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Biomedical subjects

C L Lai

Publications and source records attributed to C L Lai.

At least 19 recordsLinked to original sources

[The changes of central and peripheral nerve conduction and the effect of thyroxine replacement in thyroidectomized rats].

The aim of this study is to make serial BAEPs and PNCS in hypothyroid rats in order to provide objective and quantitative methods of detecting dysfunction of the central and peripheral nervous system in hypothyroid status and elucidating the relationship between the recovery potential and the duration of hypothyroid status. Thyroidectomy was performed in eighteen naive 5-month-old Sprague-Dawley rats in order to induce hypothyroid status, which was confirmed by RIA study 1-2 months after the surgery. Initial BAEP and PNCS were performed in two groups of the hypothyroid animals 1 and 3 months after thyroidectomy. Following the initial examination, thyroxin replacement therapy was given to each hypothyroid group, and then followed by BAEPs and PNCS at two month intervals, up to twice normal studies or six months after the initiation of therapy. In the BAEP study, the prolonged I-V inter-peak latency was the most consistent abnormal finding in all hypothyroid rats. Delayed peak latencies as well as prolonged I-III and III-V inter-peak intervals occurred when the hypothyroid status was longer than one month. We noted that the longer the hypothyroid status, the more severe the central conduction dysfunction. Nonetheless, these abnormalities always returned to normal after the replacement therapy if the hypothyroid state was shorter than 3 months in duration. For the PNCS study, all groups of thyroidectomized rats showed the normal results. We think the peripheral nervous system of rats may be more resistant to damage by hypothyroidism than the central nervous system.

Animals

Pathogenic role of hepatitis B virus in hepatitis B surface antigen-negative decompensated cirrhosis.

This study was conducted to determine the rate of detection of serum hepatitis B virus (HBV) DNA in hepatitis B surface antigen (HBsAg)-negative decompensated cirrhotic patients who had hepatitis B core and/or surface antibodies (anti-HBc and/or anti-HBs), and to compare the outcome of HBsAg-positive cirrhotic patients who did or did not clear HBsAg during follow-up. Six (5%) of 121 HBsAg-positive cirrhotic patients lost HBsAg after 0.2 to 17.1 years (mean, 9.1 +/- 6.2 yr) of follow-up. The cumulative rates of loss of HBsAg at 1, 5, 10, and 15 years were, respectively, 1.3%, 1.3%, 7.4%, and 44.5%. Compared with the patients who remained HBsAg-positive, those who lost HBsAg had milder disease at presentation and significantly longer survival. Of the patients who lost HBsAg, 83% had improvement in liver function after the loss of HBsAg, and all were alive at the time of writing (0.8 to 5.7 years after loss of HBsAg), whereas 27% of those who remained HBsAg-positive had died and 29% had deterioration in liver function. The rate of detection of serum HBV DNA by polymerase chain reaction (PCR) assay was higher in HBsAg-positive cirrhotic patients who lost HBsAg:67% versus cirrhotic patients who had no previous history of chronic HBV infection; 16% (cryptogenic) and 29% (hepatitis C virus and/or alcohol-induced liver disease). In summary, we found that using PCR, serum HBV DNA can be detected in 28% of HBsAg-negative cirrhotic patients who were studied, but the pathogenic significance of such small amounts of virus is not clear.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

The hepatitis C virus genome: a guide to its conserved sequences and candidate epitopes.

A comprehensive analysis of reported hepatitis C virus genomic sequences comprising 151 partial or complete nucleotide sequences and 159 partial or complete amino acid sequences revealed an irregular composition of conserved and variable regions. There were but eight conserved nucleotide sequences, none outside the 5' noncoding and structural regions. A search among conserved amino acid sequences revealed 14 candidate B-cell epitopes, which were chosen mainly on the basis of their hydrophilicity profiles. Twenty five candidate T-cell epitopes were selected according to the criteria of absolute conservation of amino acid sequence, together with characteristic sequence motifs, amphipathic helical structure, or both. Conserved peptide sequences, with the characteristics of both B- and T-cell epitopes, were identified in the nonstructural 5 (NS5) region of the genome.

Amino Acid Sequence

Seroepidemiological survey of hepatitis E in Hong Kong by recombinant-based enzyme immunoassays.

