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Biomedical subjects

E K Yeoh

Publications and source records attributed to E K Yeoh.

At least 19 recordsLinked to original sources

Five-year follow-up of a prospective randomized trial of hepatitis B recombinant DNA yeast vaccine vs. plasma-derived vaccine in children: immunogenicity and anamnestic responses.

In a prospective randomized trial, 318 children aged between 3 mo and 11 yr who were negative for all hepatitis B markers were randomized to receive two 5-micrograms doses of hepatitis B recombinant DNA yeast vaccine at 0 and 1 mo (group 1), three 5-micrograms doses of hepatitis B recombinant DNA yeast vaccine at 0, 1 and 6 mo (group 2) or three 10-micrograms doses of plasma-derived hepatitis B vaccine (group 3). The HBs antibody response rate at 8 mo was between 93% and 99%; it was still 75% to 87% at 5 yr in all three groups. Geometric mean titers at 1 yr were 83, 1,085 and 858 mIU/ml in groups 1, 2 and 3, respectively. These values had decreased after 5 yr to 47, 131 and 250 mIU/ml. Subjects in group 1 showed a significantly less proportional drop in geometric mean titer at the fifth year than did subjects in group 2 (p = 0.05) or group 3 (p = 0.015). None of the children developed HBc antibody, even after 5 yr of follow-up. We noted 42 episodes of significantly increased HBs antibody titers, probably due to anamnestic response, even when the titers had dropped to low levels. The mean age at which anamnestic response occurred was 8.7 yr.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors

Gastrointestinal function in chronic radiation enteritis--effects of loperamide-N-oxide.

The effects of loperamide-N-oxide, a new peripheral opiate agonist precursor, on gastrointestinal function were evaluated in 18 patients with diarrhoea caused by chronic radiation enteritis. Each patient was given, in double-blind randomised order, loperamide-N-oxide (3 mg orally twice daily) and placebo for 14 days, separated by a washout period of 14 days. Gastrointestinal symptoms; absorption of bile acid, vitamin B12, lactose, and fat; gastric emptying; small intestinal and whole gut transit; and intestinal permeability were measured during placebo and loperamide-N-oxide phases. Data were compared with those obtained in 18 normal subjects. In the patients, in addition to an increased frequency of bowel actions (p < 0.001), there was reduced bile acid absorption, (p < 0.001) a higher prevalence of lactose malabsorption (p < 0.05) associated with a reduced dietary intake of dairy products (p < 0.02), and faster small intestinal (p < 0.001) and whole gut transit (p < 0.05) when compared with the normal subjects. There was no significant difference in gastric emptying between the two groups. Treatment with loperamide-N-oxide was associated with a reduced frequency of bowel actions (p < 0.001), slower small intestinal (p < 0.001), and total gut transit (p < 0.01), more rapid gastric emptying (p < 0.01), improved absorption of bile acid (p < 0.01), and increased permeability to 51Cr EDTA (p < 0.01). These observations indicate that: (1) diarrhoea caused by chronic radiation enteritis is associated with more rapid intestinal transit and a high prevalence of bile acid and lactose malabsorption, and (2) loperamide-N-oxide slows small intestinal transit, increases bile acid absorption, and is effective in the treatment of diarrhoea associated with chronic radiation enteritis.

Adult

Significance of isolated anti-HBc seropositivity by ELISA: implications and the role of radioimmunoassay.

Hepatitis B virus (HBV) surface antigen (HBsAg) and antibody to HBsAg (anti-HBs) are excellent markers for HBV infection and its immunity. The significance of isolated antibody to HBV core antigen (anti-HBc) seropositivity is not certain. To elucidate this, sera from 638 Chinese adult subjects, aged 18-52 years, seronegative for both HBsAg and anti-HBs, were tested for anti-HBc. Fifty-one (8%) were found to have an isolated anti-HBc seropositivity by ELISA, and all were negative for IgM-anti-HBc. The anti-HBc persisted in all subjects who attended follow-up for hepatitis B vaccination (n = 48) for a period of 8 months. These 48 subjects received 3 doses of hepatitis B vaccine (HB-VAX, 10 micrograms or 20 micrograms) at 0, 1, and 6 months: 72.9% developed a primary anti-HBs response (suggestive of a false-positive anti-HBc seropositivity), 4.2% developed an anamnestic or secondary anti-HBs response, and 22.9% did not develop an anti-HBs response. Increasing the cutoff point of the ELISA or reconfirmation with radioimmunoassay (RIA) reduced only a minor half of the false positives. This low specificity of anti-HBc ELISA/RIA, together with the high rate of anti-HBs response to hepatitis B vaccine, indicates that subjects with isolated anti-HBc seropositivity should be included in vaccination programs.

Adolescent

Hepatitis B virus infection in children.

