ISSN:1075-2765    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Antimicrobial resistance is reaching epidemic proportions. Bacteria have developed an impressive array of defenses to protect themselves against potent compounds. The widespread emergence of resistance has complicated the treatment of infections due toStaphylococcus, Streptococcus, Enterococcus, Neisseria, Haemophilus, gram-negative enteric bacilli, andPseudomonas.Multidrug-resistant tuberculosis poses a grave public health problem, particularly among the homeless and those infected with HIV. HIV resistance to nucleoside analogs such as zidovudine is increasingly common and seriously threatens their clinical usefulness. It is apparent that simply producing new drugs is not a viable solution to the resistance crisis. Rational use of existing antimicrobial agents is vital, and combination regimens must be intelligently deployed. State-of-the-art molecular epidemiology will aid in the detection, analysis, and termination of resistance epidemics. Control of drug-resistantMycobacterium tuberculosiswill require appropriate initial treatment regimens, proper therapeutic modification using the latest susceptibility testing methods, and strong emphasis on measures ensuring compliance. HIV resistance is a challenging problem, and novel strategies will be necessary to combat it. Recognition that drug resistance among bacteria and viruses is a rapidly growing threat worldwide is an important first step toward finding effective long-term solutions.

ISSN:1075-2765    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

This article offers clinical suggestions for the design of a patient-specific outpatient treatment plan for managing and reducing short-term pain associated with outpatient procedures. These procedures may actually produce pain, or they may be perceived as causing pain and anxiety. The article will also focus on the design of a patient-specific outpatient treatment plan for managing and reducing short-term procedural-induced anxiety, as perceived pain and anxiety or pain and anxiety themselves may be a reason for which patients are noncompliant with their office visits. The treatment plan will focus on pre-procedure, prei-procedure, and post-procedure interventions using nonsteroidal anti-inflammatory drugs and anxiolytics (benzodiazepines, opiate agonists, and sedative hypnotics). The plan also includes adjuvant therapy to decrease the patient's perception of pain, anxiety, fear of procedure, and fear of outcomes in order to facilitate a higher degree of compliance with office procedures. This article also accounts for the patient's physiology, pathophysiology, pathology, and iatrogenic effects from drug treatment plans.

ISSN:1075-2765    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

We estimated the effect of an angiotensin-converting enzyme inhibitor, ramipril, on the sympathetic and parasympathetic input to the sinoatrial node of hypertensive patients using spectral and time domain analysis of heart rate variation (HRV). The heart rate of patients with essential hypertension was recorded during spontaneous breathing at rest and during controlled deep breathing. The periodic HRV was quantified at low-frequency (0.025–0.075 Hz), mid-frequency (0.075–0.125 Hz) and high-frequency (0.15–0.40 Hz) bands. Ramipril changed the balance of autonomic nervous system assessed by spectra: the parasympathetic tone increased (p< 0.05) and the sympathetic tone decreased (p< 0.01). There was an inverse correlation between the decrease in diastolic blood pressure and increase in the mid-frequency HRV, which is connoted with resetting of the baroreceptor reflex by ramipril. Thus, ramipril treatment was associated with improved autonomic control of the circulatory system.

