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Biomedical subjects

S S Hwang

Publications and source records attributed to S S Hwang.

At least 37 records · Page 2Linked to original sources
PubMed1994

Effect of noise on the detection of rib fractures by residents.

RATIONALE AND OBJECTIVES: The authors assessed the effect of noise on the detectability of rib fractures by residents. METHODS: Eight radiology residents read chest posterior-anterior radiographs of 92 subjects with rib fracture(s) and 28 normal subjects to detect rib fracture(s) according to a five-point scale of confidence, under quiet and "noisy" conditions. Each individual's attitude toward noise was measured by a multiple-choice questionnaire. RESULTS: The readers were divided into two groups depending on the questionnaire result: group A readers were accustomed to a quiet environment, and group B readers were accustomed to noisy environments or were unaffected by noise. Group A's performance, measured by the area (Az) under the receiver operating characteristic (ROC) curve, was better in quiet conditions when compared with their performance in noisy conditions; however, the opposite tendency was observed for group B. There was a significant individual difference of performance in response to noise. CONCLUSION: Effect of noise on the detection of rib fractures depends on an individual's attitude toward sound and noise.

Attitude of Health Personnel↗
PubMed1994

In search of Asian war brides.

Because of the long presence of U.S. soldiers in Asia, war-bride marriages involving servicemen and Asian women have been formed throughout the century. The literature, however, contains little empirically sound information on Asian war brides. This analysis develops a methodology to identify war brides and applies it to estimate the number of war brides from the six major Asian groups, using the national 1980 Public Use Microdata Sample. Further analysis comparing Asian war brides with other groups of Asian wives tends to support the traditional and lower socioeconomic images commonly associated with Asian war brides.

Acculturation↗
PubMed1993

In vivo evaluation of controlled-release products.

A theoretical investigation has been conducted to understand the deconvolution method used for evaluating the in vivo release rate of an oral controlled-release product from the plasma drug concentration versus time profile. The theory is based on well-accepted pharmacokinetic compartmental models. The cumulative amount of drug released from a dosage form can be partitioned into two parts: the amount already absorbed and the amount released but still remaining at the absorption site in the gastrointestinal tract. The cumulative amount absorbed at any time, t, can be estimated from the plasma concentration versus time profile by the compartmental model-based Wagner-Nelson method or Loo-Riegelman method. We have derived a mathematical expression relating the amount at the absorption site with the plasma drug concentration versus time profile assuming a first-order absorption rate process. The difference between the in vivo release profile and the in vivo absorption profile is illustrated. Because what determined in vitro is the release profile, it should preferentially be correlated with the in vivo release profile, not the absorption profile. However, when absorption is much faster than elimination, the estimated absorption profile is a good approximation of the release profile. In this circumstance, it is advantageous to use absorption profiles to demonstrate correlation of in vitro and in vivo dosage form performance to avoid the noise inherent in the numerical method of deriving the exact in vivo release profile.

Absorption↗
PubMed1993

Interpretation and utilization of effect and concentration data collected in an in vivo pharmacokinetic and in vitro pharmacodynamic study.

The effect (E) of some drugs may be monitored in vitro using the plasma drug concentration (C) following the in vivo dosing of drug. When using a specific analytical assay, counterclockwise hysteresis in the E vs C relationship can be explained only by the presence of an agonistic metabolite (MA); the extent of hysteresis will depend upon the pharmacokinetics and relative "potency" of C and MA. If a nonspecific assay is used, plots of E vs C may actually relate to E vs total agonist (C + MA), and unusual hysteresis may be observed, e.g., clockwise hysteresis when C is more "potent" than MA. Here, we simulate data for three models of relative C and MA pharmacokinetics. The E vs C and E vs MA data are simulated for both linear and noncompetitive agonist Emax models. When C and MA are equally potent, hysteresis will not be observed in a plot of E vs C + MA. However, when C and MA are of differing "potencies," hysteresis will be observed (the direction of hysteresis is dependent on the relative potency of C and MA). By appropriately "weighting" a respective agonist (C or MA), hysteresis will "collapse" and the relative potencies of C and MA can be estimated.

Models, Theoretical↗
PubMed1992

Identification of envelope V3 loop as the major determinant of CD4 neutralization sensitivity of HIV-1.

Laboratory isolates of human immunodeficiency virus type-1 (HIV-1) such as HTLV-IIIB are generally T cell line-tropic and highly sensitive to neutralization by soluble CD4 (sCD4), a potential antiviral agent that is undergoing clinical trial. However, many primary HIV-1 isolates are macrophage-tropic and sCD4-resistant. Envelope V3 loop sequences derived from primary HIV-1 isolates were sufficient to confer on HTLV-IIIB not only the tissue tropism but also the degree of sCD4 neutralization resistance characteristic of their HIV-1 strains of origin. Single amino acid changes in the V3 loop enhanced sCD4 resistance by up to tenfold. These observations suggest that the tissue tropism and sCD4 neutralization sensitivity of HIV-1 isolates are regulated by similar mechanisms.

