Evaluation of the efficacy of flecainide acetate in the treatment of ventricular premature contractions

The efficacy of flecainide acetate in suppressing ventricular premature contractions in 14 patients was evaluated in a double-blind, cross-over, placebo controlled, randomized and balanced study. Each treatment period was 2 weeks followed by a 3-4 d placebo washout period and the study lasted 5 weeks. Flecainide was given in a dose of 200 mg twice daily. A significant reduction in the total number of QRS complexes in a 24 h period was observed during the active compared with placebo treatment (P less than 0.05). In comparison with placebo, flecainide reduced the number of aberrant and premature aberrant QRS complexes (P less than 0.01). The mean suppression rate of aberrant QRS complexes during flecainide treatment was 85.4% and that of premature aberrant complexes was 93.2%. Maximum heart rate measured by 24 h ECG decreased significantly during flecainide therapy (P less than 0.01), although no change occurred with resting heart rate measured clinically or by ECG. Severe dizziness associated with flecainide therapy necessitated withdrawal of 2 patients from the study. A proarrhythmic effect of flecainide, ventricular tachycardia, was observed in one patient.     

Prolongation of the QT interval by ketanserin

In hypertensive patients single doses of ketanserin 40 mg prolonged the corrected QT interval (QTc) for at least 8 hours, with a maximal increase of 35 ms (P less than 0.001, n = 6) after 2 hours. During chronic dosing (20 and 40 mg b.d.) the QTc was further prolonged, by 46 and 45 ms respectively. QTc prolongation after treatment with a mean dose of 73 mg/day for 7 weeks (n = 26) was significantly related to body weight (r = -0.58, P less than 0.01), and to the dose of ketanserin corrected for body weight (r = 0.63, P less than 0.01), but not to plasma concentrations of ketanserin, ketanserinol, potassium or calcium. High doses of ketanserin (mean dose 167 mg/day, n = 9) increased the QTc by 40 ms (P less than 0.001), with prolongation of up to 80 ms in individual patients. Treatment with ketanserin at doses proposed for clinical use (40-80 mg/day) may carry a risk of ventricular arrhythmias.     

Effect of an oral serotonin antagonist, ketanserin, on plasma ACTH concentrations in Nelson's syndrome

A study was performed to see whether ketanserin, a serotonin antagonist, would reduce the raised concentrations of adrenocorticotrophic hormone (ACTH) in patients with Nelson's syndrome. Six patients who had undergone bilateral adrenalectomy for Cushing's disease and who had Nelson's syndrome were given ketanserin 40 mg twice daily and placebo, for at least two months each, in a double blind crossover study. Ketanserin had no effect on ACTH concentrations. In healthy people serotonin seems to have a stimulatory role in the regulation of ACTH secretion, and the effect of ketanserin in reducing the ACTH response to hypoglycaemia suggested that it might prove useful in Nelson's syndrome. These results show that it is not indicated in these patients.     

Biochemical effects of urapidil on red cell membrane ion transport systems in a population of elderly essential hypertensives

The aim of our work was to verify the effect of urapidil on membrane ion transport systems. This was a randomized, double-blind, cross-over study which evaluated the clinical and biochemical effects of urapidil (30 mg twice daily in comparison with placebo) in a group of 10 elderly hypertensive patients (3 male, 7 female ranging from 68 to 90 years, mean age 79.2 +/- 7.6 years). For the evaluation in fresh erythrocytes of principal ion transport systems (cotransport Na+/K+, countertransport Na+/Li+, Na+/K+ ATPase pump. intracellular Na+ and K+) we used the nystatin technique. We found that urapidil activated the red cell membrane ions cotransport system (basal values: 83.7 +/- 50.3 mumol Na+ RBC 1-1.h-1, after 1 month of urapidil therapy: 181.5 +/- 89.3 mumol Na+ RBC 1-1.h-1) (P less than 0.01), without significant changes in the other biochemical parameters evaluated. Our data suggest that one of the mechanisms of the urapidil antihypertensive effect could involve an increase in the membrane sodium cotransport system.     

Comparison of nifedipine (retard formulation) and mefruside in the treatment of mild to moderate hypertension--a prospective randomized double-blind crossover study in general practice

Twenty-two patients under general practice care, suffering mild to moderate hypertension and receiving no active treatment had three baseline blood pressure measurements taken during a single blind 4-week placebo run-in period. One patient was secondarily excluded at this stage because of a placebo response and one patient dropped out for personal reasons. The remaining 20 patients were randomized to receive either nifedipine 20 mg twice a day or mefruside 25 mg once a day in a classical two-period crossover design with 8-week treatment periods separated by a 4-week single-blind placebo washout. During 8 weeks nifedipine therapy the mean supine blood pressure was reduced from 173 (s.d. = 15.4)/107(s.d. = 6.4) mmHg to 150(s.d. = 16.7)/93(s.d. = 10.8) mmHg whereas the corresponding reduction for mefruside was from 174(s.d. = 15.9)/107(s.d. = 9.4) mmHg to 153(s.d. = 19.1)/94(s.d. = 9.7) mmHg. Neither drug affected postural changes in blood pressure. Standing blood pressure measurements under 8 weeks nifedipine therapy fell from 172(s.d. = 12.3)/103(s.d. = 5.6) mmHg to 150(s.d. = 17.9)/94(s.d. = 10.0) mmHg with corresponding changes for mefruside being 174(s.d. = 14.7)/106(s.d. = 9.0) mmHg to 150(s.d. = 20.2)/95(s.d. = 9.4) mmHg. Since blood pressures returned to within 4% of baseline values by the end of the placebo washout period it can be inferred that each therapy was a significant (P less than 0.05 for all blood pressure variables) antihypertensive treatment in its own right.     

Mechanism of antihypertensive action of ketanserin in man

A randomised double blind crossover study was carried out to determine whether ketanserin, a serotonin antagonist with an antihypertensive action in animals, has an alpha 1 adrenergic mediated antihypertensive effect in man. Steady state plasma ketanserin concentrations (mean 88 (SD 19) micrograms/1) and cardiovascular responses measured in five healthy volunteers showed that therapeutic doses of ketanserin significantly antagonised the alpha 1 receptor mediated increase in arterial blood pressure after treatment with methoxamine. Thus the antihypertensive action of ketanserin in man appears to originate from a blockade of peripheral vascular alpha 1 receptors.     

Efficacy of atenolol and oxprenolol in the treatment of arterial hypertension. A comparison.

Twenty-seven patients with mild to moderate arterial hypertension were treated "double-blind" with either atenolol of oxprenolol. Placebo was given for four weeks before the beta-blocking drugs were administered. Atenolol was given in doses of either 50 mg twice a day, 100 mg twice a day or 100 mg once a day for periods of four weeks. Oxprenolol was given in doses of either 80 mg or 160 mg twice a day for the same duration. Patients were assessed at the end of each four-week period. The mean blood pressure and pulse rate did not vary significantly for the two different dose regimens at which each drug was administered. There was no statistical difference between the reduction of systolic blood pressure produced by the two drugs, but there was a significant difference in the reduction in diastolic blood pressure in favour of atenolol (P less than 0.05 supine; P less than 0.01 erect). A single, 100-mg daily dose of atenolol was just as effective as 50 mg or 100 mg twice a day. Similarly, an 80 mg twice a day dose of oxprenolol was just as effective as that of 160 mg twice a day. Side effects for each drug were not statistically different from those recorded with placebo.     

The association between haemospermia and severe hypertension

The association between haemospermia and hypertension was examined in a case-control study comparing 5 hypertensive patients with haemospermia to 20 age-matched hypertensive men. Patients with haemospermia had much higher blood pressures than hypertensive controls (200/131 mmHg vs 147/90 mmHg; P less than 0.0005/P less than 0.0001), higher left ventricular voltage on ECG (P less than 0.02), and higher concentrations of serum creatinine, proteinuria and renovascular disease (all P = 0.06 vs controls). Haemospermia is associated with severe uncontrolled hypertension. It is not, however, associated with hypertension per se, as the prevalence of hypertension in published series of patients with haemospermia is no higher than that expected in the general population. Men presenting with haemospermia should have their blood pressure measured carefully as they may require antihypertensive treatment urgently.     

The effect of caffeine on postprandial blood pressure in the frail elderly

In a double-blind, random-order, cross-over study the effects of placebo and 100 mg of caffeine on postprandial sitting and erect blood pressure and heart rate were studied in 20 frail elderly subjects (mean age 84, range 75-93 years) after a standardized 400 K-calorie glucose drink. Maximal postprandial reduction in sitting systolic blood pressure occurred, at 60 minutes post-placebo, of - 11 mmHg (95% confidence interval -5 to -17 mmHg, P less than 0.01), and was attenuated by caffeine (P less than 0.05) with changes in systolic blood pressure, at 60 minutes post-drink, of 1 mmHg (95% CI -6 to 7 mmHg, not significant). Four subjects developed symptomatic postprandial hypotension after placebo which was prevented by caffeine. There were no significant changes in erect systolic blood pressure, postural systolic blood pressure change, sitting and erect, diastolic blood pressure and heart rate between treatment phases. Caffeine attenuates the postprandial fall in sitting blood pressure in frail elderly subjects and in particular prevented symptomatic blood pressure reductions in subjects with postprandial hypotension.     

槐白皮对高血压大鼠的降压作用研究

目的研究槐白皮（水提取物）对高血压大鼠血压的影响。方法选取Wistar大鼠一批（雌雄各半）,测正常血压。用N-硝基-L-精氨酸甲酯（L-NAME）灌胃给药,0.6mg/100g.d,早晚各1次,复制高血压模型,选取血压值≥140/90mmHg的大鼠进行实验,75%槐白皮灌胃,0.15ml/100g,待30min后测量血压值,观察降压效果。结果给槐白皮前高血压大鼠的平均血压值154/122mmHg,给槐白皮后平均血压值132/105mmHg,数据经统计学处理具有非常显著的差异（P〈0.01）。结论槐白皮对高血压大鼠具有显著的降压作用。     

大鼠红细胞抗高血压因子的降压作用

本实验表明,从自发性高血压大鼠(SHR)红细胞提取的抗高血压因子(antihyper-tensive factor,AHF)可明显而持久地降低SHR和肾性高血压大鼠(RHR)的血压,而对正常大鼠血压无影响,表明AHF的降压作用与动物原来的血压水平密切相关,即具有血压依赖性;AHF耐热,在沸水中处理15min仍保持其强烈的降压效果,提示其不可能是体内已知的一些舒血管物质。目前,作者正在对AHF的理化特性和降压机理进行更深入的研究。     

Efficacy of enalapril in essential hypertension and its comparison with atenolol

The effect of enalapril was evaluated in 67 patients with essential hypertension, and its therapeutic efficacy was compared with atenolol in a placebo run-in, single-blind, cross-over trial. Enalapril significantly reduced blood pressure in all grades of essential hypertension. As monotherapy it 'normalized' blood pressure in 88%, 50% and 25% of patients with mild, moderate and severe hypertension respectively. Optimal dose for most of the patients was 20 to 40 mg/day. Comparison with atenolol revealed almost parallel efficacy of the two drugs, although enalapril produced a significantly greater reduction in systolic blood pressure in patients with mild and moderate hypertension (P less than 0.01 in each group). No serious side effects were encountered with either drug. Enalapril, therefore, has a potent and slightly superior antihypertensive effect to that of atenolol, and may be used as a 'first-step' drug in the treatment of hypertensive patients.     

Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza: a randomized controlled trial. US Oral Neuraminidase Study Group

CONTEXT: Previous studies have shown oseltamivir, a neuraminidase inhibitor, to be effective in preventing influenza and treating experimental influenza. OBJECTIVE: To evaluate the efficacy and safety of oseltamivir in the treatment of naturally acquired influenza infection. DESIGN: Randomized, placebo-controlled, double-blind study conducted January through March 1998. SETTING: Sixty primary care and university health centers throughout the United States. PARTICIPANTS: A total of 629 healthy nonimmunized adults aged 18 to 65 years with febrile respiratory illness of no more than 36 hours' duration with temperature of 38 degrees C or more plus at least 1 respiratory symptom and 1 constitutional symptom. INTERVENTIONS: Individuals were randomized to 1 of 3 treatment groups with identical appearing pills: oral oseltamivir phosphate, 75 mg twice daily (n = 211) or 150 mg (n = 209) twice daily, or placebo (n = 209). MAIN OUTCOME MEASURES: Duration and severity of illness in individuals infected with influenza. RESULTS: Two individuals withdrew before receiving medication and were excluded from further analyses. A total of 374 individuals (59.6%) were infected with influenza. Their duration of illness was reduced by more than 30% with both oseltamivir, 75 mg twice daily (median, 71.5 hours; P < .001), and oseltamivir, 150 mg twice daily (median, 69.9 hours; P = .006), compared with placebo (median, 103.3 hours). Severity of illness was reduced by 38% (median score, 597 score-hours; P < .001) with oseltamivir, 75 mg twice daily, and by 35% (median score, 626 score-hours; P < .001) with oseltamivir, 150 mg twice daily, vs placebo (median score, 963 score-hours). Oseltamivir treatment reduced the duration of fever and oseltamivir recipients returned to usual activities 2 to 3 days earlier than placebo recipients (P < or = .05). Secondary complications such as bronchitis and sinusitis occurred in 15% of placebo recipients compared with 7% of combined oseltamivir recipients (P = .03). Among all 629 subjects, oseltamivir reduced illness duration (76.3 hours and 74.3 hours for 75 mg and 150 mg, respectively, vs 97.0 hours for placebo; P = .004 for both comparisons) and illness severity (686 score-hours and 629 score-hours for 75 mg and 150 mg, respectively, vs 887 score-hours for placebo; P < .001 for both comparisons). Nausea and vomiting occurred more frequently in both oseltamivir groups (combined, 18.0% and 14.1%, respectively; P = .002) than in the placebo group (7.4% and 3.4%; P < .001). CONCLUSIONS: Our data suggest that oral oseltamivir treatment reduces the duration and severity of acute influenza in healthy adults and may decrease the incidence of secondary complications.     

Prevention of recurrent acute cystitis by methenamine hippurate: double blind controlled crossover long term study

In a randomised, double blind, long term, crossover study 1 g twice daily of methenamine hippurate was compared with placebo for its preventive effect on recurrent attacks of acute cystitis. Methenamine hippurate and placebo were interchanged every six months for two years. During one of the years patients took 250 ml extra fluid every morning and evening. Out of 21 enrolled patients, 14 completed the first year and 13 both years of treatment, which permitted the evaluation of 27 patient years. There were 52 episodes of acute cystitis caused by reinfection: 41 occurred during placebo treatment and only 11 during the methenamine hippurate regimen (p less than 0.01). Extra fluid intake did not reduce the incidence of acute cystitis, nor did it reduce the effect of methenamine hippurate. Methenamine hippurate is an effective prophylactic agent against recurrent acute cystitis and has the advantage of not inducing cross resistance to conventional antibiotics.     

不同价格降压药物对高血压患者血压达标的影响

目的了解高血压患者不同价格降压药物使用情况及其对血压达标的影响。方法调查高血压患者2100例,年龄28～80岁,平均年龄（62．5±12．1）岁。调查的项目包括：文化程度、用药前后血压、病史、所用药物的名称及每日剂量等。结果自费患者中：①不同文化程度患者之间不同价格药物的使用有明显差异（P〈0．01）,大多数低学历患者使用低价格药物,许多高学历患者也使用低价格药物;②不同病史的患者用药也有明显差异（P〈0．05）,随着病史的延长,高价格药物的使用逐渐增多;③高价格药物单用或与其他价格药物联合使用,治疗达标率都较高。结论文化程度的高低及病史的长短可以影响自费高血压患者对降压药物的选择,从而影响对血压的控制。     

苯磺酸左旋氨氯地平治疗轻、中度原发性高血压临床观察

目的探讨钙离子拮抗剂苯磺酸左旋氨氯地平对轻、中度原发性高血压的降压疗效及其安全性。方法采用自身对照开放试验方法。103例轻、中度原发性高血压患者经1~2周安慰剂导入期后口服苯磺酸左旋氨氯地平片（5 mg/d）,共8周,不服其他降压药,观察患者血压、心率及各项实验室检查指标的改变。结果治疗8周后：患者收缩压（SBP）由（154.59±12.16）mmHg降至（131.10±10.21）mmHg,舒张压（DBP）由（100.55±3.99）mmHg降至（82.79±7.01）mmHg,治疗前后差异有显著统计学意义（P〈0.01）;动态血压监测（ABPM）显示SBP、DBP谷/峰比分别为0.72±0.36、0.83±0.54。治疗期间未出现明显不良反应,疗程结束后复查血常规、血糖、血脂、血电解质、肝肾功能等实验室指标均未出现明显变化。结论苯磺酸左旋氨氯地平对轻、中度原发性高血压具有较好的疗效及安全性。     

