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Biomedical subjects

A S Chang

Publications and source records attributed to A S Chang.

At least 37 records · Page 2Linked to original sources

Measurement of lumbar lordosis. Evaluation of intraobserver, interobserver, and technique variability.

STUDY DESIGN: Sixty radiographs were measured on two separate occasions by three physicians using four different techniques to evaluate the reliability and reproducibility of the measurement of lumbar lordosis. OBJECTIVE: To evaluate clinical methods of measuring lumbar lordosis, determining intraobserver and interobserver reliability. SUMMARY OF BACKGROUND DATA: Several different methods are used to measure lumbar lordosis. The reliability and reproducibility of these has not been well studied. METHODS: Sixty lateral full spine radiographs were obtained, labeled, and the lumbar lordosis measured independently by three practitioners who routinely perform these measurements. Four measurement techniques were used. These included measurements from the inferior endplate of T12 to the superior endplate of S1; the superior endplate of L1 to the superior endplate of S1; the inferior endplate of T12 to the inferior endplate of L5; and the superior endplate of L1 to the inferior endplate of L5. The measurements then were repeated after relabeling. RESULTS: Intraobserver reliability coefficients ranged from 0.83 to 0.92, indicating excellent reproducibility. Ninety-two percent of repeat measures were within 10 degrees. High overall and pairwise agreement among the three observers also was present; the interobserver reliability coefficients ranged from 0.81 to 0.92. CONCLUSIONS: The measurement of lumbar lordosis is reproducible and reliable if the technique is specified and one accepts 10 degrees as acceptable variation. Factors that affect the reproducibility of measurement include end vertebra selection (especially with transitional segments) and vertebral endplate architecture.

Adult↗

Trigeminal motor nerve conduction: deep temporal and mylohyoid nerves.

This article describes nerve conduction studies of the deep temporal nerve (DTN) and the mylohyoid nerve (MHN) motor branches of the trigeminal nerve. These nerves were stimulated intraorally with a pediatric surface stimulator. Compound muscle action potentials were recorded over the temporalis and mylohyoid muscles with surface electrodes. Forty-two subjects were studied. In all subjects the MHN response was elicited bilaterally, giving an upper latency limit of 2.3 ms. The mean MHN amplitude was 4.9 mV (SD = 1.8 mV, minimum = 1.3 mV). The maximal side-to-side amplitude difference was 0.4 ms. and the maximal side-to-side amplitude difference was 2.2 mV. The DTN response was only elicited bilaterally in 25 (60%) subjects. The average DTN latency was 2.1 ms (SD = 0.3, maximum = 2.7 ms). The average DTN amplitude was 4.3 mV (SD = 2.0, minimum = 0.3 mV). The MHN responses were the least technically demanding, and were more consistently elicited than the DTN responses. These nerve conduction techniques should prove useful in patients with trigeminal nerve disorders.

Adult↗

The role of serotonin in the actions of psychostimulants: molecular and pharmacological analyses.

Cocaine is a highly abused psychostimulant which is a local anesthetic and inhibitor of the reuptake of dopamine (DA), serotonin (5-HT) and norepinephrine (NE). This manuscript details a brief summary and the primary conclusions of several presentations geared to present recent pharmacological analyses of the interaction of cocaine with 5-HT systems. These data illustrate the complexity of actions for cocaine in the brain and emphasize that, to fully understand the mechanisms which underlie its potent behavioural effects, the impact of this drug on 5-HT function as well as the interactions between 5-HT and the function of DA mesolimbic pathways must be considered.

Animals↗

Reductions in platelet force development by cardiopulmonary bypass are associated with hemorrhage.

Quantitative assessment of platelet dysfunction after cardiopulmonary bypass (CPB) and prediction of excessive microvascular bleeding remain elusive goals. We used a sensitive instrument capable of simultaneously measuring the force generated by platelets during plasma clot retraction and global clot strength. We hypothesized that CPB would significantly reduce these two variables. Platelet-rich plasma was obtained from eight patients undergoing aortocoronary revascularization prior to induction, after 90 min of CPB, and after protamine administration. Platelet force development was measured using a standardized technique that controlled for platelet number and permitted clot formation in the presence of heparin. Despite the presence of a measurable elastic modulus, platelet force development during bypass was abolished. Peak platelet force development after CPB was significantly lower than before CPB (5255 +/- 955 dynes vs 11,600 +/- 780 dynes, P = 0.01). The percent recovery (after/before bypass) of peak platelet force development inversely correlated with tube thoracostomy drainage during the first 24 h after placement (rs = -0.71, P = 0.048). This study demonstrates that CPB has dramatic effects on platelet force development. The correlation between the percent recovery of peak platelet force development and blood loss supports the clinical relevance of this measurement.

Aged↗

Mothers' parenting self-appraisals: the contribution of perceived infant temperament.

To learn how a mother's perception of her infant's temperament contributes to her appraisal of her parenting and of her problem-solving competence during the first 3 months postpartum, we explored a conceptual model, including infant gender and maternal attributes (education and parity) and the personal and social context of the parenting experience (infant centrality and life change), in a sample of 117 mothers. The set of temperament variables contributed to the variance in both parenting evaluation and problem-solving competence at 1 and 3 months. The pattern of infant temperament variables contributing to maternal self-appraisal variables at 1 and at 3 months suggests change in the temperament variables that are salient to mothers as the infants grow older.

Adolescent↗

Choline pharmacokinetics during intermittent intravenous choline infusion in human subjects.

A study of choline pharmacokinetics was undertaken in four patients receiving long-term total parenteral nutrition. On consecutive days, 7, 14, 28, and 56 mmol choline chloride were intravenously infused over a 12-hour period in each subject. The choline concentration was determined in plasma at baseline, 1/4, 1, 3, 6, and 12 hours, and 3 and 12 hours after the infusion ended, and in daily 24-hour urine collections. Analysis of variance showed the data fit a two-compartment model in which elimination from the central compartment was saturable significantly better than a one-compartment model in all four subjects (p < 10(-8) in all cases), and significantly better than a nonsaturating model in three of the four subjects (p = 1.0 x 10(-9), 7.5 x 10(-6), 9.4 x 10(-11), respectively). The model allowed estimates of the rate constant for choline elimination at ambient levels, first-order rate constants for transfer between central and peripheral compartments, the dissociation constant for the saturable elimination process, the apparent volume of distribution in the central compartment, the steady-state volume of distribution, and the quantities of choline in the central compartment and in the readily exchangeable pool.

Adult↗

Structure-activity relationships of serotonin transport: relevance to nontricyclic antidepressant interactions.

A transfectant cell model was used to examine the structure-activity relationships of serotonin (5-hydroxytryptamine, 5-HT) transport. The findings suggest that 5-HT interacts largely with nonpolar and sterically-confining environments on the transport system, and that a particular spatial coordination of the amino and phenyl groups (separated by an alkyl backbone) is important for transport interaction. Molecular modelling analyses revealed that this motif is also present in the structures of several nontricyclic antidepressants and specific inhibitors of 5-HT transport, as well as adrenergic agents which also possess 5-HT transport-inhibitory activities. While this amino-phenyl coordination motif seems to be a necessary structural requisite for transport interaction, and therefore likely to be part of the transport pharmacophore, additional phenyl rings present in some of the nontricyclic antidepressants may help to account for their relatively higher affinities in 5-HT transport interaction.

Animals↗

Antidepressant- and cocaine-sensitive human serotonin transporter: molecular cloning, expression, and chromosomal localization.

A Na(+)- and Cl(-)-coupled serotonin (5-hydroxytryptamine, 5HT) transporter is expressed on human neuronal, platelet, placental, and pulmonary membranes. The brain 5HT transporter appears to be a principal site of action of therapeutic antidepressants and may mediate behavioral and/or toxic effects of cocaine and amphetamines. Oligonucleotides derived from consensus transporter sequences were used to identify human placental cDNAs highly related to the rat brain 5HT carrier. Transfection of one of these cDNAs into HeLa cells yields a high-affinity (Km = 463 nM), Na(+)- and Cl(-)-dependent 5HT transport activity which can be blocked by selective 5HT transport inhibitors, including paroxetine, fluoxetine, and imipramine, and which is antagonized by cocaine and amphetamine. Sequence analysis reveals a 630-amino acid open reading frame bearing 92% identity to the cloned rat brain 5HT transporter, with identical predicted topological features and conserved sites for posttranslational modifications. Unlike the rodent, where a single mRNA appears to encode 5HT transporters, multiple hybridizing RNAs are observed in human placenta and lung. Somatic cell hybrid and in situ hybridization studies are consistent, however, with a single gene encoding the human 5HT transporter, localized to chromosome 17q11.1-17q12.

