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Biomedical subjects

W H Chang

Publications and source records attributed to W H Chang.

At least 55 records · Page 3Linked to original sources

Gelatin-derived bioadhesives for closing skin wounds: an in vivo study.

Bioadhesives have been used in surgery as hemostatic and wound healing agents. GRF (gelatin + resorcinol + formaldehyde) glue, composed of a mixture of gelatin and resorcinol polymerized by the addition of formaldehyde, has been used for this purpose. Widespread acceptance of the GRF glue, however, has been limited by reports of cytotoxicity due to its release of formaldehyde upon degradation. It has been suggested by Wertzel et al. that the cytotoxicity problem of GRF glue may be overcome by changing its cross-linking method. The study was, therefore, undertaken to assess the feasibility of using a water-soluble carbodiimide or genipin to cross-link gelatin as new bioadhesives to close skin wound lesions in a rat model. Formaldehyde-cross-linked counterpart (GRF glue) and a resorbable suture were used as controls. It was noted that the tensile strength of the skin across each wound treated by either application of test glues or suture increased consistently with time during the healing process. Also, the wounds repaired by test glues or suture caused no calcification. The suture used in the study was completely resorbed at the wound area in about 6 days postoperatively. However, the durations required to completely resorb the carbodiimide- or genipin-cross-linked glues were approximately the same (9 days), while it took about 14 days to completely resorb the formaldehyde-cross-linked glue. The healing process for the suture wound repaired was more rapid than those treated by test glues. Of the test glues, the wounds treated by the carbodiimide- or genipin-cross-linked glues induced less inflammatory response and recovered sooner than that treated by the formaldehyde-cross-linked glue. This indicated that the biocompatibility of the carbodiimide- or genipin-cross-linked glues was superior to the formaldehyde-cross-linked glue. The results of this study may serve as a preliminary experimental model for the further investigation of both the carbodiimide- and genipin-cross-linked glues when applied to human skin closure.

Animals↗

Effects of gender and age on plasma levels of clozapine and its metabolites: analyzed by critical statistics.

BACKGROUND: Previous reports concerning the effects of gender and age on steady-state plasma concentrations of clozapine and its major metabolites, norclozapine and clozapine-N-oxide, have been controversial. Since the frequency distribution of the plasma levels is asymmetrical and skewed to the right, the statistical methods (such as analysis of variance and regression analysis) used earlier are actually inappropriate for analyzing the effects of the variables on the concentrations and might contribute to the inconsistent results. The goal of the present study, with befitting statistics, is to measure the potential effect of dose, gender, age, and body weight on plasma levels of clozapine and its 2 major metabolites. METHOD: We retrospectively analyzed data from a therapeutic drug monitoring study for steady-state plasma clozapine, norclozapine, and clozapine-N-oxide levels that was conducted in a large group of Chinese schizophrenic inpatients (male:female ratio = 83:79; age range, 33.8 +/- 9.3 years). The daily doses of clozapine had ranged from 100 to 900 mg, with a mean +/- SD value of 379.5 +/- 142.2 mg. Plasma concentrations had been measured using high-performance liquid chromatography with ultraviolet detection. Multiple linear regression was adopted to quantify the effects of various factors on the plasma levels. The natural logarithm of the plasma level was used as the dependent variable to overcome the skewness problem. RESULTS: After adjusting the effects of gender, age, and body weight by multiple linear regression, each 1-mg increment in the daily dose could raise the clozapine level by 0.31%, norclozapine by 0.27%, and clozapine-N-oxide by 0.16%. Female patients had 34.9% higher clozapine levels and 36.3% higher norclozapine, with other variables being controlled. No sex differences were demonstrated for clozapine-N-oxide levels. Each 1-year increment in age would elevate the clozapine level by 1.1%, norclozapine by 1.0%, and clozapine-N-oxide by 1.0%. Body weight could not influence the levels of these compounds. CONCLUSION: The present results suggest that women possess higher plasma levels (about one third higher) of clozapine and norclozapine, but not the N-oxide metabolite. Each addition of 1 year in age elevated clozapine and either metabolite's levels by about 1%. Furthermore, every 1-mg increase in the daily dose raised clozapine and norclozapine concentrations by approximately 0.3%. These findings could assist clinicians in optimizing clozapine dosing strategies.

Adult↗

Failure of screening to detect HIV in a foreign laborer who died of toxoplasmosis of the central nervous system.

The most common neurologic complication in patients with acquired immunodeficiency syndrome (AIDS) is cerebral toxoplasmosis. Patients with cerebral toxoplasmosis have characteristic findings on clinical examination and neuroimaging. They require prolonged treatment and have a considerable mortality rate. We report a case of cerebral toxoplasmosis in a foreign laborer with AIDS, in whom a human immunodeficiency virus (HIV) screening test failed to detect-HIV infection. The patient, a 23-year-old man from Thailand, presented in a confused state 2 weeks after his arrival in Taiwan. Computed tomography showed a mass effect, and magnetic resonance imaging showed multiple ring-enhanced lesions in the cerebrum. Serologic tests were positive for anti-HIV antibody and also showed high anti-Toxoplasma immunoglobulin G titers. Although symptomatic treatment was initiated, the patient's condition deteriorated rapidly and he died of multiple organ failure due to brain stem herniation a few days after admission. As the number of foreign laborers working in Taiwan has increased dramatically in recent years, the issues raised by this case are the efficacy of our screening protocols for foreign laborers and the increased occupational hazards encountered by medical personnel in Taiwan.

AIDS Serodiagnosis↗

Influence of hydroxyapatite particle size on bone cell activities: an in vitro study.

Over the past decade, a large number of biomaterials have been proposed as artificial bone fillers for repairing bone defects. The material most widely used in clinical medicine is hydroxyapatite. The aim of our investigation was to study the effect of hydroxyapatite size mechanism on osteoblasts. The osteoblasts were cultured in vitro with 0.1% (1 mg/mL) of various sized hydroxyapatite particles (0.5-3.0, 37-63, 177-250, and 420-841 microm) for 1 h, 3 h, 1 day, 3 days, and 7 days. The results showed that adding hydroxyapatite particles to osteoblast cultures can significantly affect osteoblast cell count. Osteoblast populations decreased significantly. Osteoblast mean surface areas also changed significantly. Transforming growth factor-beta1 (TGF-beta1) concentrations in culture medium decreased significantly with the addition of hydroxyapatite particles. Prostaglandin E2 (PGE2) concentrations in medium increased significantly. The changes in TGF-beta1 and PGE2 concentration were more significant and persisted longer in smaller-particle groups. The inhibitory effects of hydroxyapatite particles on osteoblast cell cultures were mediated by the increased synthesis of PGE2. Caution should be exercised before using a hydroxyapatite product which could easily break down into fine particles.

Alkaline Phosphatase↗

Identification of antigenic differences between the phosphorylated and nonphosphorylated forms of the E7 protein of human papillomavirus type 16.

To analyze the antigenic properties of the human papillomavirus type 16 E7 oncoprotein, two monoclonal antibodies, VD6 and IB10, that have different reactivities to the E7 protein were generated. While the VD6 antibody reacted strongly with E7 protein in CaSki cell extracts, the other antibody, IB10, showed much weaker reactivity with E7. This reactivity increased in a dose-dependent manner in the presence of the casein kinase II-specific inhibitor DRB (5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole). Antigenic site estimation and an in vitro phosphorylation assay, using bacterially expressed E7 protein, demonstrated that the weak reactivity of IB10 was related to the phosphorylation status of the E7 protein. Phosphorylation of E7 reduced considerably the reactivity of IB10 but did not affect the reactivity of VD6, which reacts with the N-terminal portion of E7. In immunoprecipitation (IP) assays, IB10 precipitated weakly the E7 protein from CaSki cell extracts. Together, these data suggest that unphosphorylated E7 protein shows distinct antigenic character compared to its phosphorylated form under denaturing conditions; however, under native conditions, the phosphorylated and nonphosphorylated E7 proteins have some antigenic cross-reactivity.