ISSN:1075-2765    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The current study analyzed the effects of different doses of the calcium channel blocker felodipine on cardiovascular response to a set of standardized laboratory tasks. We randomly allocated 21 essential hypertensive patients to receive extended release felodipine 5 mg, felodipine 10 mg and placebo, each given once daily for 2 weeks, according to a double-blind 3-period design. At the end of each treatment period, patients were examined at resting baseline and while performing a mental arithmetic test, a handgrip test and a cycle ergometry test. Compared to placebo, the average fall in resting blood pressure (BP) was of 7.9 ± 5.6/6.1 ± 4.5 mm Hg with felodipine 5 mg (p< 0.01) and of 15.1 ± 5.8/13.9 ± 4.5 mm Hg with felodipine 10 mg (p< 0.001). During mental arithmetic, BP decrease was 11.6 ± 8.1/9 ± 5 mm Hg with felodipine 5 mg (p< 0.01) and 20.4 ± 8.1/15.3 ± 5 mm Hg with felodipine 10 mg (p< 0.001). During handgrip test, BP was significantly reduced after both felodipine doses by 11.7 ± 9.3/9.5 ± 6.5 mm Hg (p< 0.05) and 22.1 ± 9.3/22.4 ± 6.5 mm Hg (p< 0.001), respectively. During cycle ergometry, systolic BP was significantly reduced after felodipine 10 mg by 20.1 ± 9.4 mm Hg (p< 0.001), whereas the fall induced by felodipine 5 mg(7.7 ±9.4 mm Hg) was not statistically significant (p> 0.05); diastolic BP was significantly reduced by both felodipine doses [average fall of 6.6 ± 5.8 mm Hg (p< 0.05) after felodipine 5 mg and of 12.7 ± 5.8 mm Hg (p< 0.001) after felodipine 10 mg]. There was no treatment effect on the magnitude of systolic BP reactivity from baseline during either mental arithmetic, handgrip test or cycle ergometry (all,p> 0.05). Heart rate values were significantly higher after both felodipine doses than after placebo, either at rest or during stress testing (all,p> 0.05). These data suggest that felodipine, especially at higher doses, may be effective in lowering BP not only at rest but also during exposure to commonly recurring stressful situations.

ISSN:1075-2765    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Plasma specimens from 59 patients undergoing cardiac operations utilizing extracorporeal circulation underwent determination of tranexamic acid concentration to explore the effect of dose administered to plasma concentration. Each patient received one of five doses of tranexamic acid in double-blinded, randomized fashion, ranging from 2.5 to 40 mg kg−1for the loading dose and from 0.25 to 4.0 mg kg−1h−1for a subsequent infusion. Plasma collections occurred after completion of the loading dose, during extracorporeal circulation, before protamine infusion, after protamine infusion, and following arrival in the intensive care unit. The samples were analyzed using high-performance liquid chromatography.The logarithm of plasma concentration varied linearly with the logarithm of dose administered at each sampling time (rvalues 0.82, 0.95, 0.89, 0.74 and 0.93 for the respective collection times). Plasma concentrations did not decrease during extracorporeal circulation despite absence of tranexamic acid in the pump prime. However, concentrations varied inexplicably following protamine administration and decreased in the intensive care unit.

ISSN:1075-2765    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

To investigate the dose-related hemodynamic effects of angiotensin-converting enzyme inhibition (ACEI) in patients with angina pectoris (AP), five patients underwent right and left heart catheterization, and left ventriculogram before and 10 min after administration of 1.25 mg enalaprilat intravenously (Group 1). The results were compared with those of five patients with similar characteristics who received 2.5 mg enalaprilat (Group 2). There were no baseline differences between groups. After enalaprilat administration, there was significant differences between Groups 1 and 2, as follows: systolic blood pressure was 138 ± 16 versus 127 ± 14 mmHg (p= 0.05), left ventricular end-diastolic pressure was 15 ± 6 versus 7 ± 4 mmHg (p= 0.04), systemic vascular resistance was 1341 ± 290 versus 965 ± 271 dyne/sec/cm−5(p= 0.05), pulmonary vascular resistance was 174 ± 39 versus 156 ± 15 dyne/sec/cm−5(p= 0.05), end-diastolic volume was 87 ± 34 versus 107 ± 17 ml (p= 0.03), cardiac index was 3.0 versus 4.5 L min−1m−2(p= 0.01), left ventricle end-systolic wall stress was 31 ± 10 versus 22 ± 9 k dyne cm−5(p= 0.01), ejection fraction was 69 ± 12 versus 81 ± 8% (p= 0.01), and wall motion index was 1.14 ± 0.1 versus 1.02 ± 0.1 (p= 0.001). These results indicate that enalaprilat has dose-related effects improving hemodynamics and ventricular function in patient with AP.