The agent that causes the enterally transmitted form of non-A, non-B hepatitis has been cloned and called hepatitis E virus (HEV). We have carried out a seroepidemiological survey on the prevalence of hepatitis E in Hong Kong. In a retrospective study, serum from 394 patients with acute viral hepatitis and 355 healthy subjects was tested for antibodies to HEV (anti-HEV) with a recombinant-based enzyme immunoassay. 65 (16.5%) patients with hepatitis were positive for IgM anti-HEV and 23 (5.8%) were also positive for IgM anti-HEV. Of 18 patients diagnosed as having acute non-A, non-B, non-C hepatitis, 6 were IgM anti-HEV positive. 17 (6%) patients in whom acute hepatitis A was diagnosed were also infected with HEV. None of 70 patients with acute hepatitis B or C or exacerbation of chronic hepatitis B was IgM anti-HEV positive. 57 (16.1%) of the healthy subjects were positive for IgG anti-HEV. The prevalence of IgG anti-HEV was higher in subjects over 20 years old than in younger subjects (24% vs 4%, p < 0.0001). IgG anti-HEV was detected in 26% of subjects who were positive for IgG antibody to HAV and in 7% of those negative for that antibody (p < 0.0001). We demonstrated the validity of the recombinant-based enzyme immunoassays for the diagnosis of hepatitis E. Our results suggest that hepatitis E accounts for a third of non-A, non-B, non-C hepatitis in Hong Kong and that coinfection of hepatitis A and E can occur.

Acute Disease

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

Fulminant hepatic failure in nonmetastatic renal cell carcinoma.

Paraneoplastic manifestations including reversible abnormal serum liver biochemistry are known to occur in at least one third of patients with renal cell carcinoma. This hepatic dysfunction has always been regarded as benign in nature and attributed to reactive nonspecific hepatitis. In contrast to this belief, we report here a more devastating course of an asymptomatic patient with nonmetastatic renal cell carcinoma which ranged from mere serum liver biochemistry derangement to a fatal end with fulminant hepatic failure within 10 days. To our knowledge, this is the first report of such a case.

Aged

Maintenance therapy for duodenal ulcer: a randomized controlled comparison of seven forms of treatment.

PURPOSE: We performed a randomized controlled trial to compare the efficacy of seven forms of maintenance treatment of duodenal ulcer, including a mealtime regimen of antacids. PATIENTS AND METHODS: We randomized 785 patients with healed duodenal ulcer to receive: (1) no treatment; (2) mealtime antacids with an acid-neutralizing capacity of 80 mmol/day; (3) an antidepressant, trimipramine 25 mg; (4) an anticholinergic, pirenzepine 50 mg; (5) cimetidine 200 mg; (6) cimetidine 400 mg; (7) ranitidine 150 mg; or (8) sucralfate 1 g twice a day. Symptomatology and side effects were assessed every 2 months and endoscopy was performed every 4 months up to 1 year. RESULTS: The patients were comparable in the majority of clinical characteristics before entry. The cumulative percentages of patients with relapse of ulcers at 12 months by life-table analysis were 61% with no treatment, 38% with mealtime antacids, 60% with trimipramine, 52% with pirenzepine, 46% with cimetidine 200 mg, 44% with cimetidine 400 mg, 30% with ranitidine 150 mg, and 40% with sucralfate. Cimetidine 400 mg, antacids, ranitidine 150 mg, and sucralfate were significantly better than no treatment and the other forms of treatment. Ranitidine was significantly better than antacids, cimetidine, and sucralfate in preventing endoscopically documented duodenal ulcer relapse by multiple comparison at 12 months, but not by life-table analysis nor when symptomatic relapses were compared. No significant difference was detected among antacids, cimetidine, and sucralfate. No major side effects occurred with the seven forms of treatment, but those receiving antacids had the highest incidence of minor adverse events (26%). CONCLUSION: This study suggests that mealtime antacids are as effective as H2-receptor antagonists and sucralfate in the maintenance treatment of duodenal ulcer disease, but have to be taken three times a day and had the highest incidence of reported minor adverse events. The relapse rate was lower with ranitidine than with cimetidine, sucralfate, and antacids, but the difference was small and may not be clinically important.

Adult

A controlled trial of interferon with or without prednisone priming for chronic hepatitis B.

In a randomized, controlled trial of recombinant interferon alfa-2b with or without prednisone priming in Chinese adults with chronic hepatitis B virus infection, stratified randomization for pretreatment serum alanine aminotransferase levels was done. Partial or complete antiviral responses were achieved in 17 (21.5%) of 79 treated patients and 3 (8.3%) of 36 controls (P = 0.14). The response to interferon treatment was significantly better in those who had elevated pretreatment transaminase levels and comparable to that reported in white patients [15 (38.5%) of 39 patients compared with 2 (5%) of 40 who had normal pretreatment transaminase levels (P = 0.0005)]. The spontaneous seroconversion rate was also higher among the controls with elevated transaminase levels [3 (18.8%) of 16 compared with 0 of 20 with normal transaminase levels], but this difference was not statistically significant (P = 0.16). Among the interferon-treated patients, prednisone priming appeared to have a marginal benefit over treatment with interferon alone in patients with elevated transaminase levels (43% vs. 33%), but not in those with normal transaminase levels (0% vs. 9.5%). It was confirmed that Chinese patients with normal transaminase levels respond very poorly to interferon alfa therapy. However, the response was significantly better in patients with elevated transaminase levels.

Adult

Hepatitis D virus superinfection remains a rare occurrence in non-drug abusers in Hong Kong.

Recent studies from Taiwan reported an increased prevalence of hepatitis D virus (HDV) superinfection as well as a spread of HDV infection to non-drug abusers. We examined the current prevalence of HDV superinfection in Hong Kong by testing sera from a large cohort of patients with acute and chronic hepatitis B virus (HBV) infection, collected between January 1988 and December 1990, for IgG antibody to HDV (anti-HDV). Anti-HDV was detected in 13 (93%) of 14 parenteral drug abusers who had HBV-related chronic liver disease. However, anti-HDV was detected in only one (0.15%) of 664 non-drug abusers who had chronic HBV infection and none of 31% patients with acute hepatitis B. We concluded that HDV superinfection remains a rare occurrence in non-drug abusers in Hong Kong.

Cohort Studies

Histologic changes in Chinese patients with chronic hepatitis B virus infection after interferon-alpha therapy.

To evaluate the histologic effects of interferon-alpha (IFN alpha) therapy on chronic hepatitis B virus (HBV) infection, a semiquantitative study using a modified Knodell's numeric histologic scoring system was performed on paired pre- and post-treatment liver biopsy specimens from 127 adult Chinese patients from two trials of IFN alpha therapy (IFN alpha, n = 86; control, n = 41). The effects of IFN alpha therapy on the hepatic expression of HBV antigens were also determined using immunohistochemical analysis. Serologic response with clearance of HBV e antigen (n = 18) was associated with reduction in lobular activity, periportal piecemeal necrosis, portal inflammation, and total histologic scores. Loss of HBV e antigen also was associated with a reduction in the amount of HBV core antigen in the hepatocytes. In contrast, there was an increase in hepatic expression of HBV surface antigen after IFN alpha therapy. Patients who lost HBV e antigen with IFN alpha therapy were characterized by more severe initial periportal piecemeal necrosis before treatment. These data indicate that (1) serologic response is associated with a reduction in hepatic HBV replication and an improvement in hepatic histology, and (2) patients with severe periportal piecemeal necrosis respond more favorably to IFN alpha therapy.

Antigens, Viral

Precore sequence variation in Chinese isolates of hepatitis B virus.

Direct sequencing of polymerase chain reaction-amplified serum hepatitis B virus (HBV) DNA was used to characterize the precore region of HBV from Chinese patients with chronic hepatitis. Two types of mutually exclusive variants were found in hepatitis B e antigen (HBeAg)-negative patients. The first (M1) contains a substitution from proline to serine at codon 15. A second group were infected with a previously described mutant (M2) containing a translational stop codon. HBeAg-positive patients were infected with the wild-type virus or the M1-containing strain. M2 emerged in patients with wild-type infection after seroconversion to anti-HBe, whereas M1 was present during the HBeAg-positive phase. In those with fluctuating HBe status, there was no correlation between prevailing HBe serology and sequence. There was an association between infection with variants and severe chronic hepatitis. Patients infected with strains containing M1 while HBeAg positive had a worse prognosis after seroconversion to anti-HBe.

Alanine Transaminase

Subclinical hepatocellular carcinoma in Hong Kong Chinese.

Of the 208 Chinese patients with histologically proven hepatocellular carcinoma (HCC) seen during a 5-year period, 191 patients presented with symptomatic HCC and 17 patients with asymptomatic HCC (subclinical HCC, SCHCC) being picked up by alpha-fetoprotein (AFP) screening. Compared with the patients with symptomatic HCC, patients with SCHCC had a better performance status (p less than 0.01), higher serum albumin levels (p less than 0.05) and lower alkaline phosphatase levels (p less than 0.01). In those patients with symptomatic HCC, 4.7% were operable and only 2 patients had a tumour diameter of less than 5 cm. In contrast, patients with SCHCC had a higher operability rate (76.5%, p less than 0.0001) and all had a tumour of less than 5 cm in diameter (p less than 0.0001). Patients with SCHCC, most of whom had their tumour resected, had a better long-term survival (p less than 0.0001). We conclude that patients with SCHCC picked up by AFP serosurveillance have a better performance status, higher operability and better prognosis.

Actuarial Analysis

Thyroid functions in patients treated with interleukin-2 and lymphokine-activated killer cells.

Treatment of malignant disease with interleukin-2 and lymphokine-activated killer cells activates autoreactive T lymphocytes, stimulates release of cytokines and induces expression of HLA-class II antigens by tumour cells. We studied eight patients with hepatocellular carcinoma treated with a total of 16 courses of recombinant human interleukin-2 and lymphokine-activated killer cells and observed them for features of autoimmune thyroid disease. During the course of treatment there were significant decreases in total serum T4 and T3 and free thyroxine levels, but no change in TSH levels when all patients were analysed as a group. This was due to a number of factors including suppression of thyroid hormone release, haemodilution during interleukin-2 infusion and actual removal of thyroid hormones from the circulation during leukapheresis. Thyroid hormones returned to normal levels during resting period. One patient subsequently developed compensated hypothyroidism (normal total T4, total T3 and free T4 but elevated TSH) and four patients had features of 'sick euthyroid syndrome' (low total T4, total T3 or free T4 but normal TSH). None of the patients studied developed antibodies to thyroglobulin or microsomes. In contrast, no abnormality of thyroid function was seen in any of the nine subjects who received no active treatment. In conclusion, thyroid dysfunction was associated with immunotherapy of malignant disease with interleukin-2 and lymphokine-activated killer cells. This may arise from direct hormonal effects of the cytokines on thyroid hormone production.

Adult

Morbidity and mortality from chronic hepatitis B virus infection in family members of patients with malignant and nonmalignant hepatitis B virus-related chronic liver diseases.

Three-hundred forty-one HBsAg-positive family members of 152 patients with chronic hepatitis B virus infection (47 asymptomatic carriers, 59 with chronic hepatitis, 17 with cirrhosis and 29 with hepatocellular carcinoma) were prospectively studied to determine the morbidity and mortality from chronic hepatitis B virus infection in the family members of patients with malignant and nonmalignant hepatitis B virus-related chronic liver diseases. Most of the family members had no history of acute hepatitis, were asymptomatic and were unaware of their carrier status. However, 5.3% had stigmata of chronic liver disease, 6% had serum ALT levels that exceeded two times the upper limit of normal and 78% of those who had biopsies had chronic hepatitis with or without cirrhosis. During a follow-up period of 12 to 90 mo (median = 39 mo), 3% had symptoms of chronic liver disease; 24% had transient, recurrent or persistent elevation in serum ALT levels, 1.4% had cirrhosis and 1% had hepatocellular carcinoma. Neither hepatocellular carcinoma in the index patient nor a previous history of hepatocellular carcinoma in the family was associated with an increase in the morbidity and mortality from chronic hepatitis B virus infection in the HBsAg-positive family members.

Adolescent

Overestimation of the prevalence of antibody to hepatitis C virus in retrospective studies on stored sera.

Serum samples (1,428) from 1,149 patients with chronic liver diseases and polytransfused subjects were tested for antibody to hepatitis C virus by first-generation enzyme immunoassays. Antibody to hepatitis C virus was detected in 87% of patients with transfusion-related chronic non-A, non-B hepatitis; 17.6% of patients with nonmalignant, chronic hepatitis B virus infection; 37.3% of patients with hepatocellular carcinoma; 14.3% of patients with alcoholic liver diseases; 22.2% of patients with cryptogenic cirrhosis; 76% of intravenous drug abusers; 16.4% of patients on hemodialysis; 1.8% of patients on peritoneal dialysis; 6.2% of kidney transplant recipients; and 3.1% of normal subjects. A high frequency of weakly positive results was found in "aged" samples: 61.9% of antibody to hepatitis C virus-positive patients whose sera had been stored for more than 2 yr had optical densities less than two times the cut-off values in contrast to 7.9% of those whose sera had been stored for less than 2 yr (p less than 0.0001). A significantly lower proportion of patients who had optical densities less than two times the cut-off values were reactive in subsequent samples, 27.5% vs. 87.5% (p less than 0.0001). On retests, only 70% and 56% of sera that were initially positive for antibody to hepatitis C virus remained antibody to hepatitis C virus positive using second-generation enzyme immunoassays and neutralization enzyme immunoassays, respectively. Our results suggest that retrospective studies on stored sera may have overestimated the prevalence of antibody to hepatitis C virus.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Viral

A randomised controlled trial of recombinant interferon-gamma in Chinese patients with chronic hepatitis B virus infection.

Nineteen Chinese patients with chronic hepatitis B virus (HBV) infection, seropositive for HBV e antigen (HBeAg) and HBV DNA on at least three occasions in 6 months, were randomised to receive either recombinant human interferon-gamma (rIFN gamma) 0.1 mg/m2 intramuscularly thrice weekly for 16 weeks (n = 11) or no anti-viral therapy (controls, n = 8). Five patients in the treatment group and four patients in the control group had persistently elevated serum alanine aminotransferases (ALT) of over two times the upper limit of normal before entering into the trial. rIFN gamma had no or minimal inhibitory effect on serum HBV DNA during treatment and no patient developed e-seroconversion or sustained loss of serum HBV DNA. Hepatitic flare, which occurred in a proportion of patients responding successfully to interferon-alpha (IFN alpha) therapy, was not observed with rIFN gamma treatment. Side-effects included pyrexia and mild headache that showed tachyphylaxis and were well tolerated by all patients. In the control group, one patient with elevated pre-entry serum ALT lost serum HBV DNA and seroconverted to anti-HBe. Another patient with elevated ALT lost serum HBV DNA transiently during therapy. In the dose given, rIFN gamma was safe but had no apparent anti-viral effects in Chinese patients with chronic HBV infection.

Adolescent

Current seroepidemiology of hepatitis A in Hong Kong.

The current seroepidemiology of hepatitis A in Hong Kong was examined by testing stored sera from 702 healthy subjects, collected between 1987-1989, for antibody to hepatitis A virus (anti-HAV). The overall prevalence of anti-HAV antibody was 45.6%. There were significant increases in prevalence of anti-HAV antibody with every 10-year increase in age up to age 40. The prevalence of anti-HAV antibody was 24% for subjects below age 30 and 89.2% for those above age 30 (P less than 0.0001). Socioeconomic factors did not appear to have any influence on the prevalence of anti-HAV antibody. In comparison with another study conducted in Hong Kong 10 years ago, the prevalence of anti-HAV antibody in the current study was significantly lower in every age group from 0 to 30 years. In summary, it was shown that HAV infection is no longer highly endemic in Hong Kong. In view of the changing epidemiology, postexposure prophylaxis will be necessary for young adults and children, and hepatitis A vaccine may be indicated for high risk groups when it is generally available.

Adolescent

Effect of omeprazole on duodenal ulcer-associated antral gastritis and Helicobacter pylori.

This study set out to investigate the effects of omeprazole or ranitidine on the progression of antral gastritis and Helicobacter pylori in patients with active duodenal ulcer. A double-blind, double-dummy trial was performed in 270 patients, 241 of whom were studied histologically for the presence of H. pylori. Patients were randomized to receive omeprazole, 10 mg every morning, omeprazole, 20 mg every morning, or ranitidine, 150 mg twice a day, for four weeks. Endoscopy was performed on entry and at weekly intervals during the study; at least two antral biopsies were taken on each occasion to assess the activity and degree of chronic inflammation, as reflected by the degree of polymorphonuclear leukocyte infiltration and mononuclear cell infiltration, respectively. Biopsy specimens also were assessed histologically for H. pylori. The sex, age and maximal acid output were comparable in the three treatment groups. The percentages of patients showing an improvement in the activity of gastritis in the four consecutive weeks of treatment were 9%, 40%, 51%, and 53% for omeprazole, 10 mg (N = 78); 14%, 42%, 49%, and 53% for omeprazole, 20 mg (N = 81); and 2%, 23%, 30%, and 33% for ranitidine, 150 mg twice a day (N = 82) (life table analysis gave P less than 0.01 for both omeprazole regimens compared with ranitidine). The degree of chronic inflammation showed similar changes. The density of H. pylori decreased significantly after treatment with omeprazole, 10 mg or 20 mg, (both, P less than 0.00001) but not with ranitidine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult