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Biomedical subjects

F K Chan

Publications and source records attributed to F K Chan.

At least 55 records · Page 3Linked to original sources
PubMed2000

Risk factors for active liver disease in HBeAg-negative chronic hepatitis B virus-infected patients.

OBJECTIVES: HBeAg-negative patients constitute approximately 70% of all chronic hepatitis B virus (HBV) infections in Southeast Asia, and some of these patients continue to suffer from active disease. We aimed to study the risk of hepatitis relapse in chronic HBV-infected patients with negative HBeAg and the predictor(s) of relapses. METHODS: This was a retrospective analysis of patients carrying HBsAg but lacking HBeAg. Patients recruited were required to have been followed for > or = 12 months with a minimum of three blood samples available for analysis. Patient demographic data, liver biochemistry, and HBV serology were analyzed in relation to relapses of hepatitis. Relapse was defined as an abrupt elevation of ALT > 200 IU/L or > 3-fold previous levels, whichever was higher. RESULTS: In a period of 3 months, 317 patients seen at the Hepatitis Clinic at the Prince of Wales Hospital in Hong Kong were recruited. The median duration of follow-up was 34 months. On initial consultation, 111 (35.0%) patients had elevated ALT (>60 IU/L). Overall, 57 (18.0%) patients developed at least one relapse, including 37 (33.3%) patients with elevated ALT and 20 (9.7%) patients with normal ALT at the first visit. Multiple logistic regression analysis showed that elevated ALT level at first presentation (odds ratio 4.17, 95% confidence interval 2.24-7.75) and male gender (odds ratio 2.83, 95% confidence interval 1.23-6.49) were the two independent factors associated with a higher risk of hepatitis relapse. The sensitivity, specificity, and positive and negative predictive values of a single ALT test for hepatitis relapse were 64.9%, 71.5%, 33.3%, and 90.3%, respectively. CONCLUSIONS: HBeAg-negative HBV carriers with normal ALT levels have a low risk of hepatitis relapse.

Adult↗
PubMed2000

The pre-ligand binding assembly domain: a potential target of inhibition of tumour necrosis factor receptor function.

Signalling by the tumour necrosis factor receptors (TNFR) is thought to be mediated by the binding of the trimeric ligand TNF to three monomeric subunits of the receptor. This ligand induced trimerisation model of TNFR signalling is mainly supported by crystallographic data of the p60 TNFR-1 and TNFbeta complex in which the trimeric ligand interdigitates between the individual receptor chains and prevents the receptor subunits from interacting with each other. Recently, a domain NH(2)-terminal to the ligand binding domain in the extracellular region of p60 TNFR-1, p80 TNFR-2 and Fas was identified that mediates receptor self association before ligand binding. This pre-ligand binding assembly domain or PLAD is critical for assembly of functional receptor complexes on the cell surface and may provide a potential target in the design of future novel therapeutics against diseases mediated by members of the TNFR family of receptors.

Arthritis, Rheumatoid↗
PubMed2000

A case of giant malignant phaeochromocytoma.

Malignant phaeochromocytoma is defined as the presence of tumour deposits at sites that are normally devoid of chromaffin cells. We report on a 63-year-old man who had a giant malignant phaeochromocytoma of the right adrenal gland that encased the inferior vena cava. The urinary excretion rates of catecholamines and their metabolites were normal, except for normetanephrine, which was excreted at a higher rate than normal. The tumour was surgically unresectable by laparotomy. Postoperatively, the patient was given a 4-month trial of subcutaneous octreotide and intravenous meta-iodobenzylguanidine I 131. Occult lung secondary tumours were first detected by meta-iodobenzylguanidine scintigraphy after 2 years, and the patient died of bone and lung metastases 1 year later. Because phaeochromocytoma is rare, local experience in managing this disease is limited. This report alerts physicians of the methods of diagnosing and managing surgically unresectable malignant phaeochromocytoma.

3-Iodobenzylguanidine↗
PubMed1999

Inherited human Caspase 10 mutations underlie defective lymphocyte and dendritic cell apoptosis in autoimmune lymphoproliferative syndrome type II.

Caspases are cysteine proteases that mediate programmed cell death in phylogenetically diverse multicellular organisms. We report here two kindreds with autoimmune lymphoproliferative syndrome (ALPS) type II, characterized by abnormal lymphocyte and dendritic cell homeostasis and immune regulatory defects, that harbor independent missense mutations in Caspase 10. These encode amino acid substitutions that decrease caspase activity and interfere with death receptor-induced apoptosis, particularly that stimulated by Fas ligand and TRAIL. These results provide evidence that inherited nonlethal caspase abnormalities cause pleiotropic apoptosis defects underlying autoimmunity in ALPS type II.

Adaptor Proteins, Signal Transducing↗
PubMed1999

CTLA-4-Mediated inhibition of early events of T cell proliferation.

CTLA-4 engagement by mAbs inhibits, while CD28 enhances, IL-2 production and proliferation upon T cell activation. Here, we have analyzed the mechanisms involved in CTLA-4-mediated inhibition of T cell activation of naive CD4+ T cells using Ab cross-linking. CTLA-4 ligation inhibited CD3/CD28-induced IL-2 mRNA accumulation by inhibiting IL-2 transcription, which appears to be mediated in part through decreasing NF-AT accumulation in the nuclei. However, CTLA-4 ligation did not appear to affect the CD28-mediated stabilization of IL-2 mRNA. Further, CTLA-4 engagement inhibited progression through the cell cycle by inhibiting the production of cyclin D3, cyclin-dependent kinase (cdk)4, and cdk6 when the T cells were stimulated with anti-CD3/CD28 and with anti-CD3 alone. These results indicate that CTLA-4 signaling inhibits events early in T cell activation both at IL-2 transcription and at the level of IL-2-independent events of the cell cycle, and does not simply oppose CD28-mediated costimulation.

Abatacept↗
PubMed1999

Endoscopic retreatment compared with surgery in patients with recurrent bleeding after initial endoscopic control of bleeding ulcers.

BACKGROUND AND METHODS: After endoscopic treatment to control bleeding of peptic ulcers, bleeding recurs in 15 to 20 percent of patients. In a prospective, randomized study, we compared endoscopic retreatment with surgery after initial endoscopy. Over a 40-month period, 1169 of 3473 adults who were admitted to our hospital with bleeding peptic ulcers underwent endoscopy to reestablish hemostasis. Of 100 patients with recurrent bleeding, 7 patients with cancer and 1 patient with cardiac arrest were excluded from the study; 48 patients were randomly assigned to undergo immediate endoscopic retreatment and 44 were assigned to undergo surgery. The type of operation used was left to the surgeon. Bleeding was considered to have recurred in the event of any one of the following: vomiting of fresh blood, hypotension and melena, or a requirement for more than four units of blood in the 72-hour period after endoscopic treatment. RESULTS: Of the 48 patients who were assigned to endoscopic retreatment, 35 had long-term control of bleeding. Thirteen underwent salvage surgery, 11 because retreatment failed and 2 because of perforations resulting from thermocoagulation. Five patients in the endoscopy group died within 30 days, as compared with eight patients in the surgery group (P=0.37). Seven patients in the endoscopy group (including 6 who underwent salvage surgery) had complications, as compared with 16 in the surgery group (P=0.03). The duration of hospitalization, the need for hospitalization in the intensive care unit and the resultant duration of that stay, and the number of blood transfusions were similar in the two groups. In multivariate analysis, hypotension at randomization (P=0.01) and an ulcer size of at least 2 cm (P=0.03) were independent factors predictive of the failure of endoscopic retreatment. CONCLUSIONS: In patients with peptic ulcers and recurrent bleeding after initial endoscopic control of bleeding, endoscopic retreatment reduces the need for surgery without increasing the risk of death and is associated with fewer complications than is surgery.

Aged↗
PubMed1999

Evaluation of three commercial enzyme-linked immunosorbent assay kits for diagnosis of Helicobacter pylori in Chinese patients.

Most of the commercial serological assays for H. pylori are developed and validated in western countries. We evaluated the accuracy of three popular commercial ELISA tests for H. pylori in the Chinese population. Eighty dyspeptic patients were recruited and diagnosis of H. pylori infection was based on biopsy urease test, histology and urea breath test. Thirty-six patients (45%) were positive for H. pylori infection by two or more positive reference tests. Anti-H. pylori IgG antibody was detected by three commercial ELISA tests: GAP IgG (Bio-Rad), HM-CAP (Enteric Products) and Pyloriset EIA-G (Orion). The respective sensitivity, specificity, positive and negative predictive values of the three tests were: GAP IgG (50%, 97.4%, 93.8%, 71.7%), HM-CAP (72.7%, 68.4%, 66.7%, 74.3%) and Pyloriset EIA-G (75%, 86.4%, 81.8%, 80.9%). Despite the high accuracy reported in the West, the performance of these commercial serological tests was unsatisfactory when used in Chinese patients.

Adult↗
PubMed1999

One-week ranitidine bismuth citrate in combinations with metronidazole, amoxycillin and clarithromycin in the treatment of Helicobacter pylori infection: the RBC-MACH study.

BACKGROUND: We have previously shown that ranitidine bismuth citrate (RBC)-based triple therapy is comparable to proton pump inhibitor-based triple therapy in eradicating Helicobacter pylori infection. AIM: To test the efficacy of different combinations of antimicrobials with RBC in the treatment of H. pylori infection. METHODS: Dyspeptic patients with H. pylori infection were prospectively randomized to receive one of the following regimens: (i) RBC 400 mg, amoxycillin 1 g, clarithromycin 500 mg [RAC]; (ii) RBC 400 mg, metronidazole 400 mg, clarithromycin 500 mg [RMC]; (iii) RBC 400 mg, metronidazole 400 mg, tetracycline 1 g [RMT] (all given twice daily for 1 week); or (iv) RBC 400 mg plus clarithromycin 500 mg twice daily for 2 weeks [RC-2]. Endoscopy (rapid urease test and culture) and 13C-urea breath test (UBT) were performed before randomization. Four weeks after finishing medication, the 13C-UBT was repeated in all cases and endoscopy was offered to patients with peptic ulcers. RESULTS: Four hundred patients were randomized but in two (one in the RAC group and one in the RMC group) H. pylori infection was not confirmed. Successful eradication of H. pylori (intention-to-treat analysis and 95% CI) of RAC (86% [79-93%]), RMC (90% [84-96%]), RMT (79% [71-87%]) and RC-2 (82% [75-90%]) were comparable, with a trend favouring clarithromycin-containing triple therapy regimens. Among 276 isolates tested for antibiotic sensitivity, primary resistance to metronidazole, clarithromycin and amoxycillin was found in 56%, 2% and 0.4%, respectively. When given RMC or RMT, patients infected by metronidazole-resistant H. pylori had success in eradicating H. pylori similar to patients infected by metronidazole-sensitive H. pylori. CONCLUSION: One-week RBC triple therapy is effective in curing H. pylori infection.

Adolescent↗
PubMed1999

Prevalence and distribution of Helicobacter pylori in gastroesophageal reflux disease: a study from the East.

OBJECTIVES: The relationship between Helicobacter pylori infection and gastroesophageal reflux (H. pylori) disease (GERD) is controversial. In Asian populations, the prevalence of H. pylori infection is high and GERD is relatively uncommon. The aim of this study was 1) to test the hypothesis that H. pylori protects the esophagus against GERD, and 2) to study the pattern of H. pylori colonization and gastritis in GERD. METHODS: We conducted a prospective case-control study in which patients with GERD and asymptomatic controls were compared for the prevalence of H. pylori infection. Diagnosis of GERD was based on symptoms of heartburn that improved with acid-suppressive therapy and/or endoscopic evidence of erosive esophagitis. H. pylori status was determined by serology and, when endoscopy was indicated, was confirmed by rapid urease test and histology. Gastric biopsies were examined under hematoxylin and eosin and Giemsa stains. Density of H. pylori colonization and activity of gastritis at different parts of stomach were graded and compared according to Updated Sydney system. RESULTS: A total of 106 patients with GERD and 120 age- and sex-matched, asymptomatic controls were enrolled. The prevalence of H. pylori infection was significantly lower in GERD patients (31%) compared with controls (61%, p < 0.001, odds ratio 0.229, 95% confidence interval 0.13-0.41). H. pylori-infected GERD patients showed significantly more severe gastritis in the antrum than in other parts of stomach (mean inflammatory scores: antrum; 3.3 +/- 1.63*, body; 1.85 +/- 1.31; fundus; 1.65 +/- 0.58; cardia, 1.65 +/- 1.39; *p < 0.005). H. pylori colonization was found less commonly and at lower density at the cardia compared with other parts of the stomach. CONCLUSIONS: H. pylori infection protects against the development of GERD, and carditis is unlikely to play an important role.

Adult↗
PubMed1998

Thymic expression of the transcription factor Nur77 rescues the T cell but not the B cell abnormality of gld/gld mice.

Fas and Fas ligand are critical regulators of lymphocyte homeostasis. Disruption of this pathway in the spontaneous mouse mutant gld leads to autoimmunity characterized by the appearance of a population of CD4- 8- B220+ T cells and the production of autoantibodies. Nur77 is a transcription factor that is induced upon TCR signaling. Constitutive thymic expression of Nur77 leads to apoptosis. We have previously shown that introduction of this Nur77 transgene can eliminate the accumulation of abnormal T cells in the periphery of gld/gld mice. In this report, we further characterized the effects of the Nur77 transgene on the gld phenotype. Nur77-mediated apoptosis is evident in the thymuses of mice with either a gld/gld homozygous or gld/+ heterozygous background. Consequently, few mature T cells are generated in these mice. In addition, mature T cells exhibit a diminished response to proliferative signals through CD3. Interestingly, the Nur77 transgene failed to reduce serum levels of Igs and anti-DNA Abs to wild-type levels. These data suggest that the rescue of the T cell lymphoproliferative syndrome in gld/gld mice by the Nur77 transgene is mediated by events in the thymus and that B cell autoimmune disease associated with the gld mutation can develop independently of the T cell abnormality.

Animals↗
PubMed1998

The effects of liver transplantation and cyclosporine on bile formation and lipid composition: an experimental study in the rat.

BACKGROUND/AIMS: Hepatic graft dysfunction is a major management problem in the early post-liver transplantation period. Our aims were to study how liver transplantation per se affects bile formation, and to investigate the role of cyclosporine in the pathogenesis of early graft dysfunction. METHODS: Syngeneic liver transplantation used male Lewis rats. Two weeks after transplantation, the rats were randomly assigned to receive either daily subcutaneous injections of cyclosporine 10 mg/kg for 1 week (n=8), or daily saline injections (Placebo, n=8). 24-h bile collections were performed 18 h after the last injection. Eight non-transplanted rats served as controls. RESULTS: Liver transplantation per se (Placebo) significantly increased basal bile flow (51%), particularly that portion which was bile salt-independent flow (81%), but did not impair bile salt kinetics or biliary lipid composition. Cyclosporine reduced basal bile flow and bile salt-independent flow by 41% and 30%, respectively. Bile salt synthesis was 52% suppressed, leading to a 22% decrease in the bile salt pool size. The recycling frequency of the bile salt pool was unaffected. The drug inhibited bile salt (37%) and phospholipid (23%) outputs; cholesterol secretion remained unaltered. This significantly elevated the cholesterol saturation of bile (25%). CONCLUSIONS: Liver transplantation per se is choleretic and does not impair bile formation or lipid composition in this inbred rat model. Parenteral administration of high-dose cyclosporine induces cholestasis by inhibiting bile salt secretion and BSIF. Bile salt synthesis is down-regulated and the bile salt pool size decreased. The drug adversely affects biliary lipid composition by differential inhibition of bile salt and phospholipid outputs relative to an unchanged cholesterol secretion.

Animals↗
PubMed1998

Tissue injury of Injection Gold Probe.

