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Biomedical subjects

J L Bauman

Publications and source records attributed to J L Bauman.

At least 19 recordsLinked to original sources

Serum nifedipine concentrations and response of patients with pulmonary hypertension.

In patients with primary pulmonary hypertension who respond to nifedipine during acute drug testing, there is a significant linear correlation of serum nifedipine concentration with pulmonary artery pressure and resistance. Although most demonstrate an initial response at readily attainable nifedipine concentrations with conventional dosages, a subset of patients seem to display delayed or incomplete oral absorption; these results may facilitate the clinical use of nifedipine in patients with primary pulmonary hypertension.

Adult

Pharmacologic profile of survivors of acute myocardial infarction at United States academic hospitals.

Optimal drug therapy for patients with acute myocardial infarction (AMI) is well described in the medical literature. However, data on the actual pharmacologic management of patients surviving AMI at academic hospitals is unavailable. The purpose of this study was to document treatment profiles in 500 patients surviving AMI at 12 academic hospitals in the United States. These profiles were compared with established guidelines and were evaluated for trends. Overall, thrombolytics (streptokinase > or = tissue-type plasminogen activator) were administered in 29% of the patients, with a greater proportion of patients receiving beta-blockers than calcium channel antagonists in the initial 72 hours (61% vs 40%; p < 0.005) and at discharge (51% vs 35%; p < 0.005). Further, women were less likely than men to receive thrombolytic therapy (odds ratio [OR] = 0.61; confidence interval [CI], 0.54 to 0.69) or beta-blocker therapy within the first 72 hours (OR = 0.61; CI, 0.55 to 0.67) or at hospital discharge (OR = 0.53; CI, 0.48 to 0.58). Overall, improvements could still be made in the number of patients who receive thrombolytic and acute and chronic beta-blocker therapies after AMI, particularly in women. Changes in treatment profiles may be a reflection of the publication of large clinical trials.

Adrenergic beta-Antagonists

Cocaine concentration-effect relationship in the presence and absence of lidocaine: evidence of competitive binding between cocaine and lidocaine.

UNLABELLED: To better understand the interaction between cocaine and lidocaine, we studied the cocaine's concentration-effect relationship for action potential duration (APD) and the rate of rise of phase 0 of the action potential (Vmax) of canine papillary muscle in the presence and absence of lidocaine. We measured APD and Vmax during programmed stimulation and superfusion with normal Tyrode's, 30 microM cocaine and 30 microM cocaine + 30 microM lidocaine. Using two microelectrodes, we simultaneously recorded action potentials from two sites during programmed stimulation and measured the conduction velocity and effective refractory period during exposure to normal Tyrode's, cocaine and cocaine + lidocaine. Cocaine with or without lidocaine delayed the plateau of the APD restitution curve. At 1000 msec cycle length, the addition of 30 microM lidocaine to the superfusate containing 30 microM cocaine shortened the time constant for reactivation of Vmax from 514 +/- 63 to 234 +/- 28 msec (P < .01). Lidocaine also improved the conduction velocity decreased by cocaine, but did not significantly change the effective refractory period. The configuration of cocaine concentration-effect curve for APD was biphasic. For cocaine concentrations < 100 microM, APD progressively shortened prolonged with increasing concentrations. As cocaine concentrations increased > 100 microM, APD progressively shortened. The addition of lidocaine to the superfusate with cocaine > 100 microM tended to attenuate the progressive APD shortening due to cocaine. Lidocaine shifted the curve correlating cocaine concentration and reduction of Vmax rightward, but preserved Emax at cocaine concentration > 225 microM. These findings suggest competitive antagonism between cocaine and lidocaine at a single sodium channel receptor. CONCLUSION: lidocaine displaces cocaine from the sodium channel receptor through competitive binding. Lidocaine may prove to be beneficial in reversing cocaine-induced slowing of ventricular conduction.

Action Potentials

Bioavailability of total and unbound disopyramide: implications for clinical use of the immediate and controlled-release dosage forms.

This study further characterized the impact of concentration-dependent protein binding on the bioavailability and clinical use of the immediate-release (IR) and controlled-release (CR) dosage forms of disopyramide after single doses and during steady-state conditions in ten healthy volunteers. Consistent with the clinical use of these products, steady state has incorporated an IR to CR conversion step. Side effects and electrocardiographic actions were quantitated using a visual analog scale and serial Holter monitor recordings, respectively. Significant decreases resulted in area under the curve for total disopyramide between single dose and steady state: IR, 47.8 +/- 13.6 versus 33.0 +/- 6.4 mg/Lxh (P < .05); and CR, 46.9 +/- 9.5 versus 31.7 +/- 5.9 mg/Lxh (P < .05). In contrast, there were no differences in area under the curve for unbound disopyramide between phases or products. During conversion, the mean IR peak significantly decreased (P < .05) to the nadir before the first CR dose for total (37%) and unbound (60%) concentrations. There were no major differences in change in QT interval or side effects detected between products or phases. These findings indicate that, because of concentration-dependent protein binding, unbound, not total, concentrations should be used to estimate the bioavailability of disopyramide. Also, although the previously recommended conversion method (first CR dose 6 hours after the last IR dose) should provide an adequate transition in most, an alternative method (combined first CR with last IR dose) is indicated in select patients.

Adolescent

Cocaine-related sudden cardiac death: a hypothesis correlating basic science and clinical observations.

Sudden, unexpected death due to cocaine in young otherwise healthy individuals occurs in an idiosyncratic manner and is commonly felt to be arrhythmogenic in nature, although the exact cause of death is rarely documented. In addition to indirect sympathomimetic actions, cocaine is a potent sodium channel blocking drug and, in this regard, most closely resembles agents such as flecainide. We suggest that sudden death due to cocaine is proarrhythmic in nature, occurring under similar circumstances as that due to specific antiarrhythmic drugs.

Adult

Invasive and noninvasive methods to predict the long-term efficacy of amiodarone: a compilation of clinical observations using meta-analysis.

BACKGROUND: The method of choice to predict the long-term efficacy of amiodarone in the treatment of complex ventricular arrhythmias is unknown. Whether electrophysiological testing or Holter monitoring better predicts long-term outcome is controversial. METHODS AND RESULTS: We performed a meta-analysis of trials using electrophysiological testing or electrocardiographic monitoring to predict the efficacy of amiodarone in patients with sustained ventricular tachycardia. Arrhythmia recurrence data were combined after homogeneity testing across trials. Bayesian estimates and 95% credibility intervals were constructed to compare the arrhythmia-free probability among groups. Nine studies using electrophysiological testing (351 patients) and three using Holter monitoring (167 patients) met criteria for inclusion determined a priori. The combined arrhythmia-free probability estimate and credibility intervals were 0.86 (0.78-0.92) for patients rendered noninducible and 0.81 (0.73-0.87) for patients with abolition of ventricular tachycardia during Holter monitoring on amiodarone. With this primary analysis, there was no significant difference between the predictive value of noninducibility during electrophysiological testing and abolition of ventricular tachycardia with Holter. However, if only those electrophysiological studies using at least triple extrastimuli were included, arrhythmia-free probability for patients rendered noninducible increased to 0.96 (0.88-0.99), significantly better than noninvasive testing. CONCLUSIONS: Noninducible ventricular tachycardia during electrophysiological testing and abolition of ventricular tachycardia during electrocardiographic monitoring on amiodarone appear equally predictive of long-term amiodarone success, but this conclusion seems dependent on the stimulation protocol used. Although the yield is lower (compared to Holter monitoring), ventricular tachycardia rendered noninducible with a stimulation protocol using triple extrastimuli is the most highly predictive test of long-term amiodarone efficacy.

Aged

Effectiveness and costs of digoxin treatment for atrial fibrillation and flutter.

Clinical outcomes and costs associated with the use of digoxin in atrial fibrillation and flutter were evaluated in a prospective, observational study at 18 academic medical centers in the United States. Data were collected on 115 patients (aged > 18 years) with atrial fibrillation or flutter who were treated with digoxin for rapid ventricular rate (> or = 120 beats/min). The median time to ventricular rate control (i.e., resting ventricular rate < 100 beats/min, decrease in ventricular rate of > 20%, or sinus rhythm) was 11.6 hours from the first dose of digoxin for all evaluable patients (n = 105) and 9.5 hours for those only receiving digoxin (n = 64). Before ventricular rate control, the mean +/- SD dose of digoxin administered was 0.80 +/- 0.74 mg, and a mean of 1.4 +/- 1.8 serum digoxin concentrations were ordered per patient. Concomitant beta-blocker or calcium antagonist therapy was instituted in 47 patients (41%); in 19 of these, combination therapy was initiated within 2 hours. Adenosine was administered to 13 patients (11%). Patients spent a median of 4 days (range 1 to 25) in the hospital; 28% spent time in a coronary/intensive care unit and 79% in a telemetry bed. Loss of control (i.e., resting ventricular rate returned to > 120 beats/min) occurred at least once in 50% of patients and was associated with a longer hospital stay (p < 0.05). Based on 1991 data, the estimated mean hospital bed cost for patients with atrial fibrillation or flutter was $3,169 +/- $3,174.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Variability in plasma lipoprotein profiles when comparing diltiazem and propranolol.

OBJECTIVE: To examine the effects of diltiazem and propranolol on plasma lipoproteins in a double-blind, comparative trial. PATIENTS: Twenty-one mild-to-moderate hypertensive patients. METHODS: Following discontinuation of previous antihypertensive treatments, and a 4-week, single-blind, placebo run-in, subjects were randomized to receive sustained-release diltiazem or propranolol. Total cholesterol, high-density lipoproteins (HDL), low-density lipoproteins (LDL), and very-low-density lipoproteins (VLDL) were measured during placebo administration and after 12-16 weeks of treatment. RESULTS: No significant changes in plasma lipoprotein concentrations were noted in either the diltiazem or propranolol group compared with baseline values or each other. Marked variation in HDL, LDL, and VLDL were noted following drug treatment and in eight subjects whose lipoprotein concentrations were remeasured prior to drug treatment during the placebo period. The alterations were bidirectional, and similar in magnitude to those found following drug treatment. CONCLUSIONS: In many cases, changes in plasma lipoproteins reported to be a consequence of antihypertensive treatment may merely reflect normal intrapatient variability.

Adult

Impact of food on the pharmacokinetics and electrocardiographic effects of sustained release verapamil in normal subjects.

To evaluate the impact of food on the pharmacokinetics and electrocardiographic effects of sustained release (SR) verapamil tablets, 9 healthy men each received 3 single doses of verapamil in a randomized, crossover manner: 10 mg of intravenous verapamil, 240 mg SR verapamil on an empty stomach, and 240 mg SR verapamil with a standardized meal. PR intervals and racemic verapamil serum concentrations were measured serially over 30 hours after administration. The time to peak concentration was longer (7.5 +/- 3.0 vs 4.4 +/- 2.3 hours), resulting in a lower peak verapamil serum concentration (118 +/- 43 vs 175 +/- 50 ng/ml) when SR verapamil was administered with food (p < 0.05). Food tended to decrease the bioavailability of SR verapamil (34 +/- 12 vs 49 +/- 14%), although this difference did not reach statistical significance (p = 0.065). Precipitous or exaggerated release of verapamil from the SR tablet was not observed in any subject during the fasting state. Prolongation of the PR interval paralleled these alterations in serum concentration. The maximal change in the PR interval was greater (21 +/- 8 vs 14 +/- 5%; p < 0.05) when SR verapamil was given in the fasting state. Although an exaggerated verapamil release or effect was not observed, food significantly altered the absorption and electrocardiographic effects of a single dose of SR verapamil. Manipulation of the administration condition may be helpful in achieving desired outcomes.

Administration, Oral

Follow-up observations on 24-hour pharmacotherapy services in the emergency department.

OBJECTIVE: To analyze the impact of 24-hour clinical pharmacy (CP) services in the emergency department (ED). DESIGN: A review of the "on-call report forms" and written consultations provided by CP between July 1985 and December 1987. SETTING: The University of Illinois Hospital. MAIN OUTCOME MEASURES: Patient-related versus non-patient-related cases; solicitor; type of and time per consultation; drug concentration determinations by CP; and comparison with other ED consultation services. RESULTS: Of 3787 consultations 3650 (96 percent) were patient-related, 137 (4 percent) were non-patient-related. Consultations were solicited from another individual in 2774 cases (73 percent); they were initiated by the clinical pharmacists in 831 cases (22 percent). Of the patient-related consultations, 1215 (33.3 percent) involved pulmonary disease, 796 (21.8 percent) toxicology, 635 (17.4 percent) seizures, 411 (11.3 percent) cardiac cases, 268 (7.3 percent) pharmacokinetics, and 325 (8.9 percent) miscellaneous. Consultations were solicited by physicians (1806, 65 percent), nurses (652, 23.5 percent), cardiac arrest page (237, 8.5 percent), patients (45, 2 percent), or pharmacists (34, 1 percent). They averaged 100 minutes each. Of 2197 drug concentrations, 1939 (88 percent) were completed by the clinical pharmacist. Concentrations were obtained for theophylline (1055, 54.4 percent), phenytoin (511, 26.4 percent), phenobarbital (324, 16.7 percent), and acetaminophen (49, 2.5 percent). Compared with other consultation services, CP ranked first in regard to frequency of use. CONCLUSIONS: The CP consultation service in the ED was as well used as most physician consultation services and tended to involve specific therapeutic areas that have implications for the training of emergency department clinical pharmacists.

Emergency Service, Hospital

Comparison of the pharmacokinetics and electrocardiographic effects of sublingual and intravenous verapamil.

Using a dog model, a sublingual form of the free base of verapamil (SLV) was developed with the intent of avoiding stereoselective first-pass metabolism and the necessity of intravenous administration. Intravenous verapamil (IVV) 5 mg and SLV 40 mg or 60 mg were sequentially administered to seven healthy human volunteers. Electrocardiograms and serum concentrations were obtained before and periodically from 5 to 480 minutes after each dose. The time to peak serum concentration (mean +/- SD) was 77.6 +/- 38.1 minutes after SLV. Bioavailability of SLV was 58.2 +/- 36.9% compared to IVV. Verapamil half-lives after IVV and SLV were 2.83 +/- 0.93 and 2.28 +/- 0.45 hours (NS), respectively. In one subject, the time to peak effect was delayed and overall change in PR interval was minimum. In the remaining six subjects, the maximum percentage increases in PR interval after IVV and SLV were 20.6 +/- 6.4% and 14.8 +/- 5.5% (p less than 0.05), respectively. Times to peak increase in PR interval were 28.3 +/- 15.7 and 57.0 +/- 17.5 minutes after IVV and SLV (p less than 0.05), respectively. Analysis of plots of percentage change in PR interval versus serum concentration revealed a shift to the right and therefore, lesser effect of SLV than of IVV in six subjects. All seven subjects complained of oral numbness and bitter taste. In conclusion, SLV is inferior to IVV in terms of rate and extent of absorption and pharmacologic effect in delaying atrioventricular nodal conduction. Probably SLV has little clinical utility because of its slow onset and poor tolerance.

Administration, Oral

Interference by antiarrhythmic agents with function of electrical cardiac devices.

The possible interference of drugs with the function of implanted electrical cardiac devices in two patients is described, and the literature on the interaction between these drugs and devices is reviewed. A 59-year-old woman had a permanent pacemaker implanted after diagnosis of tachycardia-bradycardia syndrome, and her drug regimen of digoxin, verapamil, and warfarin was supplemented with flecainide to prevent paroxysmal atrial fibrillation. A Holter monitor recording performed after five days of flecainide therapy showed the pacemaker was sensing and pacing normally. Approximately three weeks after pacemaker implantation and initiation of flecainide therapy, a Holter monitor recording showed high-grade atrioventricular block and failure of the pacemaker to capture. A chest roentgenogram showed that the pacemaker lead was properly placed. The pacemaker's pulse amplitude and pulse width were increased, and the device again functioned reliably. Six months later the pacing threshold was noted to have returned to normal. A 64-year-old man had a history of aborted sudden cardiac death from ventricular tachyarrhythmias. The patient received an automatic implanted cardioverter-defibrillator (AICD); at that time, a 15-J discharge was required to terminate induced ventricular fibrillation (VF). Three years later, the AICD was replaced; the energy required for VF termination with the new unit was 16 J. Seven months after implantation of the new unit, the patient had several episodes of ventricular tachycardia (VT). Moricizine therapy was initiated. An electrophysiologic study (EPS) three days later showed that a larger shock (28 J) was required to terminate VF and that the pacing threshold had increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Arrhythmia Agents

Evaluation of the pharmacokinetics and electrocardiographic effects of intravenous verapamil with intravenous calcium chloride pretreatment in normal subjects.

To evaluate the effects of calcium pretreatment on the disposition and electrocardiographic effects of verapamil, 8 healthy male volunteers received treatment in each of 3 phases in a randomized, double-blind, crossover manner. Phase I denoted 10 ml of 0.9% intravenous sodium chloride followed by 10 mg of intravenous verapamil; phase II denoted 10 ml of 10% intravenous calcium chloride followed by 4 ml of 0.9% intravenous sodium chloride; and phase III denoted 10 ml of 10% intravenous calcium chloride followed by 10 mg of intravenous verapamil. Blood samples for the determination of verapamil concentrations were drawn at 5, 10, 15, 20, 30, 45, 60 and 90 minutes, and at 2, 4, 6, 10 and 24 hours. Blood pressure, heart rate and PR intervals were also measured at these times. Pretreatment of verapamil with intravenous calcium did not alter the disposition of intravenous verapamil. Blood pressure was not significantly altered in any treatment phase, although calcium tended to increase mean arterial pressure and verapamil abolished this effect. Calcium had no significant affect on verapamil-induced PR prolongation (maximum percent change in PR interval: phase I = 19 +/- 11%, phase III = 18 +/- 7%; time to maximal prolongation: phase I = 0.38 +/- 0.21 hours, phase III = 0.37 +/- 0.26 hours; and area under the percent change in PR vs time curve: phase I = 15.5 +/- 10, phase III = 21 +/- 9). Verapamil caused a reflex increase in heart rate of similar magnitude in both phases I and III (24 +/- 10% and 21 +/- 7%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Digoxin-like immunoreactive substance in renal transplant patients.

Digoxin-like immunoreactive substance (DLIS) has been detected in several patient populations that were not receiving digoxin, including those patients with end-stage renal disease. The structure and physiologic significance of this compound are unknown, and the fate of DLIS after renal transplantation has not been studied. The authors prospectively evaluated 163 patients (not receiving digoxin) before and after transplantation for the presence of DLIS. Three different assays were used: radioimmunoassay (RIA), affinity mediated immunoassay (ACA), and fluorescence polarization immunoassay (TDX I). Depending on the assay method used, 11% (RIA), 6% (ACA), and 9% (TDX) of patients had detectable DLIS pretransplant. Using all 3 assays, a total of 34 patients (21%) were found to have DLIS. The mean serum digoxin concentration was 0.41 +/- 0.13 ng/mL (range: 0.2-1.2 ng/mL) and DLIS was detectable by greater than 1 assay method in seven patients. DLIS persisted longer in patients who had delayed allograft function (13.7 +/- 7 days) than in those who did not (3 +/- 1.9 days), P less than .05. In summary, detection of DLIS in renal transplant recipients appears to be an infrequent occurrence when using a single digoxin assay method. When detected, the concentration of DLIS is often below the usual therapeutic range for digoxin and disappears once allograft function is established. The authors conclude that the presence of DLIS is unlikely to be clinically significant in the renal transplant population.

Adult

Evaluation of drug therapy for treatment of hypertensive urgencies in the emergency department.

Oral nifedipine (N) and clonidine (C) are often used in the treatment of hypertensive urgencies; however, until recently, there were no comparative studies using the same patient population. The authors reviewed the records of hypertensive patients treated in the emergency department between October 1, 1987 and September 30, 1988. Selected patients had a diastolic blood pressure (DBP) of greater than 115 mm Hg without evidence of acute end organ damage. Patients were stratified into three treatment groups: N, C, and group 3 (G3). G3 received a variety of drug therapies but not exclusively N or C. Systolic blood pressure (SBP), DBP, mean arterial pressure (MAP), percent decrease in MAP (%MAP), time to lower blood pressure, admissions, and discharges were evaluated. Efficacy and safety were defined as reaching a DBP less than 110 mm Hg but %MAP of no greater than either 25% or 40%, respectively. Thirty-five N, 32 C, and 27 G3 patients were identified with no statistical difference between groups in race, gender, pretreatment SBP, DBP, or MAP. N, C, and G3 significantly reduced SBP, DBP, and MAP (P less than .01). Comparing N, C, and G3, no differences were observed in %MAP, admissions, discharges, efficacy, or safety. Time required to decrease blood pressure differed between all three groups (44 +/- 32 N v 77 +/- 57 C v 152 +/- 94 min G3) (p less than .05). These results indicate that N, C, and a variety of drug therapies are equally effective and safe in the treatment of hypertensive urgencies.

Adolescent