Biomedical subjects
K A Conrad
Publications and source records attributed to K A Conrad.
Response to doxycycline vs. mefloquine.
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Interobserver variability in interpreting chest radiographs.
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Clinical pharmacology and drug safety: lessons from hirudin.
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Drug susceptibility of Mycobacterium tuberculosis isolates from recent Haitian migrants: correlation with clinical response.
Between November 1991 and June 1993, approximately 11,000 Haitian migrants were screened for active tuberculosis and human immunodeficiency virus type 1 (HIV-1) infection at the U.S. Naval Base in Guantánamo Bay, Cuba. Cultures of specimens from 37 of these patients yielded Mycobacterium tuberculosis; eight (22%) of these isolates were resistant to standard medications, including isoniazid (22%), rifampin (0), ethambutol (3%), and streptomycin (3%). Two isolates (5.4%) were resistant to two drugs simultaneously. All but one of 340 patients who were treated for presumptive active tuberculosis and who were followed up for about 1 month had a favorable initial clinical response to a standard four-drug regimen. Among 259 HIV-1-infected patients who had normal findings on screening chest radiographs and who received prophylaxis with isoniazid, there were 1.8 incident cases of active tuberculosis per 100 person-years; this rate was 76% lower than that (reported by others) among HIV-1-infected Haitian patients who were not treated with isoniazid. No serious toxic effects due to standard four-drug regimens or to prophylaxis with isoniazid were observed. These data suggest that standard empirical therapeutic interventions for tuberculosis are adequate and well tolerated in Haitian migrants.
Chylous transport of amiodarone.
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The absolute bioavailability and dose proportionality of intravenous and oral dosage regimens of recainam.
Recainam is a novel class I antiarrhythmic agent with electrophysiologic characteristics of all three subclasses. The authors evaluated the absolute bioavailability and dose proportionality of three oral doses and two 2-stage intravenous (IV) infusion doses. Single oral doses of 200, 400, and 800 mg and IV infusions consisting of 0.8 mg/kg/5 min + 1.2 mg/kg/hr (3.75 mg/kg) and 1.6 mg/kg/5 min + 1.2 mg/kg/hr for 4 hours and 55 minutes (7.50 mg/kg) were administered to 15 healthy men. Plasma and urine samples were collected during the 36-hour period after drug administration and analyzed for recainam concentrations by HPLC. No significant differences were found in any of the pharmacokinetic parameters between the two IV dosage regimens. The absolute bioavailability of orally administered recainam increased from 73% for the 200 mg dose to 81% and 84% for the 400 and 800 mg doses, respectively. Dose proportionality deviated from linearity by 13% for the 200 vs. 400 mg doses, and 10% for the 400 vs. 800 mg doses. The slight deviation from linearity was apparently caused by increased absorption at the higher oral doses. The slight disproportionality in the disposition of recainam is not expected to be clinically significant.
The influence of age on salicylate pharmacokinetics in humans.
The pharmacokinetics of salicylate after a single oral solution dose of 600 mg of sodium salicylate were investigated in 22 male subjects. Subjects were healthy nonsmokers and were not taking any regular medication. The plasma concentration and urinary excretion of salicylic acid and its metabolite, salicyluric acid, as well as the urinary excretion of salicyl glucuronides were determined. Urinary recovery essentially accounted for the administered dose and was not influenced by age, nor was the apparent oral clearance of salicylic acid. Assuming no presystemic elimination, it could be concluded that systemic availability is unaffected by age. An increase in the apparent volume of distribution, Varea, and a decrease in the maximum plasma salicylic acid concentration with age were observed. Renal clearance of salicyluric acid decreased significantly with age and was found to correlate significantly with creatinine clearance. The authors conclude that age does not have a major influence on salicylate disposition in healthy adult men.
Relationship between age and the cardiovascular response to meals.
In 82 healthy normotensive and hypertensive subjects aged 19-79, blood pressure and heart rate were measured for 1 hour before and 2 hours after a meal. Mean blood pressure decreased from 147/93 to 139/83 mmHg supine and from 148/101 to 142/94 mmHg standing (all p less than .001). Older subjects had higher premeal blood pressures. There were significant correlations between age and the reductions in supine systolic and diastolic blood pressures and standing systolic blood pressure, i.e., older patients had greater reductions. However, after statistical correction for premeal blood pressure, there was no longer any significant relationship between age and the cardiovascular response to meals. The greater blood pressure reduction after meals in older patients may be due to decreased baroreflex sensitivity in association with higher arterial pressures. The changes in blood pressure due to meals may confound the diagnosis of hypertension and interfere with the interpretation of the response to antihypertensive treatment.