BACKGROUND: The Injection Gold Probe, which incorporates an injection needle and a bipolar electrocoagulation probe, potentially offers better anchoring of the probe for electrocoagulation. This study compares the tissue injury caused by the Injection Gold Probe with or without protrusion of the needle. METHODS: A 10F Injection Gold Probe was applied perpendicularly on the antrum of porcine stomach. At each site of testing, one pulse of treatment at 12 W was given for 10 seconds. The extent of tissue injury was studied under different forces of application (light touch or maximal force) and different probe conditions (needle-in, needle-out, needle-out plus 1 mL saline solution injection). Each maneuver was repeated 8 times. The depth and width of tissue injury were assessed histologically by a pathologist blinded to the treatment. RESULTS: The depth and width of tissue injury did not differ significantly with needle-in, needle-out, or needle-out plus 1 mL saline solution injection on both light touch. But the tissue injury was significantly deeper and wider with maximal force applications than with light touch under the same probe condition. CONCLUSION: The extent of tissue injury inflicted by electrocoagulation using the Injection Gold Probe is not affected by the position of the injection needle.

Analysis of Variance↗
PubMed1998

Injection sclerotherapy for variceal bleeding in patients with hepatocellular carcinoma: cyanoacrylate versus sodium tetradecyl sulphate.

BACKGROUND: Patients with hepatocellular carcinoma complicated by variceal bleeding have a very limited life span. Recurrent bleeding after endoscopic injection sclerotherapy is common. Our aim was to compare the efficacy of endoscopic injection of cyanoacrylate versus sodium tetradecyl sulphate in the control of variceal bleeding in patients with hepatocellular carcinoma. METHODS: Patients known to be suffering from inoperable hepatocellular carcinoma who presented with upper gastrointestinal bleeding underwent endoscopy within 24 hours of admission. After bleeding from esophageal varices was confirmed, they were randomized to receive endoscopic injections of either cyanoacrylate (1:1 mixture with Lipoidol) or sodium tetradecyl sulphate (1.5%). Injection were given intravariceally into each visible column for up to four injections for cyanoacrylate and up to 30 mL for sodium tetradecyl sulphate. RESULTS: A total of 50 patients were recruited for this study with 25 cases randomized to each endoscopic treatment group. Control of acute bleeding failed in four patients (16%) in both treatment groups, and two patients in each group died during the index episode of bleeding. Six patients (24%) in the cyanoacrylate group and four patients (16%) in the sodium tetradecyl sulphate group developed recurrent bleeding during their hospital stay (p = 0.48). Recurrent bleeding within 30 days after the index episode of bleeding was documented in seven patients (28%) who received cyanoacrylate injection and five patients (20%) who received sodium tetradecyl sulphate injection (p = 0.51). Median survival in the cyanoacrylate group was 16 days (range 1 to 485 days) and that of the sodium tetradecyl sulphate group was 13 days (range 1 to 407 days). There was no difference in cumulative survival between the two groups as analyzed by the Kaplan-Meier method. Patients with portal vein thrombosis had a higher risk of recurrent hemorrhage. Patients with Child's C liver disease had a significantly higher mortality. CONCLUSIONS: Cyanoacrylate did not improve the outcome of hepatocellular carcinoma patients with variceal hemorrhage.

Carcinoma, Hepatocellular↗
PubMed1998

Bile immunoglobulins and blockage of biliary endoprosthesis: an immunohistochemical study.

BACKGROUND: Endoscopic biliary stenting for pancreaticobiliary malignancy is often limited by recurrent stent occlusion as a result of bacterial biofilm formation and sludge deposition. Bile immunoglobulins are thought to be important in combating biliary sepsis. OBJECTIVES: To investigate whether bile immunoglobulins are involved in the pathogenesis of stent blockage. DESIGN: Immunohistochemical technique was used to study the distribution of bile immunoglobulins, bacteria and sludge in blocked biliary stents. METHODS: Patients with malignant obstructive jaundice were palliated by endoscopic insertion of a 10-FG polyethylene stent into the biliary tract. Blocked stents were retrieved from those who presented with recurrent jaundice and fever. The stents were cross-sectionally cut into slices and fixed in formalin. Immunoglobulins were demonstrated by the peroxidase-anti-peroxidase staining procedure using rabbit anti-serum. RESULTS: The central bulk of the stent deposits appeared as an amorphous, structureless material. IgA was found as a rim of dark brown discoloration at the periphery. IgG showed similar distribution and intensity to that of IgA whereas little IgM was detected. CONCLUSIONS: Bile immunoglobulins may facilitate bacterial adhesion, clumping, and hence biofilm formation on the stent surface.

