摘要:

Study Objectives. To discern the frequency of torsades de pointes and QT prolongation in patients receiving intravenous erythromycin lactobionate; to examine the degree of QT prolongation and QT dispersion due to intravenous erythromycin in a typical clinical setting; and to identify any concurrent factors that might predispose patients to excessive QT prolongation or torsades de pointes while receiving intravenous erythromycin.Design. Retrospective cohort trial.Setting. A university teaching hospital.Patients. All inpatients who received intravenous erythromycin lactobionate during a 1‐year period.Measurements and Main Results. The records of 278 consecutive patients were analyzed, of whom 49 had 12‐lead electrocardiograms while receiving and not receiving erythromycin. The dosages of erythromycin ranged from 18–83 (42 pL 18) mg/kg/day. Of the 49 patients, the baseline QTc was 432 ± 39 msec, compared with 483 ± 62 msec during erythromycin therapy (p<0.01). In 30 of 49 patients with heart disease, the increase in QTc due to erythromycin was 15 ± 11%, compared with 8.6 ± 10% in the 19 patients without heart disease (p<0.05). The degree of QTc dispersion was 34 ± 16 msec at baseline, compared with 80 ± 35 msec with erythromycin (p<0.01). Overall, 19 (39%) of 49 patients had a moderate to severe delay in ventricular repolarization (QTc ≥ 500 msec). Of the 278 patients prescribed intravenous erythromycin over the year, it caused torsades de pointes in just one (≤ 0.4%).Conclusion. Erythromycin lactobionate‐induced torsades de pointes is rare, although QT prolongation is common. Some patients may be at risk for suffering torsades de pointes due to this agent, particularly if heart disease or other factors that may further delay ventricular repolariz

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1995.tb02883.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Study Objectives. To compare three quantitative metabolic markers used to assess hepatic function, indocyanine green (ICG), a high‐extraction marker; antipyrine, a low‐extraction marker; and dextromethorphan, a P‐450IID6 marker, with the clinically used Pugh's classification.Design. Comparison of 12 healthy controls with 12 age‐ and sex‐matched patients with different degrees of liver disease.Setting. Research center in a university‐affiliated teaching hospital.Patients. The 12 patients had different degrees of liver disease: 4 mild (Pugh's score 6 or 7); 4 moderate (Pugh's score 8 or 9); and 4 severe (Pugh's score ≥ 10). Each level had an equal number of men and women subjects.Measurements and Main Results. Clearance of ICG detected mild alterations in hepatic function as efficiently as it did for moderate and severe impairment, but it lacked the specificity to distinguish among the classification groups. In contrast, antipyrine was effective in identifying moderate and severe hepatic impairment; however, its clearance was not reduced in mild liver disease. Pugh's classification appears to be a clinically useful method of assessing the global degree of hepatic impairment in patients with chronic disease, and there was a significant correlation between it and antipyrine clearance (r=0.67, p=0.0003) and ICG clearance (r=0.86, p=0.0001). Four of eight patients with a Pugh's score greater than 8 had a dextromethorphan metabolic ratio expression reflective of a poor metabolizer phenotype based on 0‐ to 4‐hour urine collection, but only two of those eight patients were classified as poor metabolizers based on 4‐ to 12‐hour urine collection. These percentages of poor metabolizers are substantially higher than for historical controls (8.5–10.4%) and most likely reflect a decrease in the P‐450IID6 functional ability with progression of liver disease. However, due to small sample size and lack of knowledge of the patients' genotypes, these data are only suggestive.Conclusion. Pugh's classification appears to be a reliable indicator of the degree of chronic liver disease and could be employed as a drug development research classification tool; however, it does not replace quantitative metabolic markers, especially

