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Biomedical subjects

W K Chang

Publications and source records attributed to W K Chang.

At least 55 records · Page 3Linked to original sources

Synthesis and receptor affinities of some conformationally restricted analogues of the dopamine D1 selective ligand (5R)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl- 1H-3-benzazepin-7-ol.

The synthesis of a structurally novel series of 6,6a,7,8,9,13b-hexahydro-5H-benzo[d]naphtho[2,1-b]azepines (2), conformationally restricted analogues of the dopamine D1 antagonist (5R)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin -7-ol (SCH 23390, 1c), is described. Affinity for D1 receptors was determined by competition for rat striatal binding sites labeled by [3H]SCH 23390; affinity for D2 receptors was similarly determined by competition experiments using [3H]spiperone. Compounds in this series having the B/C-trans ring junction (2b and related analogues), where the D ring is unequivocally fixed in an equatorial orientation, possess considerably more D1 receptor affinity and selectivity vs the D2 receptor than the conformationally mobile cis stereoisomers (2a), thus leading to the conclusion that axial substituents at the 4- or 5-positions of the benzazepine nucleus are detrimental to D1 receptor affinity. Resolution and X-ray analysis demonstrated that D1 receptor affinity was preferentially associated with the (-)-6aS,13bR enantiomer of 2b.

Animals↗

Hepatitis B infection and renal transplantation: the absence of anti-delta antibodies and the possible beneficial effect of silymarin during acute episodes of hepatic dysfunction.

The incidence of hepatitis B infection among renal transplant recipients was reviewed. Among 90 patients, 13 were HBsAg positive prior to renal transplantation. Episodes of hepatic dysfunction were seen in eight and one died of fulminating hepatitis and disseminated tuberculosis. Silymarin, a herbal extract, appears to confer some benefits in ameliorating hepatic dysfunction. Antibodies to the delta agent were not detected during any of these episodes. One patient contracted hepatitis B after transplantation and rapid reduction in steroid dose was associated with deterioration of liver function. He developed antibodies and cleared the virus. Four HBsAg-negative patients received kidneys from HBsAg positive donors without becoming HBsAg positive.

Adult↗

Acute viral hepatitis: aetiology and evolution.

Over a period of three and a half years, 348 consecutive children with acute hepatitis were studied. There were 205 boys and 143 girls aged from 3 months to 12 years old. The most common type was hepatitis A, of which there were 281 cases, 81% of the total; there were 41 in the under 4 years old age group (63% of that group), 99 in the 5-8 year old age group (87% of that group) and 141 in the 8-12 year old age group (83% of that group). Hepatitis B occurred in 29 (8% of the total), and non-A, non-B hepatitis occurred in 35 (10%). All the children with hepatitis A and all but one with hepatitis B recovered. There were three deaths from fulminant hepatitis, one in the group with hepatitis B and two with non-A, non-B. Clearance of the hepatitis B surface antigen was fast, by six months 26 patients having cleared the antigen and 21 (77%) being positive for hepatitis B surface antibody. One patient became a carrier of hepatitis B surface antigen.

Acute Disease↗

Study of Chinese periodontal patients at National Taiwan University Hospital. Part I: Basic periodontal information and oral hygiene status.

A cross-sectional study of 288 subjects with complete periodontal documentation was evaluated to determine the clinical status of periodontal disease. The patients were divided into age group intervals of ten years. The conditions of oral hygiene and their association with the clinical status of periodontal disease were compared and analyzed. Chronological features of the disease and its background development among Chinese patients is also explored. Our results indicated that in the mind of Chinese patients the loss of teeth was considered to be a natural fate of aging, and dental and periodontal problems were viewed merely as a symptom of pain, but not as disease entity. Most patients were completely ignorant of both the importance of oral hygiene care and prevention of periodontal diseases. A high incidence of ill-fitted restorations, lack of motivations, and insufficient knowledge on prevention were common in our subjects. In this study, the oral hygiene index (OHI) in females was found to be lower than that of males. The OHI dropped abruptly after 20 years of age in females and after 30 years of age in males. The lowest gingival index (GI) was found in the 31-40 age group in both sexes. During the later periods of life, the OHI again rose, and this increase appeared earlier in females than in males. The GI corresponded to chronological changes in OHI. There was no statistical difference in GI between the corresponding age groups of males and females. The periodontal disease index (PDI) increased progressively with age in both sexes. However, no significant difference was noted between males and females. The progression of the PDI appeared stationary in the 31-40 age group, which corresponded to the period of lowest GI. In conclusion, our Chinese subjects exhibited poor oral hygiene and had an associated high incidence of periodontal disease. Irrespective of sex, OHI showed a positive correlation with GI. However, there was no obvious correlation between OHI and PDI. In contrast, GI was highly correlated to PDI in the 21-30 and 31-40 age groups in the present study. In addition, the paroxysmal nature of clinical periodontal parameters supports the recently held concept that the onset and progression of periodontal disease is intermittent.

Adolescent↗

Comparison of histological effects of different bioceramic implants on surgically created periodontal defects in monkeys.