Amino Acid Sequence↗

Hypoxia and beta-hydroxybutyrate acutely reduce glucose extraction by the brain in anesthetized dogs.

Induced ketosis may acutely prolong hypoxic tolerance by altering glucose and (or) beta-hydroxybutyrate extraction by the brain. Anesthetized dogs were ventilated and instrumental for arterial and cerebral venous blood sampling, taken during baseline, infusion, test, and recovery periods. Each dog received one of four different beta-hydroxybutyrate doses and 25 min of either a normoxic or hypoxic (8% oxygen) test period. Arterial glucose and beta-hydroxybutyrate were stable in the saline and 3 mg.kg-1 x min-1 beta-hydroxybutyrate infusion groups, but glucose declined and beta-hydroxybutyrate increased in the 10 and 20 mg.kg-1 x min-1 beta-hydroxybutyrate infusion groups. During normoxia glucose arteriovenous differences across the brain decreased significantly only in the 20 mg.kg-1 x min-1 beta-hydroxybutyrate infusion groups, and during hypoxia the differences decreased for all groups. beta-Hydroxybutyrate arteriovenous differences tended to increase with a 100-fold increase in beta-hydroxybutyrate concentrations, but the trend was not statistically significant. Hypoxia further decreased glucose extraction, but did not change beta-hydroxybutyrate extraction. We conclude that beta-hydroxybutyrate may protect during hypoxia by depressing glucose uptake and consumption rather than by acting as an alternative cerebral energy substrate.

3-Hydroxybutyric Acid↗

Differential regulation of the imipramine-sensitive serotonin transporter by cAMP in human JAr choriocarcinoma cells, rat PC12 pheochromocytoma cells, and C33-14-B1 transgenic mouse fibroblast cells.

The imipramine-sensitive serotonin transporter appears to be the receptor for clinically important antidepressants. Some studies suggest that this protein may fall under the influence of abnormal and as yet uncharacterized regulatory effects during depressive illness. Despite these putative disease-related effects, regulation has never been demonstrated in either the platelet or synaptosome model systems. Here we demonstrate for the first time that the imipramine-sensitive serotonin transport activity in either JAr choriocarcinoma or PC12 pheochromocytoma cell lines is subject to regulation by cAMP. Unexpectedly, the regulatory effect is opposite in the two cases, causing stimulation in JAr (increased Vmax) and inhibition in PC12 (kinetically complex). Appearance of these kinetic effects lagged 15 to 20 hours behind peak cAMP levels. The results are consistent with the interesting possibility that different tissues may express isoforms of the recently cloned serotonin transporter cDNAs. We suggest, therefore, that JAr and PC12 are attractive models in which to pursue detailed analysis of serotonin transport and its manner of regulation by cAMP.

1-Methyl-3-isobutylxanthine↗

Incomplete reversibility of an experimentally induced hypocholinergic state: biochemical and physiological, but not behavioral, recovery.

In previous reports, we described the experimental development of a hypocholinergic state in rats following the total replacement of dietary choline by an artificial isostere, N-aminodeanol (NADe). NADe shares most of the physicochemical and biochemical characteristics of choline (Ch) but is utilized less efficiently in pathways leading to the formation of both acetylcholine and phospholipids. This experimental model mimics many of the features of human degenrative dementias. We now discuss the behavioral and physiological effects of restoring a normal diet after the hypocholinergic state has become well established. The procedure by which that state was induced has been described in detail in earlier publications. After replacing Ch in the diets of weanling rats for 270 days, NADe replaced 70-85% of the phospholipid-bound Ch in plasma, brain, and peripheral tissue. When dietary NADe was removed and Ch was restored in the diet, NADe disappeared and plasma and erythrocyte (RBC) choline levels returned to normal within 30-60 days. Quinuclidinyl benzilate (QNB) binding showed that muscarinic receptors continued to be depressed in animals remaining on the NADe diet, but returned to control levels in the reversal group. There were no differences in cholinesterase activity among the three treatments. Choline acetyltransferase activity returned to control levels, while continuing to be lower in the NADe animals. Liver lipids were elevated in the latter and not significantly different in the control and reversal groups. Among physiological functions, body weight increased more rapidly in the reversal group than in animals continuing on the NADe diet. Brain weights of the reversal animals were significantly greater than those of animals not reversed, but less than controls. Core body temperatures did not differ from controls at any time during the reversal period. Behaviorally, nociceptive thresholds indicative of sensory-reflexive and sensory-perceptual responses remained significantly below normal, that is, a hyperalgesic state. Reversal animals also remained hyperactive and displayed memory significantly poorer than those on the normal diet, that is, no improvement over animals continuing on NADe. In general, the results suggest that behavioral losses induced by NADe reflect persisting changes in the CNS, despite essentially complete recovery of biochemical parameters. The changes may be morphological or be associated with adaptive changes in other neurochemical events in the CNS.

