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Biomedical subjects

R L Williams

Publications and source records attributed to R L Williams.

At least 253 records · Page 14Linked to original sources
PubMed1987

Effects of formulation and food on the absorption of hydrochlorothiazide and triamterene or amiloride from combination diuretic products.

The absorption of three combination formulations of hydrochlorothiazide and either triamterene or amiloride was studied over a 5-year period in seven separate investigations under varying conditions of food and fasting. The most widely prescribed combination, containing 25 mg of hydrochlorothiazide and 50 mg of triamterene, demonstrated impaired absorption in the fasting state that was partially corrected by the addition of a breakfast high in fat. The increase in the fat content of the food appeared to correlate directly with the amount of both drugs absorbed from this formulation. The second formulation studied, a new combination formulation of 50 mg of hydrochlorothiazide and 75 mg of triamterene, demonstrated acceptable absorption in the fasting state that was not altered by the concurrent administration of a high-fat breakfast. The absorption of the third formulation, a combination of 50 mg hydrochlorothiazide and 5 mg amiloride, was acceptable in the fasting state and demonstrated a slight reduction in the absorption of the amiloride component when administered concurrently with a high-fat meal. The clinical and biopharmaceutic implications of these observations are discussed.

Amiloride↗
PubMed1987

Optimism and locus of control for health and affiliation among elderly adults.

Ninety-two elderly adults ranging in age from 69 to 100 and residing in a retirement community were administered the Life Orientation Test (LOT) (a self-report measure of optimism), the Multidimensional-Multiattributional Causality Affiliation Scale (MMC-AF), and the Multidimensional Health Locus of Control Scale (MHLC). It was hypothesized that optimism would be correlated positively with internal locus of control measures and correlated negatively with external locus of control measures in the areas of affiliation and health. Five of nine comparisons between optimism and locus of control measures yielded significant relationships, all in the expected direction.

Aged↗
PubMed1986

The impact of neglecting nonlinear plasma-protein binding on disopyramide bioavailability studies.

Disopyramide has nonlinear protein binding and thus the relationship between the extent of its bioavailability and AUC, the area under the plasma concentration-time curve, is nonlinear and absorption rate-dependent. The unbound species follows linear pharmacokinetics. A solution of disopyramide, the innovator's product, and two generic formulations were found to be statistically indistinguishable in their bioavailability of disopyramide, whether comparison was based upon AUC or area under the plasma unbound concentration-time curve (AUCu). The AUC and AUCu gave similar results because of truly similar bioavailability, coupled with sufficiently similar release rates, among the four preparations chosen for study. The concentration dependence of disopyramide protein binding and the time course of unbound plasma concentrations were fit by models which then allowed prediction of AUC under various biopharmaceutical scenarios. Nonlinear binding of disopyramide to plasma proteins renders AUC an insensitive parameter for the discrimination of products with different extents of bioavailability; immediate-release products allowing bioavailabilities of 75 or 125% relative to the solution can generate AUCs 86 and 112%, respectively, of that from the solution. Nonlinear binding, furthermore, leads to a tendency for AUC to overestimate the bioavailability of slower release products in single-dose studies; if AUC were the index of bioavailability, products permitting the same bioavailability as the solution but releasing over 12 hr could appear to allow 114% relative bioavailability. Moreover, in some situations the bias arising from the insensitivity of AUC to product differences can be reinforced by the dependence of AUC on release rate; an apparent relative bioavailability of 80% can be achieved by a 12-hr release product allowing a true relative bioavailability of a mere 58%. While multiple-dose studies appear largely to avoid the tendency to overestimate low bioavailability in slow-release products, in these studies AUC appears to be even more insensitive in resolving discrepancies between products. Assay technology now available makes AUCu a feasible and more reliable index of bioavailability than AUC when plasma protein binding of drugs is nonlinear.

Administration, Oral↗
PubMed1986

Intracardiac teratoma in an infant.

We report the only infant known to us who has survived surgery for a primary right ventricular teratoma. Included is a review of other reported cases of teratoma of the heart in infancy and childhood.

Heart Neoplasms↗
PubMed1986

Absorption and disposition of two combination formulations of hydrochlorothiazide and triamterene: influence of age and renal function.

