Decreased elimination of theophylline after influenza vaccination.

The elimination of theophylline is decreased after vaccination against influenza. In three patients receiving 200 mg of oxtriphylline (equivalent to 128 mg of theophylline) every 6 hours by mouth the serum theophylline levels rose after vaccination, and in four healthy volunteers given the same dose of oxtriphylline 24 hours after vaccination the half-life of theophylline increased by an average of 122%. Two of the three patients showed signs of a toxic reaction to the drug. These results suggest that the elimination of theophylline is impaired to a clinically important degree after influenza vaccination and that the resulting levels of the drug can be toxic even when conventional therapeutic doses of theophylline are given.     

Serum theophylline concentrations during multiple dosing with two sustained release methylxanthine preparations in normal subjects.

In normal subjects, receiving multiple dosing regimens with Slophyllin and Phyllocontin in does calculated to give either 4 mg/kg or 6mg/kg theophylline free acid twice daily, serum theophylline concentrations were frequently less than 8 mg/l. Accumulation of the serum theophylline trough concentration occurred during the first 3 days of multiple dosing, and was followed by subsequent stabilization or even decline in serum theophylline trough concentrations. Side effects were noted with both Slophyllin and Phyllocontin, but only on the higher dosage regimens; they occurred within 24--48 hr of starting the drug, and tended to diminish if dosing was continued. The accumulation effect of serum theophylline concentrations may explain the timing of adverse effects, and should be avoided by starting methylxanthine therapy at a low dose. This may be increased after a few days. Further dosage adjustment may be necessary in some patients and should be facilitated by measurement of serum theophylline trough concentrations.     

Serum Digoxin by Radioimmunoassay

Using the radioimmunoassay technique for measuring serum digoxin, it was found that patients who were given 0.25 mg. digoxin orally per day had a mean serum level of 0.83 ± 0.06 ng. per ml. In patients given 0.5 mg. daily the mean level was 1.30 ± 0.14 ng. A higher 24-hour urinary excretion of digoxin was associated with the higher serum levels in the latter group. Individuals who exhibited electrocardiographic evidence of digoxin toxicity had a mean serum level of 2.81 ± 0.21 ng. The majority of patients with high serum levels had evidence of impaired renal function, and it is in this clinical situation that knowledge of serum digoxin levels is likely to be most helpful in determining dose schedules.     

Relationship among dosages of aminophylline, plasma levels of theophylline and variation of pulmonary arterial pressure]

The relationship among the dosages of aminophylline, plasma levels of theophylline and variations of mean pulmonary arterial pressure (mPAP) in 72 patients with COPD was investigated. The results showed that after a different loading dosage of aminophylline (6 mg/kg, 5 mg/kg and 4 mg/kg) was administered by intravenous injection, mPAP in the 6 mg/kg group was decreased more significantly (P less than 0.01) than that in the 4 mg/kg group. In the 6 mg/kg group, the decreased mPAP period sustained for 120 min, which was longer than that in the other 2 groups. The plasma levels of theophylline in the 6 mg/kg group of patients 30 to 120 min after loading dose injected were 115.54-79.04 mumol/L, which were higher than that in the others. Within the 120 min period of observation after the drug was administered no patients in any of these groups showed severe untoward effects. According to the results of this experiment, we suggest that the 6 mg/kg as a loading dose should be advised for the treatment of pulmonary hypertension in COPD. The optimum time to give the maintenance dosage should be set within 2 h after the loading dose. It is necessary to monitor the plasma levels of theophylline while aminophylline is administered, so that optimal therapeutic effects could be achieved without side effects.     

Massive theophylline overdose. Rapid elimination by charcoal hemoperfusion.

Shock, seizures, cardiac arrhythmias, and respiratory and cardiac arrests developed in a patient who ingested 8.5 g of theophylline. Her condition improved and her serum theophylline concentration decreased from 170 to 20 mg/ml during six hours of charcoal hemoperfusion. Theophylline was removed from the serum by the uncoated charcoal column, as shown by an extraction efficiency approaching 100%. The maximum charcoal clearance of theophylline was 163 ml/kg/hr. The average endogenous theophylline clearance in adults is 50 ml/kg/hr and that achieved with hemodialysis is only 24.3 ml/kg/hr. Uncoated charcoal efficiently removes theophylline from the serum; charcoal hemoperfusion should be considered in severe theophylline toxic reactions.     

