口服华法令抗凝致出血的原因分析

目的:探讨口服华法令抗凝治疗期间患者出血的相关原因。方法:收集60例因口服华法令抗凝治疗期间合并出血的急诊患者的临床资料,分析在不同凝血酶原时间(PT-INR)值范围内导致出血的相关病因。结果:60例服用华法令合并出血的病例中,24例(40.0%)所测PT-INR在2.0~3.0的目标值内,并且9例患者INR<2.0;进一步检查发现这33例患者基本都合并有不同的易促使出血的疾病。结论:服用华法令抗凝治疗期间发生出血与否并不完全取决于PT-INR值,还决定于自身潜在的疾病等相关原因;临床应用华法令时应因人而异地调整剂量并决定其抗凝强度。     

华法令在肺栓塞抗凝治疗中的剂量与使用方法

目的探讨华法令抗凝治疗肺血栓栓塞症（PTE）时尽快达到国际标准化比值（INR）在2—3之间时的剂量及方法。方法分析94例接受华法令口服抗凝治疗的PTE患者的临床资料；比较起始量3mg组与6mg组在华法令治疗第3、5、10天时INR达标情况；计算达标者每日人均华法令用量。结果94例患者中56例有明确达标剂量，占59．6％；所有达标者每日人均华法令用量为4．097mg；3mg组达标25例，6mg组达标22例；抗凝第3、5、10天时6mg组达标人数及百分比均明显高于3mg组（P〈0．05），两组达标时所用的华法令总量平均数皆为29mg左右；6mg组平均达标天数为第5—6天，3mg组为第8～9天（P〈0．05）；随年龄增大华法令需求量下降；94例PTE患者在华法令抗凝期间无一例发生出血，6mg组有1例出现再栓塞。结论使用6mg负荷量的给药方法可使PTE患者在第5～6天尽快达标同时又能避免早期再栓及出血；本组华法令平均个体维持量在4mg／d左右。     

65岁以上老年患者口服华法林抗凝的安全性探讨

目的 探对65岁以上老年患者口服华法林抗凝治疗的安全性.方法 对2003年1月-2007年11月具有华法林抗凝适应证的65岁以上住院患者进行回顾性分析,并进行随访.结果 ①201例具有华法林抗凝适应证的患者,服用华法林98例,其中发生出血并发症14例(14.3%),患者出血时国际标准化比值(INR)>3.0者8例(57.1%).在INR<2.0的出血患者中75%合并有出血潜在的基础疾病或合并用影响华法林抗凝作用的药物.②201例患者中非瓣膜病心房颤动患者98例,其中具有华法林抗凝指征并接受抗凝治疗者42例(42.86%).结论 65岁以上具有华法林抗凝适应证的老年患者口服华法林时,应密切监测有无出血并发症发生.     

心脏瓣膜置换术后抗凝观察

目的分析心脏瓣膜置换术后华法令抗凝治疗的影响因素、给药方法和国际标准比值（INR）的关系。方法我院2008年6月—2011年6月323例行心脏机械瓣膜置换术后患者进行随访研究。术后使用华法令抗凝,出院后定期复查随访。记录年龄、性别、华法令剂量和INR值等,观察出血、栓塞、死亡等不良事件发生情况。结果在患者术后抗凝达到稳定状态后,总体INR值为1.5～2.5,术后413例无不良事件的发生,10例出现抗凝相关并发症,其中血栓栓塞3例,抗凝有关出血7例。出院随访因抗凝出现不良事件的发生率与国外文献报道相近。结论心脏机械瓣膜置换术后根据INR给予个体化剂量华法令,控制INR值在1.5～2.5可以达到相对安全的抗凝效果。     

抗凝门诊非瓣膜性心房颤动患者口服抗凝药物出血发生情况分析

目的:分析非瓣膜性心房颤动(NVAF)患者服用华法林和新型口服抗凝药物(NOACs)的出血发生情况。方法:纳入2014年11月至2019年1月中国医学科学院阜外医院抗凝门诊接受口服抗凝药(OAC)治疗的682例NVAF患者,对其3 102次就诊时报告的出血及其他安全性事件发生情况进行回顾性分析。服用华法林、达比加群酯、利伐沙班的患者分别有551例(80.79%)、83例(12.17%)和48例(7.04%)。出血类别包括小出血、临床相关非大出血(CRNMB)和大出血。同时分析华法林抗凝患者中国际标准化比值(INR)在不同范围内的百分比以及INR危急值(4.5)的发生率和原因等。结果:682例患者共发生174例次(25.5%)出血事件,其中16例(2.3%)患者发生CRNMB,10例(1.5%)患者发生大出血。小出血148例次,占就诊次数的4.8%。接受华法林、达比加群酯、利伐沙班治疗的患者中出血发生率无明显差异。在使用华法林的患者共2 869次就诊中,INR危急值共出现27例(0.94%),其中10例(37.0%)与药物相互作用有关,6例(22.2%)为华法林快代谢型。华法林抗凝期间发生小出血的患者INR多在目标范围内。结论:在抗凝门诊接受华法林和NOACs治疗的NVAF患者中,小出血和CRNMB事件发生率较高。分析华法林抗凝治疗期间出现INR危急值的原因以及出血事件与INR的相关性能够为临床提供预见性的实践指导。     

