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Biomedical subjects

B H Ackerman

Publications and source records attributed to B H Ackerman.

At least 19 recordsLinked to original sources

Pharmacokinetic characterization of the postdistribution phase of prohormone atrial natriuretic peptides amino acids 1-98, 31-67, and atrial natriuretic factor during and after rapid right ventricular pacing in dogs.

Release rate constants and disappearance rate constants were determined for three atrial natriuretic peptides consisting of amino acids 1-98 (i.e., proANF 1-98), the midportion of the ANF prohormone consisting of amino acids 31-67 (i.e., proANF 31-67) and amino acids 99-126 (i.e., ANF) after right ventricular pacing at 100, 125, 150, and 180 bpm in six male mongrel dogs. Right atrial and femoral vein blood was obtained at baseline, and at 5, 12, 19, 26, 56, 86, 116, 146, and 206 minutes after right ventricular pacing. Resulting plasma concentration-time data derived parameters were compared. The disappearance rate constants for atrial and femoral venous proANF 1-98 were 0.0144 +/- 0.0087 (X +/- SD) and 0.0175 +/- 0.0075 min-1, respectively (t = 0.6158) and release rate constants were 0.1569 +/- 0.1504 and 0.0670 +/- 0.0393 min-1, respectively (t = 1.8269; P greater than .05). The proANF 31-67 disappearance rate constants were 0.0139 +/- 0.0082 and 0.0148 +/- 0.0132 min-1, respectively (t = 0.1192) and release rate constants were 0.0957 +/- 0.0414 and 0.1984 +/- 0.1762 min-1, respectively (t = 1.4812). The ANF elimination phase disappearance rate constants were 0.0663 +/- 0.0273 and 0.1116 +/- 0.0539 min-1 (t = 2.0923, P greater than .05), respectively, and the release rate constants were 0.1335 +/- 0.0532 and 0.1638 +/- 0.0520 min-1 (t = 0.7878, P greater than .05), respectively. These data indicate that proANF 1-98 and proANF 31-67 circulating beta post-distribution half-lives are approximately 45 minutes whereas beta half-life of ANF is 10 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Analysis of vancomycin time-kill studies with Staphylococcus species by using a curve stripping program to describe the relationship between concentration and pharmacodynamic response.

Mono- and biexponential killing curves for vancomycin over a 2- to 50-micrograms/ml concentration range were generated for 11 Staphylococcus aureus isolates and 12 coagulase-negative Staphylococcus species in the logarithmic phase of growth. Nonlinear least-squares regression of the initial growth rate and disappearance were not significantly different for lower or higher concentrations of vancomycin in broth.

Coagulase

Disseminated Nocardia asteroides diagnosed by blood culture in a patient with disseminated histoplasmosis.

We describe herein a provocative case involving an immunosuppressed patient with disseminated Histoplasma capsulatum and also disseminated Nocardia asteroides, which was documented by multiple routine blood culture samples. Nocardia asteroides was isolated from 15 routine blood cultures using the nonradiometric blood culture system (Bactec NR-660, Becton Dickinson, Towson, Md). Several different species of the genus Nocardia proved to thrive in blood culture bottles (Bactec) when experimental inoculations were performed. The paucity of reports in the literature of disseminated nocardiosis with positive blood cultures has led us to consider cause for the apparent poor recovery of these organisms from blood culture media. We suggest that the media (Bactec) can successfully support growth of Nocardia species and that other variables, such as incubation times and subculture, should be considered to optimize isolation of this pathogen in blood culture systems.

Aged

Isopropanol ingestion: a report of six episodes with isopropanol and acetone serum concentration time data.

The disposition of isopropanol and its major metabolite acetone were observed in six isopropanol ingestion episodes among five patients. Serum admission isopropanol and peak acetone concentrations ranged from 16.5 to 220 mg/dL and 141 to 585 mg/dL respectively. Ingestions ranged from 120 to 300 mL of 70% isopropanol with concomitant ethanol ingestion in two episodes. The isopropanol and acetone apparent half-lives ranged from 2.9 to 16.2 hours (h) and 7.6 to 26.2 h respectively. Two episodes of isopropanol ingestion were observed within a 9 month period in patient one. Isopropanol terminal elimination rate constants were 0.043 and 0.085 per hour (per h) with no marked difference in acetone terminal elimination rate constants (0.025 and 0.033 per h). Discrepancy between the two isopropanol elimination rate constants reflected concomitant ethanol abuse with the first ingestion. Reductions in isopropanol and acetone half-lives were also noted among patients requiring ventilatory support.

1-Propanol

The N-terminus, C-terminus, and vessel dilator of the ANF prohormone are present in the urine and increase with ventricular fibrillation.

The N-terminus consisting of amino acids (a.a.) 1-98 (i.e., proANF 1-98), C-terminus (i.e., ANF; a.a. 99-126) and midportion of N-terminus consisting of a.a. 31-67 (proANF 31-67; Vessel Dilator) of the 126 a.a. ANF prohormone were present in the urine in 5-to-8-fold increased concentrations versus their plasma concentrations in 6 dogs under basal conditions. With acute coronary occlusion the right atrial plasma concentrations of these peptides increased two-to-three-fold, while in the urine only proANF 31-67 increased (3.5-fold). Ventricular fibrillation caused a 4-to-10-fold increased secretion into the right atrial chamber with a simultaneous 3-to-4.7-fold increase in the urine of proANF 1-98, proANF 31-67, and ANF. This investigation demonstrates that proANF 1-98, proANF 31-67 and ANF are normally present in urine and increase in the urine with cardiac stimuli that cause their release from the heart.

Animals

Thermal injury effects on drug disposition: a prospective study with piperacillin.

The disposition of piperacillin was prospectively evaluated in nine severely burned patients who had normal renal and hepatic function. Wide interpatient variations were demonstrated in the drug's distribution volume, half-life, and clearance, with mean (+/- SD) values of 55.0 (+/- 44.2) liters, 3.6 (+/- 5.2) hours, and 14.9 (+/- 6.3) liters/hour, respectively. Piperacillin clearance was best explained by patient factors other than age, renal function, and the percentage of body surface area burns. Piperacillin disposition was related to the patients' serum albumin, total bilirubin, blood urea nitrogen, and the amount of urea nitrogen excreted daily in urine. Altered piperacillin disposition thus appeared to occur secondary to changes in the patients' physiologic and metabolic state caused by injury-related stress and fluid therapy. The patient's physiologic and metabolic response to injury, along with age and renal function, should be considered when instituting treatment with piperacillin or other agents cleared from the body in a similar manner.

Adult

Effects of treatment and the metabolic response to injury on drug clearance: a prospective study with piperacillin.

The disposition of piperacillin was prospectively evaluated in 11 critically ill surgical patients who had no evidence of pre-existing renal and hepatic disease. Interpatient variations were demonstrated in the drug's half-life, distribution volume, and clearance, with values of 1.50 +/- 2.05 (SD) h, 25.0 +/- 17.2 L, and 23.8 +/- 17.2 L/h, respectively. Variations in piperacillin disposition were best explained by serum concentrations of albumin, total protein, and bilirubin, and the amount of urea nitrogen excreted daily in urine. Age and renal function were moderately associated with piperacillin elimination rate and clearance. Altered piperacillin disposition thus appeared to occur as secondary to changes in the patients' physiologic and metabolic state caused by injury-related stress and fluid/colloid therapy. These alterations may necessitate dosage modifications to achieve optimal patient response when treating patients with piperacillin as well as with other similar drugs eliminated via renal and nonrenal routes.

Adult

Postoperative analgesic requirements following flumazenil administration.

The effect of flumazenil (RO 15-1788) on postoperative analgesic requirements was evaluated in 30 postoperative patients. This prospective investigation was a double-blind, placebo-controlled trial in patients undergoing general anesthesia supplemented by midazolam and fentanyl or sufentanil. Patients received either flumazenil (n = 20) or placebo (n = 10) by random assignment. Analgesic requirements were measured in morphine equivalents (MEs) and were recorded for a three-hour period following the administration of flumazenil. All patients received the assigned treatment within five minutes of arrival to the postanesthesia room. Total ME requirements were 4.1 +/- 3.8 mg for the flumazenil group and 4.5 +/- 4.6 mg (p = 0.71) for the placebo group. Patient analgesic requirements were also assessed when patients were adequately alert. For the flumazenil group this time period was 6.2 +/- 12.7 minutes versus 52.9 +/- 28.4 minutes for placebo (p less than 0.01). MEs (flumazenil 4.1 +/- 3.8 mg vs. placebo 3.7 +/- 3.2 mg) were not significantly different (p = 0.57) when similar levels of consciousness were compared. The onset of pain was more rapid with flumazenil patients as evidenced by the first analgesic dose at 15.7 +/- 25.1 minutes for the flumazenil group versus 34.7 +/- 43.7 for the placebo group; however, these data were not statistically different (p = 0.144). These results suggest that flumazenil does not increase postoperative analgesic requirements during the immediate postanesthesia period; however, patients receiving flumazenil may experience an earlier onset of postoperative pain.

Adult

Comparison of disposition values obtained by two assay methods for quinidine gluconate in patients with ventricular tachycardia.

Eight patients with previously untreated ventricular tachycardia, age 48.54 +/- 28.02 years (mean +/- SD), were enrolled in a protocol evaluating the disposition of quinidine gluconate as determined by two assay methods. Patients received two infusions of 5 mg/kg over 30 minutes separated by 20-30 (24.9 +/- 4.0) minutes of electrophysiologic testing. Blood samples were obtained at 0.17 hours and just prior to the second infusion, and then at 0.17, 0.25, 0.33, 1.0, 6.0, 12.0, and 24.0 hours after the second infusion. Paired serum samples were assayed for quinidine concentrations by fluorescence polarization immunoassay and high-performance liquid chromatography. The two assays compared well, with a linear regression equation of Y = 0.927X + 0.247 with a correlation coefficient of 0.985. With the exception of the beta elimination rate constant and beta distribution volume, t test comparison of disposition values demonstrated no significant difference. Differences in the estimates of the beta elimination rate constant reflected differences in the two methods and indicated that even though both assays were comparable, subtle differences in specificity could be reflected in significant differences in this variable.

Adult

Effect of age and renal function on cefonicid pharmacokinetics.

Cefonicid (15 mg/kg) was administered intravenously at a constant rate of infusion over 15 min to 10 geriatric patients (mean age, 77 years) and to 4 young subjects (mean age, 35 years). Model-dependent and noncompartmental pharmacokinetic parameters were calculated and found to be congruous; noncompartmental data are reported. Significant differences in the values for area under the curve, mean residence time, total body clearance, and renal clearance were observed between the geriatric and young groups. Mean elimination half-life values were 9.59 and 4.88 h for the geriatric and young groups, respectively. Total body and renal clearances were inversely correlated to age and directly correlated to creatinine clearance. Free fraction was not correlated to albumin concentration but was correlated exponentially to total cefonicid concentration. Despite the prolonged half-life values observed in our geriatric patients, the difference in mean trough concentrations was slight. Daily administration of a 15-mg/kg dose should provide adequate concentrations in serum and should not produce appreciable accumulation in geriatric patients.

Adult

Evaluation of three methods for determining initial vancomycin doses.

Dosing methods proposed by Matzke et al., Moellering et al., and Lake and Peterson were used to predict initial doses of vancomycin for serum concentration simulation using a two-compartment open model. Previously reported pharmacokinetic data from 25 of 28 patients were used to simulate steady-state serum vancomycin concentrations for doses derived from the three methods. The Matzke method failed to provide simulated one-hour postinfusion levels less than 30 micrograms/mL in 48 percent and troughs greater than 5 micrograms/mL in more than 88 percent of the patients. The Moellering method succeeded in achieving this goal in 96 percent of the simulated one-hour levels, and in 72 percent of the troughs when a six-hour dosing interval was selected. For the 8 mg/kg Lake-Peterson doses, one-hour levels greater than 30 micrograms/mL occurred in 28 percent of the simulations, and for the 10 mg/kg doses this increased to 40 percent. The 8 mg/kg doses resulted in trough simulations less than 5 micrograms/mL in 28 percent and the 10 mg/kg reduced this to only 20 percent. These simulations indicated that the Moellering nomogram with the six-hour dosing interval was the most successful method for initial dose selection, but early serum concentration monitoring and adjustment of initial empirical and nomogram-derived doses is necessary to assure safe and effective vancomycin serum concentrations.

Analysis of Variance

Disposition of 3-hydroxyquinidine in patients receiving initial intravenous quinidine gluconate for electrophysiology testing of ventricular tachycardia.

The formation rate constant and elimination rate constant for 3-hydroxyquinidine were determined in eight patients with ventricular tachycardia. These two parameters (mean +/- SD) were found to be 0.784 +/- 0.202 and 0.042 +/- 0.058 h-1, respectively. Coefficients of determination for the computer-generated line of best fit for serum concentration-time data were 0.986 +/- 0.008. Patients received two infusions of quinidine gluconate 5 mg/kg over 30 minutes separated by a 20-30 minute electrophysiologic testing period. Unbound and total 3-hydroxyquinidine concentrations were also determined. Among the eight patients, 3-hydroxyquinidine was 61.9 percent bound. Studies in healthy volunteers had shown 50 percent binding. Linear regression of unbound and total 3-hydroxyquinidine was described by the equation Y = 0.3814X-1.448, r = 0.813. Although half-lives of 3.5-12.4 hours had been reported in healthy volunteers, prolonged half-lives were observed in all but two of our arrhythmia patients.

Adult

Vancomycin serum protein binding determination by ultrafiltration.

Sixty-two serum concentrations were obtained from 12 infected patients enrolled in a vancomycin pharmacokinetic study. Both unbound and total serum vancomycin concentrations were measured using ultrafiltration and a commercial fluorescent polarization immunoassay. Ultrafiltrates were obtained by centrifugation at 1000 X g for ten minutes at room temperature and their assay indicated a range in protein binding from 7.9 to 71 percent. The mean protein binding (mean +/- SD) was 41.95 +/- 14.15 percent. No measurable adsorption of vancomycin onto the ultrafiltration membrane was noted. Orthogonal regression of unbound versus total vancomycin concentrations was described by the equation y = 0.597x-0.362 with a correlation coefficient of 0.948.

Adult

Pruritic rash with actinic keratosis and impending exfoliation in a patient with hypertension managed with minoxidil.

Dermatological toxicity has been reported following initiation of therapy with minoxidil, but no cases have been reported following prolonged use. We report the emergence of an erythematous weeping rash with impending exfoliation three years after the initiation of minoxidil therapy. Minoxidil was withdrawn and the patient responded to therapy with topical corticosteroids. Following minor surgery, the patient was inadvertently rechallenged with minoxidil. Within 24 hours of exposure bullous lesions reappeared in the extremities which again resolved with topical corticosteroids. Dermatological lesions observed on this patient were similar to those reported following acute minoxidil exposure and strongly implicate chronic minoxidil therapy.

Drug Eruptions