Vitamin C disposition in young and elderly men.
The pharmacokinetics of vitamin C after a 500-mg oral tablet dose were compared in 15 healthy young men aged 25.20 +/- 2.54 (means +/- SD) and in 15 healthy elderly men aged 69.31 +/- 2.52 y. The doses were characterized with the subjects in two states of vitamin C nutriture: a depleted state, which was achieved by 4-5 wk of compliance with a vitamin C-restricted diet of less than 10 mg/d and a supplemented state, in which the subjects were given 500 mg vitamin C/d for 3 wk. Plasma and urine samples were collected for 72 h after the dose of vitamin C from depleted subjects and for 24 h from supplemented subjects and analyzed for vitamin C. Several of the pharmacokinetic indices measured were different in depleted vs supplemented subjects but none exhibited any age-related differences. This indicates that vitamin C nutriture affects vitamin C pharmacokinetics but age does not.
Comparison of methods for estimating body composition in young and elderly women.
Estimates of percent body fat and fat-free mass (FFM) were made in healthy young and elderly female subjects using five different methods: bioelectrical impedance analysis (BIA); regression equations involving skinfold measurements at two (Durnin and Womersley; SKF-DW) or three (Jackson and Pollack; SKF-JP) sites; the body mass index (BMI); and an equation relating height and weight to total body water (TBW). Three of the five methods indicated that the percent body fat was significantly greater in the elderly age group. Similarly, three methods estimated FFM values that were significantly lower in the elderly group. In the young group the SKF-DW and TBW methods produced percent fat estimates significantly higher than the other three methods. In the elderly group the percent fat estimates were as follows: SKF-DW greater than BIA greater than SKF-JP = TBW greater than BMI. FFM estimates in both age groups were in inverse rank order to the percent fat estimates. In elderly subjects SKF-DW produced results closest to those from BIA, whereas in young subjects SKF-JP provided the best agreement with the BIA procedure.
Effects of age and intake on vitamin C disposition in females.
The pharmacokinetics of vitamin C following a 500 mg oral tablet dose were compared in a group of fourteen healthy young women whose age was 26.0 +/- 2.8 years (mean +/- s.d.), and in a group of fourteen healthy elderly women aged 68.1 +/- 2.6 years. The body composition of each subject was assessed using several anthropometric measurements in order to help explain any observed differences in the pharmacokinetic behavior of vitamin C. The vitamin C doses were characterized with the subjects in two states of vitamin C nutriture: a 'depleted' state which was achieved by 4-5 weeks on a vitamin C-restricted diet of less than 10 mg/d and a 'supplemented' state in which the subjects were given daily doses of 500 mg of vitamin C for 3 weeks. Plasma and urine samples were collected for 72 h following the dose of vitamin C from subjects in a 'depleted' state and for 24 h from subjects in a 'supplemented' state and analysed for their vitamin C content. None of the pharmacokinetic parameters measured differed significantly between the two age groups. In contrast, the vast majority of these parameters were significantly different in depleted and supplemented subjects. The peak times (tmax) were greater in the depleted state in both young and elderly groups whereas the peak concentrations (Cmax) were greater in the supplemented state. The absorption rate constant (Ka) was significantly larger in the supplemented state compared to the depleted state in the young group and the absorption half-life (t 1/2, Ka) was significantly greater in the depleted state in the young group only. The absorption lag time (tlag) did not differ with respect to age or nutritional status. The elimination half-life (t 1/2, Ke) was significantly longer in supplemented subjects. Although the apparent high volume of distribution (Vd) was not significantly different within each age group the Vd was significantly greater in the depleted state when the two age groups were combined. The clearance (CL), and the nonrenal clearance (CLNR) were significantly greater in the depleted state. The renal clearance (CLR) and the amounts of vitamin C excreted in the 0- to 12- and 12- to 24-h intervals were significantly larger in the supplemented state. The urinary excretion data also indicate that, in supplemented subjects, an average of about 40 percent of the administered dose is excreted as unchanged vitamin C in the first 12 h after dosing, with very little being excreted thereafter.
