909例结核病患者一线抗结核药物血药浓度监测结果分析

目的 分析结核病患者一线抗结核药物血药浓度监测情况。方法 选取2010年1月至2016年11月于首都医科大学附属北京胸科医院住院并进行一线抗结核药物血药浓度测定者作为研究对象,共909例;其中,服用INH者909例,服用EMB者783例,服用PZA者587例,服用RFP者503例。患者服药剂量:INH 300mg/d、RFP 450mg/d或600mg/d、PZA 1500mg/d、EMB 750mg/d。收集研究对象性别、年龄、并发糖尿病情况,以及血药浓度监测结果,并进行分析。结果 服用INH、EMB、PZA和RFP(450mg/d和600mg/d)2h后,患者血药浓度低于目标浓度范围者分别占57.3%(521/909)、82.2%(644/783)、29.8%(175/587)、51.6%(190/368)和36.3%(49/135)。其中,男性患者中INH、EMB、PZA、RFP(450mg/d)出现低血药浓度者分别占67.2%(396/589)、85.9%(451/525)、39.9%(153/383)、60.0%(135/225),均高于女性患者[39.1%(125/320)、74.8%(193/258)、10.8%(22/204)、38.5%(55/143)],差异均有统计学意义(χ ²值分别为67.26、14.59、54.10、16.24,P值均<0.01)。体质量≥50kg的患者,INH、EMB、PZA、RFP(450mg/d)出现低血药浓度者分别占61.7%(428/694)、83.3%(513/616)、35.3%(159/451)、55.6%(154/277),均高于体质量<50kg者[30.3%(40/132)、72.4%(76/105)、4.7%(4/86)、37.1%(23/62)],差异均有统计学意义(χ ²值分别为44.44、7.12、32.00、6.95,P值均<0.05)。结核病并发糖尿病患者,INH和PZA出现低血药浓度者分别占72.6%(143/197)和53.8%(71/132),高于未并发糖尿病者[53.1%(378/712)和22.9%(104/455)],差异均有统计学意义(χ ²值分别为23.98和46.78,P值均<0.01)。 结论 结核病患者服用一线抗结核药物后出现低血药浓度情况较为普遍,患者性别、体质量、并发症等因素均会影响其血药浓度水平;提示开展一线抗结核药物血药浓度监测工作,并根据患者个体情况调整治疗方案对结核病治疗是必要的。     

结核分枝杆菌能量代谢对吡嗪酰胺抗结核作用的影响

目的研究结核分枝杆菌能量代谢对吡嗪酰胺抗结核作用的机制和作用靶点。方法将饥饿3、5和10d的结核分枝杆菌及未经过营养饥饿的结核分枝杆菌分别加入100μg／ml吡嗪酰胺和脂肪酸、苯甲酸和水杨酸进行处理，观察营养饥饿处理过程对于吡嗪酰胺抗结核分枝杆菌作用的影响，以及酸性物质对吡嗪酰胺抗菌活性的影响。同时用流式细胞仪检测结核分枝杆菌膜电位和平均荧光强度，以探讨吡嗪酰胺的作用机制。结果未经过营养饥饿的结核分枝杆菌和饥饿3、5和10d的结核分枝杆菌经吡嗪酰胺处理后，菌落形成单位（CFU）分别减少23．08％、37．75％、82．32％和81．03％；营养饥饿5d后，结核分枝杆菌的膜电位明显降低，经吡嗪酰胺处理后的膜电位则大幅降低，加入能量物质葡萄糖后，因吡嗪酰胺作用而降低的膜电位可得到恢复。脂肪酸、苯甲酸和水杨酸对于正常生长的和营养饥饿后的结核分枝杆菌均有促进吡嗪酰胺抗菌效果的作用，对营养饥饿后的结核分枝杆菌作用更明显。结论饥饿状态和弱酸能增强吡嗪酰胺对结核分枝杆菌的抗菌作用，吡嗪酰胺可能是通过于扰结核分枝杆菌的膜电位及其能量代谢而产生作用。     

吡嗪酰胺致过敏反应1例

患者，男，66岁，因咳嗽、咯痰40d，伴咯血2d。于2004年4月8日来我所就诊。查体：T36．8℃，P86次／min，R19次／min，Bp102／64mmHg(1mmHg=0．133Pa)，胸廓对称，两肺未闻及干湿性啰音，心率84次／min，律齐，各瓣膜区未闻及病理性杂音。X线胸片示两上中肺野见片絮状条索状模糊阴影；     

口服吡嗪酰胺血,脑脊液浓度测定结果

本文比较了吡嗪酰胺(PZA)顿服及分服,血、脑脊液药物高峰浓度。结果:5例健康人和10例肺结核病人顿服后,血高峰浓度分别为43.46mg/L和43.14mg/L;分服为24.89mg/L和23.28mg/L。10例结脑病人脑脊液顿服及分服高峰浓度为42.94mg/L和23.57mg)L。顿服组药物高峰浓度超过PZA对大多数菌株的MIC水平(30mg/L),而分服均未达到。认为PZA应以顿服为宜。     

结核分枝杆菌吡嗪酰胺耐药相关基因研究进展

吡嗪酰胺是治疗结核病的重要抗结核药物之一,特别是用于耐多药结核病的治疗。近年来结核分枝杆菌对吡嗪酰胺的耐药逐渐增多,其耐药机制尚未明确。本文针对结核分枝杆菌吡嗪酰胺耐药及其与基因变异之间的关系研究进展进行综述,以供研究者参考。     

三种方法检测结核分枝杆菌吡嗪酰胺耐药性的比较

目的 探讨绝对浓度法、液体培养基最低抑菌浓度（MIC）法和噬菌体生物扩增（PhaB）法检测结核分枝杆菌（MTB）吡嗪酰胺（PZA）耐药性的临床应用价值。方法 应用3种方法同时检测90株MTB临床分离株PZA耐药性，并比较检测结果的敏感度、特异度、阳性和阴性预测值及准确度。结果 90株MTB临床分离株用绝对浓度法、液体培养基MIC法和PhaB法3种方法分别测得21株、33株、22株敏感株和69株、57株、68株耐药株。若以绝对浓度法测定结果为判断标准，则PhaB法检测PZA耐药性的敏感度、特异度、阳性和阴性预测值及准确度分别为94．2％、85，7％、95．6％、81．8％、92．2％；若以液体培养基MIC法测定结果为判断标准，则PhaB法检测的敏感度、特异度、阳性和阴性预测值及准确度分别为98．2％、63．6％、82．4％、95．5％、85．6％；若以绝对浓度法和液体培养基MIC法测定结果为判断标准，则PhaB法检测的敏感度、特异度、阳性和阴性预测值及准确度分别为96．4％、90．0％、96．4％、90．0％、94．7％。结论 绝对浓度法尽管是目前国内常用的方法，但影响因素较多；液体培养基MIC法测定虽能提早报告药物敏感结果，但检测条件尚需优化；PhaB法检测快速、简便、安全，有一定的应用价值。     

结核分支杆菌吡嗪酰胺酶活性与敏感性比较试验

本文用Wayne方法测定186株临床分离结核杆菌PZA酶(PZase)的活性和用蛋黄琼脂培养基测定PZA敏感性。结果:PZase阳性符合率93.3％阴性符合100％。测定PZase活性代替PZA敏感性试验是一种快速,简单,可靠的方法。     

Follow-up of compliance with tuberculosis treatment in children: monitoring by urine tests

This study was designed to follow up patient compliance by detection of antituberculous drugs in urine during the course of treatment. It was conducted in the Outpatient Clinic of Pediatric Infectious Diseases, Sisli Etfal Hospital (Istanbul, Turkey). In total, 45 children with pulmonary tuberculosis participated. Patients were seen twice in the first month and once a month thereafter during the 6-month course of treatment. The second urine of the day was collected at each visit. Urine was tested for isoniazid (INH), rifampicin (RIF), and pyrazinamide (PZA). In the presence of these drugs or their metabolites, the addition of certain chemicals caused a color change in the urine. On day 15 of treatment, urine tested positive for INH in 82% of patients, for RIF in 67%, and for PZA in 73%. At the end of the second month, the ratio of adherence was 96, 89, and 96% for each drug, respectively. All patients were found to be adherent at months 5 and 6. We recommend detection of antituberculous drugs in urine to assess compliance to treatment. Once the defaulting patients were identified, adherence was improved by repeatedly providing patient education throughout the treatment.     