不同剂量瑞舒伐他汀对急性冠脉综合征患者血脂和高敏c反应蛋白水平的影响

目的研究不同剂量的瑞舒伐他汀对急性冠脉综合征患者血脂和高敏C反应蛋白水平的影响。方法将100例急性冠脉综合征患者随机分为高剂量、低剂量两组。高剂量组每天服用瑞舒伐他汀20mg,低剂量组每天服用瑞舒伐他汀10mg,分别对比两组治疗前后的血脂（TG、TC、HDL-C、LDL-C）及hs-CRP的变化及不良反应。结果治疗后,高低剂量组患者TG、TC、LDL-C、hs-CRP均下降,HDL-C水平均升高;两组对比,高剂量组治疗后TG、TC、LDL-C、hs-CRP下降更多,HDL-C水平升高更多。结论一定范围内,高剂量的瑞舒伐他汀对急性冠脉综合征患者血脂和高敏C反应蛋白水平的影响更大,效果更好。     

不同剂量阿托伐他汀对不稳定性心绞痛患者血清高敏C反应蛋白水平变化的影响

目的观察不同剂量阿托伐他汀对不稳定性心绞痛（UA）患者血清高敏C反应蛋白（hs—CRP）水平的影响。方法54例UA患者,随机分为两组：对照组28例,在常规治疗基础上给予阿托伐他汀10mg／d;治疗组26例,在常规治疗基础上给予阿托伐他汀20mg／d;连续用药8用。测定给药前及治疗8周后患者血脂水平及血清hs—CRP水平,比较两组患者血脂、hs—CRP的变化。结果两组治疗后总胆固醇（TC）、甘油三脂（TG）、低密度脂蛋白胆固醇（LDL-c）、hs—CRP均较治疗前下降,两组治疗后血脂水平比较无显著性差异（P〉O．05）,hs-CRP水平比较有显著性差异（P〈0．05）。结论应用不同剂量阿托伐他汀治疗均能够在调脂的同时显著降低UA患者血清hs—CRP水平,且较大剂量用药的作用更显著。使用较大剂量阿托伐他汀治疗UA具有更好的抗炎作用。     

柴胡消瘿汤联合小剂量泼尼松治疗亚急性甲状腺炎30例

目的 观察柴胡消瘿汤联合小剂量泼尼松治疗亚急性甲状腺炎（subacute thyroiditis,SAT）患者的临床疗效以及对甲状腺功能和炎症因子水平的影响。方法 将60例SAT毒热炽盛证患者随机分成对照组与治疗组,每组30例。对照组患者口服泼尼松,每次10 mg,每日3次,服药2周后,每周递减5 mg,待血沉降至正常,热退痛减后再减量至5 mg,每日1次;治疗组患者口服加减柴胡消瘿汤,每日1剂,同时口服泼尼松5 mg,每日2次,服药2周后,改为每日5 mg。两组疗程均为8周。观察并比较两组临床疗效及退热时间、疼痛消退时间、肿胀消退时间,治疗前后分别检测血清游离三碘甲状腺原氨酸（free triiodothyronine,FT3）、游离甲状腺素（free thyroxine,FT4）、促甲状腺激素（thyroid-stimulating hormone,TSH）、C-反应蛋白（C-reactive protein, CRP）、白细胞介素-6（interleukin-6, IL-6）、血沉（erythrocyte sedimentation rate,ESR）水平及不良反应发生率。结果 治疗组临床疗效明显优于对照组（P<0.05）;治疗组退热时间,甲状腺疼痛、肿胀消退时间较对照组明显缩短（P<0.05）;治疗组在降低ESR,血清FT3、FT4、CRP、IL-6水平及升高血清TSH水平方面明显优于对照组（P<0.05）。两组不良反应发生率比较,差异无统计学意义（P＞0.05）。结论 中药联合小剂量泼尼松治疗SAT的临床疗效明显,能有效改善患者甲状腺功能,同时可以下调患者炎症因子水平。     