Animals↗

Transition to being the mother of a new infant in the first 3 months: maternal problem solving and self-appraisals.

This study explored components of a model of transition to being the mother of a new infant during an infant's first 3 months. Personal and situational conditions and maternal problem-solving factors (issue formulating and the use of help with issues) that may influence transition markers (maternal appraisal of problem-solving competence and evaluation of parenting) were examined for two study periods: the first 30 days postpartum and the next 60 days. For the second study period, variables contributing to maternal attention to infant growth, development and temperament (knowing issues) were also explored. Questionnaires and a daily log kept by 62 mothers of healthy term infants were data sources. Everyday supports (situational condition) contributed to use of lay help for the second period. Caretaking issues positively influenced use of clinician help throughout the study. The number of knowing issues a mother formulated contributed positively to problem-solving competence and to parenting evaluation; the use of problem-solving help had no effect. More clinician help received during the first month meant higher need for maternal action for both knowing and caretaking issues in the second and third months. Further study of the mechanisms of these relationships and examination of factors contributing to shifts in the transition process are needed.

Adult↗

A pharmacokinetic analysis of 3,4-methylenedioxymethamphetamine effects on monoamine concentrations in brain dialysates.

Interpretation of the in vivo actions of 3,4-methylenedioxymethamphetamine (MDMA) is complicated by the formation of the active metabolite, 3,4-methylenedioxyamphetamine (MDA). This study evaluates the role of MDA in the dopamine releasing actions of (+)-MDMA. In the study, rats were given subcutaneous doses of (+)-MDMA and concentrations of monoamines and their metabolites in striatal dialysate were measured at 15 min intervals. In parallel experiments, plasma concentrations of (+)- and (-)-MDMA and MDA were determined by GC/MS procedures. The time course of MDMA levels was comparable for the two isomers as were their bioavailabilities. In contrast, the plasma levels of MDA were about three times higher after (+)-MDMA. (+)-MDMA caused a rapid increase in striatal dialysate levels of dopamine and decreased extracellular levels of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). There was a significant correlation between dopamine concentration in striatal dialysate and plasma MDMA concentration, but not with plasma MDA. These results indicate that MDMA itself has stereoselective actions on dopamine neurons. However, the higher plasma MDA levels after (+)-MDMA may account for part of the enantiomeric differences in the behavioral and neurotoxicological effects of MDMA.

3,4-Dihydroxyphenylacetic Acid↗

Association between hepatitis C virus antibodies and hepatocellular carcinoma in Taiwan.

In order to assess the association between antibodies to hepatitis C virus (anti-HCV) and hepatocellular carcinoma (HCC), as well as the interaction of anti-HCV with other HCC risk factors in Taiwan, a total of 127 pairs of newly diagnosed HCC patients and healthy community controls were studied. Case-control pairs were individually matched for age (+/- 3 years), sex, residence, and ethnicity. Serum samples from study subjects were examined for anti-HCV by enzyme immunoassays as well as hepatitis B surface antigen (HBsAg) and e antigen (HBeAg) by radioimmunoassays using commercial kits. The habits of cigarette smoking, alcohol drinking, and peanut consumption were obtained through standardized interviews according to a structured questionnaire. Both the anti-HCV as well as the carrier status of HBsAg and HBeAg were significantly associated with HCC showing a multivariate-adjusted odds ratio of 24.8 for carriers of HBsAg alone, 33.5 for carriers of both HBsAg and HBeAg, and 23.7 for those who were positive for anti-HCV. The population-attributable risk percentage was estimated as 3% for anti-HCV alone, 69% for HBsAg carrier status alone, and 6% for both anti-HCV and HBsAg in Taiwan. There were also synergistic effects on HCC development for anti-HCV with HBsAg carrier status, cigarette smoking, and habitual alcohol drinking.

