ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb04693.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

From social outcast to citizen of the year in less than a decade is the stuff of fiction. That is precisely what has happened, however, to a remarkably simple molecule, nitric oxide. Nitric oxide is still an environmental pollutant, suspected carcinogen, and precursor of acid rain, but biologists are looking past its dark side. They now see a molecule that is uniting neuroscience, physiology, and immunology. Its ubiquitous distribution in the body and its multifaceted roles are revising our understanding of how cells communicate and protect themselves. This report examines nitric oxide's role in physiology and pathophysiology and reviews novel therapeutic approaches which involve inhibition or induction of the activity of endogenous nitric oxide.

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb04694.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

The appropriate implementation of the various modalities of gastrointestinal (GI) decontamination is critical in the management of the pediatric patient who is examined in the emergency department or private office after an acute ingestion. Gastrointestinal decontamination includes gastric lavage, syrup of ipecac, activated charcoal, and whole bowel irrigation. Clinical studies have delineated the role and efficacy of these procedures. Trends in GI decontamination place less emphasis on ipecac and gastric lavage and more emphasis on activated charcoal alone in the patient with a mild overdose. Gastric lavage is indicated in serious ingestion and is most effective if done soon after the exposure. Whole bowel irrigation is the newest addition and has important clinical use in the treatment of serious iron ingestions as well as in older adolescent cocaine body stuffers and packers. Indications and contraindications of the various forms of GI decontamination are discussed and relevant clinical studies are reviewed.

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb04695.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Initially synthesized in 1960, Sotalol is a novel beta‐adrenoreceptor blocking agent that also possesses class III anti‐arrhythmic properties. The drug's ability to lengthen repolarization and prolong effective refractory periods in all cardiac tissues in addition to its beta‐blocking effects make Sotalol an attractive agent for use in a variety of supraventricular and ventricular arrhyt

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb04696.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Anecdotal reports from clinical trials assessing the use of cyclosporine in the treatment of rheumatoid arthritis suggest an association between enhanced renal impairment and combined use of cyclosporine with nonsteroidal anti‐inflammatory drugs. To explore possible pharmacokinetic contributions to this phenomenon, a randomized, two‐period crossover investigation was performed in 24 healthy volunteers in which a single oral dose of 300 mg cyclosporine was administered alone and on day 10 of multiple oral dosing of aspirin 960 mg three times daily. Serial blood samples were obtained over 48 hours after each cyclosporine dose and over a steady‐state dosing interval for aspirin on day 9 (aspirin alone) and day 10 (coadministration of cyclosporine and aspirin). Cyclosporine whole blood concentrations were determined by a specific monoclonal radioimmunoassay and plasma concentrations of acetylsalicylic acid and metabolites by high‐performance liquid chromatography. Lack of a pharmacokinetic interaction was conclusively demonstrated for the rate and extent of cyclosporine and acetylsalicylic acid absorption and for the rate and extent of salicylic acid formation after a single dose of cyclosporine was coadministered during steady‐state aspirin dosing. If a clear association between enhanced renal impairment and the combined use of cyclosporine and aspirin is substantiated, the underlying mechanism appears to be pharmacodynamic rather than pharma

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb04697.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

The pharmacokinetics of azathioprine (AZN) were examined in 28 renal transplant patients treated orally with 25 to 150 mg AZN once daily in combination with cyclosporin A and prednisone, and after single intravenous (IV) injection of 5 mg/kg AZN using the rabbit as an in vivo model. The steady‐state concentrations of AZN observed in these patients ranged from 6 to 583 μg/L, and the interday coefficients of variation of the concentration in three randomly selected patients were 38%, 12%, and 4.6%. The frequency distribution pattern of the apparent oral clearance (TCLor) of AZN separates the patients almost equally into poor (TCLor= 0.126 to 4 L/hour · kg) and extensive metabolizers (TCLor= 5 to 12 L/hour · kg). The data obtained from the IV administration displayed the two‐compartment model characteristics with mean (standard error of the mean) of α, β, Vc, and total body clearance of 15.3 (2)/hour, 2.38 (.64)/hour, 1.05 (.3)L/kg, and 8.12 (1.26) L/hour · kg, respectively. The large variability in the pharmacokinetic parameters of AZN in patients and even in rabbits under carefully controlled conditions that may be ascribed to the complexity of its metabolism necessitates a careful approach to its dose

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb04698.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Sulindac was administered as a single 300‐mg oral dose to six patients with end‐stage renal failure and six normal subjects. Plasma concentrations of sulindac and its sulfide and sulfone metabolites were examined over a 48‐hour period. As determined by ultrafiltration methods at 37°C, the percentage free of sulindac and sulindac sulfide in plasma was greater, respectively, in the patients with renal failure (10.50 ± 2.42 and 9.96 ± 1.21) than in the normal subjects (6.78 ± 0.45 and 6.01 ± 0.37). Free sulindac plasma concentrations were not different between the two groups. However, sulindac sulfide, total and free, plasma concentrations were substantially decreased in the group with renal failure. Total area under the curve (AUC) of the sulfide metabolite was 18% in the normal subjects and the free AUC was 29%. In patients with renal failure, the apparent half‐lives of sulindac (1.98 ± 0.76 hours) and sulindac sulfide (15.6 ± 5.8 hours) were not different from those of normal subjects. Sulindac sulfone half‐life was highly variable and longer in the patient group. Studies of dialysis clearance showed that sulindac and its metabolites are poorly dialyzed. A 4‐hour dialysis period increased the plasma binding of both sulindac and sulindac sulfide in the patient group. Based on the decreased plasma concentration of the active sulindac sulfide metabolite in the patient group, dosage adjustments may be required in patients with end

