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Biomedical subjects

I Chang

Publications and source records attributed to I Chang.

At least 55 records · Page 3Linked to original sources
PubMed1996

Drinking environment and sociodemographic factors among DWI offenders.

OBJECTIVE: This study was designed to identify issues for public health/traffic safety in prevention of DWI and alcohol-related traffic injuries/deaths by investigating the relationships among drinking locations, sociodemographic characteristics and drinking-environment-related factors of convicted DWI offenders. METHOD: Subjects were clients (N = 5,154, 79% male) referred to the Lovelace Comprehensive Screening Program for alcohol-related assessment and were interviewed by counselors using a structured, computer-based questionnaire. Differences among ethnic/racial and gender categories were analyzed by logistic regression. RESULTS: (1) Some groups showed a higher rate of DWI convictions, compared to the adult county population: young, single male: Hispanic and Mexican National; divorced/ separated/widowed (increasing with age): (2) older, educated or employed offenders reported drinking more in bars/lounges, while younger offenders were more likely drinking in private parties; (3) Hispanic and Mexican National men showed equal likelihood of drinking with friends and relatives in bars/lounges, whereas non-Hispanic white males reported drinking more with friends; and (4) Native Americans were associated with higher blood alcohol concentration (BAC) and alcohol-related problems. CONCLUSIONS: (1) Young offenders' drinking and social behavior in private parties has implications for traffic safety; (2) divorced/separated offenders suggest a need for attention to underlying emotional problems; (3) strong family ties among Hispancies and Mexican Nationals may be a factor in remedial treatment; (4) Native American BAC statistics showed a need for further study; (5) multiple offenders' association with away-from-home drinking locations increased their risk of being involved in fatal crashes; and (6) server intervention programs should be emphasized to minimize intoxication of customers in commercial establishments.

Accidents, Traffic↗
PubMed1995

The interaction of objective and subjective organizations in a localization search task.

We investigated how both objective and subjective organizations affect perceptual organization and how this perceptual organization, in turn, influences observers' performance in a localization search task. Two groups of observers viewing exactly the same stimuli (objective organization) performed in significantly different ways, depending on how they were induced to parse the display (subjective organization). In Experiments 1 and 2, the observers were asked to describe the location of a tilted target among a varying number of vertical or horizontal distractors. Subjective organization was induced by instructing observers to parse the display into either three horizontal regions (rows) or three vertical regions (columns). The position of the target was critical: location performance, as assessed by reaction time and errors, was consistently impaired at the locations adjacent to the boundaries defining the regions, producing what we refer to as the subjective boundary effect. Furthermore, the extent of this effect depended on whether the stimulus-driven and conceptually driven information concurred or conflicted. This made location information more or less accessible. In Experiment 1, the strength of objective grouping was a function of the proximity of the items (near or far conditions) and their orientation in a 6 x 6 matrix. In Experiment 2, the strength of objective grouping was a function of similarity of color (items were color coded by rows or by columns) and the orientation of the items in a 9 x 9 matrix. The subjective boundary effect was more pronounced when the display promoted grouping in the direction orthogonal to that of the task (e.g., when observers parsed by rows but vertical distractors were closer together [Experiment 1] or color coded [Experiment 2] to induce global columns). In contrast, this effect decreased when the direction of both objective and subjective organizations was parallel (e.g., when observers parsed by rows and horizontal distractors were closer together [Experiment 1] or were color coded [Experiment 2] to induce global rows). A localization search task proved to be an ideal forum in which objective and subjective organizations interacted. We discuss how these results indicated that observers' performance in a localization task was determined by the interaction of objective and subjective organizations, and that the resulting perceptual organization constrained coarse location information.

Adult↗
PubMed1995

The eccentricity effect: target eccentricity affects performance on conjunction searches.

The serial pattern found for conjunction visual-search tasks has been attributed to covert attentional shifts, even though the possible contributions of target location have not been considered. To investigate the effect of target location on orientation x color conjunction searches, the target's duration and its position in the display were manipulated. The display was present either until observers responded (Experiment 1), for 104 msec (Experiment 2), or for 62 msec (Experiment 3). Target eccentricity critically affected performance: A pronounced eccentricity effect was very similar for all three experiments; as eccentricity increased, reaction times and errors increased gradually. Furthermore, the set-size effect became more pronounced as target eccentricity increased, and the extent of the eccentricity effect increased for larger set sizes. In addition, according to stepwise regressions, target eccentricity as well as its interaction with set size were good predictors of performance. We suggest that these findings could be explained by spatial-resolution and lateral-inhibition factors. The serial self-terminating hypothesis for orientation x color conjunction searches was evaluated and rejected. We compared the eccentricity effect as well as the extent of the orientation asymmetry in these three conjunction experiments with those found in feature experiments (Carrasco & Katz, 1992). The roles of eye movements, spatial resolution, and covert attention in the eccentricity effect, as well as their implications, are discussed.

Adult↗
PubMed1994

Stress exacerbates neuron loss and cytoskeletal pathology in the hippocampus.

Glucocorticoids (GCs), the adrenal steroids secreted during stress, endanger the hippocampus, compromising its ability to survive neurological insults. GCs probably do so by disrupting energetics in the hippocampus, thus impairing its ability to contain damaging fluxes of excitatory amino acids and calcium. Superficially, these observations suggest that stress itself should also exacerbate the toxicity of neurological insults. However, most studies have involved unphysiologic GC manipulations, limiting speculations about the endangering effects of stress. In this study, rats were infused with the excitotoxin kainic acid (KA) after either having been adrenalectomized and replaced with a range of physiologic concentrations of GCs, or having been stressed intermittently. We observed that within the CA3 region, increasing CORT concentrations exacerbated the KA-induced neuron loss, the extent of tau immunoreactivity, and of spectrin proteolysis. The transitions from low to high basal GC concentrations and from high basal to stress GC values were both associated with significant exacerbation of neuron loss and tau immunoreactivity; the extent of spectrin proteolysis was less sensitive to increments in GCs. As would be expected from these data, exposure to intermittent stress prior to KA infusion also exacerbated neuron loss, tau immunoreactivity, and spectrin proteolysis in CA3. Thus, physiological elevations of GCs, and stress itself, can exacerbate hippocampal neuron loss and the attendant degenerative markers following an excitotoxic insult. Of significance, seizure and hypoxia-ischemia provoke considerable GC stress responses, which may thus worsen the resultant damage. Furthermore, a number of neuropsychiatric disorders, as well as aging, are associated with elevated basal GC concentrations, which may endanger the hippocampus in the event of neurological insult.

Animals↗
PubMed1993

Corticosterone exacerbates kainate-induced alterations in hippocampal tau immunoreactivity and spectrin proteolysis in vivo.

Aberrant elevations in intracellular calcium levels, promoted by the excitatory amino acid glutamate, may be a final common mediator of the neuronal damage that occurs in hypoxic-ischemic and seizure disorders. Glutamate and altered neuronal calcium homeostasis have also been proposed to play roles in more chronic neurodegenerative disorders, including Alzheimer's disease. Any extrinsic factors that may augment calcium levels during such disorders may significantly exacerbate the resulting damage. Glucocorticoids (GCs), the adrenal steroid hormones released during stress, may represent one such extrinsic factor. GCs can exacerbate hippocampal damage induced by excitotoxic seizures and hypoxia-ischemia, and we have observed recently that GCs elevate intracellular calcium levels in hippocampal neurons. We now report that the excitotoxin kainic acid (KA) can elicit antigenic changes in the microtubule-associated protein tau similar to those seen in the neurofibrillary tangles of Alzheimer's disease. KA induced a transient increase in the immunoreactivity of hippocampal CA3 neurons towards antibodies that recognize aberrant forms of tau (5E2 and Alz-50). The tau immunoreactivity appeared within 3 h of KA injection, preceded extensive neuronal damage, and subsequently disappeared as neurons degenerated. KA also caused spectrin breakdown, indicating the involvement of calcium-dependent proteases. Physiological concentrations of corticosterone (the species-typical GC of rats) enhanced the neuronal damage induced by KA and, critically, enhanced the intensity of tau immunoreactivity and spectrin breakdown. Moreover, the GC enhancement of spectrin proteolysis was prevented by energy supplementation, supporting the hypothesis that GC disruption of calcium homeostasis in the hippocampus is energetic in nature. Taken together, these findings demonstrate that neurofibrillary tangle-like alterations in tau, and spectrin breakdown, can be induced by excitatory amino acids and exacerbated by GCs in vivo.

Animals↗
PubMed1991

Proteoglycan molecules in keratoconus corneas.

Proteoglycan molecules in keratoconus corneas were studied by immunohistochemical and electron microscopic histochemical methods. Compared with normal human control subjects, the staining intensity with monoclonal antibody 9-A-2 was enhanced in the stroma of scarred keratoconus corneas, whereas the intensity with antibody J-19 was reduced. The 9-A-2 experiment showed an increased immunoreactivity of dermatan sulfate proteoglycan epitopes, and the J-19 experiment indicated a decreased immunoreactivity of sulfated keratan sulfate epitopes. Uronic acid analyses were consistent with the 9-A-2 data. Electron microscopy performed after cuprolinic blue staining showed apparent accumulation of abnormally thick, chondroitinase ABC-sensitive, dermatan sulfate proteoglycan filaments in keratoconus corneas. Such filaments were especially prominent in scarred areas. In addition, Keratan sulfate proteoglycan filaments appeared to be less abundant than those found in normal control corneas. Similar alterations of both types of proteoglycan molecules were also seen and reported in scarred corneas. The similarity suggests that the proteoglycan abnormalities found in keratoconus corneas may be secondary, at least in part, to scarring.

