阿托品对麻醉家兔血压及心率的影响

目的探讨不同剂量阿托品静脉推注对家兔动脉血压及心率的影响。方法采用动脉血压直接测定法,通过BL-420生物信号采集系统,记录用药后家兔收缩压、舒张压及心率的变化情况。结果阿托品剂量〈2.5mg/kg,对家兔血压及心率无明显影响;剂量超过5mg/kg时,可显著降低家兔收缩压及舒张压,尤以舒张压为明显,降压作用持续约5min,对心率无明显影响。结论阿托品大剂量静脉推注,可致家兔血压短暂下降。     

Fluoxetine in social phobia: a double-blind,placebo-controlled pilot study

The objective of the study was to examine the efficacy of fluoxetine in social phobia. Sixty subjects were randomly assigned to 14 weeks of double-blind therapy with either fluoxetine or placebo. Dose was fixed at 20 mg for fluoxetine during the first 8 weeks of double-blind treatment; during the final 6 weeks, the dose could be increased every two weeks by 20 mg to a maximum of 60 mg/day. An intentto-treat analysis was used. A significant change from baseline to endpoint was found for both fluoxetine and placebo on the Liebowitz Social Anxiety Scale. However, no significant difference was found between fluoxetine and placebo. The change for fluoxetine was somewhat lower than that found with other selective serotonin reuptake inhibitors, whereas the placebo response was greater. Fluoxetine failed to separate from placebo in this trial. It is unknown whether a larger dose for longer duration would have yielded separation from placebo. A higher than usual placebo response rate was found.     

Sustained antihypertensive activity of diltiazem SR: double-blind, placebo-controlled study with 24-hour ambulatory blood pressure monitoring.

A new polymeric matrix technology provides a sustained-release formulation of diltiazem hydrochloride (diltiazem SR) suitable for once-daily therapy. The efficacy and safety of diltiazem SR were evaluated in a multicenter, randomized, double-blind, placebo-controlled, parallel-group study. After a single-blind, placebo lead-in period, 275 patients with mild to moderate essential hypertension were assigned to receive placebo or diltiazem SR 120, 240, 360, or 480 mg once daily for 4 weeks. The efficacy evaluation was based on office and 24-hour ambulatory blood pressure monitoring. Twenty-four hours after the last dose in the 4-week, double-blind treatment period, the mean reduction from baseline in supine diastolic blood pressure ranged from 5.1 to 10.6 mm Hg in the diltiazem SR 120- to 480-mg groups, resulting in a significant linear trend across all treatments (P less than .001). Reductions in systolic blood pressure were similar. Ambulatory blood pressure monitoring, performed in 138 patients, confirmed the dose-response relationship and showed consistent antihypertensive activity throughout the 24-hour dosing interval. The percentage of patients reporting adverse events was similar in the placebo- and active-treated groups. The results of this study indicate that diltiazem SR is well tolerated, lowers blood pressure in a dose-related manner, and provides sustained activity throughout the 24-hour dosing interval.     

Effect of nifedipine and nitrendipine on insulin release in non-diabetic obese patients: a double-blind, placebo-controlled study

Calcium antagonists are known to decrease insulin release in vitro. In vivo, their effects on insulin secretion and glucose tolerance are more controversial. We carried out a double-blind, double-dummy, controlled trial to study the effects of nifedipine (40 mg/day; n = 9), nitrendipine (20 mg/day; n = 9) and placebo (n = 10) on insulin release in 3 parallel groups of obese patients with mild or transient hypertension and a normal oral glucose tolerance test. The treatment lasted one week. Patients were asked not to modify their diet throughout the trial, and their body weight did not vary significantly. A 2-hour i.v. glucose tolerance test was performed twice in every patient, just before the first drug intake and one hour after the last one. The following parameters were measured or calculated during each test: basal, peak and early phase levels of blood glucose, insulin and C-peptide; glucose disappearance rate; and glucose, insulin and C-peptide incremental areas under the time-curves. On day 1, the 3 groups of patients were comparable for age, sex, body weight and every biological parameter. One-way analysis of variance did not show any significantly different evolution of those parameters between the 3 treatment groups, but calcium antagonists tended to slightly reduce the early phase of insulin release compared with placebo.     