The biological response to the resorbable and nonresorbable bone grafting materials implanted in the surgically created defects was compared in 4 Maccaca cyclopsis. Intraosseous angular defects were created on the mesial side of both upper canines and premolars by an air driven fissure bur. The root surface was planed, then hydroxylapatite (HA) and tricalcium phosphate (TCP) were inserted into the right side defects respectively. The left side canine received no implants and served as the control site. The animals were sacrificed 6 and 16 weeks after the experiment. Histologically, the two implant materials were well tolerated by the surrounding tissues and did not elicit any adverse inflammatory reaction. During the 16 weeks periods, TCP was biodegraded through phagocytosis by histiocytes and multinucleated giant cells. The residual particles were incorporated into the new bone matrix and displayed the bone growth guiding property. HA particles were dense and larger in size with low resorption rate, therefore, encapsulation by fibrous tissue was more commonly seen. Although direct bone deposition adjacent to the HA particle surface was apparently found, new bone formation was observed only at the apical portion adjacent to the host alveolar bone. These findings suggested that HA might rather play the role as a biocompatible filler. However, HA was more effective in blocking the downgrowth of the junctional epithelium. Nevertheless, these two implant materials could not hasten the healing process, because new bone formation was observed to be more distinct in the control site.

Animals↗

Effects of dietary polyunsaturated fatty acid on platelet aggregation in rats.

In the present study, we changed the fatty acid profile in blood and platelet membranes by dietary manipulation, and examined the effect on platelet aggregation in rats. Fifty-five rats were divided into five groups and fed for 56 days with 1% cholesterol and different types of fatty acid-rich diets: basal, lard, lard + fish oil, soybean oil, and soybean oil + fish oil. a decrease in serum arachidonic acid (20:4, omega-6, AA) and an increase in serum eicosapentaenoic acid (20:5, omega-3, EPA) were found in all experimental dietary groups fed with refined fish oil. Similar changes in the polyunsaturated fatty acids were also found in the platelet membrane phospholipids. Platelet aggregation, quantitated by the slope and height of the aggregation curve induced by different concentrations of ADP in a platelet aggregometer, was inhibited in all groups fed with refined fish oil. This inhibition of platelet aggregation may be related to an increase in the ratio of EPA and AA in the platelet membrane phospholipids after dietary manipulation. The differences in the platelet aggregation and thromboxane B2 (TXB2) concentration between the lard and the lard + fish oil groups were more profound than that between the soybean oil and the soybean oil + fish oil group. However, the malondialdehyde (MDA) concentration revealed no significant differences between the five groups.

Animals↗

[Continuous thoracic epidural fentanyl in postoperative pain control--a comparison of two different dosages].

We evaluate the postoperative pain relief using continuous epidural fentanyl infusion in two different dosages for thoracic and upper abdominal surgeries. A total of 21 ASA class III patients were studied. A thoracic epidural catheter was placed before surgery but pain control was begun when the patients became fully awake and complained of pain in the recovery room. Patients were divided into group A (n = 9) and group B (n = 12). Those in group A were given fentanyl 1.5 micrograms/kg in saline solution as initial dose followed by continuous infusion at a rate of 1 microgram/kg/h for 23 hours. In group B the initial dose and the maintenance dose were respectively 1.0 microgram/kg and 0.5 micrograms/kg/h. Following the initial dose, the intensity of pain was assessed hourly for a total of 24 hours using a visual analogue pain scale with scores from 0 to 10. In group A, the pain scale fell from the baseline level of 7.7 +/- 2.6 to 2.3 +/- 2.0 at the first hour while in group B it fell from 8.9 +/- 1.4 to 4.3 +/- 2.1. The pain scores following continuous infusion in groups A and B were respectively 1.3 +/- 1.5 and 2.9 +/- 1.7. Although the analgesic effect appeared to be better in group A, pain relief was satisfactory in both groups (p less than 0.01). Regarding respiratory depression, there was a greater degree of rise in PaCO2 in group A and some of the patients even had a PaCO2 value above 50 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Affinity chromatography of the D1 dopamine receptor from rat corpus striatum.

The D1 dopamine receptor from rat corpus striatum has been purified 200-250-fold by using a newly developed biospecific affinity chromatography matrix based on a derivative of the D1 selective antagonist SCH 23390. This compound, (RS)-5-(4-aminophenyl)-8-chloro-2,3,4,5-tetrahydro-3-methyl-1H-3-benz azepin-7-o l (SCH 39111), possesses high affinity for the D1 receptor and, when immobilized on Sepharose 6B through an extended spacer arm, was able to adsorb digitonin-solubilized D1 receptors. The interaction between the solubilized receptor and the affinity matrix was biospecific. Adsorption of receptor activity could be blocked in a stereoselective fashion [SCH 23390 greater than SCH 23388; (+)-butaclamol greater than (-)-butaclamol]. The elution of [3H]SCH 23390 activity from the gel demonstrated similar stereoselectivity for antagonist ligands. Agonists eluted receptor activity with a rank order of potency consistent with that of a D1 receptor [apomorphine greater than dopamine greater than (-)-epinephrine much greater than LY 171555 greater than serotonin]. SCH 39111-Sepharose absorbed 75-85% of the soluble receptor activity, and after the gel was washed extensively, 35-55% of the absorbed receptor activity could be eluted with 100 microM (+)-butaclamol with specific activities ranging from 250 to 450 pmol/mg of protein. The affinity-purified receptor retains the ligand binding characteristics of a D1 dopamine receptor. This affinity chromatography procedure should prove valuable in the isolation and molecular characterization of the D1 dopamine receptor.

Animals↗

In-vitro and in-vivo studies of a cytotoxin from Campylobacter jejuni.

Studies were performed on a cytotoxin (CT) from human strains of Campylobacter jejuni isolated in Malaysia. CT was detected by cytopathic effect (CPE) on HeLa cells at titres from 8 to 32, in culture filtrates from 14 (48%) of 29 human isolates. The CPE correlated well with a quantitative 51Cr-release assay where a specific release of 54-68% was noted. CT production was lost after 5-7 subcultures. CT activity was also detected in 5 (26%) of 19 faecal filtrates from which CT-producing isolates were subsequently obtained. The mol. wt of CT was estimated by Sephadex G-50 chromatography to be greater than 30,000. In a suckling-mouse assay, CT consistently failed to demonstrate fluid accumulation after intragastric inoculation of culture filtrate. The Removable Intestinal Tie Adult Rabbit Diarrhoea (RITARD) assay was also used. Rabbits given CT-producing strains of C. jejuni developed bacteraemia and severe watery mucus-containing diarrhoea for the duration of the experiment with death of some animals. Rabbits given CT non-producing strains had less severe disease and none died. Rabbits given partially-purified CT had diarrhoea for 3 days but none died.

Animals↗

Efficacy and safety of recombinant hepatitis B vaccine in infants born to HBsAg-positive mothers.

Infants born to HBsAg-positive women were randomly assigned to receive either the plasma-derived hepatitis B vaccine or the yeast-derived recombinant hepatitis B vaccine within 12 h of birth, simultaneously with HBIg. The second and third doses of both vaccines were given at 1 and 6 months of age respectively. Two hundred and twenty-two infants received two doses, and 80 infants received three doses of either vaccine. Five infants were found to be HBsAg-positive at 6 months of age. Four of these infants had received the plasma vaccine and the remaining infant the recombinant vaccine. Anti-HBs was present in all the HBsAg-negative infants at 6 months of age. The titres of anti-HBs were similar in both groups of infants who had received either the plasma or the recombinant hepatitis B vaccine. No major adverse reactions were reported with either vaccine. The preliminary results from this study suggest that the yeast-derived recombinant hepatitis B vaccine is safe, immunogenic and at least as effective as the plasma-derived hepatitis B vaccine in preventing the HBsAg carrier state in infants born to HBsAg-positive women.

Carrier State↗

Use of the hepatitis B recombinant DNA yeast vaccine (H-B-VAX II) in children: two doses vs. three doses of 5 micrograms regime; an interim report.

In a prospective randomised trial, children of hepatitis B carriers who were 3 months to 11 years of age and negative for all hepatitis B viral markers were randomised to receive (a) two doses of 5 micrograms of hepatitis B recombinant DNA yeast vaccine (H-B-VAX II) at 0 and 1 month (Group I), (b) three doses of 5 micrograms of H-B-VAX II at 0, 1 and 6 months (Group II) and (c) three doses of 10 micrograms of plasma-derived hepatitis B vaccine (H-B-VAX) (Group III). In the 141 children receiving H-B-VAX II, i.e. in Group I and Group II, side-effects were few and transient. Fever occurred in 10% of the vaccinees. Anti-HBs response rate was 96-100% by 8 months. None of the vaccinees became positive for anti-HBc. The geometric mean of the anti-HBs titre at 8 months was higher for Group II than for Group I (P less than 0.001). The practical and theoretical necessity for this higher titre of anti-HBs in the prevention of future infection by the hepatitis B virus is discussed. Both the two-dose regime and the three-dose regime of 5 micrograms of H-B-VAX II were safe, effective and immunogenic in children.

Child↗

Comparison of the immunogenicity, efficacy and safety of 10 micrograms and 20 micrograms of a hepatitis B vaccine: a prospective randomized trial.

Four thousand and one hospital staff were screened for hepatitis B virus (HBV) markers in a vaccination programme in Hong Kong. The seropositivity rate for HBsAg, anti-HBs and anti-HBc were significantly higher in the 3160 existing hospital staff than in 841 new recruits. Of the subjects negative for HBV markers, 605 were randomized to receive three doses of either 10 or 20 micrograms of the Merck Institute vaccine (HB-VAX). Compared with the 20 micrograms dose, vaccination with the 10 micrograms dose results in equal immunogenicity and efficacy at the completion of the three injections but induced a slower response rate and lower anti-HBs titres with the first two doses. The commonest side-effect of local soreness was less with the 10 micrograms dose. We conclude that (1) hospital staff working in high endemic areas should be vaccinated on recruitment and (2) the 10 micrograms dose of HB-VAX can replace the recommended 20 micrograms dose for adults, being cheaper and as efficacious.

Adolescent↗