Alcohol Drinking↗

Early postpartum transition: progress in maternal identity and role attainment.

Sets of early postpartum transition variables and relationships among them examined in this study were: (a) Maternal attributes (parity, age, education); (b) infant feeding plan (extent of breast-feeding); (c) birthing conditions (supports and stressors during labor and delivery); (d) birthing experience (how well labor and delivery went, usefulness of postpartum learning resources, adequacy of hospital stay); and (e) transition markers (evaluation of parenting and of infant- and self-care capability). Infant feeding plan was related to supports but not to how well labor and delivery went. Whereas preparation for birthing was positively related to how well labor and delivery went, stressors were negatively related. The direct contribution of preparation for birthing to both parenting evaluation and infant- and self-care capability and of supports and usefulness of postpartum resources to self-care capability merits clinical attention to these variables. Research concerning types of birthing experience that may contribute to evaluation of parenting is needed.

Adaptation, Psychological↗

Effects of hepatitis B virus, alcohol drinking, cigarette smoking and familial tendency on hepatocellular carcinoma.

Independent and interactive effects related to the development of hepatocellular carcinoma were assessed using a community-based case-control study for hepatitis B virus, habitual alcohol drinking, cigarette smoking, peanut consumption and history of hepatocellular carcinoma among the immediate family. All 200 male newly diagnosed hepatocellular carcinoma patients were recruited consecutively through the period of study as the case group from two teaching medical centers in northern and southern Taiwan. Healthy community residents matched one-to-one with cases on age, sex, ethnic group and residential area were selected as the control group. The carrier status of HBsAg and HBeAg was determined by blind radioimmunoassays, and other risk factors were obtained through standardized interviews according to a structured questionnaire. Conditional logistic regression analysis showed a significant association between hepatocellular carcinoma and the carrier status of HBsAg and HBeAg with an odds ratio of 16.7 and 56.5, respectively, for carriers of HBsAg alone and for carriers of both HBsAg and HBeAg. There was a dose-response relationship between cigarette smoking and hepatocellular carcinoma with an odds ratio of 1.1, 1.5 and 2.6, respectively, for those who smoked 1 to 10, 11 to 20 and more than 20 cigarettes a day. A significant association with hepatocellular carcinoma was also observed for the habitual alcohol consumer with an odds ratio of 3.4. Those whose immediate family had a history of hepatocellular carcinoma were more likely to have the disease develop, with an odds ratio of 4.6. However, the frequency of peanut consumption was not significantly associated with hepatocellular carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Pharmacological characteristics of high-affinity serotonin uptake systems established through gene transfer.

Inactivation of a neurotransmitter, after its stimulated release, via high-affinity uptake mechanisms is an essential regulatory step of neurotransmission in both the central and peripheral nervous systems. To initiate explorations of the molecular mechanisms and the underlying biochemical architecture of high-affinity neurotransmitter uptake systems, we have used gene transfer technology to establish and identify novel cellular models that express these systems. Human genomic DNA was transfected into mouse L-M fibroblasts and two independently arising, clonal cell lines (L-S1 and L-S2) have been identified as expressing high-affinity serotonin (5-HT) uptake systems. The 5-HT uptake characteristics of L-S1 and L-S2 are essentially comparable (in terms of Na+ dependence, temperature sensitivity, imipramine antagonizability, kinetic saturability and high affinities) and those of L-S1 have been reported previously. Furthermore, competition studies utilizing catecholamine neurotransmitters and their amino acid precursors demonstrated that these systems are highly specific for 5-HT. Several known inhibitors of high-affinity 5-HT uptake systems (including amitriptyline, desipramine, fluoxetine, imipramine, nortriptyline, tryptamine, 5-methoxytryptamine and N-acetyl 5-methoxytryptamine) were assessed in terms of their respective potencies to inhibit 5-[3H]HT uptake by L-S1 and L-S2 cells. For L-S1 cells, the rank order of inhibitor potencies is imipramine greater than amitriptyline greater than fluoxetine greater than desipramine = nortriptyline greater than tryptamine greater than 5-methoxytryptamine greater than N-acetyl-5-methoxytryptamine. For L-S2, the rank order is similar to that of L-S1 except that fluoxetine is more potent than amitriptyline.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