Chronic oral amrinone therapy in congestive heart failure: a double-blind placebo-controlled withdrawal study

Eighteen patients with congestive heart failure were studied in a double-blind, randomized, placebo-controlled withdrawal trial to evaluate the effectiveness of chronic oral amrinone therapy when added to conventional heart failure therapy. All patients received a four-week lead-in of amrinone 100 mg orally every 8 h, then were randomly assigned to either continued amrinone (nine patients) or placebo (nine patients) groups. Compared to placebo, chronic amrinone therapy did not significantly improve clinical status, left ventricular function as measured by non-invasive testing techniques, or exercise tolerance. Side-effects occurred in every patient receiving amrinone and abated in those patients who received placebo for the last 12 weeks of the study. The limited effectiveness of oral amrinone and the high frequency of side-effects preclude the widespread use of this drug in the chronic therapy of congestive heart failure.     

Ranitidine for erosive oesophagitis: a double-blind, placebo-controlled study

A multicentre, randomized, double-blind, placebo-controlled study was conducted to evaluate the efficacy and safety of ranitidine 150 mg and 300 mg in 342 patients with erosive oesophagitis. Treatment was given four times daily, and continued for 12 weeks or until healing (that is, normal or only erythematous mucosa). Erosive oesophagitis healing rates, as determined by endoscopy, were significantly greater in ranitidine-treated patients by 4 weeks compared with those of placebo-treated patients. By 12 weeks, erosive oesophagitis healing rates were 83 and 81% for ranitidine-treated patients (150 and 300 mg, respectively) and 58% for placebo-treated patients (P less than or equal to 0.001, ranitidine vs. placebo). Symptomatic relief was achieved within 24 hours after starting either dosage of ranitidine. Heartburn frequency (P less than 0.001) and severity (P less than 0.001), as well as antacid consumed per week (P less than 0.001), were reduced in both ranitidine groups in comparison with placebo. Healing rates and symptom relief were similar in the two ranitidine groups. Both dosages of ranitidine were well tolerated. Ranitidine (150 mg) given four times daily appears to be as effective as 300 mg ranitidine given four times daily in patients with moderate to severe oesophageal erosions.     

Modafinil and cocaine: a double-blind,placebo-controlled drug interaction study

Modafinil is a novel compound that is approved for the treatment of narcolepsy. It is now being studied as a potential treatment for cocaine dependence. Cocaine withdrawal symptoms are associated with poor clinical outcome and are likely to be reversed by modafinil. In addition, the neurotransmitter actions of modafinil are opposite to cocaine-induced neuroadaptations affecting dopamine and glutamate reward circuits. Since cocaine-dependent subjects might use cocaine during a clinical trial with modafinil, this study tested the safety of intravenous cocaine (30 mg) in combination with modafinil. Each of seven subjects received a baseline (open-label) cocaine infusion. Three subsequent cocaine infusions were administered after subjects received 4 days of low dose modafinil (200 mg/day), high dose modafinil (400 mg/day), or placebo in randomized double-blind sequences. One subject received placebo prior to all infusions. Our results indicate that co-administering modafinil and a single dose of intravenous cocaine is not associated with medical risk in terms of blood pressure, pulse, temperature, or electrocardiogram measures. Furthermore, pretreatment with modafinil did not intensify cocaine euphoria or cocaine-induced craving. In fact, cocaine euphoria was significantly blunted (P=0.02) in one of our subjective measures.     

Metyrapone and cocaine: a double-blind, placebo-controlled drug interaction study

Pre-clinical research suggests that suppression of adrenocorticosteroid synthesis might decrease susceptibility to stress-induced relapse. Metyrapone effectively suppresses cortisol synthesis and thus might have promise as a cocaine dependence treatment. The present inpatient study evaluated the interaction of metyrapone and cocaine to assess the safety of conducting an outpatient trial. Twelve nontreatment-seeking cocaine-dependent individuals completed this double-blind, placebo-controlled, crossover study with two factors: medication (750 mg of metyrapone vs. placebo) and infusion (40 mg of cocaine vs. saline). Safety measures included vital signs, adverse events, and electrocardiogram. Efficacy measures included visual analog scale (VAS) ratings of craving and drug effect. Neuroendocrine measures included cortisol and ACTH. As predicted, metyrapone was well tolerated and did not exacerbate cocaine's physiological effects. Also as predicted, metyrapone did not significantly alter cocaine's subjective effects. The results of the present study suggest that metyrapone at the dose studied can likely be used safely in an outpatient study with active cocaine users.     