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb04699.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Left ventricular end‐diastolic volume increased after 4 1/2 to 6 hours of space flight, but was significantly decreased after 5 to 6 days of space flight. To determine the role of acute gravitational effects in this phenomenon, responses to a 6‐hour bedrest model of 0 gravity (G; 5° head‐down tilt) were compared with those of fractional gravity loads of 1/6G, 1/3G, and 2/3G by using head‐up tilts of 10°, 20°, and 42°, respectively. On 4 different days, six healthy male subjects were tilted at one of the four angles for 6 hours. Cardiac dimensions and volumes were determined from two‐dimensional and M‐mode echocardiograms in the left lateral decubitus position at control (0), 2, 4, and 6 hours. Stroke volume decreased with time (P<.05) for all tilt angles when compared with control. Ejection fraction (EF) at −5° was greater than at +20° and +42° (not significant); EF at +10° was greater than at +42° (not significant). For the tilt angles of −5°, +10°, and +20°, mean heart rate decreased during the first 2 hours, and returned to control or was slightly elevated above control (+20°) by 6 hours (not significant). At the +42° angle of tilt, heart rate was increased above control at hours 2, 4, and 6. There were no significant differences in cardiac output at any time point for any tilt angle. Left ventricular end‐diastolic volume did not change significantly with time or tilt angle, but there was a trend to a decrease by hour 2. Left ventricular end‐systolic volume was increased at hour 2 (not significant) and at hour 4 (not significant) for subjects at −5°. Systolic blood pressure did not change significantly. Left ventricular end‐diastolic volume, left ventricular end‐systolic volume, stroke volume, ejection fraction, heart rate, and cardiac output were at control values by hour 6 for all tilt angles. The lack of a significant immediate change in left ventricular end‐diastolic volume despite decrements in stroke volume (P<.05) and heart rate (not significant) suggests that multiple factors may play a role in the adaptation to simulated hypogravity. The data indicate that no angle of tilt, whether head‐down or head‐up for 4 to 6 hours, mimicked exactly the changes in cardiovascular function recorded after 4 to 6 hours of flight. Thus space and bedrest changes in left ventricular end‐diastolic volume may be similar but possess a different time course. Nevertheless, head‐down tilt at 5° for 6 hours mimics some (stroke volume, systolic and diastolic blood pressure, mean arterial blood pressure, total peripheral vascular resistance), but not all, of the chan

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb04700.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

In animals, the R‐enantiomer of timolol causes a significant reduction in intraocular pressure but had only 1/80 the activity of the S‐enantiomer at extraocular receptors. The beta1‐ and beta2‐adrenoceptor blocking properties of orally administered R‐and S‐timolol were compared in a double‐blind placebo controlled trial in two groups of healthy men. Each subject in group A (n = 6) received placebo, 1 and 3 mg S‐timolol and 25 and 75 mg R‐timolol in random order, group B (n = 5) received placebo, 0.5, and 1 mg S‐timolol and 3 and 10 mg R‐timolol. In both groups, R‐and S‐timolol comparably inhibited isoproterenol‐induced increases in heart rate (P<.05), forearm blood flow (P<.05, except at 3 μg/minute of isoproterenol after the R‐doses in group B), and finger tremor (P<.05) in comparison with placebo. The findings for the R‐enantiomer in this study were unexpected based on the animal studies and previous studies that demonstrated marked differences in beta blocking effects of other beta‐blockers in which the

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb04701.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Thirty‐three patients with severe systemic hypertension defined as a diastolic blood pressure (DBP) ≥ 120 mm Hg were randomized in a single‐blind fashion to be treated with either intravenous fenoldopam mesylate (FNP) or sodium nitroprusside (NTP). Fenoldopam mesylate and NTP infusion rates began at 0.1 μg/kg/minute and 0.5 μg/kg/minute, respectively and were titrated to achieve a goal DBP of between 95 and 110 mm Hg; or a reduction of at least 40 mm Hg if the baseline DBP was>150 mm Hg. Fenoldopam mesylate (n = 15) reduced blood pressure from 217/145 ± 6/5 to 187/112 ± 6/3 mm Hg (P<.001) at an average infusion rate of 0.5 ± 0.1 μg/kg/minute. The average time to achieve goal DBP with FNP was 1.5 ± 1.4 hours. Nitroprusside (n = 18) reduced blood pressure from 210/136 ± 5/2 to 172/103 ± 6/2 mm Hg (P<.001) at an average infusion rate of 1.2 ± .24 μg/kg/minute. Nitroprusside response time averaged 2 ± 2.5 hours. There was no significant difference between the magnitude of effect seen with either FNP or NTP; nor was there any difference observed in the adverse effect rates of the two agents. Fenoldopam mesylate and NTP demonstrate similar overall efficacy in the treatment of severe syst

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb04702.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY