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Biomedical subjects

B J Zarowitz

Publications and source records attributed to B J Zarowitz.

At least 19 recordsLinked to original sources
PubMed1992

Review of randomized trials of digoxin therapy in patients with chronic heart failure.

Although digitalis glycosides were introduced in the treatment of cardiac maladies greater than 200 years ago, controversy persists regarding the precise role of digoxin in any multidrug approach to the treatment of congestive heart failure (CHF). Despite its widespread use for more than 2 centuries, only recently have double-blind, randomized, placebo-controlled trials of digoxin therapy been conducted in patients with moderate CHF and sinus rhythm. These trials demonstrate that digoxin is superior to placebo in improving left ventricular (LV) ejection fraction, increasing exercise capacity, and preventing CHF worsening. Digoxin produces benefits similar to those seen with angiotensin converting enzyme (ACE) inhibitors with regard to clinical compensation and improvement in LV function. However, improved survival is demonstrated only in response to ACE inhibitors. The recently completed RADIANCE study addresses the value of combining digoxin with ACE inhibitor therapy in patients with mild-to-moderate CHF. Because increased mortality has been reported with the newer oral inotropic agents, it currently appears that digoxin is the only oral inotropic agent useful in clinical practice in the treatment of CHF. However, the effects of digoxin on mortality in patients with CHF remain unknown. In the large, double-blind, randomized trial conducted by the National Heart, Lung, and Blood Institute, the effects of digoxin on mortality in patients with CHF and already being treated with ACE inhibitors are currently being evaluated. Presently, based on the results of placebo-controlled studies, it appears that digoxin, alone or in combination with ACE inhibitors, is beneficial in patients with any signs or symptoms of CHF due to systolic LV dysfunction.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Determination of free serum digoxin concentrations in digoxin toxic patients after administration of digoxin fab antibodies.

Digoxin fab antibody therapy is known to interfere with digoxin immunoassays causing spurious serum digoxin concentrations. The reliability and precision of three digoxin immunoassays--Baxter Dade Stratus (BDS), Syva affinity column enzyme-mediated immunoassay (EMIT), and the reference assay Abbott TDx fluorescence polarization immunoassay following ultrafiltration (FPIA-UF)--were compared in eight digoxin toxic patients treated with digoxin fab antibodies. Five to eight blood samples were drawn serially up to 204 h post digoxin fab therapy. The serum digoxin concentration in each sample was determined by each of the three assays. The mean (+/- SD) area under the serum digoxin concentration-time curve was significantly lower for FPIA-UF than for BDS or EMIT (86.1 +/- 58.2 vs 158.1 +/- 88.6 and 176.3 +/- 115.3 h.ng/ml p less than 0.01, respectively). BDS correlated better with FPIA-UF (r2 = 0.71) than did EMIT (r2 = 0.45). Predictive performance of the BDS and EMIT assays demonstrated that the mean prediction error (bias) (0.62 vs 0.78 ng/ml) and the mean squared prediction error (precision) (0.48 vs 0.76) differed significantly from zero (p less than 0.05). However, BDS had significantly less bias and greater precision than did EMIT (p less than 0.05). In the presence of digoxin fab antibodies, BDS is a better predictor of free serum digoxin concentration than is EMIT, but both have considerable bias. Based on these results, FPIA-UF should be the assay of choice for determining free serum digoxin concentrations during fab therapy.

Adult↗
PubMed1992

"Brain attack": an indication for thrombolysis?

OBJECTIVE: The primary objective of this article is to introduce the reader to the use of thrombolytics in the acute treatment of ischemic stroke. Theory and experimental evidence to support this approach are emphasized in addition to potential adverse effects of thrombolysis. DATA SOURCES: A MEDLINE search was used to identify pertinent literature, including reviews. STUDY SELECTION: Studies were selected for detailed review if they involved stroke patients and addressed possible toxicities of therapy. Any abstracts concerning ongoing clinical trials also were reviewed. DATA EXTRACTION: Data from animal investigations using tissue plasminogen activator for the acute treatment of several models of cerebral ischemia were used to support the importance of early treatment (within six hours of symptom onset). Also, studies performed in animal models of stroke revealed that thrombolysis could be accomplished safely in acute ischemic stroke. All human studies published to data are anecdotal case reports, but point to the safety of thrombolysis if administered early. Reviews of ongoing multicenter trials are taken from published abstracts and proceedings. DATA SYNTHESIS: Thrombolysis holds promise as a hyperacute therapy for acute stroke; however, the risk of intracerebral hemorrhage remains. Crucial to the success of this and any other therapy for acute stroke is the ability to treat patients within hours of symptom onset. Also, the importance of concomitant medications such as heparin and aspirin has not yet been addressed. CONCLUSIONS: Pharmacists need to be knowledgeable of new treatments of stroke and the risks associated with them. As patient educators, pharmacists can contribute to public awareness by promoting the early recognition of stroke symptoms. As pharmacotherapists, pharmacists need to understand the risks and the important monitoring parameters related to thrombolysis. The results of ongoing multicenter clinical trials are awaited before making a final judgment on the usefulness of thrombolysis in acute ischemic stroke.

Anistreplase↗
PubMed1992

Prediction of glomerular filtration rate using aminoglycoside clearance in critically ill medical patients.

OBJECTIVE: The aim of this preliminary investigation was to evaluate the use of aminoglycoside serum concentrations as a surrogate measure of the glomerular filtration rate (GFR) in comparison with other measured and empiric methods against inulin, the criterion standard measure of GFR. DESIGN: A consecutive sample of all eligible patients. SETTING: An eight-bed medical intensive care unit in a university-affiliated tertiary-care teaching hospital. PATIENTS: Ten critically ill medical patients receiving gentamicin or tobramycin for presumed or documented gram-negative bacillary infection were enrolled in the study. The patients were mechanically ventilated and had underlying organ system dysfunction. All ten patients completed the study. INTERVENTION: Patients underwent renal functional assessment by measured inulin (Cl(in)) and 24-hour urinary creatinine clearance (Clcr). Aminoglycoside serum concentrations were used to estimate GFR and were compared with the two measured methods and a creatinine clearance calculated with the Cockcroft-Gault method (ClCG). All evaluations were performed the same day. RESULTS: Cl(in) averaged 51.6 +/- 35.0 mL/min and serum creatinine ranged from 0.3 to 5.4 mg/dL (26.5 to 477.3 mumol/L). Steady-state peak and trough aminoglycoside concentrations were 6.1 +/- 1.4 and 1.3 +/- 0.9 micrograms/mL, respectively. There were no statistically significant differences between the various methods, although the aminoglycoside-calculated GFR (Cl(amg)) 95 percent confidence intervals were smaller than Clcr and ClCG compared with Cl(in). Mean absolute errors were smaller with Cl(amg) than with Clcr and ClCG. Regression results indicated that only Cl(amg) and ClCG demonstrated agreement with Cl(in) (lines not different from y = x). However, the Cl(amg) showed closer agreement, with a mean square error almost half that of ClCG (9.6 vs. 18.1). CONCLUSIONS: Cl(amg) can be used routinely as an estimate of GFR in critically ill patients, with less error than empiric methods.

Adult↗
PubMed1992

Population pharmacokinetics of gentamicin. Use of the nonparametric expectation maximisation (NPEM) algorithm.

A new nonparametric expectation maximisation (NPEM) algorithm for the estimation of population pharmacokinetic parameter values was evaluated. The algorithm, in the form of a personal computer program, was used to compute population pharmacokinetic parameter densities of gentamicin in a group of 9 patients with indicators of malnutrition. The 1-compartment parameter values for clearance (CL), volume of distribution (Vd) and elimination rate constant (k) were compared with values generated using a standard 2-stage (STS) approach. NPEM was used with a full data set (72 gentamicin concentrations) and a sparse data set (only peak and trough concentrations for each patient; 18 in total). There were no differences in parameter value estimations between the STS and NPEM with all the data (p greater than 0.05) or with the sparse data (p greater than 0.05). Mean parameter value estimates from the STS and NPEM (with sparse data) were used as a priori data sets in the USC*PACK gentamicin Bayesian program to predict concentrations in 8 subsequent patients with similar indicators of malnutrition. There were no differences in predicted gentamicin concentrations between STS (3.75 +/- 2.06 mg/L) and NPEM (3.75 +/- 2.17 mg/L). NPEM was able to generate population pharmacokinetic parameter values for gentamicin in a defined population of patients using sparse routine clinical data. It was also shown to function with only a single data point per patient.

Aged↗
PubMed1991

Is there a reliable index of glomerular filtration rate in critically ill patients?

Assessment of renal function in critically ill patients is important for appropriate individualization of dosage regimens and nutrition, but is complicated by a high incidence of acute renal failure (ARF). The most common cause of ARF in intensive care unit (ICU) patients is hypoperfusion. Other causes of ARF include intrinsic injury, nephrotoxicity, and postrenal obstruction. ARF is associated with a decreased glomerular filtration rate (GFR), reduced or maintained urine output (nonoliguric renal failure), and alterations in other commonly obtained urinary indices. Twenty-four-hour or shorter urinary creatinine clearance studies may overpredict GFR as creatinine is both filtered and secreted. The use of serum creatinine in empiric predictive equations is impaired in ICU patients because of decreases in creatinine production due to immobilization and malnutrition or increases in creatinine production due to catabolic illnesses. Adjustment of empiric methods by employing lean body weight, ideal body weight, or corrected serum creatinine values has not been evaluated against uncorrected values in this population, but is routinely performed in clinical practice. Inulin and radiolabeled substances are not practical for routine clinical use and may overpredict GFR in ARF due to backleak of large molecular-weight substances through the tubules. Comparative clinical trials have shown essentially equivalent performance of empiric methods relative to 24-hour urinary creatinine clearance in adults. No studies have compared these methods to a reference method for determination of GFR. Until conclusive data become available, clinicians should cautiously compare results from at least two independent methods of assessment to estimate renal functional impairment in ICU patients.

Acute Kidney Injury↗
PubMed1991

Monitoring serum digoxin concentrations during digoxin immune Fab therapy.

Measurement of serum digoxin concentrations (SDCs) is used routinely in the diagnosis of digoxin toxicity. Following administration of the antidote, digoxin immune antigen binding fragments (Fab), SDC monitoring is hampered by assay-related problems because of the presence of Fab in the serum. Recent evidence has suggested several available methods to monitor free SDC during Fab therapy. This report describes the utility of monitoring free SDC following Fab administration. Free SDCs were obtained using an ultrafiltration and fluorescence polarization immunoassay system in three patients over periods of up to 204 hours after Fab administration. In each case, the decline in free SDC was temporally related to the resolution of digoxin toxicity; in one case, digoxin intoxication recurred and was associated with a rebound increase in free SDC. In addition to the therapeutic benefits, prospective monitoring of free SDC in two of the patients also may have resulted in cost savings secondary to reduced hospital stay or less use of Fab.

Adult↗
PubMed1991

Body composition analysis by bioelectrical impedance: the effects of time of day and body side on estimated gentamicin pharmacokinetics.

To assess if repetitive measures are useful in a clinical setting, the effects of time of day and body side on bioelectrical impedance (BI) measurements were evaluated. Fifteen healthy, male volunteers underwent serial BI measurements at 0, 3, 6, 9, 24, and 48 hours on both sides of the body using a four-electrode plethysmograph. Analysis of variance for repeated measures indicated that the mean resistance (R) value of the right side was statistically lower from that of the left side (447 +/- 27.9 vs 457 +/- 29.1 ohms; p = 0.006). Both R and reactance (Xc) varied significantly over time. For R, the mean response at 0, 6, 9, and 48 hours was different from the overall mean of the remaining time points (p less than 0.007). Only times 6 and 24 hours were significantly different for Xc (p less than 0.006). No relevant time and side effects were noted in calculated gentamicin pharmacokinetic parameters on incorporation of BI measurements into impedance-derived predictive equations for clearance, volume of distribution, and elimination constant. Correlation coefficients of reliability were high within 1 day and across days (R greater than or equal to 0.8407). These data suggest that under normal conditions, BI analysis provides reliable results, and that time and side standardizations in its measurements are not necessary.

Adult↗
PubMed1990

Bioimpedance assessment of antipyrine pharmacokinetics before and after enzyme induction.

Bioimpedance (BI) technology, a noninvasive method of measuring body composition, has been previously used to develop a predictive model for metabolic clearance under basal conditions. The present investigation was conducted to assess the ability of BI-derived models to predict drug disposition in a perturbed system. An antipyrine pharmacokinetic and impedance analysis of 15 healthy male subjects was performed before and on the 14th day of phenobarbital administration (i.e., after enzyme induction). The all subsets multiple regression technique was used to develop preinduction models for clearance (CI), (p = 0.021, R2 = 0.654) and volume of distribution at steady-state (Vdss) (p = 0.001, R2 = 0.867), using demographic and mean BI parameters. The preinduction Cl model significantly underestimated postinduction measurements and was not predictive of changes in Cl. The preinduction Vdss model was predictive of postinduction Vdss. It appears that the BI-derived model is unable to predict perturbations in metabolic clearance caused by enzyme induction.

Adult↗
PubMed1990

Expanded gentamicin volume of distribution in patients with indicators of malnutrition.

Visceral protein, body weight, and body composition were assessed in patients receiving gentamicin to determine whether a meaningful analysis of nutritional status can be used to identify patients with an expanded gentamicin volume of distribution (V). Adults with gram-negative infections were selected sequentially from among hospitalized patients being treated with gentamicin. Serum gentamicin concentrations before and after an intravenous dose of gentamicin were determined by an enzyme-mediated immunoassay. Noncompartmental analysis was used to determine pharmacokinetic variables. Body composition was assessed by bioelectric impedance techniques. Of 26 patients, 10 were considered to be at high risk of malnutrition by meeting at least two of the following criteria: serum albumin concentration, less than or equal to 3.5 g/dL; actual weight, less than 80% of ideal weight; and ratio of exchangeable sodium to exchangeable potassium (Nae/Ke), greater than 1.22. The non-high-risk group (n = 16) had a gentamicin V at steady state of 0.294 +/- 0.105 L/kg (mean +/- S.D.), which was significantly lower than that observed in the high-risk group (0.415 +/- 0.294 L/kg). The accuracy of the high risk classification in identifying patients with an expanded gentamicin V was improved by revising the definition of the high-risk group. In the revised definition, patients were considered to be at high risk for malnutrition if they met at least two of the following criteria: serum albumin concentration, less than or equal to 3.1 g/dL; actual weight, less than 90% of ideal weight; and Nae/Ke' greater than 1.22.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Relationship between values of bioelectrical impedance and creatinine clearance.

This investigation was conducted to determine if measurements of bioelectrical impedance in conjunction with serum creatinine concentrations are useful in predicting creatinine clearance. Twenty-eight healthy volunteers between 23 and 50 years of age followed an individualized protein diet to provide 1.2 g protein/kg/day for 3 consecutive days. At the beginning of day 3, a 24-hour urine collection was initiated. At the midpoint of urine collection, bioelectrical impedance measurements of resistance and reactance were taken, together with a single blood sample for assessment of serum creatinine concentration. Multiple linear regression techniques were used to identify significant values for predicting creatinine clearance. Resistance and serum creatinine concentration were identified as significant predictors. The measured creatinine clearance was compared to that predicted by the impedance-derived model that we developed, as well as other established estimation methods. Mean absolute prediction errors in creatinine clearance using this model were significantly lower than those obtained using four empiric methods. Bioelectrical impedance may provide a noninvasive, quick, and accurate method for predicting creatinine clearance from serum creatinine concentration values.

Adult↗
PubMed1989

Bioelectrical impedance modelling of gentamicin pharmacokinetic parameters.

1. Bioelectrical impedance analysis was used to develop descriptive models of gentamicin pharmacokinetic parameters in 30 adult in-patients receiving therapy with gentamicin. 2. Serial blood samples obtained from each subject at steady state were analyzed and used to derive gentamicin pharmacokinetic parameters. 3. Multiple regression equations were developed for clearance, elimination rate constant and volume of distribution at steady state and were all statistically significant at P less than 0.05. 4. Clinical validation of this innovative technique is warranted before clinical use is recommended.

Aged↗
PubMed1989

Relationship of bioelectrical impedance to pharmacokinetic parameters of theophylline in healthy males.

Bioelectrical impedance is a reliable, safe, non-invasive and valid method of determining body composition, using measures of resistance and reactance by passing a low voltage alternating current through the body. This study investigates relationships between the pharmacokinetics of theophylline and parameters of bioelectrical impedance in 15 non-smoking, healthy, adult male volunteers. After an overnight fast, subjects received 5 mg/kg of aminophylline intravenously over 30 minutes. Blood samples were obtained serially over a period of 12 hours. Bioelectrical impedance measurements were made in triplicate, using a 4-electrode plethysmograph. Sera were assayed in duplicate by enzyme-mediated immunoassay (coefficient of variation less than 5%), and data were fitted to a non-compartmental regression program. An all-subsets multiple-regression technique was employed to arrive at predictive equations for theophylline clearance (CL) and volume of distribution at steady-state (Vss) using age, height, weight and mean bioelectrical impedance parameters. Equations for Vss and CL revealed p-values of less than 0.001 and coefficients of variation of 8.5 and 13.33% respectively. Although the equations display some degree of colinearity they account for 95 and 86.5% of the variability in Vss and CL respectively, and represent an innovative approach to the estimation of pharmacokinetic parameters.

Adult↗