Adolescent↗
PubMed1990

Hydralazine dose-response curve analysis.

A multicenter, parallel, double-blind, 181-patient study compared the safety and antihypertensive efficacy of immediate-release (IR) and extended-release (ER) hydralazine. After 2 to 4 weeks on diuretic, patients were maintained on diuretic and randomized to a hydralazine treatment regimen: IR thrice daily, ER twice daily, or ER once daily. Daily doses of hydralazine were 75, 150, or 300 mg. Although designed as a titration study, important dose-response data were available for analysis with nonlinear mixed effect modeling (NONMEM). Sitting diastolic blood pressure (BP) was selected as the response variable. Several factors were tested for importance, including body weight, time (week) effects, concomitant beta-blocker (BB) therapy, acetylator class, and treatment regimen. All factors were important (p less than 0.05) except treatment regimen (p greater than 0.30). The maximum antihypertensive response (Emax) to hydralazine was 9.4 mm Hg. The daily dose that elicited 50% of the maximum response (D50) was 0.87 mg/kg for slow acetylators and 1.68 mg/kg for fast acetylators. BP fell 0.52 mm Hg per week independent of other effects, and concomitant BB therapy induced a drop of 6.6 mm Hg in addition to hydralazine, diuretic and week effects. NONMEM's use assisted in evaluations and provided information not obtainable through traditional means.

Administration, Oral↗
PubMed1990

Application of NONMEM to routine bioavailability data.

Although NONMEM has been proposed as a modeling tool for sparse data sets, little work has described its application to pharmacokinetic data which is also amenable to typical evaluations. An analysis was performed with NONMEM using plasma concentration data obtained during the development of liquid and capsule extended-release (ER) pseudoephedrine products. A total of four studies (single dose and steady-state studies for both the liquid and capsule formulations) were evaluated, each with an immediate-release (IR) control, and consisting of 18 to 20 subjects. NONMEM analyses provided additional information which could not be obtained through traditional means. Specifically, NONMEM provided not only estimates of residual error from single dose and steady-state studies but also a stochastic measure of bioinequivalence and dose-dumping. It permitted hypothesis testing in the same process as pharmacokinetic parameter estimation, such as contrasting absorption rates from capsule and suspension ER products. A less biased estimate of absorption rate was obtainable for ER formulations by utilizing IR runs. Finally, these NONMEM runs confirmed that, even when data are plentiful and amenable to two-stage analyses, NONMEM provides estimates that may in fact be more meaningful and less susceptible to assay or residual variability. Fundamental differences between population and two-stage approaches are discussed.

Analysis of Variance↗
PubMed1989

The effects of mood changes and antidepressants on the cognitive capacity of elderly depressed patients.

Seventy-eight nondemented elderly depressed patients underwent an extensive battery of cognitive tests both before and after seven weeks of treatment with nortriptyline, phenelzine, or placebo. Clinical and cognitive evaluations of the patients were under double-blind conditions. Response to treatment did not appear to significantly affect cognitive capacity; neither did treatment with an active substance as compared to placebo. In addition, the baseline level of cognitive functioning did not appear related to whether a patient responded to treatment. The authors conclude that under optimal conditions neither antidepressant produces measurable changes in the cognitive capacity of nondemented elderly patients.

Affect↗
PubMed1988

How effective and safe is continuation therapy in elderly depressed patients? Factors affecting relapse rate.

Sixty elderly depressed patients who had responded to either nortriptyline hydrochloride or phenelzine sulfate were followed up under double-blind conditions during four to eight months of continuation treatment. Over 70% of patients (43) remained well during this period, while 11 (18.3%) had relapses, three (5.0%) dropped out because of side effects, and three (5.0%) prematurely terminated in good clinical condition. There was no significant difference in the relapse rate between patients receiving nortriptyline (five [16.7%]) and those receiving phenelzine (six [20.0%]). Patients receiving phenelzine were more likely to require dose reductions, and all three patients who dropped out because of side effects were receiving phenelzine. Patients with chronic depression (greater than two years' duration) accounted for all of the relapses.

Age Factors↗
PubMed1987

Clinical predictors of response to antidepressants in elderly patients.

A group of 42 patients, ages 55 and above, suffering from major depression were examined in an attempt to isolate clinical variables that would predict response to antidepressants. These patients were part of a placebo-controlled, double-blind study and were given either nortriptyline or phenelzine for 5-7 weeks. There was no significant difference in response rates between patients subclassified as endogenous or nonendogenous by either RDC or Newcastle criteria. No difference in response rates was found between the DSM-III melancholic and nonmelancholic subtypes. Neither drug preferentially treated a subtype. None of the 21 variables representing symptoms, demographic traits, or characteristics of the depressive illness were found to be significant predictors of antidepressant response.

Aged↗