Amino Acid Sequence↗
PubMed1992

Treatments of depression and the functional capacity to work.

This study evaluated the effects of antidepressants and psychotherapy on work impairment in depressed patients. Original databases from 10 published treatment studies were compiled and analyzed (N = 827). Functional work impairment was common at baseline, manifested by unemployment (11%) or on-the-job performance problems (absenteeism, decreased productivity, interpersonal problems, 44%). Generally, work outcomes were good when treatment was symptomatically effective, but the trajectories of work restoration and symptom remission were different, with work recovery appearing to take considerably longer. Relapse was an important determinant of long-term occupational outcome, particularly for seriously ill patients for whom relapse meant rehospitalization or other profound social disruption. Affective impairment was distinguished from functional impairment, with the former characterizing milder depression and the latter characterizing moderate to severe depression. Some methodological recommendations are discussed.

Absenteeism↗
PubMed1992

System functionality and physicochemical model of fentanyl transdermal system.

Fentanyl is an opioid traditionally administered by infusion or injection and more recently in a rate-controlled transdermal dosage form. This system is a four-layer laminate on a protective liner. A backing layer seals and protects the drug reservoir, the source for continuous delivery of fentanyl. A membrane controls the release rate of fentanyl from the system. An adhesive layer attaches the system to skin and releases an initial loading dose of fentanyl. The rate of fentanyl delivery through skin is determined by the system and the skin at the application site. The release rate from the system is approximated by Fick's first law of diffusion and is controlled by the rate-controlling membrane. A complete simulation model that combines both in vitro release data and the pharmacokinetic model has been developed and used to show the influence of various physiologic and system variables on serum fentanyl concentrations.

Administration, Cutaneous↗
PubMed1992

cis-acting lesions targeted to the hydrophobic domain of a poliovirus membrane protein involved in RNA replication.

The structural requirements of the hydrophobic domain contained in poliovirus polypeptide 3AB were studied by using a molecular genetic approach in combination with an in vitro biochemical analysis. We report here the generation and analysis of deletion, insertion, and amino acid replacement mutations aimed at decreasing the hydrophobic character of the domain. Our results indicated that the hydrophobicity of this region of 3AB is necessary to maintain normal viral RNA synthesis. However, in vitro membrane association assays of the mutated proteins did not establish a direct correlation between 3AB membrane association and viral RNA synthesis. Some of the lethal mutations we engineered produced polyproteins with abnormal P2- and P3-processing capabilities due to an alteration in the normal cleavage order of the polyprotein. A detailed analysis of these mutants suggests that P2 is not the major precursor for polypeptides 2A and 2BC and that P2 protein products are derived from P2-P3-containing precursors (most likely P2-P3 or P2-3AB). Such precursors are likely to result from primary polyprotein cleavage events that initiate a proteolytic cascade not previously documented. Our results also indicated that the function provided by the hydrophobic domain of 3AB cannot be provided in trans. We discuss the implications of these results on the formation of limited-diffusion replication complexes as a means of sequestering P2- and P3-region polypeptides required for RNA synthesis and protein processing.

Amino Acid Sequence↗
PubMed1992

Comparison of plasma nicotine concentrations after application of nicoderm (nicotine transdermal system) to different skin sites.

Drug absorption through the skin can vary according to the application site. The nicotine transdermal system, Nicoderm (Alza Corp., Palo Alto, CA) contains a rate-controlling membrane designed to regulate delivery of nicotine to the skin and thus limit variability in nicotine plasma levels. Plasma nicotine concentrations were compared after application of NTS 14 mg/day to three different skin sites (upper back, upper outer arm, upper chest) in a randomized, crossover study involving 12 healthy male smokers. Plasma nicotine profiles from all three sites were similar: nicotine concentrations increased rapidly within 2 to 4 hours, reached broad peaks of approximately 11 to 14 ng/mL, and then remained relatively constant between 8 and 24 hours after application. The mean nicotine maximum peak plasma concentration values for nicotine transdermal system application to the arm, back, and chest were equivalent (13.8, 14.6, and 13.2 ng/mL, respectively). The mean time to reach peak concentration (tmax) (3 to 6 hours), and area under the curve (168, 186, and 183 ng.h/mL) values for the arm, back, and chest, respectively, were not significantly different. Thus, bioequivalent plasma nicotine concentrations were achieved irrespective of the application site on the upper body.

Administration, Cutaneous↗
PubMed1991

Identification of the envelope V3 loop as the primary determinant of cell tropism in HIV-1.

Cells of the monocyte-macrophage lineage are targets for human immunodeficiency virus-1 (HIV-1) infection in vivo. However, many laboratory strains of HIV-1 that efficiently infect transformed T cell lines replicate poorly in macrophages. A 20-amino acid sequence from the macrophage-tropic BaL isolate of HIV-1 was sufficient to confer macrophage tropism on HTLV-IIIB, a T cell line--tropic isolate. This small sequence element is in the V3 loop, the envelope domain that is the principal neutralizing determinant of HIV-1. Thus, the V3 loop not only serves as a target of the host immune response but is also pivotal in determining HIV-1 tissue tropism.