58例华发令的抗凝作用和护理

目的：探讨华发令抗凝治疗的使用笔护理注意事项。方法：随访例服用华发令的心血管病患为观察组，给予强化健康教育并密切观测凝血酶原时间（PT）及其国际标准比率（INR），观察其抗凝效果及主要不良反应。另设传统服用华法令的50例患为对照组。结果：经过规范的抗凝治疗，58例病人中有4例因原发疾病死亡，1例失访，1例严重副反应，2例因病停药，8例发生一般副反应，均较常规华发令用药的不良反应明显减少（P＜0．05－＜0．01）。结论：研究提示心血管科护士在华发令使用中具有十分重要的作用，要对病人加强相关的健康教育，密切观察并教育病人学会发现早期出血的征象，定期测定PT及其INR，以达到既有疗效，又无副反应的目的。     

华法令不同抗凝强度对老年房颤栓塞事件的影响

目的观察华法令不同抗凝强度对老年房颤栓塞事件的干预作用。方法200例房颤患者,随机分为3组,低等强度组,中等强度组及对照组。华法令抗凝治疗中强度组即国际标准化比率(INR)在1.9～2.4,低强度组即INR在1.3～1.8,对照组服用阿司匹林。结果对照组栓塞事件发生7例,显著高于中强度抗凝组。不良反应为出血,抗凝中强度组3例,低强度组1例,对照组出血1例。三组比较无显著性差异。结论华法令抗凝强度在中度时能减少老年房颤的栓塞发生,安全性与阿司斯林比较,无明显差异。     

华法令在老年房颤患者中应用的临床观察

目的　探讨老年房颤患者中应用华法令抗凝的安全性及疗效。方法　采用前瞻性定群研究 ,入选华法令组和对照组各 10 0例 ,两组基础用药相似。华法令组通过小剂量滴定口服华法令 ,目标INR2 0 - 2 5 ,门诊随访记录各类并发症及脑卒中和血栓性并发症 ,随访 1年。结果　华法令组 98例完成随访 ,6例牙龈、皮肤出血 ,1例脑梗死。对照组 96例完成随访 ,4例出血并发症 ,8例脑卒中 ,1例股动脉栓塞。两组出血并发症无差异 ,血栓性并发症华法令组显著低于对照组 (P <0 0 5 )。结论　老年房颤病人应用适量华法令抗凝安全、有效。     

非瓣膜病房颤的华法林抗凝治疗研究

目的：应用华法林对非瓣膜病性心房颤动患者进行抗凝治疗,观察其抗栓疗效和安全性。方法：服用华法林．从3．0mg。1次／d开始．根据血浆凝血酶原时间国际标准化比率（INR）调整华法林剂量．低抗凝强度组患者（46例）INR为1．5～2．1．标准抗凝强度组患者（66例）INR为2．2～3．0．两组均持续服药,随访1～4年．观察有无血栓栓塞事件及出血并发症。结果：低抗凝强度组中有1例发生脑栓塞,当时INR为1．5．栓塞年发生率为2．2％;标准抗凝强度组无栓塞并发症．两组比较差异无显著性（P〉0．05）。服用华法林期间．低抗凝强度组1例肉眼血尿,出血年发生率为2．2％;标准抗凝强度组发生皮肤黏膜出血4例．牙龈出血3例,球结膜出血1例．出血年发生率为12％。当时的INR除3例为〉3．其余均在2．6～3．0之间,未发生严重大出血．低抗凝强度组出血发生率显著低于标准抗凝血组（P〈0．05）。结论：房颤患者华法林抗凝目标INR值在1．5-3．0安全有效。     

华法林在非瓣膜病性房颤患者中的应用观察

目的探讨华法林对于非瓣膜病性心房纤颤（房颤）患者抗凝治疗的安全性及疗效。方法对符合本研究标准的60例老年房颤患者随机分为治疗组和对照组；治疗组30例，给予华法林3mg／d开始，监测国际标准化比值（INR），连续观察4周，目标INR 2．0～3．0，后每个月查1次INR，据INR结果调整华法林口服剂量。对照组30例，给予阿司匹林300mg／d。门诊随访记录各类并发症及脑卒中和血栓性并发症，随访2年。结果治疗组2例牙龈、皮下出血，1例脑梗死。对照组1例出血，8例脑卒中，1例动脉栓塞，两组出血并发症，差异无统计学意义（P〉0．05），血栓性并发症治疗组显著低于对照组（P〈0．01）。结论非瓣膜病性心房纤颤患者应用适量华法林抗凝治疗是安全有效的。     

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.     

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.     