Negative association between plasma aldosterone concentration/plasma renin activity and morning blood pressure surge in never-treated hypertensive patients

Morning blood pressure (BP) surge (MS) has been known to be a predictor of cardiovascular events. Currently, few studies have evaluated the underlying mechanism underlying MS, which may include neurohormonal factors and the renin–angiotensin–aldosterone system (RAAS). This study aimed to examine plasma aldosterone concentration (PAC) and plasma renin activity (PRA) and BP parameters with or without MS in never-treated subjects with essential hypertension. This cross-sectional study included a total of 261 patients (mean age: 48.8 years; 60.5% male) with never-treated essential hypertension who were registered in a working group at The Catholic University of Korea. The patients were divided into the MS group, which was defined as having the highest quartile of morning BP increase from sleep (>31?mmHg; n?=?66) and the non-MS group (≤31?mmHg; n?=?195). We collected 24-h ambulatory BP, pulse wave velocity, ankle brachial index, PAC and PRA from all patients. The measured PAC and PRA were lower in the MS group than in the non-MS group (PAC: 9.0?±?5.4?ng/dl versus 12.2?±?8.7?ng/dl, p?p?=?0.002). The MS group had greater variations in daytime, nighttime and 24-h systolic blood pressure (SBPs) than the non-MS group (24-h SBP: 15.6?±?4.4?mm Hg for the non-MS group and 18.9?±?4.9?mmHg for the MS group; p?相似文献   

The relationship between active renin concentration and plasma renin activity in Type 1 diabetes.

AIMS: Circulating activity of the renin-angiotensin-aldosterone system (RAAS) can be assessed by measuring plasma active renin concentration (ARE), as well as by measuring plasma renin activity (PRA). We aimed to assess the relationships between ARE and PRA in Type 1 diabetic compared with non-diabetic control subjects. We also assessed concentrations of the active renin precursor, prorenin. PATIENTS AND METHODS: Thirty-five Type 1 diabetic subjects and 34 non-diabetic control subjects were assessed. Groups had similar ages, sex distributions, body mass indices, systolic and diastolic blood pressures. PRA was measured by radioimmunoassay of angiotensin I generation from endogenous substrate. ARE and total renin concentration (TRE) were measured by immunoradiometric assay (Nichols Institute Diagnostics, USA). Prorenin concentration was calculated as the difference between ARE and TRE. RESULTS: PRA was significantly lower in Type 1 diabetic than in control subjects (0.8 (0.4-1.1) vs. 1.1 (0.9-1.9) pmol/ml per h; P < 0.005), while ARE was similar (17 (9-33) vs. 18 (15-25) mU/l; P = 0.548). PRA (loge transformed) correlated strongly with ARE in diabetic (r = 0.49; P = 0.003) and control subjects (r = 0.59; P = 0.0002), but there was significant vertical separation of the regression lines for the two groups (P < 0.0001). Prorenin concentrations were significantly higher in Type 1 diabetic subjects (249 (170-339) vs. 171 (153-219) mU/l; P = 0.005). Diabetic subjects with high prorenin concentrations (> 400 mU/l (control mean + 3 SD)) were more likely to have microalbuminuria (P = 0.027) and peripheral neuropathy (P = 0.049). CONCLUSIONS: Type 1 diabetes is associated with an altered relationship between ARE and PRA, such that ARE is higher for a given PRA compared with non-diabetic control subjects. Both ARE and PRA are used to assess circulating RAAS activity. The altered relationship between the two in Type 1 diabetic subjects suggests that neither parameter alone is necessarily an adequate and reliable index of such activity. Higher prorenin concentrations, particularly in association with microvascular complications, were confirmed in the Type 1 diabetic subjects. Diabet. Med. 18, 451-458 (2001)     

136例结核病患者一线抗结核药物耐药监测结果分析

目的分析我院结核病患者对一线抗结核药物的耐药监测结果,为我市结核病控制及用药提供参考。方法回顾性分析我院2012年1月~2014年12月期间门诊及住院肺结核患者结核分枝杆菌培养阳性440例的临床资料。结果 136例患者对一线抗结核药物耐药,总耐药率为30.9%,初始耐药率为20.3%,获得性耐药率为52.8%,对四种一线抗结核药物的耐药率由高到低依次为:SMINHRFPEMB。初治组耐药率依次为SMINHRFPEMB,复治组耐药率依次为INHSMRFPEMB。结论我院肺结核患者一线抗结核药物的耐药性较高,复治组患者耐药比例明显高于初治组患者,在临床工作中应规范结核病的治疗,制定合理的抗结核治疗方案,减少耐药发生。     