ISSN:1075-2765    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Information on the pharmacokinetic behavior of a new anticonvulsant agent (CGP 33101) was obtained after oral administration of ascending doses to male epileptic patients maintained on existing antiepileptic drug (AED) therapy, as well as to healthy male subjects. Single doses of 400, 800 and 1200 mg were administered to 12 of the 16 epileptic patients participating in the clinical trial and all 3 healthy subjects; the remaining patients received placebo doses on each dosing occasion.The study's primary objectives were to obtain single-dose add-on tolerability information, as well as preliminary pharmacokinetic data for the drug candidate. Either placebo or 400, 800 and 1200 mg of the compound, administered as 200-mg tablets, were coadministered with enzyme-inducing antiepileptic medications to the patients participating in the trial. These AEDs (dilantin, tegretol, depakote, mysoline and tranxene) were administered individually or as combination therapy of two or three, with each patient being on the existing therapy for a minimum of 3 weeks prior to receiving the drug candidate (CGP 33101) as an add-on. Three healthy male subjects were included in the study to provide concurrent pharmacokinetic data at equivalent doses, as well as additional safety data in the absence of concomitant medication.Plasma concentrations of the new drug candidate were determined in samples obtained predose through 120-h postdose, with a 5-day washout period between doses. Preliminary pharmacokinetic parameters, such as peak plasma concentrations (Cmax), times to peak levels (Tmax), areas under the plasma concentration-time curve (AUC) and terminal half-lives (T1/2), were determined in both epileptic patients and healthy subjects following all three doses.The meanTmaxvalues were similar for all three dose levels in both patients and subjects, indicating that the rate of absorption was comparable. MeanCmaxvalues increased in a dose-related manner with increasing dose in epileptic patients. The corresponding values showed a dose-proportional relationship in healthy subjects. The relationship betweenCmaxvalues and the administered dose did not change in patients or subjects when the data was corrected for dose and/or body weight. After the peak, plasma levels declined, but were still quantifiable in most patients and subjects at 36 h following all three doses. The mean AUC values increased in a dose-proportional manner with increasing dose in healthy subjects. The corresponding mean patient data appeared to increase in a dose-related manner. The relationship between AUC values and size of the administered dose did not change in either patients or subjects when the data was corrected for dose and/or body weight. The terminal elimination half-lives (T1/2) were apparently shorter in patients compared to the healthy subjects and were independent of the dose administered.

ISSN:1075-2765    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

This was a pilot, single-center, single-dose, open-label, randomized three-way crossover study comparing the relative bioavailability of pamidronate disodium after oral doses of the drug administered as four capsules, each containing 75 mg enteric-coated pellets, two 150-mg enteric-coated tablets and 300 mg in solution (reference standard) in patients with postmenopausal osteoporosis. Results from seven patients are reported; five subjects completed all three phases of the study-one received solution and pellets, and another one received pellets and tablets. The onset of urinary excretion (an indicator of relative onset of oral absorption) of pamidronate disodium occurred in the first 2 h in all (except one) patients for solution and pellets, whereas the onset of urinary excretion for the tablets was prolonged and more variable. The extent of absorption was estimated in terms of percent of administered dose excreted in urine up to 72 h after dosing. The extend of absorption was highest after the pellets (mean ± S.D., 0.37 ± 0.27%), followed by the solution (0.20 ± 0.16%). The extent of absorption after the tablets (0.09 ± 0.10%) was the lowest and most variable. The poorer and more variable bioavailability of the tablets may be explained by the longer and more variable residence time of the tablets in the stomach.

ISSN:1075-2765    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The objective of this study was to determine the pharmacokinetics of pamidronate disodium in plasma and urine after a single intravenous infusion of the drug to cancer patients at risk for developing bone metastases. Thirty-six patients were randomized into six treatment groups to receive 30-, 60− or 90-mg doses of the drug by 4− or 24-h intravenous infusions. Plasma and urine samples were collected at intervals for up to 144 h after drug administration and were assayed for pamidronate disodium using validated reversed-phase HPLC methods. The percentage of the administered dose excreted in urine following a 4− or 24-h infusion of 30-, 60− or 90-mg pamidronate disodium ranged from 30% to 60% except for one individual who excreted 96% by this route of elimination. There was a linear relationship between amount of drug excreted in urine and dose. Curve fitting of ARE (amount of drug to be excreted in urine) data indicated that the disposition kinetics of the drug was consistent with a biexponential process with overall mean ± S.D. half-life values of 2.1 ± 1.8 and 26.9 ± 8.7 h for the À and β phases, respectively. The results of this study showed that the drug exhibited dose proportionality in its pharmacokinetic behavior over the 30–90-mg range regardless of whether it was infused over a 4− or 24-h interval.

ISSN:1075-2765    

出版商:OVID    

年代:1994

数据来源: OVID