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1995.tb02884.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Study Objective. To evaluate the possibility of a drug interaction with zidovudine and histamine2‐receptor antagonists in individuals infected with the human immunodeficiency virus.Design. Randomized crossover study.Setting. University‐affiliated research center.Patients. Six HIV‐infected individuals.Interventions. The subjects received 7‐day regimens of zidovudine 600 mg/day alone, zidovudine with cimetidine 1200 mg/day, and zidovudine with ranitidine 300 mg/day.Measurements and Main Results. The renal clearance of zidovudine when given alone was 0.41 L/kg/hour, and was reduced to 0.18 L/kg/hour (p=0.002) when given with cimetidine. In the presence of cimetidine the urinary excretion of zidovudine decreased from 89.5 to 53.7 μM (p=0.01), the urinary ratio of metabolite to parent increased from 5.16 to 9.96 (p=0.0001), and the fraction of zidovudine converted to metabolite increased from 0.86 to 0.92 (p=0.0025).Conclusion. Cimetidine presumably inhibits the renal clearance of zidovudine by competing for tubular secretion. Based on the observation that neither cimetidine nor ranitidine had a significant effect on serum concentrations of zidovudine or zidovudine glucuronide, a change in the dosage of zidovudine is not w

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1995.tb02885.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Study Objective. To determine the variation of prothrombin times and international normalized ratio (INR) over 24 hours in humans.Design. Prospective, parallel study.Setting. University‐affiliated general clinical research center.Patients. Six patients receiving long‐term warfarin therapy and six sex‐matched controls.Interventions. Warfarin was administered to the patients at 6:00 P.M.Measurements and Main Results. Prothrombin times and INR were determined every 2 hours over 24 hours. Time of study entry, meals, and sleep cycles were controlled. A significant cosinor rhythm for prothrombin times and INR (p≤0.03) occurred in warfarin‐treated patients, suggesting that diurnal variation occurs. The mean difference between the peak and trough prothrombin times was 1.8 ± 0.9 seconds (range 0.8‐3 sec) with a mean change of 9.3% ± 3.7%. The peak prothrombin time and INR values occurred between 4:00 A.M. and 8:00 A.M. in five patients, and trough values between 6:00 P.M. and midnight in five. No significant cosinor rhythm was noted for controls (p>0.5).Conclusion. Significant variations in prothrombin time and INR occurred in patients receiving warfarin therapy, with the highest values occurring in the morning and the lowest in the evening. These results may have clinical implications for patients receiving either high‐ or low‐intensity

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1995.tb02886.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

The refeeding syndrome (RS) is a complication of nutritional support that potentially causes considerable morbidity and mortality. Compensatory metabolic alterations secondary to chronic starvation predispose malnourished patients to RS. Providing nutritional support initiates an intracellular shift of potassium, magnesium, and phosphate that results in many adverse effects. The literature addressing RS focuses on only one electrolyte abnormality, hypophosphatemia; however, often all three electrolyte levels are perturbed. Thus RS should be characterized as a syndrome of generalized fluid and electrolyte imbalance. Recommended electrolyte supplementation and laboratory monitoring can help prevent the disorder in susceptible patients.

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1995.tb02887.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

In a comparison of drug safety and efficacy, 40 adult outpatients with clinical signs and symptoms of nongonococcal urethritis or mucopurulent cervicitis were treated with either clarithromycin 250 mg or doxycycline 100 mg twice/day for 7 days. Clinical and laboratory evaluations were repeated during, at the end, and 3 weeks after the completion of therapy. Isolation and susceptibility tests ofChlamydiaandMycoplasmaisolates were performed at each visit. All but one patient who received doxycycline were clinically cured or improved at the end of treatment. Two (10%) patients who received clarithromycin and three (15%) who received doxycycline had clinical relapses of the infection. All isolates ofChlamydia trachomatiswere eradicated and did not recur in both groups. Doxycycline was more effective than clarithromycin in eradicatingUreaplasma urealyticum(p<0.01). Both groups reported a high frequency of minor adverse effects, but no patient discontinued therapy. Overall, clarithromycin was clinically safe and effective treatment in patients with nongonococcal urethritis and mucopurulent cervicitis.

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1995.tb02888.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