In this study we compared the absorption and disposition of two commonly used combination formulations of hydrochlorothiazide and triamterene (Dyazide and Maxzide) in 48 patients with essential hypertension after dosing with each formulation to steady state. Interdose AUC and urinary recovery of hydrochlorothiazide, triamterene, and the major metabolite of triamterene, hydroxytriamterene sulfate (adjusted for dose), documented marked impairment in the absorption of hydrochlorothiazide (approximately two third as bioavailable) and triamterene (about half as bioavailable) from Dyazide in comparison to Maxzide. The study also demonstrated a reduction in the clearance of triamterene, hydrochlorothiazide, and hydroxytriamterene sulfate with increasing age. Linear correlation analyses suggested that this effect was a result of the reduction in renal function that occurs with increasing age.

Absorption↗
PubMed1986

Type A and B subjects' self-reported cognitive/affective/behavioral responses to descriptions of potentially frustrating situations.

This study compared Type A and Type B individuals' self-reported thoughts and behavioral responses to descriptions of potentially frustrating situations. The Jenkins Activity Survey was first administered to 181 adults to assess their TYpe A tendencies. The Type A scores were then used in forming two groups of 40 extreme Type A's and 40 extreme Type B's. These 80 subjects were subsequently presented with written descriptions of 16 potentially frustrating situations included in the questionnaire "What Pushes Your Button?" and asked to provide two responses to each situation: what they might think if confronted with that situation and what they might actually do in that situation. Their self-reported thoughts and behaviors were classified by independent raters into designated categories. The results showed that Type A individuals' self-reported thoughts reflected significantly more negative than neutral affect and significantly more negative affect than the Type B individuals' thoughts. However, the two groups did not differ significantly in any of the self-reported behavior categories (e.g., nonassertion, aggression, assertion, problem solving, and neutral). Some gender differences were evidenced for the Type A subjects. Women were more inclined than men to report negative affect at the covert level but much less inclined than men to report aggressive responses at the behavioral level.

Adaptation, Psychological↗
PubMed1986

Pregnancy outcomes among Spanish-surname women in California.

We compared pregnancy outcomes among United States-born and Mexican-born women having Spanish surnames with US-born Whites and Blacks using California's 1981 matched birth-death cohort file. Maternal risk characteristics between US-born Black women and US-born women with Spanish surnames were similar. In contrast, Latino women, regardless of national origin, delivered small proportions of low weight infants as compared to Blacks. Birthweight-specific mortality rates during the fetal and neonatal periods for the offspring of Mexican-born Spanish surname women were generally higher than those for other ethnic groups. Our findings are consistent with the underreporting of postneonatal deaths among Mexican-born Latinos, yet suggest that their relatively low reported infant mortality rates compared to Blacks can be explained by a more favorable birthweight distribution.

Adolescent↗
PubMed1986

Alternative to diagnosis-related groups for newborn intensive care.

Clinical and billing data were collected on all admissions to six California newborn intensive care units during a 6-month period. Charges were adjusted to costs using Medicaid cost to charge ratios and for inflation, and patients were classified by the diagnosis-related group (DRG) system. Costs were from 97% to 708% more than the proposed DRG reimbursement levels. Regression analysis showed that DRGs explained 22% of the variation in costs. An alternative model using binary variables to control for birth weight, assisted ventilation, surgery, survival, multiple births, and mode of discharge explained 42% of the variation in costs. In contrast to other proposed DRG alternatives, this simple model does not require special training or subjective decision-making.

Birth Weight↗
PubMed1985

Reducing black neonatal mortality. Will improvement in birth weight be enough?

To study some of the factors contributing to the higher rate of black neonatal mortality in the United States, we used matched cohort records for California between 1980 and 1981 and for Georgia between 1979 and 1981. We found that at any combination of birth weight and gestational age, black neonates weighing less than 3,000 g had lower mortality rates than whites, but this survival advantage was outweighed by considerably higher rates of low birth weight among blacks. At 3,000 g or more, whites had the survival advantage; even at optimal survival weight, the black mortality rate was nearly twice that for whites. If a reduction in the black mortality rate is to occur, improvements are needed both in the black birth-weight distribution and in birth-weight-specific mortality rates, particularly in the normal birth-weight ranges.

Black or African American↗
PubMed1985

Dose dependent pharmacokinetics of nitroglycerin after multiple intravenous infusions in healthy volunteers.

