ISSN:1075-2765    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

We have previously reported a metoclopramide-induced vascular hyperreactivity to the cold pressor test (CPT) in normotensive and hypertensive subjects. The present study was designed to determine whether the state of physical training influences the cardiovascular responses to the CPT in normotensive subjects under metoclopramide (MTC) treatment. In 20 untrained subjects and 32 athletes (football players and runners), the blood pressure and heart rate responses to the CPT were studied after a 30-minute infusion of MTC (7.5 μg/kg per minute) and two placebo periods, before and after MTC, with 5% glucose solution. Under placebo conditions, the CPT produced significant increases of systolic blood pressure (SBP) in the untrained subjects and the runners, but not in the football players (17.2, 17.8, and 6.5 mm Hg for untrained subjects, runners, and football players, respectively). The runners responded with a lesser increase in diastolic blood pressure (DBP) during the CPT than did the others (15.8,17.9, and 18.2 mm Hg for runners, untrained subjects, and football players, respectively). In the presence of MTC, the CPT induced a larger increase in blood pressure (SBP/DBP) in the untrained subjects (21.4/24.1 mm Hg) than in the football players (10/18.7 mm Hg) and runners (18.7/13.9 mm Hg). MTC diminished the hyperreactivity responses to the CPT in the trained subjects (41 and 56% for football players and runners, respectively). Our conclusions are as follows: (1) Vascular responses to cold stress are attenuated in athletic subjects compared with untrained subjects. (2) The metoclopramide-induced vascular hyperreactivity, formerly reported for normotensive and hypertensive subjects, seems to be absent in trained subjects. (3) It is suggested that a probable dopaminergic system adaptation occurs during exercise.

ISSN:1075-2765    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Vesnarinone, a quinoline derivative with modest positive inotropic action, has been shown in several studies to benefit patients with clinical congestive heart failure. The cellular basis of its clinical benefit is not known, although the drug has several pharmacologic effects demonstrated both in isolated cardiac myocytes and in other noncardiac cell types. To investigate the possibility that the clinical benefit of vesnarinone is based, at least in part, on the inhibition of pathologic myocardial fibrosis, we examined its effects on cultured cardiac fibroblasts isolated from both normal and aortic regurgitant New Zealand White rabbit hearts. As in people, rabbits with moderate-to-severe aortic regurgitation often develop congestive heart failure that, at necropsy, is characterized by exuberant myocardial fibrosis. A dose-response curve was constructed with vesnarinone concentrations ranging from 10-4to 10-9mol/L. Cellular survival was decreased by exposure to nanomolar concentrations of drug but not at the higher doses tested. Fibroblasts isolated from normal hearts responded maximally at 10-7mol/L vesnarinone, whereas fibroblasts from aortic regurgitant hearts responded maximally at 10-8mol/L. These concentrations of drug are more than an order of magnitude lower than those believed to be associated with clinical benefit from earlier studies. Our results indicate that vesnarinone can suppress cardiac fibroblast proliferation and suggest that this action may be useful in therapies designed to prevent congestive heart failure in aortic regurgitation.

ISSN:1075-2765    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

This article describes a simple method for the estimation of absorption rate constant (ka) after oral administration and compares the proposed method with some of the existing methods. The proposed method is based on a previous work of Urso and Aarons known as theregression method of truncated areasfor the estimation of absolute bioavailability for drugs with a long elimination half-life. The following equation was used to estimate ka: Y(t) = ka. F – ka. X(t). Simple linear regression of Y(t) on X(t) results in a straight line with a slope of -ka, intercept on y-axis of kaF, and abscissa intercept F (absolute bioavailability). Different sets of plasma concentration versus time data for a hypothetical drug were generated by simulation. The estimated ka from the proposed method was compared with the Wagner-Nelson, Loo-Riegelman, and statistical moments methods. The results of this study indicated that the proposed regression method performed satisfactorily for a hypothetical drug that follows a one-compartment or two-compartment model with short or long half-life when tested under variable conditions (different absorption and elimination rate constants). The regression method of truncated areas can be used for the accurate estimation of kafor both short and long half-life drugs.