The primary objective of this study was to determine if a pharmacist‐managed anticoagulation monitoring service (AMS) improved the outcomes of patients receiving warfarin in a family practice setting and was cost effective in treating and preventing thromboembolic disorders. A retrospective chart review was performed on all patients at the University of Florida's Family Practice Residency Program who received warfarin pharmacotherapy between October 1, 1988, and December 15, 1993. The outcomes of patients followed by AMS were compared with those of a control group consisting of patients receiving warfarin but followed only by their physician. Outcomes were evaluated based on the number of thromboembolic and hemorrhagic events, as well as unplanned clinic visits, emergency room visits, and hospital admissions. Cost of hospital admissions, emergency room visits, and participation in the AMS were analyzed. During 28 person‐years of treatment, control subjects sustained 12 thromboembolic events (2 pulmonary embolisms, 1 cerebrovascular accident, and 9 deep venous thromboses) and 2 minor and 5 major hemorrhagic events. The study group reported two minor hemorrhagic events during a total of 60 person‐years. The control group was 20 times more likely than the study group to experience any event (rate ratio 20, 95% CI 5–87). In addition, hospitalization and emergency room charges indicated an actual cost of $119,074.95 for the control group's events. The cost to this group for 28 person‐years of participation in the AMS would have been $5040.00. A potential cost avoidance of $4072.68 per person‐year of follow‐up may have been possible if these patients had been followed by the AMS. A pharmacist‐managed AMS in a family practice setting can result in improved outcomes for patients receiving warfarin and is

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1995.tb02889.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

In a review of medical records of 530 recipients of danazol at Group Health Cooperative of Puget Sound, we identified 154 (29%) people who reported at least one adverse event that occurred within 45 days after receiving the drug. In no patient did the event require hospitalization, and there were no known long‐term sequela

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1995.tb02890.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Elevated aluminum concentrations have been implicated in several disease states in the elderly. We examined the effects of sucralfate, a basic aluminum salt of sucrose sulfate, and ranitidine, administered individually and in combination, on plasma and urine aluminum concentrations in the elderly in a prospective, randomized, three‐arm crossover study. Subjects were 20 healthy volunteers over age 65 years, with no clinically significant comorbidities or recent use of aluminum‐containing drugs or histamine (H)2‐antagonists. The three regimens were ranitidine 300 mg at bedtime, sucralfate 1 g 4 times/day, and ranitidine 300 mg at bedtime plus sucralfate 1 g 4 times/day, administered for 4 weeks, with a washout period of at least 1 week between regimens. Plasma and urine aluminum concentrations were measured on days 0, 1, 7, 14, and 28 of each regimen. After 28 days, mean plasma aluminum concentrations were significantly higher in subjects receiving sucralfate alone (8.5 ± 1.8 μg/L) and sucralfate plus ranitidine (5.1 ± 1.3 μg/L) compared with those receiving ranitidine alone (2.4 ± 0.7 μg/L). Urine aluminum concentrations were significantly higher in subjects receiving sucralfate alone (133.2 ± 32.8 μg/g creatinine) and sucralfate plus ranitidine (148.1 ± 51.9 μg/g creatinine) compared with those receiving ranitidine alone (11.0 ± 3.7 μg/g creatinine). There was no significant difference in plasma or urine aluminum concentrations between subjects who received sucralfate alone versus those who received sucralfate plus ranitidine. Sucralfate 4 g/day in elderly subjects produces a significant increase in both plasma and urine aluminum concentrations, compared with ranitidine 300 mg/day. This increase most likely is secondary to gastrointestinal absorption of aluminum in the sucralfate formulation. The clinical relevance of this increase requires f

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1995.tb02891.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

We compared agreement between creatinine clearance values in obese, critically ill patients calculated using three common empirically derived formulas and modifications thereof, with creatinine clearance obtained by conventional 24‐hour urine collection. We selected the charts of of 22 patients in intensive care units (86% medical, 14% surgical) according to the following criteria: actual body weight greater than 150% of ideal body weight; serum creatinine variation of less than 15% from the day of starting 24‐hour urine collection to the day before or after the collection; presence of a urinary bladder catheter; no history of renal dialysis; and clinical indication for renal function assessment. Mean measured 24‐hour urinary creatinine clearance for all patients was 72 ± 64 ml/minute (range 8–248 ml/min). The method of estimating creatinine clearance that showed the least mean bias was the equation of Salazar and Corcoran using a corrected serum creatinine concentration (mean bias −2 ml/min); however, the corresponding 95% confidence intervals were wide (‐133‐129 ml/min). The narrowest range of 95% confidence intervals were seen with Jelliffe's equation (mean bias 25 ml/min, 95% confidence intervals −41–90 ml/min). In this sample, estimated creatinine clearances did not agree acceptably with measured values. Despite low mean bias values, none of the empirically derived equations that we studied had clinically acceptable 95% confidence intervals. We recommend using the 24‐hour urine collection method when assessing creatinine clearance in obese, cri

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1995.tb02892.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY