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Biomedical subjects

R L Williams

Publications and source records attributed to R L Williams.

At least 271 records · Page 15Linked to original sources
PubMed1985

Recent developments in the diagnosis and treatment of sleep disorders.

The publication of a new nosology of sleep and arousal disorders in 1979 established the need for differential diagnosis of sleep disorders based on polysomnographic evaluations as well as medical history and physical examination. This review of recent developments in diagnosing and treating sleep disorders covers such topics as prevalence, findings related to sleeping pills and insomnia, effects of depression on sleep, and managing the elderly patient with disturbed sleep. The authors caution against misuse of hypnotic drug therapy for treatment of insomnia and encourage physicians to inquire about sleep patterns even when a patient is presenting a seemingly unrelated problem.

Aged↗
PubMed1985

Vehicular carbon monoxide screening: identification in a cross-cultural setting of a substantial public health risk factor.

A community program of screening and education for prevention of vehicular carbon monoxide (CO) poisoning among a high-risk population in a cross-cultural setting is presented. The program was developed after two infant deaths in separate incidents of vehicular CO poisoning. The results of the screening show 18.6 per cent of vehicles exceeding the Environmental Protection Agency eight-hour standard for CO exposure, and 2.6 per cent exceeding the one-hour standard. Extension of such programs to other high-risk populations is recommended.

Automobiles↗
PubMed1984

A new antihypertensive agent: Maxzide (75 mg triamterene/50 mg hydrochlorothiazide).

The combination of potassium-sparing diuretics with hydrochlorothiazide is extensively used by hypertensive patients. In the United States, a capsule formulation containing 50 mg triamterene and 25 mg hydrochlorothiazide (Dyazide) is the most popular fixed-combination product. However, several investigators have confirmed that absorption of both the triamterene and hydrochlorothiazide components of Dyazide is markedly reduced. This reduced bioavailability may reduce its effectiveness in hypertensive patients who change from optimally bioavailable hydrochlorothiazide tablets to Dyazide capsules in an effort to correct hypokalemia. Scored tablets containing 75 mg triamterene/50 mg hydrochlorothiazide (Maxzide) have been developed using a patented parallel granulation manufacturing process and evaluated in a series of bioavailability-bioequivalence studies. The triamterene and hydrochlorothiazide components of Maxzide tablets were found to be as bioavailable as liquid preparations of the active ingredients given singly or in combination. Unlike Dyazide capsules, the hydrochlorothiazide component of Maxzide tablets was found to be absorbed to the same extent as single-entity hydrochlorothiazide tablets. These studies demonstrated that two Dyazide capsules (total of 100 mg triamterene/50 mg hydrochlorothiazide) deliver to the bloodstream approximately one-half the quantity of hydrochlorothiazide as one Maxzide (75 mg triamterene/50 mg hydrochlorothiazide) tablet or one 50 mg hydrochlorothiazide tablet. Similarly, two Dyazide capsules deliver approximately one-half the quantity of triamterene as one Maxzide tablet. The safety of Maxzide tablets (dose of one tablet a day) was then evaluated in three groups of hypertensive patients: those who previously had been given two Dyazide capsules a day, those who had received four Dyazide capsules a day, and newly diagnosed patients who had received no medication. The clinical condition of the patients who changed from two or four Dyazide capsules to one Maxzide tablet was not compromised. Indeed, significant reductions in blood pressures were observed, especially in some patients who had remained hypertensive while receiving Dyazide. As expected, the blood pressures of the previously untreated group also decreased significantly with Maxzide tablets. Clinically significant hyperkalemia or hypokalemia did not develop. There were no clinically significant changes in blood urea nitrogen, creatinine, or uric acid levels. In addition to enhanced bioavailability, Maxzide tablets offer the advantages of once-a-day dosing.

Antihypertensive Agents↗
PubMed1984

Bioequivalence study of a new tablet formulation of triamterene and hydrochlorothiazide.

