高脂餐与空腹顿服胺碘酮的药代动力学对比研究

目的　比较空腹和高脂餐后顿服胺碘酮的药代动力学变化 ,探讨饮食对胺碘酮药代动力学的影响。方法　 8名健康男性志愿者 ,年龄 (2 1 6± 1 2 )岁 ,体重 (6 5 8± 5 6 )kg。志愿者分别在空腹12h和进食标准脂肪早餐 (含黄油 1 5 g/kg体重 )后顿服胺碘酮 80 0mg ,两次服药间隔 12周。高效液相色谱法测定胺碘酮及其代谢产物去乙基胺碘酮浓度 ,计算餐后与空腹服药后药代动力学参数及相对生物利用度。结果　结果显示高脂餐后胺碘酮的血浆浓度较空腹服药明显增高。餐后胺碘酮的峰浓度(Cmax)和血药浓度 时间曲线下面积 (AUC0 t)均较空腹服药显著升高 [Cmax(2 330± 12 14)ng/ml对 (90 3± 35 3)ng/ml;AUC0 t(2 72 6 6± 86 6 7)ng·h·ml-1对 (12 82 5± 5 985 )ng·h·ml-1](P <0 0 1) ;消除半衰期 (t1/ 2 )明显延长 [(2 9 6± 9 8)h对 (17 0± 5 3)h](P <0 0 1) ;达到峰值时间 (Tmax)基本不变 [(4 6±1 2 )h对 (4 6± 1 5 )h]。根据各受试者的AUC计算出高脂餐后服药的相对生物利用度为 2 39%±75 %。结论　高脂餐后服药增加胺碘酮的吸收 ,显著增加胺碘酮的血药浓度 ,同时减慢胺碘酮自体内的消除 ,提示进食高脂餐可能影响药物的疗效。     

胺碘酮和普罗帕酮治疗冠心病并室性心律失常的疗效比较

比较胺碘酮和普罗帕酮治疗冠心病心肌缺血患者室性心律失常的疗效。6 9例冠心病心肌缺血合并室性心律失常患者 ,均接受冠心病正规治疗 ,其中 35例同时口服胺碘酮片 (胺碘酮组 ) ,34例口服普罗帕酮片 (普罗帕酮组 ) ,疗程 4周。疗程开始及结束时均行 2 4h动态心电图及 12导联心电图检查。结果 :两组患者用药后 2 4h室性早搏 ,短阵室性心动过速的发作次数均明显减少 (胺碘酮组用药后与用药前比较分别为 2 70 5± 14 77个vs 6 834± 45 2 8个 ,7.4 2± 3.30次vs 1.2 9± 0 .93次 ;普罗帕酮组则分别为 6 712± 3385个vs 396 2± 1983个 ,8.0 5± 3.37次vs4 .2 2± 2 .5 9次 ,P均 <0 .0 1)。胺碘酮组的疗效高于普罗帕酮组 (P <0 .0 1)。两组未见严重副作用。结论 :胺碘酮对冠心病伴室性心律失常的疗效优于普罗帕酮。     

围术期应用胺碘酮预防治疗心脏术后心房颤动

目的评价心脏手术围术期预防性应用胺碘酮对术后心房颤动(简称房颤)的预防作用。方法采用双盲、随机研究,将124例心脏手术者随机分为胺碘酮组(n=64),对照组(n=60)。胺碘酮组术前每天服用胺碘酮200mg,3次/天,至少7天,术后改为每天口服200mg,1次/天,直到出院。对照组则服用安慰剂,其剂量及服药方法与胺碘酮组相同。术前服用时间为13±7天,总剂量为4.8±0.9g。结果胺碘酮组术后房颤发生率、房颤时的心室率均较对照组低(23.4%vs41.7%,112±21次/分vs135±31次/分,P均<0.05),两组围术期并发症的发生率及死亡率均无显著差异。胺碘酮组的住院时间较对照组短(14.9±3.3天vs20.5±2.6天,P<0.05)。结论心脏手术围术期预防性服用胺碘酮是安全的,并且能显著降低术后房颤的发生率及房颤发生时的心室率,缩短住院时间。     

胺碘酮与美托洛尔联合应用对非瓣膜病心房颤动的疗效及安全性观察

观察静脉胺碘酮与美托洛尔联合应用对非瓣膜病心房颤动 (简称房颤 )的疗效及安全性。 49例冠心病伴发房颤的患者 ,按既往是否常规服用美托洛尔或氨酰心安而分入A组 ( 2 5例 )、B组 ( 2 4例 )。全部病例先给予胺碘酮负荷量 ( 3～ 5mg/kg)静脉推注 1 0min ,然后以 60 0 μg/min的速度静滴 48h ,B组同时口服美托洛尔 6.2 5～ 2 5mg ,2次/日。行心电、血压监测 ,观察 48h房颤转复率。B组 48h后转复率为 83.3% ( 2 0 /2 4 ) ,A组为 76% ( 1 9/2 5 ) ,P >0 .0 5。A、B两组转复时间、胺碘酮用量及转复后心率比较 ,差异有显著性 ( 1 7.2± 1 0 .6hvs 9.4± 9.2h ;880 .2±395 .3mgvs5 76.4± 331 .9mg ;86.3± 1 8.2次 /分vs76.8± 1 7.9次 /分 ,P均 <0 .0 5 )。副反应发生率A组为 8.0 % ,B组为 8.3% ,P >0 .0 5。结论 :静脉胺碘酮与美托洛尔联合应用对非瓣膜病房颤安全有效 ;与单用胺碘酮相比 ,转复时间短、胺碘酮用量少。     