Sustained release choline theophyllinate in nocturnal asthma

Nocturnal wheeze is common in patients with asthma, and slow release theophyllines may reduce symptoms. As theophyllines are stimulants of the central nervous system the effect of 10 days' twice daily treatment with sustained release choline theophyllinate or placebo on symptoms, overnight bronchoconstriction, nocturnal oxygen saturation, and quality of sleep were studied in a double blind crossover study in nine stable patients with nocturnal asthma (five men, four women, age range 23-64 years; forced expiratory volume in one second (FEV1) 0.85-3.8 1; vital capacity 1.95-6.1 1). When treated with the active drug all patients had plasma theophylline concentrations of at least 28 mmol/l (5 micrograms/ml) (peak plasma theophylline concentrations 50-144 mmol/l (9-26 micrograms/ml]. Morning FEV1 was higher when treated with sustained release choline theophyllinate (2.7 (SEM 0.3) 1) than placebo (2.1 (0.3) 1) (p less than 0.01). Both daytime and nocturnal symptoms were reduced when the patients were treated with sustained release choline theophyllinate and subjective quality of sleep was improved (p less than 0.002). When treated with the active drug, however, quality of sleep determined by electroencephalography deteriorated with an increase in wakefulness and drowsiness (p less than 0.05) and a reduction in non-rapid eye movement sleep (p less than 0.005). Treatment with choline theophyllinate had no effect on either the occurrence or the severity of transient nocturnal hypoxaemic episodes or apnoeas or hypopnoeas. In conclusion, sustained release choline theophyllinate prevents overnight bronchoconstriction, but impairs quality of sleep defined by electroencephalography.     

干体重控制及低钠透析对血透患者高血压控制的作用

目的探索基于不同病因的个体化治疗模式对改善血液透析(HD)患者高血压控制率的影响。方法选取我院部分稳定维持性HD患者进行家庭血压(Home-BP)监测,以家庭血压的收缩压(Home-SBP)≥150mmHg为未控制的高血压的诊断标准,对入组高血压患者进行干预研究。行生物电阻抗检测,血清钠测定,药物使用情况调查,了解水、钠负荷及药物应用合理性情况,有针对性地分别进行降低干体重、低钠透析和合理使用降压药物的干预措施。随访2个月,观察患者高血压控制情况。结果 105例稳定维持性HD患者接受了Home-BP监测,其中未控制的高血压患者60例(57.1%)。其中30例患者容量超负荷,针对性地降低干体重后,Home-SBP下降12.0mmHg(P0.001),家庭血压的舒张压(Home-DBP)下降5.0mmHg(P=0.002),降压药用量显著减少(P=0.030)。12例透析前血钠低于标准透析液钠浓度(138mmol/L)的患者使用低钠透析(136mmol/L)后,Home-SBP下降14.0mmHg(P=0.003),Home-DBP下降8.1mmHg(P=0.014),降压药用量无明显变化(P=0.390)。余18例患者通过增加肾素-血管紧张素抑制剂和抗交感治疗,Home-SBP下降11.6mmHg(P0.001),Home-DBP下降4.2mmHg(P=0.021)。通过上述治疗,患者未控制的高血压比例从57.1%(60例)降至31.4%(33例)(P0.001)。结论对HD高血压患者进行有针对性的、个体化的干预治疗措施,能够有效地改善HD高血压患者血压状况。     

Ketanserin in the treatment of traumatic vasospastic disease

The specific serotonin receptor blocker ketanserin was given orally to 12 patients with traumatic vasospastic disease in a double blind crossover study. The effect of treatment was assessed by measuring finger systolic pressure and rewarming time after cold provocation and by medical interview and diaries. Median (range) percentage change in finger systolic pressure after cooling was 50 (0-100)% after treatment with ketanserin compared with 0 (0-90)% after placebo. Median (range) rewarming time after cooling decreased from 320 (236-972)s with placebo to 160 (88-404)s after treatment with ketanserin. These changes were not significant. Ninety five percent confidence intervals for difference between the treatments, however, showed that finger systolic pressure may be 80% better and rewarming time 256 seconds faster after treatment with ketanserin than after placebo. The number of attacks did not differ significantly between the two treatments. Two patients had a feeling of warmth in their hands during treatment with ketanserin. The results suggest that orally administered ketanserin may improve digital circulation in patients with traumatic vasospastic disease, but larger numbers of patients are required to assess the true effect of treatment with ketanserin in this disease.     

Low dose danazol in the treatment of the premenstrual syndrome.

This double-blind, randomized, crossover study compared the efficacy and safety of danazol (100 mg twice daily) with matching placebo in the treatment of severe premenstrual syndrome. Nineteen patients were randomly allocated to receive danazol for 3 months followed by placebo, and 18 to receive treatment in the reverse order. Assessments of overall condition showed improvement to be statistically significantly more likely with danazol than with placebo (P less than 0.001) after 3 months' treatment. Furthermore, daily visual analogue scale assessments demonstrated statistically significantly better premenstrual scores with danazol in comparison to placebo for breast discomfort, irritability, depression, anxiety, mood swings, crying, depressed libido and abdominal swelling. It is concluded that danazol provides effective and generally well tolerated treatment for severe premenstrual syndrome.