Several modes of transmission can account for the high hepatitis B virus (HBV) carrier rate observed in children and young adults; perinatal transmission, horizontal transmission from household members and playmates, transmission due to sexual contact with a carrier. An inverse correlation has been reported between the age at which HBV infection occurs and the development of the carrier state. The epidemiology of HBV infection in children has important implications on strategies for prevention and control of this disease.

Adolescent

Recombinant alpha 2 interferon is superior to doxorubicin for inoperable hepatocellular carcinoma: a prospective randomised trial.

In a prospective trial of 75 Chinese patients with histologically proven inoperable hepatocellular carcinoma (HCC), 25 patients were randomised to receive doxorubicin 60-75 mg m-2 intravenously once every 3 weeks, 25 to receive recombinant alpha 2 interferon (rIFN) (Roferon) 9-18 x 10(6) IU m-2 intramuscularly (i.m.) daily and 25 to receive rIFN 25-50 x 10(6) IU m-2 i.m. three times weekly. Patients were switched to the other drug if: (a) there was progressive disease after 12 weeks, (b) unacceptable toxicity developed and (c) they had received a total of 500 mg m-2 of doxorubicin. Six patients had switching over of therapy, three on doxorubicin and three on rIFN. In the remaining 69 patients on single drug therapy, the median survival rate of patients on doxorubicin and rIFN was 4.8 and 8.3 weeks respectively (P = ns.). rIFN induced tumour regression of 25-50% in 12% of patients and of over 50% in 10% of patients. When compared with doxorubicin, rIFN was associated with more tumour regression (P = 0.00199) and less progressive tumours (P = 0.00017). It caused less prolonged and less severe marrow suppression (P = 0.01217), and had significantly less fatal complications than doxorubicin (P = 0.01383). Doxorubicin caused fatal complications due to cardiotoxicity and neutropenia in 25% of patients. rIFN was associated with fatal complications due to dementia and renal failure in 3.8% of patients. In the treatment of inoperable HCC, rIFN is superior to doxorubicin in causing more tumour regression, less serious marrow suppression and less fatal complications.

Adult

Placebo-controlled trial of recombinant alpha 2-interferon in Chinese HBsAg-carrier children.

24 Chinese children aged 1.5-5 years and positive for hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), hepatitis B virus DNA polymerase (HBV DNAp), and HBV DNA on at least three occasions in the 6 months before the trial were randomised to receive either vitamin B complex or intramuscular recombinant alpha 2-interferon (r-IFN) ('Roferon') 10 X 10(6) IU/m2 thrice weekly for 12 weeks. In all 12 subjects receiving r-IFN, HBV DNAp and HBV DNA levels fell during the course of r-IFN injections. Within 4 weeks of cessation of r-IFN injection, the HBV DNAp and HBV DNA returned to pre-trial levels except in 2 subjects, in whom loss of HBV DNAp and HBV DNA was sustained for up to 18 months from onset of the trial. 1 child lost HBeAg at 18 months. 2 of the 12 children in the placebo group also had a sustained loss of HBV DNAp and HBV DNA during the 18 months, with 1 child losing HBeAg at 18 months. All 24 subjects remained positive for HBsAg. r-IFN produced very slight side-effects except for pyrexia and the "flu" syndrome, both of which showed rapid tachyphylaxis. In the dose given r-IFN was safe but had no long-term beneficial effects on HBsAg carriage in Chinese children.

Carrier State

Radiation therapy in hyperbaric oxygen for head and neck cancer at Royal Adelaide Hospital--1964 to 1980.

This report describes experience with radiation therapy in hyperbaric oxygen in 201 patients with squamous carcinoma arising in the mobile portion of tongue (anterior 2/3), oropharynx, hypopharynx, and supraglottic larynx, treated between the years 1964 and 1980. Although not statistically different, the overall 5-year determinate survival figures of 35% for all patients with tumors arising in the hypopharynx, 87.5% for Stage I and II, 55% for Stage III, and 27.1% for Stage IV supraglottic carcinoma were perceptibly better than those obtained in a contemporary but not randomly controlled series of patients treated in air at Royal Adelaide Hospital from 1970 to 1980. The results obtained for tumors arising in the oropharynx and mobile portion of tongue however were found to be very similar to those achieved in air. The results achieved in this series are discussed in the context of experience at other centers and the role of randomly controlled clinical studies in evaluating new treatment modalities is emphasized.

Carcinoma, Squamous Cell

Hepatitis B virus infection in Chinese families in Hong Kong.

Between January 1983 and July 1984, 731 family members of 240 hepatitis B surface antigen (HBsAg) carriers were screened for hepatitis B virus markers. The percentage of those who were positive for HBsAg was 28.3 and that for antibody to hepatitis B surface antigen/antibody to hepatitis B core antigen was 43.1. The carrier rate was higher among siblings (53%) and offspring (50.5%) of female carriers, but similar to that of the age-matched general population for spouses (10.8%). Maternal transmission was the most important mode of spread of hepatitis B virus infection within the family. The HBsAg-positive offspring and siblings were clustered within certain families. Intrafamilial spread is important in perpetuating hepatitis B virus infection in Chinese persons. Susceptible family members, especially newborns and other young children of female carriers, should be vaccinated.

Adolescent

Radiation enteritis.

Acute radiation enteritis is almost inevitable in the curative treatment of malignant tumors of the abdomen and pelvic area. It is frequently a self-limiting disorder of intestinal function associated with reversible mucosal changes of the intestine. The prevalence of chronic radiation enteritis has been underestimated in most surgical series and the majority of patients with symptoms probably do not seek medical advice until a serious complication occurs. Although associated with specific histologic features, the mechanism of chronic radiation injury is poorly understood. The prevalence, pathogenesis, diagnosis and approaches to the treatment and prevention of acute and chronic radiation enteritis are discussed herein. Recent investigative techniques should lead to a better understanding of the physiopathologic characteristics of radiation enteritis and, thereby, provide a more rational basis for treatment which, at the present time, is unsatisfactory. Attempts to reduce the prevalence of radiation enteritis should be directed toward careful patient selection for radiation treatment of the pelvis and to minimize injury to the small intestine, by reducing the volume of small intestine in the radiation area and providing more individualized dosimetry.

Abdominal Neoplasms

The treatment of carcinoma of the cervix and poor-risk endometrial carcinoma using the Cathetron at the Middlesex Hospital: experience since 1979.

This study reports on 5 years experience of the treatment of carcinoma of the cervix and poor-risk carcinoma of the body of the uterus using a combination of external beam radiotherapy and high-dose-rate intracavitary 60Co-brachytherapy using the Cathetron since 1979 at the Middlesex Hospital, London. Despite a reduction in external beam dose of 20% since 1979, survival rates for both diseases remain unchanged and also compare favourably with those of other centres; they are 70.02% for carcinoma of the cervix of all stages except Ia, and 81.17% for 'poor-risk' carcinoma of body of uterus of all stages. The complication rates were acceptable. Analysis of the results of treatment by stage of disease in those patients with carcinoma of the cervix revealed that, except for Stage I cases, the results were comparable with those reported in the literature. The reason for the poor results in Stage I was found to be due to the high proportion of patients of 35 years of age and under with Stage I disease who fared significantly worse than older patients.

Age Factors

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

Integration of HBV-DNA may not be a prerequisite for the maintenance of the state of malignant transformation. An analysis of 110 liver biopsies.

Hundred and ten liver biopsy specimens from various parts of the world were examined for episomal and integrated HBV-DNA sequences. In 54 patients with HBsAg chronic liver disease episomal HBV-DNA was found in 83% of HBeAg-positive patients, compared to only 22% of patients with anti-HBe. Furthermore episomal HBV-DNA in the latter predominated among the Asians. Integrated HBV-DNA was found only in 5.5% of HBeAg-positive patients but in 16.5% of patients with anti-HBe. In 28 HBsAg-positive patients with hepatoma, episomal HBV-DNA was found in 50% of HBeAg-positive patients but in only 11% of anti-HBe patients. Conversely integrated sequences were less common (25%) in HBe-Ag-positive patients than in anti-HBe patients (50%), giving an overall incidence of integration in this group of 45%. No episomal, and only one case of integrated sequences of HBV-DNA, could be detected among 10 patients with HBsAg-negative hepatoma. In addition neither episomal nor integrated HBV-DNA could be detected in 18 patients with non-HBV-related liver disease. Our data suggests that stable integration of HBV-DNA into the host's genome is not necessarily a prerequisite for the maintenance of the state of malignant transformation but may be necessary for its initiation. Alternatively, the detection of integrated HBV-DNA may represent a 'snap shot' of a random integration event amplified by clonal expansion promoted by other factors.

Base Sequence

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

The mechanism of diarrhoea resulting from pelvic and abdominal radiotherapy; a prospective study using selenium-75 labelled conjugated bile acid and cobalt-58 labelled cyanocobalamin.

An attempt was made to elucidate the mechanism of diarrhoea resulting from pelvic and abdominal radiotherapy in a prospective study of 10 patients undergoing treatment for curable pelvic malignant tumours using the synthetic trihydroxy 75Se-labelled conjugated bile acid, SeHcat and 58Co-labelled cyanocobalamin (58Co Vit B12). Evidence of malabsorption of vitamin B12 measured as a significant fall in whole body percentage retention of 58Co Vit B12 from baseline levels was found in all nine patients who developed diarrhoea during radiotherapy. Only four out of these nine patients also had malabsorption of the trihydroxy conjugated bile acid, cholic acid, measured as a significant fall in SeHcat whole body percentage retention and these patients had the most severe diarrhoea. The findings are discussed in the light of what is known about the pathophysiology of diarrhoea during pelvic and abdominal radiotherapy and lend support to previous work which implicated increased bowel motility in the pathogenesis of radiation-induced diarrhoea. The hypothesis that local neuroendocrine mechanisms in the gut may be involved is put forward, with possible implications for treatment.

Adult