Hepatitis B vaccine programs give ICPs a shot in the arm. Results of a national survey.
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Nicardipine and hydrochlorothiazide in essential hypertension.
Nicardipine is an investigational dihydropyridine calcium channel blocking agent. One hundred fifty-one patients with hypertension received either 30 mg nicardipine t.i.d. or 25 mg hydrochlorothiazide b.i.d. in a double-blind, randomized, multicenter trial. After 4 weeks of therapy and at the end of the dosing interval, nicardipine reduced arterial pressure by 10/6 mm Hg and 12/6 mm Hg in the supine and standing positions, respectively (all p less than 0.01). In the hydrochlorothiazide group, the reductions were 12/6 mm Hg and 14/6 mm Hg, respectively (all p less than 0.01). The maximum reduction in blood pressure of 16/14 mm Hg supine and 20/15 mm Hg standing occurred within 1 hour after administration of nicardipine. The mean reduction in the hydrochlorothiazide group after 1 hour was 14/11 mm Hg supine and 16/12 mm Hg standing. Neither drug affected autonomic reflexes associated with maximum exercise. Nicardipine increased urinary sodium excretion during the 4-hour period after the first dose. Adverse effects of nicardipine were primarily extensions of its vasodilator effect and included flushing, headache, and edema.
Comparison of plasma, mononuclear and polymorphonuclear leucocyte vitamin C levels in young and elderly women during depletion and supplementation.
The levels of vitamin C in plasma, mononuclear (MN) and polymorphonuclear (PMN) leucocytes were measured in healthy, free-living, young and elderly women on three occasions over an 8-10-week period: (a) at entry into the study, (b) following 5 weeks of dietary depletion of vitamin C, and (c) following 3 weeks of supplementation with 500 mg of vitamin C per day. The combined mean vitamin C levels (expressed as microgram/10(8) cells) in MN cells were higher than those found in PMN cells at all three times, although the difference was only statistically significant in the depleted state. There were no age-related differences in the levels of vitamin C in plasma, MN or PMN cells at any of the three times. Significant overall differences in vitamin C levels between the entry and depleted and the depleted and supplemented states were observed for plasma and PMN cells but not for MN cells, possibly indicating that plasma and PMN cells are more sensitive indicators of vitamin C status than MN cells. The mean levels of vitamin C found in plasma clearly do 'track' those found in MN and PMN cells. However, attempted correlations between plasma and MN, plasma and PMN, and MN and PMN vitamin C levels at each time proved to be non-significant. In addition, the changes in vitamin C levels from entry to depleted and from depleted to supplemented times were non-significant when comparing plasma to MN and plasma to PMN, whereas the MN vs PMN comparison indicated a significant change in vitamin C levels between the depleted and supplemented states.(ABSTRACT TRUNCATED AT 250 WORDS)
The influence of hydrochlorothiazide and tripamide on serum and urinary amylase.
Pancreatitis and asymptomatic elevations of serum amylase have been reported after therapy with thiazide diuretics. In the current study, the effects of hydrochlorothiazide and tripamide treatment on serum and urinary amylase excretion were investigated in 12 hypertensive volunteers. Two patients developed modest elevations of the serum amylase above the normal range after 12 weeks of treatment with hydrochlorothiazide 50 mg daily, but the mean serum amylase did not change. Hydrochlorothiazide did not produce a statistically significant increase in urinary amylase excretion but did reduce the ratio of salivary amylase/creatinine clearance in a two-hour urine collection. Tripamide 10 mg daily had no effect on serum or urinary amylase.
Doxazosin in patients with hypertension.
The antihypertensive effects and steady-state pharmacokinetics of doxazosin, as well as the bioequivalence of four dosage forms, were studied in 25 hypertensive patients. For an 8 mg daily dose mean Cmax at steady-state for all patients was 108 ng/ml; the mean tmax was 1.8 h. The mean terminal elimination half-life was 22 h. The four tablets containing 1, 2, 4, or 8 mg of doxazosin were bioequivalent in delivering the 8 mg dose. In patients with mild to moderate hypertension, 26-day treatment with doxazosin resulted in blood pressure reduction of 10/7 mmHg in the supine and 13/18 mmHg in the standing position. Adverse effects were generally mild and of brief duration.