A three-treatment, single-dose, crossover bioequivalence study was conducted in healthy volunteers to compare urinary drug recovery following administration of hydrochlorothiazide tablets, the currently marketed capsule formulation of triamterene and hydrochlorothiazide (Dyazide), and a new tablet preparation of these active ingredients (Maxzide). No significant differences were observed in the urinary recovery of hydrochlorothiazide after the administration of hydrochlorothiazide tablets and Maxzide tablets. However, only about one-half as much hydrochlorothiazide was recovered following the administration of Dyazide capsules. Similarly, the urinary recovery of triamterene and the sulfate ester of hydroxy-triamterene after administration of Dyazide capsules was approximately one-half the levels observed after giving the new tablet formulation. The clinical consequences of the limited bioavailability of the active ingredients of Dyazide are discussed.

Adult↗
PubMed1984

Clinical experience with a new combination formulation of triamterene and hydrochlorothiazide (Maxzide) in patients with mild to moderate hypertension.

The results of an investigation to assess the clinical responses of patients with mild to moderate hypertension to a new combination formulation containing 75 mg triamterene and 50 mg hydrochlorothiazide are reported. One hundred fifty-six subjects entered the investigation. Subjects were divided into three groups, depending on whether they took two (group 1) or four capsules per day of a currently available formulation of triamterene and hydrochlorothiazide (Dyazide), or no antihypertensive medication prior to the start of the study. These medications were continued for an additional two weeks to generate baseline data. Thereafter, subjects received one tablet of the new combination formulation for four weeks. Seventy of the 156 participants received the new formulation for an additional period of at least 20 weeks. Observations during the study included sitting and standing pulse and blood pressure, weight, and serum electrolytes, uric acid, creatinine, and blood urea nitrogen levels. The results of the investigation indicated that subjects transferred to the new combination drug maintained normal serum electrolyte values, including potassium, with no or minor changes in the levels of uric acid, creatinine, and blood urea nitrogen. Reductions in systolic and diastolic blood pressure were observed in all three study groups, including subjects receiving two or four capsules of Dyazide per day in the two-week baseline period. We conclude that mild to moderately hypertensive subjects taking no medication or either two or four capsules of Dyazide per day may be transferred safely to the new combination product of triamterene and hydrochlothiazide.

Adult↗
PubMed1984

Naproxen disposition in patients with alcoholic cirrhosis.

Chronic liver disease is known to alter the absorption and disposition of many drugs. To assess the influence of chronic alcoholic liver disease on the disposition of naproxen, we administered the drug both as a single dose and to steady state to 10 individuals with alcoholic cirrhosis and to 10 healthy controls. Plasma and serum samples collected after naproxen dosing were assayed for both total and (following equilibrium dialysis) unbound drug concentration. Clearance calculated based on both total and unbound naproxen concentration revealed no change in total plasma clearance of the drug at steady state but a marked reduction of approximately 60% in clearance based on unbound drug. Naproxen volume of distribution changed only minimally. Because clearance based on unbound drug concentration at a given dosing rate determines the plasma or blood free drug concentration, this concentration may increase significantly in patients with alcoholic liver disease given usual doses of naproxen. Unbound drug concentration is thought to determine the pharmacologic effect of a drug. We therefore recommend that naproxen dosing be reduced by at least half in patients with chronic alcoholic liver disease. In the absence of data to the contrary, this recommendation can be extended to individuals with other forms of hepatic disease.

Adult↗
PubMed1984

Pharmacokinetic-pharmacodynamic analysis of unbound disopyramide directly measured in serial plasma samples in man.