ISSN:1075-2765    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The current study investigated the concentration of sevoflurane that could be achieved when sevoflurane was administered using standard agent-specific halothane, isoflurane, and enflurane vaporizers. An artificial lung analog model was made by attaching the 3-L reservoir bag to the 15-mm end of the anesthesia circle system. The lung analog was attached and ventilated with oxygen and air at flow rates of 2 L/min each (total gas flow = 4 L/min), a tidal volume of 800 mL, a rate of 10 breaths/min, and an inspiratory-to-expiratory ratio of 1:2. The vaporizer was filled with sevoflurane and the dial turned to 1%. After a 10-minute equilibration period, the concentration of sevoflurane was measured. The vaporizer concentration was increased in 1% increments, and after a 10-minute equilibration, the sevoflurane concentration was recorded. The dial was increased from 1% to 5% for the halothane and isoflurane vaporizer and from 1% to 7% for the enflurane vaporizer. Each study was repeated five times at each incremental increase of 1% for each of the three vaporizers. The series of studies were repeated using a total gas flow of 8 L/min (oxygen 4 and air 4) instead of 4 L/min (oxygen 2 and air 2). Using the halothane or isoflurane vaporizers at the 5% setting, the maximum sevoflurane concentrations achieved were 3.0% and 3.1%, respectively. The sevoflurane concentration was a maximum of 6% using the enflurane vaporizer set at 7%. The sevoflurane concentration decreased significantly when using any of the three vaporizers at all concentrations when the gas flow was increased from 4 to 8 L/min. The current study demonstrates that clinically useful concentrations of sevoflurane can be achieved with the administration of sevoflurane through an enflurane vaporizer. Although this is not routinely recommended, in specific circumstances it may allow the use of sevoflurane in third-world countries if sevoflurane vaporizers are not available and the use of sevoflurane is clinically necessary.

ISSN:1075-2765    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The increasingly reported cholestatic course of liver disease in hemophiliacs coinfected with human immunodeficiency virus (HIV) and hepatitis C (HCV) has been linked with impaired azidothymidine (AZT) metabolism in this patient group. Therefore, we compared the pharmacokinetics of AZT and its glucuronidated metabolite (glucuronylazidothymidine [GAZT]) in HIV/HCV-coinfected hemophiliacs without cirrhosis to HIV-infected patients without chronic hepatitis. Sixteen HIV/HCV-coinfected hemophiliacs without cirrhosis and six HIV-infected patients with negative hepatitis serology and normal liver transaminases received a single 100-mg oral dose of AZT. Subsequently, plasma concentrations of AZT and GAZT were measured during a 6-hour period by high-pressure liquid chromatography (HPLC). Blood samples were taken before and 30, 60, and 90 minutes and 2, 3, 6, and 8 hours after the intake of AZT. Pharmacokinetic parameters of AZT in HIV-infected patients with concomitant chronic hepatitis did not differ significantly as compared to patients without concomitant liver disease. GAZT half-life and mean residence time of GAZT, however, were significantly longer in HIV/HCV-coinfected hemophiliacs as compared to HIV-positive controls without hepatitis. In HIV-infected patients, underlying chronic hepatitis C does not require AZT dose adaptation. Yet despite normal oral clearance of AZT and GAZT, the increase of half-life and mean residence time of GAZT indicates a prolonged hepatic release of GAZT into the circulation of HIV-infected hemophiliacs with noncirrhotic hepatitis C.

ISSN:1075-2765    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Lipid removal using a continuous-flow extracorporeal system is of proven efficacy in severe hypercholesterolemia. Because of the inconveniences and expenses of extracorporeal removal of lipids, the effects of two treatment intervals (weekly versus biweekly) were assessed in two adolescents with circulating cholesterol higher than 20.0 mmol/L. In both patients, circulating levels were largely lower on a weekly lipid removal interval when compared with a biweekly interval. A rapid reaccumulation of cholesterol was noted after lipid removal. Treatment with simvastatin decreased the rapid reappearance of total cholesterol noted during the first 2 days after lipid removal but without any major effect on the subsequent reaccumulation of cholesterol. Aggressive treatment of severe hypercholesterolemia with statins and especially with extracorporeal lipid removal is now possible and of proven efficacy. The minimal practical lipid removal treatment interval should be used.

ISSN:1075-2765    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Intravenous immune globulin (IVIG) therapy has been used more commonly to treat a number of clinical disorders. During the past 10 years, IVIG infusion has been associated with a variety of complications. Acute renal failure, which was not described in the initial drug trials, was recognized as an adverse effect of IVIG therapy in 1987. Since the original report, a number of cases have been described in the literature. Older age and preexisting renal impairment appear to predispose to the development of acute renal failure. Acute renal insufficiency develops within days and resolves over several days to weeks. However, in some cases, recovery is delayed and initiation of renal replacement therapy is required. Chronic renal insufficiency requiring maintenance dialysis is extremely rare. The precise cause of IVIG-associated acute renal failure is unknown but may be attributable to either the direct effects of the immunoglobulin or the stabilizing agent used in the IVIG preparation.

ISSN:1075-2765    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

It is known that intermittent dobutamine therapy improves the symptoms and physical condition of patients with chronic heart failure, but its arrhythmogenic effect is insufficiently described. The aim of this study was to assess ventricular arrhythmias and the condition of patients before, during, and after intermittent dobutamine therapy. The 23 patients participating in the study were in New-York Heart Association functional classes III and IV despite therapy with digitalis, diuretics, and angiotensin-converting enzyme inhibitors. Starting dosage of dobutamine was 2 μg/kg/min, which was raised gradually up to 12 μg/kg/min, or until the appearance of complaints or symptoms. In group I (7 patients), for 24 hours before dobutamine infusion, Holter monitoring had been performed. In the subsequent 24 hours, during the infusion, patients were monitored in the critical care unit, but the second Holter test was performed only after the infusion, i.e., in the third 24 hours. In group 11 (16 patients), the Holter monitoring was started 4 hours before dobutamine infusion and was continued for an additional 20 hours, during the drug administration. In the 24 hours after dobutamine treatment, another Holter monitoring was performed. There was no increase in frequency of ventricular arrhythmias after the dobutamine infusion compared with the preinfusion period, but during dobutamine administration, ventricular arrhythmias occurred more frequently than in the preinfusion and postinfusion periods. No ventricular fibrillation was observed in the 23 patients. In conclusion, ventricular arrhythmias are frequent in congestive heart failure, and dobutamine infusion increases their incidence. The arrhythmogenic effect of dobutamine subsides on the day after the dobutamine infusion. Because of the arrhythmogenic effect of dobutamine, admission to the critical care unit is suggested during the infusion, but monitoring is not necessary after the end of the infusion.

ISSN:1075-2765    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

In clinical practice it is far from uncommon that antihypertensive drugs fail to meet their expectations. This is mainly due to mechanisms counteracting their antihypertensive effects. These mechanisms include stimulation of the sympathetic nervous system (SNS), inhibition of the parasympathetic nervous system (PSNS), stimulation of the renin-angiotensin-aldosterone system (RAAS), as well as endothelium-dependent mechanisms. To review whether the activation of such mechanisms follows differential patterns depending on the type of antihypertensive therapy being used. The antihypertensive effects of diuretics and calcium channel blockers are largely offset by all of the mechanisms enumerated. The antihypertensive effects of angiotensin-converting enzyme (ACE) inhibitors/angiotensin II (All) receptor antagonists and β-blockers are counteracted by all of the mechanisms enumerated except for the effects of a stimulated RAAS and SNS, respectively. ACE inhibitors/All receptor antagonists and p-blockers display a better profile of mechanisms counteracting their antihypertensive effects than other categories of drugs currently available. However, because this is not routinely confirmed by random trial evidence, additional determinants of drug performance must be considered including between-subject disparities in drug response, metabolic effects, and proliferative effects.

ISSN:1075-2765    

出版商:OVID    

年代:1998

数据来源: OVID