Amino Acid Sequence↗
PubMed1990

A mutant poliovirus containing a novel proteolytic cleavage site in VP3 is altered in viral maturation.

A six-amino-acid insertion containing a Q-G amino acid pair was introduced into the carboxy terminus of the capsid protein VP3 (between residues 236 and 237). Transfection of monkey cells with full-length poliovirus cDNA containing the insertion described above yields a mutant virus (Sel-1C-02) in which cleavage occurs almost entirely at the inserted Q-G amino acid pair instead of at the wild-type VP3-VP1 cleavage site. Mutant Sel-1C-02 is delayed in the kinetics of virus production at 39 degrees C and exhibits a defect in VP0 cleavage into VP2 and VP4 at 39 degrees C. Sucrose gradient analysis of HeLa cell extracts prepared from cells infected by Sel-1C-02 at 39 degrees C shows an accumulation of fast-sedimenting replication-packaging complexes and a significant amount of uncleaved VP0 present in fractions containing mature virions. Our data provide in vivo evidence for the importance of determinants other than the conserved amino acid pair (Q-G) for recognition and cleavage of the P1 precursor by proteinase 3CD and show that an alteration in the carboxy terminus of VP3 or the amino terminus of VP1 affects the process of viral maturation.

Amino Acid Sequence↗
PubMed1989

Absorption characteristics of transdermally administered fentanyl.

Fentanyl was administered intravenously and transdermally to eight surgical patients to determine the systemic bioavailability and rate of absorption of the transdermally administered drug. Serum fentanyl concentrations reached a plateau approximately 14 h after placement of the transdermal fentanyl delivery system. This plateau was maintained until removal of the system at 24 h. The decline in serum fentanyl concentrations after removal of the transdermal system had a terminal half-life of 17.0 +/- 2.3 h (mean +/- SD), considerably longer than the terminal elimination half-life seen after intravenous administration of fentanyl in the same patients (6.1 +/- 2.0 h). The rate of fentanyl absorption, predicted to be 100 micrograms/h from in vitro data, appeared to be relatively constant during a period starting 4-8 h after placement of the transdermal system until removal of the system at 24 h. The rate of absorption during this period was 91.7 +/- 25.7 micrograms/h. After removal of the transdermal fentanyl delivery system, absorption continued at a declining rate. This indicates that the long terminal half-life of serum fentanyl concentrations after transdermal system removal is due to continued slow absorption of fentanyl, probably from a cutaneous depot of drug at the site of prior transdermal system placement. At the time of removal of the transdermal fentanyl system, 1.07 +/- 0.43 mg of drug remained in this depot. Systemic fentanyl bioavailability was found to be 0.92 +/- 0.33, with no evidence of significant cutaneous metabolism or degradation by the skin's bacterial flora. The transdermal administration of fentanyl produces relatively constant serum fentanyl concentrations for significant periods of time in the postsurgical patient requiring analgesic therapy.

Administration, Cutaneous↗
PubMed1987

Simultaneous quantification of cycloserine and its prodrug acetylacetonylcycloserine in plasma and urine by high-performance liquid chromatography using ultraviolet absorbance and fluorescence after post-column derivatization.

D-Cycloserine is a broad-spectrum antibiotic used with other antibiotics to treat various forms of tuberculosis. Its prodrug sodium (R)-4-[(1-methyl-3-oxo-1-butenyl)amino]-3-isoxazolidinone hemihydrate, developed for better aqueous stability and solubility, is combined with another broad-spectrum antibiotic, fludalanine. An ion-pair, reversed-phase high-performance liquid chromatographic assay has been developed to simultaneously detect cycloserine and its prodrug in plasma and urine. The prodrug is detected directly by ultraviolet absorbance and cycloserine by fluorescence following post-column derivatization.

Adult↗
PubMed1985

Effect of nonlinear protein binding on equilibration times for different initial conditions.

The dynamics in the equilibration of free drug in a two-compartment closed system, exhibiting nonlinear binding in one of the compartments, are elucidated. The dynamics of the free drug in the compartment containing the binding sites are first studied under the two initial conditions when the drug is added to the same and the other compartment; the dynamics of the drug in the compartment devoid of binding sites are then studied under the two initial conditions. Dynamic asymmetries are shown to exist among the four cases in the nonlinear region using an equilibrium limit which symmetrizes the dynamics for all four cases in the linear region. In the two cases where the dynamics are viewed in the compartment devoid of binding sites, the dynamic asymmetry is manifested by a reduction in the time required to reach the limit for the drug added to the compartment containing the binding sites compared with the other compartment. The time difference between these two cases becomes magnified when limits, reflective of the relative error in the estimate of the equilibrium value, are applied. In the linear region, application of these limits results in a time difference. This time difference again favors addition to the compartment containing the binding sites from a time-conservation perspective.

Binding Sites↗