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Background

Cyclopropyl-methoxycarbonyl metomidate, or ABP-700, is a second generation analogue of etomidate, developed to retain etomidate's beneficial haemodynamic and respiratory profile but diminishing its suppression of the adrenocortical axis. The objective of this study was to characterise the safety and efficacy of 30-min continuous infusions of ABP-700, and to assess its effect on haemodynamics and the adrenocortical response in healthy human volunteers.

Methods

Five cohorts involving 40 subjects received increasing infusion doses of ABP-700, propofol 60 μg kg?1 min?1 or placebo. Safety was evaluated through adverse event (AE) monitoring, safety laboratory tests, and arterial blood gasses. Haemodynamic and respiratory stability were assessed by continuous monitoring. Adrenocortical function was analysed by adrenocorticotropic hormone (ACTH) stimulation tests. Clinical effect was measured using the modified observer's assessment of alertness/sedation (MOAA/S) and continuous bispectral index monitoring.

Results

No serious AEs were reported. Haemodynamic and respiratory effects included mild dose-dependent tachycardia, slightly elevated blood pressure, and no centrally mediated apnoea. Upon stimulation with ACTH, no adrenocortical depression was observed in any subject. Involuntary muscle movements (IMM) were reported, which were more extensive with higher dosing regimens. Higher dosages of ABP-700 were associated with deeper sedation and increased likelihood of sedation. Time to onset of clinical effect was variable throughout the cohorts and recovery was swift.

Conclusions

Infusions of ABP-700 showed a dose-dependent hypnotic effect, and did not cause severe hypotension, severe respiratory depression, or adrenocortical suppression. The presentation and nature of IMM is a matter of concern.

Clinical trial registration

NTR4735.  相似文献   
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The in vitro activity of gemifloxacin against 316 bloodstream isolates of staphylococci, pneumococci, and enterococci was compared with the activities of six fluoroquinolones and three other antimicrobial agents. Of the antimicrobial agents tested, gemifloxacin was the most potent against penicillin-intermediate and -resistant pneumococci, methicillin-susceptible and -resistant Staphylococcus epidermidis isolates, and coagulase-negative staphylococci.  相似文献   
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The sampling of exhaled breath is a noninvasive procedure that can be performed easily in adults, children, and patients with respiratory disease. Several studies have demonstrated increased exhaled nitric oxide in patients with pulmonary disease, including asthma. In addition, exhaled nitric oxide may be an elegant tool for monitoring of environmental health effects of air pollution and the prevalence of atopy in epidemiological surveys. Recent literature about exhaled nitric oxide is presented in this article. Technical, physiological, and behavioral confounding factors of exhaled nitric oxide measurement are outlined.  相似文献   
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Research suggests that depressed patients’ beliefs about the causes of their depression affect the course and outcomes of treatment. However, changes in such beliefs during treatment have not been investigated. Before and after treatment, participants in a randomized control trial comparing cognitive therapy (CT) with antidepressant medication (ADM) in the treatment of depression were asked about their beliefs concerning the reasons for their depression. The reason clusters of interest were: Characterological, conceptually related to CT; and Biological, conceptually related to ADM. Contrary to predictions, endorsement of treatment-relevant reasons did not increase after a successful treatment. Rather, endorsement of treatment-irrelevant reasons decreased significantly. Thus, successful treatment may preserve people’s beliefs in causes of depression most closely related to the treatment, and diminish beliefs in unrelated causes.  相似文献   
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BACKGROUND: A number of innovative approaches have been investigated for their value in the early detection of acute ischemia or infarction in patients presenting to the emergency department (ED) with chest pain suggestive of a cardiac origin. Prior investigations have demonstrated the utility of adding right precordial and posterior chest leads to the standard 12-lead electrocardiogram (ECG) for identifying right ventricular and posterior wall infarctions in the ED. HYPOTHESIS: To assess the utility of additional ECG leads in low-risk patients presenting to the ED with symptoms suggestive of acute coronary syndromes who are managed in a chest pain evaluation unit (CPEU). METHODS: We studied low-risk patients who presented to the ED with chest pain compatible with myocardial ischemia. Low-risk patients were identified by a normal 12-lead ECG, no arrhythmias or hemodynamic instability, and one negative serum cardiac troponin I. Patients were admitted to the CPEU where a 16-lead ECG was recorded by the addition of 2 right-sided precordial leads (V4R, V5R) and 2 posterior leads (V8, V9) to the standard 12-lead ECG. RESULTS: The 16-lead ECG system was applied to 316 consecutive patients. The study group was a middle-aged population with equal numbers of men and women and an average of 2 cardiac risk factors per patient. The 16-lead ECG demonstrated evidence of myocardial injury in only 1 patient and no evidence of ischemia in any of the 316 patients. CONCLUSION: In patients presenting to the ED with chest pain and evidence of low clinical risk by our criteria, the addition of both right-sided precordial and posterior chest leads to the standard 12-lead ECG did not provide additional information for risk stratification.  相似文献   
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