The pharmacokinetics and pharmacodynamics of the antiarrhythmic drug, disopyramide, were investigated in 12 volunteers who took 300 mg doses of 3 different capsule preparations and an aqueous oral solution of the drug at 1-week intervals. Concentrations of drug unbound to plasma proteins were measured by a sensitive immunoenzyme assay after ultrafiltration of plasma samples taken serially after dosing. QT interval was measured on serial ECG recordings with correction for changes in heart rate. Unbound concentrations of disopyramide were modelled by an open one-compartment pharmacokinetic model with a zero-order absorption rate and a lag time. There was no significant difference in parameter estimates between the four preparations, except for the lag time, which was significantly shorter for the solution preparation. The saturable protein binding of disopyramide was described by a hyperbolic model including a specific binding site and additional nonspecific binding. The pharmacodynamic relationship between unbound drug concentration and QT prolongation was fit by a simple linear model. This fit was better using unbound concentration of the drug than using total concentrations.

Adult↗
PubMed1984

Absence of a significant pharmacokinetic interaction between hydrochlorothiazide and triamterene when coadministered.

Hydrochlorothiazide, triamterene, and hydroxytriamterene sulfate were monitored in the plasma and urine of 24 healthy young men taking single doses of a liquid preparation containing both hydrochlorothiazide and triamterene, liquid preparations containing either of these drugs alone, and a combination tablet recently formulated with a dose ratio of hydrochlorothiazide : triamterene (1 : 1.5) found to give optimal potassium-sparing effect. In contradiction to a recent publication, no interaction between the drugs affecting the bioavailability or renal clearance of either could be demonstrated. The previous report of drug-drug interaction probably arose from formulation-related problems with bioavailability from the two capsule and two tablet products which had been studied. A well-formulated hydrochlorothiazide-triamterene combination tablet promotes plasma concentrations and urinary excretion of hydrochlorothiazide, triamterene, and hydroxytriamterene sulfate which are virtually identical to those seen after either a combination liquid dosage form or simple liquid forms containing only one of the two drugs.

Adult↗
PubMed1984

Aortic anomalies in an adolescent with the Williams' elfin facies syndrome.

An adolescent with classical Williams' syndrome who presented with hypertensive encephalopathy is described. He had the unusual combination of supravalvular aortic stenosis, long segment coarctation of the aorta, aortic hypoplasia and a high bifurcation of the abdominal aorta. Surgical resection of the coarctation was required; however, the patient has remained moderately hypertensive. The aortic anomalies in this syndrome are reviewed and their frequency and importance examined.

Adolescent↗
PubMed1984

Naproxen pharmacokinetics in the elderly.

While naproxen pharmacokinetics appear to be altered in the presence of both diminished renal and hepatic function, the degree to which naproxen disposition might be influenced in the elderly by concurrent alteration in these functions is not obvious. Total plasma clearance/bioavailability (CL/F) of naproxen after a single 375 mg oral dose was found to be less in a group of 10 healthy men between 66 and 81 years of age than in 10 healthy men between 22 and 39 years (0.318 +/- 0.078, 0.416 +/- 0.061 l/h). At steady state (375 mg, 12 hourly), however, CL/F was statistically indistinguishable between the two groups. The fraction of naproxen unbound to plasma protein was doubled in elderly subjects, both at peak and trough drug concentrations. The lowered protein binding tended to obscure a 50% decrement in the intrinsic clearance of naproxen in the elderly as estimated by unbound clearance/bioavailability (213 +/- 64, 396 +/- 155 l/h). As a result, mean steady-state plasma concentrations of naproxen were indistinguishable between the elderly and young (64.2 +/- 8.5, 58.2 +/- 8.1 mg/l) but the elderly generated twice the mean steady-state unbound plasma drug concentration (0.157 +/- 0.039, 0.0859 +/- 0.0212 mg/l). Since it is the unbound drug concentration which appears in general to relate more closely to pharmacological and toxic effect, it may be advisable to reduce naproxen doses by half in the elderly, pending plasma drug concentration-response studies in this age group. If a similar perturbation with age occurs in benoxaprofen protein binding as was observed with naproxen, benoxaprofen intrinsic clearance in the elderly might be only one quarter of that in younger individuals; a factor which may contribute to the toxicity of this drug in the elderly.

Adult↗
PubMed1984

Perinatal outcomes among Medicaid recipients in California.