Evaluation of the pharmacokinetics of nitroglycerin has been hindered in the past by the lack of specific and sensitive analytical procedures, and the unavailability of parenteral nitroglycerin and infusion sets which did not adsorb nitroglycerin. The purpose for this present study was to determine the pharmacokinetic parameters of nitroglycerin and the dinitrate metabolites after multiple intravenous infusions of nitroglycerin in healthy volunteers. Six volunteers received variable infusion rates of nitroglycerin. Generally, at 0, 40, 80, and 120 min, the infusion rates were adjusted to 10, 20, 40, and 10 micrograms/min, respectively. Plasma samples were drawn and analyzed for nitroglycerin and its 1,2- and 1,3-dinitrate metabolites using capillary GC. Steady-state nitroglycerin plasma concentrations attained at 10, 20, 40, and 10 micrograms/min were 0.44 +/- 0.31, 1.32 +/- 0.71, 4.23 +/- 1.50 and 1.04 +/- 0.43 ng/ml, respectively. As the infusion rate was increased, the steady-state concentrations increased disproportionately. When the dose was decreased from 40 to 10 micrograms/min, the steady-state nitroglycerin concentrations were always higher than those at the initial low infusion rate. Thus, in the majority of subjects, a hysteretic type of response was present. The hysteresis observed in the dose versus steady-state concentration curve may be explained by either end-product inhibition or saturable binding of nitroglycerin to blood vessels. The clearance values (5.5 to 711/min) were very high and far exceed the maximum possible hepatic clearance suggesting that nitroglycerin is metabolized by organs other than liver. Clearance was not directly related to plasma concentrations but was found to decrease to a constant value (approximately 11 +/- 6 l/min) as nitroglycerin concentrations initially increased.

Adsorption↗
PubMed1985

Oral triamterene disposition.

Earlier studies of triamterene (T) disposition in man have reported hydroxytriamterene (T-OH) and hydroxytriamterene sulfate (T-O-SO3H) conjugate to be the major metabolites. We describe T kinetics through use of an HPLC method and confirm that after hydroxylation, T is rapidly converted to T-O-SO3H. The intermediate T-OH metabolite could not be detected in urine or plasma. Plasma concentrations of T-O-SO3H exceeded those of T by sevenfold to 26-fold, whereas concentrations of that metabolite in the urine were fourfold to thirteenfold higher than those of the parent. Renal clearance of T was 314.5 +/- 121.6 ml/min, exceeding that of the metabolite, which was 206.1 +/- 93.6 ml/min. Coadministration of hydrochlorothiazide increased urine flow and urinary pH, but it did not affect renal clearance of the parent drug or the metabolite. T bioavailability from capsules was poorer and more variable than that from a suspension. Hydrochlorothiazide did not influence the bioavailability of T.

Absorption↗
PubMed1985

A computer method for scanning and analysis of dot blots.

A system is described for computer analysis of autoradiograms produced from dot blots. The autoradiograms are first digitized on a rotating drum densitometer. The system automatically locates, integrates, and corrects the intensity of each spot for background. A linear range of exposures for each series of dilutions on the dot blot is calculated, and the amount of specific RNA is reported relative to other samples or to an internal standard. Without operator intervention, the system can directly scan and analyze all possible spots produced by the commercial filtration devices which use the geometry of a 96-well microtiter plate.

Computers↗
PubMed1985

Origin binding by a 100,000-dalton super-T antigen from SVT2 cells.

The SVT2 line of simian virus 40-transformed mouse cells expresses little or no wild-type-size A protein (T antigen). Instead, a variant form is produced in these cells that is larger than normal-size A protein. This variant form has an Mr of 100,000 (100K super-T antigen) and is found primarily in complexes with the host-cell-coded p53 protein. Binding of the 100K super-T antigen to simian virus 40 origin region DNA was assayed by immunoprecipitation of super-T antigen-DNA complexes and then digestion with DNase I. DNA sequences associated with super-T antigen were protected from digestion and retained in the immune complex, while unprotected sequences were digested and released. The 100K super-T antigen efficiently protects DNA sequences in the previously defined regions I and II (P. Tegtmeyer, B. A. Lewton, A. L. DeLucia, V. G. Wilson, and K. Ryder, J. Virol. 46:151-161, 1983). Within region II (the origin of replication), the pattern and size of protected fragments are identical for super-T antigen and purified wild-type A protein. Thus, even though super-T antigen is larger than wild-type A protein, both must bind with the same alignment on origin DNA. Furthermore, complexes between the host-cell-coded p53 protein and the 100K super-T antigen also retain the ability to bind in regions I and II.

Antigens, Polyomavirus Transforming↗