Animals↗

Outcome in patients with bifurcation tumors who undergo unilateral versus bilateral hepatic duct drainage.

BACKGROUND: There is much controversy as to the importance of establishing drainage of both liver lobes in malignant hilar obstruction. The purpose of the present study was to compare survival data in patients with malignant hilar obstruction, stratified according to the Bismuth classification, who had cholangiography with filling of one or both hepatic ducts and subsequently endoscopic or percutaneous drainage of one or both ducts. METHODS: A retrospective review was performed for the time period from July 1990 to July 1995, and 224 patients were identified with a presumed diagnosis of a bifurcation tumor. All x-ray films were reviewed and 150 patients finally diagnosed as hilar tumor were classified according to Bismuth type I, II, or III. Type II and III patients were further subclassified with respect to contrast injection into a single or both hepatic duct systems and whether one or both sides were eventually drained. RESULTS: Data were obtained in 141 patients (4 patients still alive); there were 43 type I, 58 type II, and 40 type III. Type II and III patients were divided into three groups: group A, one lobe opacified with same lobe drained; group B, both lobes opacified with both lobes drained; and group C, both lobes opacified with one lobe drained. Overall median survival for type I, II, and III patients was 160, 131, and 62 days, respectively. Among type II and III patients the median survivals of groups A, B, and C were 145, 225, and 46 days, respectively. Survival was significantly longer in group A vs. group C (p < 0.001), group B vs. group C (p < 0.001, and group A + B (165 days) vs. group C p < 0.001). There was no difference in group A + B versus type I (p=0.90). In addition, when comparing single drain only (group A + C, 80 days) versus double drains (group B, 225 days), there was a significant survival advantage (p < 0.0001). CONCLUSION: In bifurcation tumors the best survival was noted in those with bilateral drainage, and the worst survival in those with cholangiographic opacification of both lobes but drainage of only one.

Adult↗

Reversible metabolism of clozapine and clozapine N-oxide in schizophrenic patients.

1. To characterize the interconversion process between clozapine and its metabolite clozapine N-oxide (CNO), eight healthy male schizophrenics were administered a single dose of clozapine or CNO in a randomized crossover manner. 2. Using a general pharmacokinetic model for the interconversion process, the mean total clearances of clozapine and CNO were 28.45 L/hr and 45.30 L/hr, respectively. These values were similar to the values obtained by the usual model-independent method of pharmacokinetic analysis. 3. When administered clozapine, mean CNO plasma concentrations of 17.7 +/- 16.4 ng/ml were slightly lower than the other clozapine metabolite-desmethylclozapine (DCLOZ) plasma levels of 24.4 +/- 8.6 ng/ml at the 12 hour time point. When CNO was administered, plasma concentrations at the 12 hour time point of clozapine were twice the amount of CNO (28.1 +/- 8.9 ng/ml vs 14.4 +/- 8.8 ng/ml). 4. DCLOZ plasma concentrations were detected in all patients upon clozapine administration. Upon CNO administration, only one patient had detectable plasma DCLOZ levels. 5. The interconversion process of clozapine and CNO could partially account for the wide interpatient variability reported for clozapine plasma concentrations in schizophrenic patients.

Adult↗

Infection rate of Leptospira interrogans in the field rodent, Apodemus agrarius, in Korea.

Leptospirosis has significantly decreased in Korea since 1988, following the leptospiral vaccination programme initiated in 1988. Whether this wholly explains the decreased incidence is uncertain. As an initial step to answer this question, infection rates of Leptospira interrogans in field rodents, Apodemis agrarius, were examined and compared with previous data. Two hundred and twenty-two A. agrarius were captured during October-December 1996. Spirochaetes were isolated from 22 (9.9%) and leptospiral DNA was detected in an additional 6 rodents (12.6%). Subsequent microscopic agglutination tests (MAT) classified all these isolates as L. interrogans serogroup Icterohaemorrhagiae serovar lai. The above data did not significantly differ from previous surveys in 1984-7. There was no significant change of L. interrogans infection in field rodents following the introduction of the vaccination programme in Korea. Further studies are needed to determine the role of human vaccination in reducing incidence.

Animals↗