Studies on serum triglyceride level in patients with myocardial infarction

Myocardial Infarction (MI) is the most common form of heart disease and the single most important cause of premature death in the developed and developing world. Unfortunately the incidence of the condition is increasing rapidly in many developing countries like Bangladesh. Effort should therefore be taken to minimize the risk factors of MI. Large scale randomized clinical trials have shown that lowering high triglyceride concentration mainly by drugs reduces the risk of cardiac events like MI. So the present work has been designed to see the serum triglyceride levels in normal healthy subjects, to compare serum triglyceride levels in patients with MI and those of healthy subjects and to evaluate the association of serum triglyceride in Bangladeshi MI patients. The present study was carried out in the Department of Biochemistry, BSMMU in collaboration with Department of Cardiology, BSMMU and NICVD, Dhaka during the period of July 2001 to December 2002. A total of 50 subjects were selected, Group A (30 subjects of control ) and Group B (20 subjects of test ). The mean level of serum triglyceride in control subjects were 117.07 +/- 32.41 mg/d1 and in test subjects were 176.87 +/- 37.15 mg/d1. So the present study showed that serum triglyceride level is significantly higher in patients with MI. From the present study, it is difficult to draw any definite conclusion but suggested that high serum triglyceride concentration is a cause of the incidence of MI.     

SARS治疗中糖皮质激素应用剂量的探讨

目的 了解糖皮质激素(GCS)在SARS治疗中的应用概况,分析糖皮质激素应用剂量对改善肺氧合功能的影响.方法 回顾性研究2003年SARS病例225例,氧合指数(OD作为糖皮质激素疗效的判别指标,治疗有效的标准是治疗后OI较治疗前上升20%以上.结果 59.56%(134/225)的SARS病例在治疗过程中使用了糖皮质激素;所有病例糖皮质激素(静脉给药)治疗前OI的平均水平为237.08 mmHg,治疗后OI的平均水平为335.08 mmHg,平均升高110.26mmHg,升幅为46.41%;GCS每日体质量用量1～3mg/kg、每日用量160-240mg、累计用量1000～2000mg组的治疗效果最好;GCS应用疗程为8～14 d的治疗效果最好.结论 在SARS治疗中,适当应用糖皮质激素,对减轻患者肺部症状、改善肺功能有一定疗效.比较适宜的静脉给药方法为:每天用量1～3 mg/kg或160～240 mg/d,累计治疗8-14 d,累计用量控制在1500mg左右.

Abstract：

Objective To survey the dose of glucocorticosteroids administered in patients with severe acute respiratory syndrome (SARS) and assess the effect of glucocorticosteroid doses in improving the patients' lung function. Methods A retrospective analysis was conducted among 225 SARS patients treated in our in 2003. Oxygenation index was used as the effectless index, and the criteria for effectiveness was defiend as increase of the value of OI by 20% or above. Results Glococoticostecoids were used in 59.56% of the SARS cases. The average value of OI before intravenous use of glucocorticosteroids was 237.08 mmHg, and that after the administration was 335.08 mmHg. The glucocorticosteroid doses that produce better effects were 1-3 mg/kg and 160-240 mg daily, with the total accumulative dose of 1000-2000 mg. The optimal duration of glucocorticosteroid use was 8-14 days. Conclusions For SARS treatment, Glucocorticosteroids can effectively ameliorate the SARS patients' lung symptoms and improve the lung function. The appropriate daily dose of glucocorticosteroids is 1-3 mg/kg or 160-240 mg/d for a duration of 8-14 d; the accumulative dose should be controlled around 1500 mg.     