Variabilité des concentrations plasmatiques de l’angiotensinogène et risque d’hypertension artérielle chez le rat transgénique

Aim

Genetic polymorphisms of the human angiotensinogen gene are frequent and may induce up to 30% increase of plasma angiotensinogen concentrations with a blood pressure increase of up to 5 mmHg. Their role for the pathogenesis of human arterial hypertension remains unclear. High plasma angiotensinogen levels could increase the sensitivity to other blood pressure stressors.

Methods

Male transgenic rats with a 9-fold increase of plasma angiotensinogen concentrations and male non-transgenic rats aged 10 weeks were treated or not with NG-Nitro-L-arginine-methyl ester for 3 weeks in their drinking water (n = 3/group). Systolic blood pressure and body weight were measured at baseline and at the end of the study when left ventricular weight and ventricular expression of angiotensin I-converting enzyme and procollagen Iα1 were determined (polymerase chain reaction).

Results

At baseline, transgenic rats had +18 mmHg higher bood pressure and –8% lower body weight compared to non-transgenic rats (P < 0.05) without significant changes for the vehicle groups throughout the study (P > 0.05). NG-Nitro-L-arginine-methyl ester increased blood pressure, left ventricular weight and left ventricular weight indexed for body weight by +41%, +17.6% and +18.6% (P < 0.05) in transgenic and +25%, +5.3% and +6.7% (P > 0.05) in non-transgenic rats compared to untreated animals, respectively. Cardiac gene expression showed no differences between groups (P > 0.05).

Conclusion

Increased plasma angiotensinogen levels may sensitize to additional blood pressure stressors. Our preliminary results point towards an independent role of angiotensinogen in the pathogenesis of human hypertension and associated end-organ damage.     

Morphological and immunocytochemical heterogeneity of cultured pinealocytes from one-week-and two-month-old rats: Planimetric and densitometric investigations

Abstract: In vitro preparations of rat pinealocytes are widely used for biochemical analyses of signal transduction processes. This paper deals with morphological and immunocytochemical features of such preparations. Special attention was paid to the problems of whether pinealocytes represent a heterogeneous cell population and how such heterogeneity may develop during ontogeny. The investigations were performed with cells which were obtained from the pineal organ of one-week-and two-month-old rats, attached to synthetic peptide-coated coverslips or tissue culture chamber slides, and maintained under in vitro conditions overnight. The attached cells were then fixed with paraformaldehyde. These preparations yielded monolayers of spherical cells of different sizes; most cells were isolated, but some of them were aggregated and formed small clusters. On the average, the cells from the one-week-old animals were smaller than the cells from the two-month-old animals. Immunocytochemical demonstration of S-antigen, a pinealocyte-specific marker, showed that the majority of the cells from two-month-old animals were intensely or moderately labelled. Pinealocytes from one-week-old animals were less S-antigen immunoreactive. Only very few cells (less than 1% displayed glial fibrillary acidic protein (GFAP)-immunoreactivity. Planimetric investigations of the cell size and semiquantitative densitometric investigations of the intensity of the S-antigen immunoreaction revealed that (i) pinealocytes kept in vitro form a heterogeneous cell population, and that (ii) this heterogeneity increases during postnatal development from one-week-old to two-month-old animals. Two groups of pinealocytes can be distinguished based on their developmental fate: pinealocytes of one group grow dramatically, but show only a moderate increase in S-antigen immunoreactivity, and pinealocytes of the other group retain their size, but display a distinct increment in S-antigen immunoreacti vitv.     

Effects of pinealectomy and melatonin administration on certain indices of ovarian hyperplasia and/or hypertrophy in rats with both ovaries intact or after unilateral ovariectomy

Abstract: In earlier studies from other laboratories it was shown that melatonin decreased ovarian weight in rats and inhibited compensatory hypertrophy of the remaining ovary after unilateral ovariectomy. This study was designed to examine the influence of melatonin on certain indices of ovarian hyperplasia and/or hypertrophy in adult female rats with both ovaries preserved and with either an intact pineal gland or with the pineal gland removed (pinealectomy, PX) or, finally, in sham-PX animals. Similar studies were conducted on rats after unilateral ovariectomy, referring the examined parameters to the remaining intact ovary. The studies included mitotic activity of granulosa layer cells and corpus luteum cells, ovarian weight, ovarian cross-sectional area, cross-sectional area of the granulosa layer of all the Graafian follicles and the cross-sectional areas of the corpora lutea, visible on the ovarian cross-section. On the basis of results, we conclude that: 1) the effect of PX on the processes of ovarian hyperplasia and hypertrophy may vary; analogously, exogenous melatonin administration may influence ovarian hyperplasia and hypertrophy in different ways; 2) PX and exogenous melatonin may, under certain conditions, exert similar biological effects, even synergistic effects; 3) melatonin inhibits ovarian growth processes, while the effects of PX are variable; 4) the results indicate that in experiments performed on rats, with the use of two control groups, i.e., intact and sham-PX, melatonin effects on these two groups may differ.