胺碘酮对心室慢性起搏阈值的影响

为探讨胺碘酮对心室慢性起搏阈值的影响 ,对 12例安置心脏起搏器 3个月后伴发症状性心律失常患者 ,予胺碘酮治疗 ,用相应的程控仪测试用药前后的起搏阈值。药前 ,药后 1h、4h、1周和 2周的起搏阈值 (输出固定为2 .5V)分别为 0 .0 8± 0 .0 2 ,0 .0 8± 0 .0 1,0 .0 7± 0 .0 2 ,0 .0 8± 0 .0 1和 0 .0 8± 0 .0 2ms(P >0 .0 5 )。结论 :胺碘酮对心室慢性起搏阈值无影响。     

小剂量美托洛尔与胺碘酮合用抗心律失常的协同作用研究

目的 从药效动力学及药代动力学方面研究不同剂量美托洛尔与胺碘酮合用对乌头碱诱发室性心律失常的防治作用,并寻找药物合用的最佳剂量.方法 采用乌头碱诱导的心律失常大鼠模型,观察不同剂量美托洛尔与胺碘酮合用抗实验性室性心律失常的作用.结果 相当于人体0.5 mg/kg剂量美托洛尔与胺碘酮合用即可推迟乌头碱诱发室性心律失常的出现时间并明显缩短心律失常持续时间(持续时间差异有统计学意义P<0.01).结论 小剂量关托洛尔与胺碘酮联合使用即具有防治室性心律失常的协同作用.     

大剂量胺碘酮对持续性室性心动过速的纠治

目的 :观察大剂量胺碘酮治疗持续性室性心动过速 ( SVT)的临床疗效及副作用。方法 :初始以胺碘酮 15 0 m g静脉注射 (静注 ) ,5～ 10 min注射完毕 ,必要时重复 1～ 2个初始量 ,继以 0 .5～ 5 m g/ min静脉维持 3～ 8d。结果 :6例 SVT均在静脉用药 2 h内得到控制 ,2 h内静脉胺碘酮用量 3 90～ 5 4 0 ( 4 68.4± 5 4 .7) m g;2 4 h内静脉平均用量 10 0 0～ 180 0 ( 14 10 .3± 3 5 6.5 ) m g,除注射局部均发生不同程度的静脉炎外 ,未见低血压、心功能恶化及致心律失常作用。结论 :短期内经静脉大剂量应用胺碘酮安全有效     

胺碘酮治疗充血性心力衰竭合并室性心律失常疗效观察

目的对胺碘酮治疗充血性心力衰竭合并室性心律失常疗效观察。方法选择此病患者52例,予口服胺碘酮,观察服药前、服药后2周、8周心功能、心律、心率、QTc、QTd等变化。结果治疗2周后总有效率73.33%,阵发性室性心动过速20例被终止,QTd由(66.5±11.16)ms减至(42.68±10.04)ms(P<0.01)。治疗8周后总有效率86.67%,QTd由(66.5±11.16)ms减至(30.82±6.14)ms(P<0.01)。结论胺碘酮是治疗此病有效的药物之一,而且副反应轻,使用安全。     

胺碘酮治疗老年人心律失常几种用药方案的观察分析

目的本文对胺磺酮治疗60岁以上老年人心律失常剂量、血药浓度与疗效、不良反应进行观察分析.方法64例患者分三组.A组39例0.2tid×7d±3d后0.2bid×7d±3d后0.2qd维持;B组11例0 2bid×7d±3d后0.2qd维持;C组14例0.2qd.各组分别于起始负荷剂量减量时测血药浓度,清晨服药前测谷浓度,服药后5.5h测定峰浓度.结果A、B、C三组平均谷浓度分别为612.2±400.0、520.8±426.2、3030.8±216.6(ng/ml);平均峰浓度分别为968.0±897.3、933.3±478.2、804.7±361.6(ng/ml).三组谷浓度和峰浓度均无显著性差异,剂量与浓度无显著相关性.起效时间(天)分别为8.111±5.766、6.900±4.748、17.20±12.28.A、C组和B、C组均有显著性差异.64例患者中13例发生不良反应,不良反应发生率20.31%.结论低负荷量和维持量的胺碘酮治疗老年人心律失常是安全有效的.     

胺碘酮对冠心病无症状心肌缺血伴室性早搏的治疗作用

探讨胺碘酮对冠心病无症状心肌缺血 (SMI)伴室性早搏 (简称室早 )的治疗效果。将 6 1例冠心病伴室早患者随机分为 2组 ,其中 31例口服胺碘酮片作为治疗组 ,30例应用硝酸异山梨酯片作为对照组。结果 :治疗组用药后SMI的发作次数显著降低 (78.7± 7.6vs 2 0 5± 11.0次 ,P <0 .0 1)及其持续总时间显著缩短 (90 .2± 11.4vs 5 0 0 .5± 39.2min ,P <0 .0 1) ,同时室早亦显著减少 (10 5± 2 7vs 90 9± 6 2次 ,P <0 .0 1)。对照组SMI发作次数亦明显降低(135 .1± 10 .8vs 2 0 4.8± 12 .5次 ,P <0 .0 1)及持续时间缩短 (2 11.7± 30 .5vs 499± 40 .3,P <0 .0 1) ,室早减少 (76 9±6 1vs 910± 6 3次 ,P <0 .0 5 )。治疗组与对照组之间比较有显著性差异 (P均 <0 .0 5 )。未见胺碘酮严重副作用。结论 :胺碘酮对冠心病伴室早有显著疗效 ,优于硝酸异山梨酯片。     

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.     

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.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

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.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.