氨茶碱对TNF-α诱导下大鼠气道平滑肌细胞中RANTES的影响

目的:观察临床治疗范围内不同浓度的氨茶碱对肿瘤坏死因子-α(TNF-α)诱导下大鼠气道平滑肌细胞(ASMC)中活化正常T细胞表达和分泌的调节物(RANTES)的影响及相应浓度的氨茶碱作用下细胞内环磷酸腺苷(cAMP)的变化,了解趋化因子在哮喘发病机制中的作用,进一步阐明茶碱类药物在治疗哮喘中的抗炎机制。方法:将分离的大鼠ASMC进行传代培养,培养液中加入TNF-α(终浓度为10μg/L)诱导后,再加入不同浓度的氨茶碱,用ELISA方法检测上清液中RANTES的浓度,用放射免疫法检测培养液中cAMP的浓度。结果:经TNF-α诱导后,不加氨茶碱组中大鼠ASMC上清液中RANTES的浓度最高,为(13.799±0.250)×10-9g/L,不同浓度氨茶碱作用后,RANTES的浓度均有所减少,其中5(即氨茶碱终浓度为5 mg/L,下同),7.5,10,12.5,15和17.5 mg/L组RANTES的浓度分别为(13.088±0.252),(12.555±0.100),(10.425±0.502),(7.943±0.500),(5.465±0.500),(4.581±0.25)ng/L。除5 mg/L组和对照组相比无显著性差异(P>0.05)外,其余氨茶碱组与对照组组差异均具有统计学意义(P<0.05)。各氨茶碱组之间相比较,除5 mg/L组和7.5 mg/L组相比无显著性意义(P>0.05)外,其余氨茶碱组两两相比均有统计学意义(P<0.05)。TNF-α诱导下,细胞内cAMP的浓度随着氨茶碱浓度的增加而增高。结论:茶碱类药物可抑制大鼠ASMC中RANTES的产生,并可能呈浓度依赖性,而且这种抑制作用与细胞内cAMP的变化有一定的关系。     

The effect of CS-514 on serum lipids and apolipoproteins in hypercholesterolemic subjects

CS-514 is a metabolic product of compactin and has a potent cholesterol-lowering effect in vitro and in animal studies by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase. The efficacy and adverse effects of the agent were studied in 41 hypercholesterolemic subjects by administering daily doses of 5, 20, or 40 mg for four weeks under double-blind conditions. Mean total serum cholesterol level was reduced by 11.1% in the 5-mg group, 18.8% in the 20-mg group, and 25.3% in the 40-mg group. Marked reduction of total serum cholesterol level was also observed in heterozygous familial hypercholesterolemics. Mean low-density lipoprotein cholesterol level and apolipoprotein B concentration decreased by 38.5% and 28.8%, respectively, in the 40-mg group, while high-density lipoprotein cholesterol level increased by 11.8%. No serious clinical and laboratory abnormalities were observed. Plasma cortisol and testosterone levels were not significantly affected. These results suggest that CS-514 will be a useful agent in the treatment of nonfamilial and heterozygous familial hypercholesterolemia.     

A comparative study of indomethacin and ibuprofen.

In a double blind trial with 20 patients ibuprofen 1600 mg daily and indomethacin 100 mg daily were shown to be of comparable efficacy in the short-term treatment of rheumatoid arthritis. Reported side effects were similar, but a slightly greater incidence of gastric irritation was noted with indomethacin necessitating withdrawal of one patient from the trial. The serum concentrations for indomethacin and ibuprofen were determined for four hours after the last dose. Peak concentrations of both drugs occurred within two hours. Five of the seven patients considered to have comparable serum concentrations of both drugs demonstrated a preference for indomethacin.     

茶碱对慢性哮喘和肺功能改善的作用

目的 了解茶碱在慢性哮喘轻症患者临床症状缓解和气道炎症抑制作用的机制。方法选择41例慢性哮喘的第1级及第2级中的轻症患者,口服缓释茶碱每天4～6mg／kg.b．w．,每12h 1次,连用16周。对照组15例,未服药治疗。对比评估临床症状,检测晨间最大呼气流黄（PEFa）、用力肺活量（FVC）、1秒钟用力呼气容积（FEV1）、1秒钟用力呼气容积降低20％所需药物累积量（PD20）,静脉血T细胞亚群（CD3^＋、CD4^＋,CD8^＋）的变化。结果 经茶碱口服治疗后,临床症状评分、PD20、PEFnm、FEV1,CD3^＋、CD4^＋与对照组比较差异有显著意义。结论 慢性哮喘轻症患者小剂量茶碱口服治疗16周后,哮喘患者临床症状有明显改善,气道高反应性与对照组比较得到改善（P〈0．01）。     

Pharmacokinetic study of single and multiple oral dose administration of antofloxacin hydrochloride in healthy male volunteers

Background  A new fluroquinolone antibacterial agent, antofloxacin hydrochloride, developed in China, is an 8-NH₂ derivant of levofloxacin. The purpose of the study was to evaluate the pharmacokinetic characteristics of single and multiple oral doses of antofloxacin hydrochloride in Chinese healthy male volunteers.

