Lawrence Warbasse

Disposition of intravenous and oral cyclosporine after administration with grapefruit juice.

To examine the effect of grapefruit juice on the disposition of cyclosporine after administration of oral and intravenous doses to healthy male subjects.

6′,7′‐Dihydroxybergamottin in grapefruit juice and Seville orange juice: Effects on cyclosporine disposition, enterocyte CYP3A4, and P‐glycoprotein

6′,7′‐Dihydroxybergamottin is a furanocoumarin that inhibits CYP3A4 and is found in grapefruit juice and Seville orange juice. Grapefruit juice increases the oral bioavailability of many CYP3A4 substrates, including cyclosporine (INN, ciclosporin), but intestinal P‐glycoprotein may be a more important determinant of cyclosporine availability.

Vancomycin pharmacokinetics in burn patients and intravenous drug abusers.

The pharmacokinetics of vancomycin were evaluated in 34 patients (10 burn patients, 14 intravenous drug abusers [IVDA], and 10 controls). Multiple serum samples were drawn following a 1-h vancomycin infusion at steady state over an 8- to 12-h dosing interval. Pharmacokinetic parameters were derived by noncompartmental analysis. There were no significant differences among the groups with respect to age, weight, serum creatinine, volume of distribution, or protein binding. Burn patients had a significantly higher creatinine clearance than did IVDA or controls. Vancomycin clearances averaged 142.8, 98.0, and 67.7 ml/min in burn patients, IVDA, and controls, respectively. The renal clearance of vancomycin was also higher in burn patients than in the other groups. IVDA tended to have a higher vancomycin clearance (31% higher) than did controls, but the difference was not statistically significant. Vancomycin clearance was much higher in burn patients requiring dosage individualization and close monitoring. A considerable amount of vancomycin was eliminated through renal tubular secretion, making dosage predictions based on creatinine clearance more difficult. Further work with IVDA will be needed to determine if they represent a group requiring aggressive vancomycin dosages.

Itraconazole and hydroxyitraconazole serum concentrations are reduced more than tenfold by phenytoin

To study the disposition of single doses of phenytoin and itraconazole when administered alone and after chronic treatment with the other drug.

The inability of physicians to predict the outcome of in-hospital resuscitation

OBJECTIVE: To measure the accuracy, reliability, and discrimination of physicians’ predictions of the outcome of in-hospital cardiopulmonary resuscitation (CPR), using a large series of detailed clinical vignettes of patients with known outcomes.DESIGN: Faculty and resident physicians at three university-affiliated generalist training programs were given one-page summaries of admission data for patients who later underwent in-hospital CPR. These summaries included all pre-arrest variables known to be related to the outcome of CPR. Physicians were asked to estimate the probability that patients would survive the resuscitation long enough to be stabilized, and the probability of survival to discharge.SETTING: Patient cases were derived from a consecutive series of patients undergoing CPR at two urban teaching hospitals in Detroit, Michigan.PARTICIPANTS: Faculty members and residents at a university-based department of internal medicine and two university-based departments of family medicine were surveyed.INTERVENTIONS: Accuracy of the physician predictions was assessed by comparing the mean predicted probability of survival with the percentage of patients who actually survived. The reliability of probability estimates of survival was evaluated by assessing the numerical proximity of the estimates to the actual outcome of the resuscitative effort. The ability to discriminate between survivors and nonsurvivors was measured by comparing the mean predicted probability of survival for those patients who survived CPR with that for those who did not, and by stratifying physician predictions and measuring the area under a receiver operating characteristic (ROC) curve.MEASUREMENTS AND MAIN RESULTS: Physicians (n=51) made a total of 713 estimates, and showed poor accuracy, reliability, and discrimination in predicting the outcome of in-hospital CPR. The mean predicted probability of survival to discharge did not differ between patients who actually survived to discharge and those who did not (29.5% vs 26.4%,z=0.35,p=.73). Similarly, the mean predicted probabilities of surviving resuscitation were the same for patients who actually survived long enough to be stabilized and those who did not (37.8% vs 39.9%,z=0.55,p=.58). Accounting for type of physician and institution by analysis of variance did not change this finding. The area under the ROC curve for the prediction of arrest survival was 0.476, which is not significantly different from 0.5, and is consistent with an ability to discriminate between survivors and nonsurvivors that is no better than random choice.CONCLUSIONS: Physicians were no better at identifying patients who. would survive resuscitation than would be expected by chance alone. Further work is needed to establish which variables are used by physicians in the decision-making process, and to design educational interventions that will make physicians more accurate prognosticators.

PATTERNS OF USE OF MAMMOGRAPHY AMONG INNER-CITY DETROIT WOMEN : CONTRASTS BETWEEN A HEALTH DEPARTMENT, HMO, AND PRIVATE HOSPITAL

This study assessed the pattern of utilization of mammography among 2,880 inner-city minority women 40 years of age or older who received ongoing primary care services during 1988 or 1989 at four practice sites operated by a health department (two sites), Health Maintenance Organization (HMO), and private hospital. Mammography referral could be documented for 23% to 32% of age eligible women and completed mammograms for 15% to 26%. Among women without a mammogram, 85% had never been referred while 15% were referred but unable to complete the procedure. In multiple logistic regression analysis, factors associated with mammography include age less than 70 years, presence of a breast cancer risk factor and more frequent clinic visits. Mammography was somewhat more frequent at the HMO and hospital clinic than at the health department, but this relationship varied with the womens previous visit and mammography experience. At sites serving uninsured women, mammography use was not associated with the presence or absence of health insurance. It is concluded that the underutilization of mammography is a substantial barrier to the early detection of breast cancer in each of the three different health care organizations studied, and that interventions to improve breast cancer control should focus upon facilitating physician referral practices.

Vancomycin protein binding in patients with infections caused by Staphylococcus aureus

The protein binding of vancomycin has been reported to range from less than 10 percent to 82 percent. We examined the binding of vancomycin in 34 patients (14 intravenous drug abusers, 10 burn patients, and 10 control patients) with Staphylococcus aureus infections. Blood samples were collected serially over an 8- or 12-hour dosing interval following a one-hour infusion. In vitro studies were also performed using albumin solutions of varying concentrations. Binding characteristics were determined through ultrafiltration with vancomycin concentrations analyzed by fluorescence polarization immunoassay. The unbound fraction of vancomycin ranged from 0.41 to 0.77 with a mean of 0.54 ± 0.08. Unbound fraction was significantly correlated with serum albumin concentration (r=-0.344, p<0.046) and renal clearance (r=0.394, p<0.021) but not with total body clearance or volume of distribution. In vitro data also showed an association between albumin concentration and unbound fraction (r=−0.94, p<0.017). Although vancomycin protein binding changes with serum albumin, this finding may have limited clinical significance.