Arabinosyladenine monophosphate in genital herpes: a double-blind, placebo-controlled study

A double-blind, placebo-controlled study was performed in 55 male patients with recurrent herpes simplex genitalis. The 29 patients who received topical arabinosyladenine monophosphate (ara-AMP) showed no significant difference in viral shedding, duration of pain, healing time or development of new lesions as compared to 26 placebo-treated patients. Ara-AMP was well-tolerated when topically applied. Serum neutralizing antibody titers did not change significantly during the acute and convalescent periods of the patient's recurrent HSG attacks. We conclude that ara-AMP, when applied topically as a 10% gel five times a day within 24 h of onset of recurrent HSG, does not influence the virologic and clinical evolution of the recurrent episode.     

A randomized, double-blind, placebo-controlled study of the effect of sustained-release bupropion on blood pressure in individuals with mild untreated hypertension

The effects of bupropion on blood pressure and heart rate were evaluated in a double-blind, placebo-controlled study of community volunteers with untreated mild (stage 1) hypertension (systolic blood pressure [SBP], 140-159 mm Hg, and/or diastolic blood pressure, 90-99 mm Hg). Three hundred subjects were randomly assigned (1:1:1:1) to 4 weeks of placebo or bupropion sustained release (SR) 150, 300, or 400 mg/d. Mean clinical blood pressures decreased from baseline to the end of protocol in all groups (n = 296): -6.53, -6.46, -4.20, -4.87 mm Hg for SBP; and -2.36, -2.27, -1.95, -1.55 mm Hg for diastolic blood pressure, for each group, respectively. Although decreases in mean clinical blood pressure were observed in all groups, the reduction in SBP was less on bupropion SR 300 mg/d than on placebo (-4.20 vs -6.53 mm Hg, respectively; Delta = 2.33, P = 0.020). Neither mean 24-hour ambulatory blood pressure measurements nor the proportion of subjects with clinically significant increases in blood pressure differed between any bupropion SR dose and placebo. Mean heart rate increases were small but statistically significant at 400 mg/d versus placebo (2.28 vs -0.64 beats/min; Delta = 2.92, P = 0.004). Although only minor effects on blood pressure were observed in this trial, an infrequent association of bupropion therapy and treatment-emergent hypertension cannot be ruled out.     

Naltrexone in autistic children: a double-blind and placebo-controlled study

A double-blind, placebo-controlled study was designed to assess critically the effects of naltrexone on behavioral symptoms and learning in autistic children, and its safety. This is a preliminary report on 18 children, ages 3.08 to 7.99 years, who completed this ongoing study. Subjects were randomly assigned to naltrexone or placebo and received daily doses over a period of 21 days. Naltrexone was superior to placebo according to blind Clinical Global Consensus Ratings (unpublished scale). However, other behavioral rating measures did not confirm this result. There was only a suggestion that naltrexone reduced fidgety and hyperactive behavior and tended to alleviate overall symptomatology in older children. Naltrexone did not appear to affect discrimination learning. Results are preliminary and, owing to the small sample size, can be considered only suggestive until this study is completed or replication is obtained from independent research.     

Effect of smoke-free cigarettes on 24 h cigarette withdrawal: a double-blind placebo-controlled study

In a double-blind randomised trial, 40 cigarette smokers used either nicotine-containing or placebo smoke-free cigarettes during 24 h abstinence from smoking. Subjects in the nicotine group experienced smaller increases in irritability and difficulty concentrating and fewer urges to smoke than those who received placebo. Nicotine smoke-free cigarettes were rated as more satisfying, more helpful and more effective in relieving craving than placebo. After 24 h use nicotine smoke-free cigarettes provided average blood nicotine levels of 6.3 ng/ml, i.e., 29.2% of smoking levels. The most frequent side effects were irritation of the throat and coughing. Overall, side effects were rated as not serious. Although the smoke-free cigarette in its present form is not very efficient in delivering nicotine, it was effective in alleviating initial tobacco withdrawal. It is possible that by providing both nicotine and behavioural replacement it may be particularly useful in the first stages of stopping smoking. The product is worth further investigation.     