Methods  An open-label, non-randomized, single and multiple dose clinical trial was conducted. In single dose study, 12 subjects took 200 mg antofloxacin hydrochloride. In multiple dose study, 12 subjects took antofloxacin hydrochloride 400 mg once on day 1 and 200 mg once daily from day 2 to day 7. HPLC was used to assay the serum and urinary concentrations of antofloxacin.

Results  In single dose study, the maximum concentration of drug in serum (C_max), the time to reach C_max (T_max), and the area under the serum concentration-time curve (AUC (0-∞)) of antofloxacin were (1.89±0.65) mg/L, (1.29±0.26) hours, and (25.24±7.26) mg∙h^-1∙L^-1, respectively. Accumulating elimination rate of antoflocaxin from urine within 120 hours was 39.1%. In multiple dose study, blood concentration of antofloxiacin achieved stable state on day 2 after dosing. The minimum concentration drug in serum (C_min), AUCss, mean concentration of drug in serum (C_av), and degree of fluctuation (DF) were (0.73±0.18) mg/L, (47.59±7.85) mg∙h^-1∙L^-1, (1.98±0.33) mg/L, and 1.74±0.60, respectively. On day 7 after dosing, T_max, C_max, and AUC (0-∞) was (1.14±0.50) hours, (2.52±0.38) mg/L, and (48.77±8.44) mg∙h^-1∙L^-1, respectively. Accumulating elimination rate of antofloxaxin from urine within 120 hours after the last dosing was 60.06%.

Conclusions  The regimen of 400 mg loading dose given on the first treatment day and then 200 mg dose once daily results in satisfactory serum drug concentration.

     

Single daily doses of saquinavir achieve HIV-inhibitory concentrations when combined with baby-dose ritonavir

Dual protease inhibitor (PI) therapy has been established either in order to increase plasma concentrations of one PI or to combine synergistic effects of two PI's on viral load. Studies with saquinavir (SQV) and small doses of ritonavir (RTV) as well as experiences from our therapeutic drug monitoring suggest that single daily doses may result in sufficient SQV serum levels throughout an interval of 24 h. A controlled, randomized trial with 20 healthy men was conducted for the comparison of serum levels with 1600 mg SQV (group 1) or 1600 mg SQV/200 mg RTV (group 2). The dosages were selected in order to use RTV as an inhibitor of cytochrome P450 3A4 and SQV as protease inhibitor. The volunteers received single daily doses following a standardized breakfast on 3 consecutive days. Serum samples were analyzed for SQV and RTV employing LC-tandem mass spectrometry. The minimum concentration of saquinavir after 24 hours, the AUC, the maximum concentration and the serum half-lives on day 3 served as target parameters. The minimum SQV concentration amounted to 469.4 ng/ml, when combined with RTV and proved to be significantly higher (p <0.05) than the corresponding concentration with SQV alone (127.3 ng/ml). The SQV maximum concentration was raised approximately 6fold and the AUC 9fold when RTV was coadministered. In combination with 200 mg of RTV the predominant elimination half-life of SQV increased from 2.6 to 6.45 hours. These data prove that under single daily doses of 1600 mg SQV/200 mg RTV HIV-inhibitory concentrations of SQV can be achieved for 24 hours. Due to the high variability of the concentrations, which can be seen with all PI s, we recommend continuous therapeutic drug monitoring of serum trough levels.     