16县(区)结核病患者HIV感染现状监测结果与分析

目的为了解安徽省结核病人HIV感染状况,为TB/HIV防治对策提供科学依据。方法选择安徽省7个第三轮全球基金艾滋病项目县和在剩下79个县区中随机抽取9个县区,对16个县区结防门诊2007年9月1日—12月31日所有新登记的结核病人,进行HIV抗体检测和结核病相关信息调查。结果检测2 738例结核病中HIV(+)8例,阳性率0.3%,男性7例,女性1例。通过异性传播感染3例,有偿采血5例。结论结核病患者是HIV感染重点人群,进行HIV抗体检测,有助于早期发现HIV/AIDS;在艾滋病流行相对高的地区,实施结核病患者HIV检测,符合成本效益原则。     

The lowest effective plasma concentration of atomoxetine in pediatric patients with attention deficit/hyperactivity disorder: A non-randomized prospective interventional study

Background:Atomoxetine (ATX) is used as a first-line, non-stimulant treatment for attention-deficit/hyperactivity disorder (ADHD), although no studies have systematically examined the relationship between plasma concentration and clinical efficacy. We conducted this non-randomized prospective interventional study to examine the relationship between plasma concentration of ATX and clinical efficacy.Methods:Forty-three ADHD pediatric patients received ATX, and the steady-state through plasma concentration of the last daily dose that was maintained for at least 4 weeks were determined by high-performance liquid chromatography.Results:The receiver operating characteristic curve suggested that when plasma concentration exceeded 64.60 ng/mL, scores on the ADHD-Rating Scale improved by 50% or more (P = .14). Although 6 of the 8 final responders were unresponsive at the initial dose (.72 ± .04 mg/kg [mean ± standard deviation]), they responded after increasing the ATX dose to the final dose (1.52 ± .31 mg/kg). Excluding 7 outlier participants, the concentration was 83.3 ± 32.3 ng/mL in 7 responders and was significantly higher than 29.5 ± 23.9 ng/mL (P < .01) for the 29 non-responders.Conclusions:These results suggest that a minimum effective plasma concentration of ATX is required to achieve sufficient clinical efficacy. We hypothesized a mechanism that results in the realization of a clinical effect when the plasma concentration exceeds a certain threshold in the potential response group, whereas will not improve even if the plasma concentration is increased in the unqualified non-responder group.     

Serum to urinary sodium concentration ratio is an estimate of plasma renin activity in congestive heart failure

We investigated the relationship between plasma renin activity (PRA) and serum ([sNa(+)]) and urinary ([uNa(+)]) sodium concentrations in 124 congestive heart failure (CHF) patients (II-IV NYHA class) and 20 healthy subjects. According to PRA (> or <3 ng ml(-1) h(-1)) and [sNa(+)] (> or <135 mEq l(-1)), patients were classified as Group A (normal PRA and normal [sNa(+)], n=39), Group B (increased PRA and normal [sNa(+)], n=62) and Group C (low [sNa(+)], n=23). Measurements were performed at rest and, in 26 cases, after extracorporeal ultrafiltration (UF). At rest, [sNa(+)] and [uNa(+)], and their difference ([sNa(+)]-[uNa(+)]), were linearly correlated with PRA, but the values did not allow differentiation of control subjects from patients or differentiation of patients with from those without renin-angiotensin system (RAS) activation. Conversely, the [sNa(+)]/[uNa(+)] ratio showed the best correlation with PRA (r=0.79, P<0.0001). UF-induced PRA changes were linearly correlated with [sNa(+)]/[uNa(+)] ratio changes (r=0.67, P=0.002), but not with those of [sNa(+)], [uNa(+)] and [sNa(+)]-[uNa(+)]. In CHF, the [sNa(+)]/[uNa(+)] ratio best correlates with PRA and reflects the basal activity as well as the rapid changes (as those induced by UF) of the RAS. Therefore, it can be considered a strong and easily available marker of PRA.     

结核病合并慢性肝病患者异烟肼血药浓度监测研究

目的 了解异烟肼在结核病合并慢性肝病患者中的药代动力学特点.方法 将60例结核病患者按是否合并慢性肝病分为观察组和对照组,每组30例.给予抗结核治疗过程中,分别于服药前、服药后1、2、4、6、8及12h检测异烟肼血药浓度,比较两组患者异烟肼代谢的特点.结果 服药后各个时间点,观察组的异烟肼血药浓度均大于对照组(P ＜0.05或P＜0.01).观察组的达峰时间较对照组快,平均峰浓度和平均有效浓度维持时间均高于对照组(P ＜0.05或P＜0.01).结论 在结核病合并慢性肝病患者治疗过程中,进行抗结核药物的血药浓度监测对制定个体化治疗方案有重要意义.