The acute effects of smoking on heart rate and blood pressure: An ambulatory study

Under laboratory conditions smoking has been found to acutely increase blood pressure and heart rate in healthy subjects. Little is known about the short-term effects of smoking under more naturalistic conditions when subjects are engaged in various activities. In this study, the short-term effects of smoking on blood pressure and heart rate in natural settings were investigated in a group of healthy smokers. The degree to which these effects are moderated by other factors known to affect the cardiovascular system was investigated as well. Subjects (eight males, seven females) were dispatchers in the greater Los Angeles area. They wore an ambulatory blood pressure and heart rate monitor on two workdays for a total of 48 h. The present study confirmed that the acute effects of smoking on blood pressure and heart rate under natural conditions are similar to results from laboratory studies. Smoking acutely increased blood pressure and heart rate. Male and female smokers displayed similar cardiovascular reactivity to smoking. There was no indication of development of intraday tolerance. The acute action of smoking on blood pressure and heart rate was additive to the influence of posture on the cardiovascular system.     

Risperidone augmentation in treatment-resistant obsessive-compulsive disorder: a double-blind, placebo-controlled study

This double-blind, placebo-controlled trial was performed to determine the efficacy and tolerability of 8 wk of risperidone augmentation of serotonin reuptake inhibitor (SRI) treatment in adult subjects with treatment-resistant obsessive-compulsive disorder (OCD) (failure of at least two SRI trials). Sixteen adult treatment-resistant OCD patients were randomly assigned to augmentation with 8 wk of either risperidone (n=10) (0.5-3.0 mg/d) or placebo (n=6) following at least 12 wk of SRI treatment. Four patients on risperidone (40%) and none (0%) on placebo were responders with both a Clinical Global Impression - Improvement (CGI-I) score of 1 or 2 and a Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) decrease >/=25%. Risperidone was generally well tolerated: there were 3 dropouts, 1 on risperidone and 2 on placebo. Better Y-BOCS insight score at baseline significantly correlated with a greater CGI-I score at endpoint on risperidone augmentation. Risperidone may be an effective and well-tolerated augmentation strategy in treatment-resistant OCD subjects, but larger sample size studies are required to demonstrate this.     

钙离子拮抗剂与血管紧张素受体拮抗剂对血压晨峰现象影响的临床对照研究

目的研究不同钙离子拮抗剂与ARBs对轻中度原发性高血压血压晨峰现象的影响。方法 160例轻中度原发性高血压患者随机分为4组:苯磺酸氨氯地平组、非洛地平缓释剂组、硝苯地平控释片组、缬沙坦组,每组40例。服药8周后,分别比较不同降压药物对血压晨峰的影响。结果治疗8周后,各组观察指标(24hS BP、24hD BP、清晨自测SBP、清晨自测DBP)较治疗前均明显降低(P<0.05)。与缬沙坦组比较,对血压晨峰的控制苯磺酸氨氯地平组优于缬沙坦组,差异有统计学意义(P<0.05);硝苯地平控释片组对血压晨峰的影响优于缬沙坦组,差异有统计学意义(P<0.05);苯磺酸氨氯地平组对晨峰现象的影响优于非洛地平缓释剂组和硝苯地平控释片组,差异有统计学意义(P<0.05)。结论钙离子拮抗剂及缬沙坦均能有效控制血压晨峰现象,其中以苯磺酸氨氯地平对清晨血压控制的有效率最为理想。     

Effect of myrtle fruit syrup on abnormal uterine bleeding: a randomized double-blind,placebo-controlled pilot study

Background

Myrtle (Myrtus communis L.) has been used in the Iranian Traditional Medicine as a treatment for abnormal uterine bleeding-menometrorrhagia. The main aim of this study is to evaluate the effect of myrtle fruit syrup on abnormal uterine bleeding-menometrorrhagia.