It is important to document the current status of health outcomes among the medically needy so as to establish baselines to gauge the impact of future program changes. We studied the birth characteristics and perinatal outcomes of women covered by Medicaid in California versus those who were not covered in 1968 and in 1978. Our findings show a high degree of equity and a trend of improvement in perinatal mortality among Medicaid beneficiaries. The results suggest that needy women who are not yet covered by public financing may have a greater risk of adverse pregnancy outcomes. It would thus seem prudent to carefully monitor the impact of any future reductions in public health care expenditures.

Adolescent↗
PubMed1984

Neonatal neuroblastoma presenting with respiratory distress.

We describe two patients to illustrate that neonatal respiratory distress can be associated with airway compression from an intrathoracic neuroblastoma. The clinical features can be either life-threatening from the time of birth or so mild as to escape detection in the immediate newborn period.

Diagnosis, Differential↗
PubMed1983

Oral bioavailability and intravenous pharmacokinetics of amrinone in humans.

Fourteen healthy males received two 75-mg doses of amrinone as a single capsule and as an intravenous solution in a single-dose crossover study. The mean (+/-SD) bioavailability, based on the area under the plasma concentration versus time curves, was 0.93 +/- 0.12. The plasma data for these subjects during the intravenous phase was described by an open two-compartment body model with a mean (+/-SD) apparent first-order terminal elimination rate constant, beta, of 0.19 +/- 0.06 hr-1, which corresponds to a half-life of 3.6 hr.

Administration, Oral↗
PubMed1983

Electroimmunoassay. A new competitive protein-binding assay using antibody-sensitive electrodes.

A novel technique is reported in which an antibody-sensitive electrode for anti-prostaglandin E2 antisera was used to measure solution-phase PGE2 in nanomolar quantities. The electrode was constructed by incorporating a cation-selective ionophore-hapten (PGE2) conjugate into a polyvinyl chloride membrane. Transmembrane potential in a fixed potassium gradient was measured. The addition of anti-PGE2 antisera changed membrane potential in a concentration-dependent manner. The effect of anti-PGE2 antibodies on membrane potential was decreased by adding free PGE2 to the buffer-containing antisera. With this technique a competitive protein-binding assay was developed, and standard curves for solution-phase PGE2 were generated over a concentration range of 1 to 1,000 nM. The assay was relatively specific for PGE2; PGD2 and PGF2a had only minor effects on transmembrane potential over the effective concentration range for PGE2.

Animals↗
PubMed1983

Use of deflector shields to reduce intramammary infection by preventing impacts on the teat ends of cows during machine milking.

A series of short duration experiments has shown that infections caused by the milking machine or the way in which it is used can be controlled by fitting deflector shields in the teatcup liners. This not only provides a simple means of controlling such infections, but demonstrates that they result from penetration of the streak canal of the teat by contaminated milk particles impacting on the teat ends.

Animals↗
PubMed1983

Effects of brotizolam, flurazepam and placebo upon nocturnal auditory arousal thresholds.

Auditory awakening thresholds (AAT) and the back-to-sleep latency (BSL) after nocturnal awakenings from Stage 2 sleep were studied in normal male subjects after placebo, brotizolam (0.25, 0.375 and 0.50 mg) and flurazepam (30 mg). AAT (dB) was measured in five trials spaced across the night in a 'double awakening' procedure with the second awakening in each trial made from Stage 2 sleep. Each drug condition was associated with elevated mean AAT across the five trials in comparison with placebo. In a trial-by-trial analysis only 0.50 mg brotizolam and 30 mg flurazepam were consistently higher in the first three trials compared with placebo. All active drug conditions decreased the mean BSL across all trials in comparison with placebo, but only 30 mg flurazepam and 0.50 mg brotizolam consistently shortened BSL in the first three trials. Brotizolam (0.50 mg) and 30 mg flurazepam are similar in their effects. The subjective improvement reported in insomniac subjects following hypnotic administration may be related to elevation in arousal thresholds and a quick return to sleep after nocturnal sleep disruption.

Acoustic Stimulation↗