Bacterial Adhesion↗
PubMed1998

One-week use of ranitidine bismuth citrate, amoxycillin and clarithromycin for the treatment of Helicobacter pylori-related duodenal ulcer.

BACKGROUND: Proton pump inhibitors have been widely used in combination with amoxycillin, clarithromycin or metronidazole for the treatment of Helicobacter pylori infection. AIM: To study the effects of 1-week ranitidine bismuth citrate (RBC)-based triple therapy in the treatment of H. pylori-related duodenal ulcers. METHOD: Patients with duodenal ulcers and H. pylori infection were prospectively randomized to receive either RBC with amoxycillin and clarithromycin for 1 week (RAC), or omeprazole with amoxycillin and clarithromycin for 1 week (OAC). No additional ulcer healing drug was used after the 1-week medication. Patients were assessed for H. pylori eradication, ulcer healing and side-effects after receiving the therapies. RESULTS: One hundred consecutive patients were recruited to this study, with 50 patients randomized to each treatment group. In the intention-to-treat analysis, duodenal ulcers were completely healed in 45 (90%) patients in the RAC group and 43 (89.6%) in the OAC group (P = 1.0). H. pylori eradication was confirmed in 47 (94%) in the RAC group and 42 (87.5%) in the OAC group (P = 0.31). There was no significant difference in the severity of side-effects experienced by the two treatment groups. CONCLUSION: One-week RBC-based triple therapy is an effective treatment for H. pylori-related duodenal ulcers. The therapeutic effects are comparable to a 1-week course of proton pump inhibitor-based triple therapy.

Adolescent↗
PubMed1998

Does eradication of Helicobacter pylori impair healing of nonsteroidal anti-inflammatory drug associated bleeding peptic ulcers? A prospective randomized study.

BACKGROUND: Despite the widely accepted view that Helicobacter pylori is the most important cause of peptic ulcer disease, recent studies have suggested that the microbe protects against nonsteroidal anti-inflammatory drug (NSAID)-associated gastroduodenal lesions and promotes ulcer healing. We investigated the effects of H. pylori eradication on the healing of NSAID-associated bleeding peptic ulcers. METHODS: Chronic NSAID users presenting with peptic ulcer haemorrhage underwent endoscopy to secure haemostasis and to document H. pylori infection by rapid urease test and culture. They were prospectively randomized to receive either omeprazole (20 mg once daily) for 8 weeks or a 1-week course of triple therapy (bismuth subcitrate 120 mg, tetracycline 500 mg, metronidazole 400 mg, all given four times daily) plus omeprazole (20 mg once daily) for 8 weeks. Endoscopy was repeated after 8 weeks. Final H. pylori status was determined by a 13C-urea breath test that was performed at least 4 weeks after discontinuation of omeprazole. RESULTS: 195 H. pylori-infected NSAID users, complicated by bleeding ulcers, were randomized to receive omeprazole alone (102) or triple therapy plus omeprazole (93). 174 patients returned for second endoscopy at 8 weeks (91 in the omeprazole group, 83 in the triple therapy group). Urea breath test was negative in 14% in the omeprazole group vs. 92% in the triple therapy group (P < 0.001). Complete ulcer healing was achieved in 88 (97%) patients in the omeprazole group and 77 (93%) in the triple therapy group (P=0. 31). On intention-to-treat analysis, ulcers were healed in 86% of the omeprazole group and 83% of the triple therapy group (P=0.50). There was no significant difference in the healing rates of gastric or duodenal ulcers between the two groups. CONCLUSION: Eradication of H. pylori did not impair the healing of NSAID-associated bleeding peptic ulcers.

Adult↗