Methods

A randomized, double-blind, placebo-controlled pilot study was conducted on 30 women suffering from abnormal uterine bleeding-menometrorrhagia. Treatment comprised of giving 15 ml oral myrtle syrup daily (5 ml three times a day) for 7 days starting from the onset of bleeding. The myrtle syrup along with placebo was repeated for 3 consecutive menstrual periods. Menstrual duration and number of used pads were recorded by the Pictorial Blood loss Assessment Chart at the end of each menstrual period. The quality of life was also evaluated using the menorrhagia questionnaire.

Results

The mean number of bleeding days significantly declined from 10.6 ± 2.7 days to 8.2 ± 1.9 days after 3 months treatment with the syrup (p = 0.01) and consequently the participants in the intervention group used fewer pads after 3 months (16.4 ± 10.7) compared with the number of pads used at the beginning of the treatment (22.7 ± 12.0, p = 0.01). Bleeding days and number of pads used by the participants in the placebo group did not change significantly. Also significant changes of quality of life scores were observed in the intervention group after 3 months compared to the baseline.

Conclusion

Myrtle syrup is introduced as a potential remedy for abnormal uterine bleeding-menometrorrhagia.     

Differential effects of escitalopram on attention: a placebo-controlled, double-blind cross-over study

Rationale

The role of serotonin (5-HT) in attention is not fully understood yet.

Objective

We aimed to investigate whether attention is modulated after treatment with escitalopram, a selective serotonin reuptake inhibitor (SSRI).

Methods

We administered 10 mg of escitalopram to 20 healthy subjects in a placebo-controlled, double-blind cross-over design for 1 day or to another 20 participants for a period of 7 days. Attention was assessed at time of plasma peak escitalopram concentration using the computerised Attention Network Test (ANT), which is a combined flanker and cued reaction time task.

Results

The results showed differential effects of serotonergic manipulation on attention depending on sequence of intake. For the acute treatment, we found significant differences between escitalopram and placebo for all warning conditions dependent of sequence of intake: participants receiving escitalopram as first treatment showed significant slower reaction times in all warning conditions as compared with placebo while participants receiving escitalopram as second treatment showed significant faster reaction times as compared with placebo. For the sub-chronic treatment, we found significant differences between escitalopram and placebo depending on sequence of intake, but only for the flanker condition: participants receiving escitalopram first had significant slower reaction times in incongruent trials with escitalopram as compared with placebo while participants starting with placebo had significant shorter reaction times in incongruent trials with escitalopram.

Conclusions

Thus, the results showed a differential effect of escitalopram in cognition, especially in attention, and are discussed with regard to an interaction between serotonin and familiarity with the attention test.     

Augmenting clozapine with sertindole: a double-blind, randomized, placebo-controlled study

Clozapine augmentation with antipsychotic drugs is widely used despite sparse evidence supporting this strategy. Sertindole is a nonsedating atypical antipsychotic drug with low affinity for cholinergic receptors, which makes it potentially suitable for augmentation of clozapine. The study design was a 12-week, double-blind, randomized, placebo-controlled study including patients with International Statistical Classification of Diseases, 10th Revision schizophrenia (F20.0-F20.3) and treated with clozapine for at least 6 months who had not achieved sufficient response. Patients were randomized 1:1 to either sertindole 16 mg or placebo, and assessment was done at baseline and after 6 and 12 weeks. Assessment included the Positive and Negative Syndrome Scale, Clinical Global Impression, Udvalg for Kliniske Unders?gelser, World Health Organization Quality of Life Brief, Drug Attitude Inventory, fasting glucose, lipids, and electrocardiogram. Clozapine augmentation with sertindole was not superior to placebo regarding total score or subscale score of the Positive and Negative Syndrome Scale, Clinical Global Impression, World Health Organization Quality of Life Brief, or Drug Attitude Inventory. No increased adverse effects compared with placebo were found. Four patients randomized to sertindole experienced a significant worsening of psychosis, and 2 of them required psychiatric admission. Metabolic parameters were unchanged during the study, but augmentation of clozapine with sertindole was associated with a 12-millisecond (SD, 20-millisecond) QTc prolongation compared with 0 millisecond (SD, 20 milliseconds) in the placebo group (P < 0.03). Augmentation with sertindole showed no benefits compared with placebo. Psychiatrists should be aware that augmentation might not add any benefits for the patients and in some cases worsen psychosis.