2 and E2 + P, as previously reported. CONCLUSIONS: Within 1 month after initiating E2 or E2 + P, SAS was reduced in all patients. The Respiratory Distress Index decreased by 25%, and the addition of progestin brought the SAS reduction to 50% in this pilot study. A randomized study in a large group of patients is justified by the findings of this study. Because SAS increases the risk of cardiovascular disease and fatal accidents, the amelioration of SAS by sex steroid hormones could have significant implications for the health of menopausal women.     

Estrogenic Modulation of Uropathogenic Escherichia coli Infection Pathogenesis in a Murine Menopause Model

Recurrent urinary tract infections (UTIs), primarily caused by uropathogenic Escherichia coli (UPEC), annually affect over 13 million patients in the United States. Menopausal women are disproportionally susceptible, suggesting estrogen deficiency is a significant risk factor for chronic and recurrent UTI. How estrogen status governs susceptibility to UTIs remains unknown, and whether hormone therapy protects against UTIs remains controversial. Here, we used a mouse model of surgical menopause by ovariectomy and demonstrate a protective role for estrogen in UTI pathogenesis. We found that ovariectomized mice had significantly higher bacteriuria, a more robust inflammatory response, and increased production of the proinflammatory cytokine interleukin-6 (IL-6) upon UPEC infection compared to sham-operated controls. We further show that response of the urothelial stem cell niche to infection, normally activated to restore homeostasis after infection, was aberrant in ovariectomized mice with defective superficial urothelial cell differentiation. Finally, UPEC-infected ovariectomized mice showed a significant increase in quiescent intracellular bacterial reservoirs, which reside in the urothelium and can seed recurrent infections. Importantly, this and other ovariectomy-induced outcomes of UTI were reversible upon estrogen supplementation. Together, our findings establish ovariectomized mice as a model for UTIs in menopausal women and pinpoint specific events during course of infection that are most susceptible to estrogen deficiency. These findings have profound implications for the understanding of the role of estrogen and estrogen therapy in bladder health and pathogen defense mechanisms and open the door for prophylaxis for menopausal women with recurrent UTIs.     

Menopause and risk factors for coronary heart disease

Postmenopausal women are believed to have a higher risk of coronary artery disease than premenopausal women. In this study, we prospectively determined changes in coronary risk factors that were attributable to natural menopause in 541 healthy, initially premenopausal women 42 to 50 years of age. After approximately 2 1/2 years, 69 women had spontaneously stopped menstruating for at least 12 months, and 32 women had stopped natural menstruation and received hormone-replacement therapy for a period of at least 12 months. An equal number of age-matched premenopausal women in the study group served as controls. In women who had a natural menopause and did not receive hormone-replacement therapy, serum levels of high-density lipoprotein (HDL) cholesterol declined as compared with those of premenopausal controls (-0.09 vs. 0.00 mmol per liter; P = 0.01), and levels of low-density lipoprotein (LDL) cholesterol increased (+0.31 vs. +0.14 mmol per liter; P = 0.04). In menopausal women who received hormone-replacement therapy, HDL and LDL cholesterol levels did not change, but the levels of triglycerides (+0.42 vs. -0.04 mmol per liter; P less than 0.001), apolipoprotein A-I (+0.18 vs. +0.03 g per liter; P less than 0.01), and apolipoprotein A-II (+0.05 vs. -0.03 g per liter; P less than 0.05) increased as compared with premenopausal controls. Natural menopause did not affect blood pressure, plasma glucose or insulin levels, body weight, the total number of kilojoules consumed in the diet, or the total number of kilojoules expended in physical activity. These results suggest that a natural menopause has an unfavorable effect on lipid metabolism, which may contribute to an increase in the risk of coronary disease. Hormone-replacement therapy may prevent some of these changes.