Effect of single high dose infusions of aminohydroxypropylidene diphosphonate on hypercalcaemia caused by cancer

Single intravenous infusions of 30 mg aminohydroxypropylidene diphosphonate were given to 16 patients who had malignant hypercalcaemia to assess host tolerance and the effect on serum calcium concentration. Ten of these patients also received intravenous rehydration or corticosteroids, or both. The serum calcium concentrations decreased significantly after treatment with aminohydroxypropylidene diphosphonate. Ten patients became normocalcaemic (normal range, adjusted for serum albumin, 2.25-2.75 mmol/l), two became hypocalcaemic, three showed decreases in serum calcium concentrations of more than 0.75 mmol/l, and one showed a decrease of more than 0.55 mmol/l. Only one patient had a minimum concentration greater than 2.77 mmol/l. Aminohydroxypropylidene diphosphonate was effective in metastatic and non-metastatic hypercalcaemia, and its hypocalcaemic effect was prolonged in some cases. There were no appreciable side effects. Single high dose infusions of aminohydroxypropylidene diphosphonate could replace conventional daily lower dose infusions, but the optimum frequency of high dose infusions remains to be determined.     

荷S-180移植瘤小鼠血清干扰素γ含量的变化及免疫调节药物的干预作用

目的 研究荷S-180肉瘤小鼠血清干扰素γ(IFN-γ)含量的变化,并采用具有调节免疫功能的药物进行干预,探讨内源性IFN-γ在抗小鼠移植瘤方面的意义.方法 建立荷S-180实体瘤小鼠动物模型,分别用灵芝多糖(GLP)、环孢素A(CsA)灌胃给药,每天1次,连续9 d,用ELISA试剂盒检测小鼠血清中IFN-γ的含量,并分离肿瘤称重.结果 首次发现荷S-180实体瘤小鼠血清中IFN-γ含量在所观察的接种后20 d内随荷瘤时间的延长而升高.GLP(400、200、100 mg/kg)使荷瘤小鼠血清中的IFN-γ含量增加、肿瘤重量减轻,但增加IFN-γ含量以高剂量最为明显,抑瘤效应以中剂量最佳,两者之间相关关系无统计学意义.CsA(20、10、5 mg/kg)可降低荷瘤小鼠血清中IFN-γ的含量,但对肿瘤重量无明显影响,两者之间无相关关系.结论 灵芝多糖增加荷瘤小鼠血清中IFN-γ含量与抑瘤效应无明显相关,环孢素A降低荷瘤小鼠血清中IFN-γ的含量对肿瘤重量无明显影响,提示内源性IFN-γ在抗小鼠S-180移植瘤方面并不是主要的免疫调节因素.     

Clinical study of ticrynafen. A new diuretic, antihypertensive, and uricosuric agent.

In a double-blind study, 20 hypertensive patients were randomly assigned to a six-week regimen of either ticrynafen or hydrochlorothiazide. Blood pressure was significantly reduced with both medications, although most patients required an increase in dosage from 250 to 500 mg ticrynafen daily. Whereas the serum uric acid level rose moderately in the hydrochlorothiazide-treated patients, it fell strikingly to less than half of the pretreatment level in patients treated with ticryafen. Body weight decreased slightly in both groups, as did serum potassium levels. Blood urea nitrogen and serum creatinine levels rose slightly in both groups. The magnitude of these changes was not significantly different between the two groups. Use of ticryafen was well tolerated. Ticryafen appears to be a useful new antihypertensive agent because of its unique combination of diuretic, antihypertensive, and hypouricemic effects.     

拉米夫定治疗慢性乙型肝炎31例临床疗效观察

目的研究拉米夫定对血清乙型肝炎病毒-脱氧核糖核酸(HBV-DNA)阳性的慢性乙型肝炎病毒感染患者的疗效和安全性.方法61例患者随机分成拉米夫定治疗组(31例)和对照组(30例).治疗组每日口服拉米夫定100mg,疗程1年,对照组采用一般保肝、退黄、降酶治疗.结果治疗组累计75%患者血清HBV-DNA阴转,最终持续阴转率70%.对照组HBV-DNA累计阴转率33.3%,最终阴转率为23.8%,两组疗效比较P＜0.05.治疗前丙氨酸转氨酶(ALT)增高的患者,52周时治疗组的复常率83.8%,对照组为25.8%,P＜0.05,治疗组累计53.8%患者血清HBeAg阴转,最终持续阴转率53.8%.对照组HBeAg累计阴转率13.3%,最终阴转率为6.0%,两组疗效比较P＜0.05.两组不良反应发生率比较,差别无显著性P＞0.05.结论拉米夫定能明显降低血清HBV-DNA水平,促使ALT恢复正常,不良反应轻,耐受性好.