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Biomedical subjects

R Guan

Publications and source records attributed to R Guan.

At least 37 records · Page 2Linked to original sources

A one-year trial of lamivudine for chronic hepatitis B. Asia Hepatitis Lamivudine Study Group.

BACKGROUND AND METHODS: In preliminary trials, lamivudine, an oral nucleoside analogue, has shown promise for the treatment of chronic hepatitis B. We conducted a one-year, double-blind trial of lamivudine in 358 Chinese patients with chronic hepatitis B. The patients were randomly assigned to receive 25 mg of lamivudine (142 patients), 100 mg of lamivudine (143), or placebo (73) orally once daily. The patients underwent liver biopsies before entering the study and after completing the assigned treatment regimen. The primary end point was a reduction of at least two points in the Knodell necroinflammatory score. RESULTS: Hepatic necroinflammatory activity improved by two points or more in 56 percent of the patients receiving 100 mg of lamivudine, 49 percent of those receiving 25 mg of lamivudine, and 25 percent of those receiving placebo (P<0.001 and P=0.001, respectively, for the comparisons of lamivudine treatment with placebo). Necroinflammatory activity worsened in 7 percent of the patients receiving 100 mg of lamivudine, 8 percent of those receiving 25 mg, and 26 percent of those receiving placebo. The 100-mg dose of lamivudine was associated with a reduced progression of fibrosis (P=0.01 for the comparison with placebo) and with the highest rate of hepatitis B e antigen (HBeAg) seroconversion (loss of HBeAg, development of antibody to HBeAg, and undetectable HBV DNA) (16 percent), the greatest suppression of HBV DNA (98 percent reduction at week 52 as compared with the base-line value), and the highest rate of sustained normalization of alanine aminotransferase levels (72 percent). Ninety-six percent of the patients completed the study. The incidence of adverse events was similar in all groups, and there were few serious events. CONCLUSIONS: In a one-year study, lamivudine was associated with substantial histologic improvement in many patients with chronic hepatitis B. A daily dose of 100 mg was more effective than a daily dose of 25 mg.

Adolescent↗

Racial differences in Helicobacter pylori seroprevalence in Singapore: correlation with differences in peptic ulcer frequency.

The aim of this study was to determine, first, whether racial differences exist in the seroprevalence of Helicobacter pylori infection in Singapore, and second, whether these differences correlate with racial differences in peptic ulcer frequency. A commercial serological test for immunoglobulin (Ig)G antibody to H. pylori which was 90% sensitive and 83% specific in our population was used to screen 403 adult blood donors of Chinese, Malay and Indian origin, aged between 15-60 years. Serum specimens from 84 paediatric patients admitted to the Paediatrics Department, National University of Singapore, with non-gastroenterological illnesses were also tested. In all three races, seroprevalence of H. pylori increased with age. Indians have the highest prevalence of infection followed by Chinese and Malays. Peptic ulcer prevalences are known to be highest in Chinese, followed by Indians and Malays. The Malays have the lowest prevalence of H. pylori and peptic ulcer among the three races in Singapore. Indians have a higher prevalence of H. pylori antibodies but a lower frequency of peptic ulcer than the Chinese. Racial differences in peptic ulcer frequency between Chinese and Indians are not explained by the prevalence of H. pylori infection; other environmental or genetic factors may be involved.

Adolescent↗

Tropical liver abscess.

Forty-one consecutive cases of liver abscesses seen at the National University Hospital, Singapore from 1988 to 1994 were reviewed. Twenty-seven cases (65%) were pyogenic, six (15%) amoebic, two (5%) tuberculous and six (15%) indeterminate. The predominance of pyogenic abscesses is in marked contrast to previous studies from the region a decade ago in which amoebic abscesses were the commonest type. The commonest pathogen causing pyogenic abscess was Klebsiella pneumoniae. Two cases were due to Mycobacterium tuberculosis, and this organism needs to be actively looked for in smears and cultures of aspirated material. As the majority of organisms isolated were resistant to ampicillin, empirical antibiotic treatment for suspected pyogenic abscess should include gentamicin or a cephalosporin. Percutaneous needle aspiration of the abscess was performed for 85% of pyogenic abscesses and surgery was necessary in only two cases because of complications. We found that percutaneous aspiration of liver abscess is helpful to confirm the diagnosis, provides a better bacteriological culture yield, gives a good outcome, and may uncover clinically unsuspected conditions like malignancy and tuberculoma which may mimic the presentation of liver abscesses. We recommend routine cytological examination of aspirated abscess material as well as stains and cultures for acid-fast bacilli.

Adult↗

Subcutaneously administered recombinant human beta-interferon in the treatment of chronic hepatitis B virus infection.

BACKGROUND: Treatment of chronic replicative hepatitis B virus (HBV) infection is aimed at stopping viral replication and preventing the development of chronic liver disease. beta-Interferon treatment has been less well studied than alpha-interferon. METHODS: The efficacy and tolerability of a 6-month course of subcutaneously administered human recombinant beta-interferon (rINF-beta ser) was studied and the results of a low-dose regime compared with a high-dose regime. Twenty patients (17 men and three women), aged 24-54 years, with chronic hepatitis B virus infection (all hepatitis B surface antigen-positive with detectable HBV-DNA in their sera for at least 3 months prior to therapy) were randomized into two treatment groups of 10 patients each. The low-dose group received 6 x 10(6) U/dose and the high-dose group received 30 x 10(6) U/dose, both groups receiving their respective doses three times a week initially for 1 month and continuing for a total of 6 months. RESULTS: The treatment was well tolerated in both groups. None of the patients required dosage reduction or cessation of treatment because of side-effects. HBV-DNA decreased in all patients during treatment, demonstrating the anti-viral efficacy of rINF-beta ser, and was undetectable in 20 and 40% of patients receiving low-dose and high-dose regimes, respectively, at the end of 6 months treatment (P = N.S.). One year after completion of treatment, HBV-DNA was undetectable in 50 and 30% of patients in the low-dose and high-dose groups, respectively (P = N.S.). However, only one patient achieved seroconversion with loss of the hepatitis B surface antigen and appearance of an antihepatitis B 'e' antigen at the end of 18 months. CONCLUSION: This study shows that subcutaneously administered rINF-beta ser is well tolerated, but the optimal dose and duration of treatment still needs to be defined by further studies.

Adult↗

Viral nucleotide changes in asymptomatic hepatitis B carriers undergoing interferon treatment.

BACKGROUND: Interferon might induce mutation in regions of hepatitis B virus DNA that encode for immunologic target of cytotoxic T lymphocytes. AIM: To investigate the short-term effect of steroid priming and interferon therapy on hepatitis B virus, we followed the nucleotide changes in the precore and core region of hepatitis B virus DNA in seven healthy asymptomatic carriers who underwent steroid priming followed by recombinant alpha interferon for 3 months. METHODS: Hepatitis B virus DNA from serial sera of the patients were polymerase chain reaction-amplified, and the precore and core region directly sequenced and analysed. RESULTS: Analysis revealed no serial changes in the hepatitis B virus nucleotide sequence in any of the patients. CONCLUSIONS: Steroid priming and short-term treatment with interferon in healthy asymptomatic patients does not select for hepatitis B virus with mutations in the precore and core region.

Adult↗

Chronic upper abdominal pain due to duodenal ulcer and other structural and functional causes: its localization and nocturnal occurrence.

The aim of the present study was to determine the degree of pain localization and frequency of nocturnal pain in duodenal ulcer and other causes of chronic upper abdominal pain. These parameters were prospectively recorded in a consecutive series of 1615 patients with chronic upper abdominal pain presenting to one gastroenterologist. The proportion of patients who were able to localize the site of their pain using a single finger was 13% for duodenal ulcer, 5% for gastric ulcer, 17% for biliary disease, 7% for functional dyspepsia and 8% for irritable bowel syndrome. The numbers of subjects with the above diagnoses who experienced nocturnal pain were 63, 63, 51, 41 and 58%, respectively. The sensitivity, specificity, positive predictive value and negative predictive value for duodenal ulcer were 13, 92, 14 and 91%, respectively, for localized pain; 63, 50, 11 and 93%, respectively, for nocturnal pain occurrence; and 9, 96, 20 and 90%, respectively, if the pain was both localized and nocturnal. If the pain was neither localized nor nocturnal, the corresponding values for the absence of duodenal ulcer disease were 49, 68, 93 and 13%, respectively. The pain of duodenal ulcer was therefore more likely to be nocturnal and well localized compared with pain from other causes. However, while the absence of these features made duodenal ulcer unlikely, their presence was less helpful in the diagnostic process.

Abdominal Pain↗

Hepatitis B virus infection in Singapore.

Although Singapore is in an endemic region for hepatitis B infection, the hepatitis B carriage rate of 5-6% is relatively low. The highest positivity rates for hepatitis B surface antigen (HBsAg) are found in the paediatric age group, with another peak in 40-49 year olds. Studies suggest that, although perinatal transmission is an important route of infection, most children acquire the virus through horizontal transmission between family members. Viral replication continues at a high rate in young carriers and tends to slow down with increasing age. Up to 50% of hepatitis B carriers in Singapore have chronic hepatitis, shown by raised serum ALT values and liver histology, and about 10% are infected with the precore mutant virus. About 20% of carriers have cirrhosis. Among patients with HCC, up to 75% are HBsAg positive, of whom 45% are still viraemic. Mass vaccination against hepatitis B was introduced into Singapore on a voluntary basis in 1983, with compulsory vaccination of babies born to HBeAg positive mothers since 1985. The number of cases of acute hepatitis B has fallen by 60% between 1989 and 1995 although the problems of the longterm complications of chronic hepatitis B still need to be tackled.

Age Factors↗

Primary biliary cirrhosis--an uncommon disease in Singapore.

Primary biliary cirrhosis (PBC) is uncommon in Singapore. Twelve consecutive patients with PBC were seen between 1987 and 1994 at the National University Hospital. Eleven were women and the mean age at presentation was 53 years. Three patients presented with pruritus and jaundice whilst three had decompensated cirrhosis. The remaining six patients had no symptoms attributed to their liver disease when first detected, three of them presented with associated conditions including sicca syndrome and interstitial lung fibrosis, lichen planus, and carcinoma of breast. All patients had elevated serum alkaline phosphatase and positive anti-mitochondrial antibodies. Liver histology (10/12) showed Stage II disease (2), Stage III (5) and Stage IV (3). Three patients also had co-existing gall bladder stones but their endoscopic retrograde cholangiograms were normal. The mean follow-up period was 32.6 months and four patients died during follow-up. The only male patient had liver transplantation, two patients had symptomatic treatment while the rest were treated with ursodeoxycholic acid. In conclusion, local patients tended to presented relatively early in the course of the disease with 50% being asymptomatic and in the precirrhotic Stages.

Adult↗

Serological profiles of hepatitis B carrier patients in Singapore with special reference to the frequency and significance of concurrent presence of HBsAg and anti-HBs.

Hepatitis B serological markers were investigated in 1,132 consecutive Singaporean HBV carriers. Hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) were found concurrently in 234 carriers (234/1132 or 21%). Serum anti-HBs levels were more than 10 mIU/mL in 80 of these carriers (80/234 or 34%). There were no difference in HBeAg positive status, as well as HBV-DNA positive status in concurrent HBsAg/anti-HBs carriers compared to carriers without anti-HBs. Our results suggested that concurrent HBsAg and anti-HBs is a common serologic pattern in Singaporean HBV carriers.

Adolescent↗

Seroprevalence of hepatitis B and C viral markers in patients with primary hepatocellular carcinoma in Singapore.

The prevalence of hepatitis B and C serological markers were studied in 55 patients (45 males and 10 females) with primary hepatocellular carcinoma (PHC). Their ages ranged from 28 years to 79 years (mean age: 56 years). Fifty-five other patients with non-hepatic diseases were used as age and sex matched controls. Forty-one PHC patients (74%) had chronic hepatitis B infection alone, 5 patients (9%) had chronic hepatitis C infection alone, 6 patients (11%) had chronic hepatitis B and C co-infection, 2 patients (4%) had evidence of previous exposure to HBV and one patient (2%) had no hepatitis B and C serological markers. Among those patients with chronic HBV infection alone, the commonest serological pattern was HBsAg and anti-HBe positive (66%; 27/41) followed by HBsAg and HBeAg positive (i.e. highly HBV infectious group) (24%; 10/41). All the positivity rate for HBsAg (including co-infection with HBV and HCV) was 85% and all the positivity rate for anti-HCV (including co-infection with HBV and HCV) was 20%. In the control group, positivity rate for HBsAg was 13%(7/55). None of the control sera was positive for anti-HCV. Positivity rates for HBsAg and anti-HCV were significantly higher in the 55 PHC cases than in controls. The odds ratio for HBsAg was 40.3 (p value: < 0.001) (95% CI limits: 12.1 to 143.3) and for anti-HCV was indeterminate.

Adult↗

Chili--protective factor against peptic ulcer?

The aim of the present study was to determine the frequency and amount of chili taken by peptic ulcer patients and control subjects. One hundred three Chinese patients with peptic ulcer and 87 control patients were interviewed using a standard questionnaire. Those subjects who deliberately avoided chili use because of symptoms or advice from friends or medical practitioners were excluded. The median number of times of chili use per month was eight in the ulcer group (25-75% quartiles 1-30) compared to 24 (8-56) in the control group (P < 0.001). The median amount of chili used per month was 312 units (25-75% quartiles 38-899) in the ulcer group compared to 834 units (274-1892) in the control group (P < 0.001). The odds ratio of having peptic ulcer disease, adjusted for age, sex, analgesic use, and smoking by multiple logistic regression, was 0.47 (95% confidence intervals: 0.25-0.89) for subjects who had a higher intake of chili both in terms of frequency as well as amount used compared to those who took less chili. Our data support the hypothesis that chili use has a protective effect against peptic ulcer disease.

Adult↗

Chili protects against aspirin-induced gastroduodenal mucosal injury in humans.

Capsaicin, the pungent ingredient of chili, has a gastroprotective effect against experimental gastric mucosal injury in animals. Such an effect has not, however, been documented in humans to date. Eighteen healthy volunteers with normal index endoscopies underwent two studies four weeks apart. Each subject took 20 g chili orally with 200 ml water in one study and 200 ml water in another study. In each case this was followed half an hour later by 600 mg aspirin BP with 200 ml water. Endoscopy was repeated 6 hr later. Gastroduodenal mucosal damage was assessed by a previously validated scoring system. The median gastric injury score after chili was 1.5 compared to 4 in the control group (P < 0.05), demonstrating a gastroprotective effect of chili in human subjects.

Adult↗

How does chili cause upper gastrointestinal symptoms? A correlation study with esophageal mucosal sensitivity and esophageal motility.

Chili ingestion produces gastrointestinal symptoms in many subjects. Some of these symptoms, such as heartburn, might well arise from the esophagus, but the pathogenesis is unknown. We studied the effects of chili ingestion on esophageal motility in 16 healthy volunteers and correlated these with the production of chili-induced upper gastrointestinal symptoms. We also studied the effects of chili instillation into the esophagus in 15 of the subjects to determine whether typical symptoms were produced. There were no changes in esophageal manometric parameters in all 16 subjects after the ingestion of a chili suspension (5 g chili powder in 100 ml water), although half of them reported one or more symptoms. Direct instillation of the same chili suspension into the lower esophagus produced typical symptoms in all 15 volunteers tested. Chili-induced upper gastrointestinal symptoms were not accompanied by changes in esophageal motility. The esophageal mucosa itself was sensitive to chili, suggesting that at least some of the upper gastrointestinal symptoms produced by chili are mediated by direct stimulation of chili-sensitive afferent nerve endings in the esophageal mucosa.

Adult↗

Treatment of hepatitis B surface antigen carriers in the early stage of the infection using recombinant alpha-interferon with steroid priming.

BACKGROUND: Alpha-interferon has been found to inhibit hepatitis B virus (HBV) replication in Chinese patients with chronic HBV infection although a sustained effect was rarely achieved in those with normal pretreatment serum alanine amino transferase (ALT) levels. Prednisolone priming has been found to be beneficial over treatment with interferon alone in these subjects. We studied the effect of steroid pre-treatment followed by recombinant interferon alpha-2a in the treatment of asymptomatic HBV carriers with positive hepatitis Be antigen (HBeAg), hepatitis B viral DNA (HBV-DNA) and minimal changes in liver histology. METHODS: The treatment regimen included a 6-week prednisolone priming, a 2 week rest followed by 14 weeks of three times weekly 9 mega units of interferon alpha-2a injection and 52 weeks of follow-up. There were seven patients in the treatment group and seven controls. RESULTS: The mean age, pre-treatment ALT (normal in all except for one in each of the treatment and control groups), HBV-DNA levels and histological scores were similar in the two groups. Serum HBV-DNA levels fell in six patients during treatment and became undetectable in two of them by the end. During follow-up, serum HBV-DNA returned to pre-treatment levels in all patients. None of the treated patients had HBeAg sero-conversion and none of the controls had spontaneous clearance of HBV-DNA or sero-conversion of HBeAg. No improvement of liver histology was observed in any of the treated patients. There were only mild flu-like side-effects noted and interferon alpha-2a was well tolerated at the doses given among treated patients. CONCLUSION: Prednisolone priming followed by interferon alpha-2a treatment has no beneficial effect on HBV carriers in the early stages of chronic hepatitis B infection.

Adult↗

The effect of polyunsaturated phosphatidyl choline in the treatment of acute viral hepatitis.

BACKGROUND: Polyunsaturated phosphatidyl choline is a preparation often advocated for diseases of the liver. METHODS: In a randomized open controlled trial, a preparation of polyunsaturated phosphatidyl choline, at a dose of 900 mg orally daily, was given to 22 patients with acute viral hepatitis. A control group of 25 patients was not treated. RESULTS: Serial serum bilirubin and alanine amino transferase levels were measured up to 12 weeks. The falls in their levels after 2 and 5 weeks, and the lengths of time to their normalization, were not significantly different in the treated group compared to the control group. CONCLUSION: The results indicated that polyunsaturated phosphatidyl choline had no beneficial effect on the course of acute viral hepatitis.

Acute Disease↗

Hepatitis C virus genotypes in Singapore and Indonesia.

5' untranslated and partial core (C) region sequence of hepatitis C virus (HCV) in 21 Singaporean and 15 Indonesian isolates were amplified by reverse-transcription polymerase chain reaction and sequenced with the use of conserved primer sequences deduced from HCV genomes identified in other geographical regions. The HCV genotypes are predominantly that of Simmonds type 1 and less of type 2 and 3 with the latter genotype currently not detected in Indonesia. The 5' untranslated sequences are related to HCV-1. DK-7 (Denmark), US-11 (United States of America), HCV-J4, SA-10 (South Africa), T-3 (Taiwan), HCV-J6, HCV-J8, Eb-1 and Eb-8. When compared with the prototype HCV-1, insertions are found within the 5' untranslated region of Singaporean isolates and not in the Indonesians. There are Singaporean and Indonesian isolates that have sequences within the 5' untranslated region that differ slightly from each other. Microheterogeneity is observed in the core region of two Singaporeans and one Indonesian isolate. Finally, not all HCV isolates can be amplified with the conserved core sequence primers when compared with the ease with which these isolates can be amplified with 5' untranslated region conserved primers.

Amino Acid Sequence↗