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Biomedical subjects

S K Lam

Publications and source records attributed to S K Lam.

At least 73 records · Page 4Linked to original sources

Treatment of acute Nipah encephalitis with ribavirin.

Nipah virus, a newly identified paramyxovirus caused a severe outbreak of encephalitis in Malaysia with high fatalities. We report an open-label trial of ribavirin in 140 patients, with 54 patients who were managed prior to the availability of ribavirin or refused treatment as control. There were 45 deaths (32%) in the ribavirin arm; 29 deaths (54%) occurred in the control arm. This represents a 36% reduction in mortality (p = 0.011). There was no associated serious side effect. This study suggests that ribavirin is able to reduce the mortality of acute Nipah encephalitis.

Adult↗

Isolation of a small chitinase-like antifungal protein from Panax notoginseng (sanchi ginseng) roots.

An antifungal protein, with a molecular weight of 15 kDa and an N-terminal sequence analogous to those of chitinases, was first isolated from the Chinese medicinal material Panax notoginseng, using cation exchange chromatography and affinity chromatography. The protein was adsorbed on CM-cellulose, Affi-gel Blue Gel and Mono S. It exerted antifungal activity against Coprinus comatus, Fusarium oxysporum and Mycosphaerella arachidicola but not against Rhizoctonia solani. The protein was devoid of ribonuclease activity against yeast tRNA.

Amino Acid Sequence↗

One-week ranitidine bismuth citrate-based triple therapy for the eradication of Helicobacter pylori in Hong Kong with high prevalence of metronidazole resistance.

AIM: To compare 1-week ranitidine bismuth citrate-based (RBC) triple therapy vs. omeprazole-based (O) triple therapy for the eradication of Helicobacter pylori infection in Hong Kong with high prevalence of metronidazole resistance. METHODS: Patients with non-ulcer dyspepsia and H. pylori infection were randomized to receive either: (i) RBCCM: ranitidine bismuth citrate (pylorid) 400 mg, clarithromycin 250 mg and metronidazole 400 mg; or (ii) OCM: omeprazole 20 mg, clarithromycin 250 mg and metronidazole 400 mg, each given twice daily for 1 week. Endoscopy (CLO test, histology and culture) and 13C-urea breath test were performed before randomization and 6 weeks after drug treatment. RESULTS: A total of 180 patients were randomized. H. pylori eradication rates (intention-to-treat, n=180/per protocol, n=166) were 83%/92% for RBCCM and 66%/70% for OCM (P=0.01, intention-to-treat and P=0.001, per protocol, respectively). RBCCM treatment was unaffected by metronidazole susceptibility and achieved a significantly higher eradication rate in metronidazole-resistant cases (89%) than the OCM group (45%, P=0.0064). CONCLUSION: One-week ranitidine bismuth citrate-based triple therapy is significantly better than omeprazole-based triple therapy for the eradication of H. pylori infection, especially in metronidazole-resistant cases. It is an effective regimen for the eradication of H. pylori infection in regions with a high prevalence of metronidazole resistance.

Adult↗

An evaluation of invasive and non-invasive tests for the diagnosis of Helicobacter pylori infection in Chinese.

BACKGROUND: Different tests are available for diagnosing Helicobacter pylori infection. AIM: To compare the most commonly used tests either alone or in combination in Chinese patients with respect to routine clinical use or research purpose. METHODS: A total of 294 consecutive dyspeptic patients without previous H. pylori treatment were recruited. During upper endoscopy, biopsies were taken from the antrum and corpus, for a commercially available CLO-test, an in-house rapid urease test, culture, polymerase chain reaction and histological examination. Patients then received a 13C-urea breath test. The H. pylori status of each patient was determined by a concordance of test results. RESULTS: For routine clinical use, histology (antral plus corpus biopsies) had an accuracy of 100%, whilst the rapid urease test had an accuracy of 99.7%. The 13C-urea breath test was equally reliable, with an accuracy of 94.5%. Combinations of two tests did not confer additional advantage over the most accurate single test. For research purposes, the accuracy of using the criteria of two positives out of three diagnostic tests was 100% and equivocal results were not found. CONCLUSION: Histology with or without a rapid urease test was highly accurate for routine clinical use. Alternatively, the 13C-urea breath test was an equally reliable non-invasive test. The two positives out of three tests approach was highly reliable in predicting H. pylori status of untreated Chinese patients in a research setting.

Biopsy↗

High prevalence of mixed infections by Helicobacter pylori in Hong Kong: metronidazole sensitivity and overall genotype.

BACKGROUND: Diversity in metronidazole susceptibility and genotypes of Helicobacter pylori have been reported with varying results in different areas. AIMS: To investigate the prevalence of multiple strain infection in a symptomatic Chinese population and to determine the metronidazole susceptibility pattern and genotypic characteristics of these infecting strains. METHODS: Gastric biopsies from antrum, body and cardia were taken during upper endoscopy in symptomatic patients referred to our department. Pooled cultures and single colony isolates were obtained and tested for metronidazole susceptibility and random amplified polymorphic DNA (RAPD) fingerprint patterns. RESULTS: A total of 461 isolates were successfully cultured from 46 patients. Fifty-seven per cent of subjects had metronidazole-resistant strains. Among them, 77% carried a mixture of sensitive and resistant strains, non-uniformly distributed in the gastric mucosa. Mixed genotypes were found by RAPD typing in 24% of subjects. These did not correlate with the metronidazole susceptibility/resistance pattern. CONCLUSION: H. pylori infections with mixed metronidazole sensitive/resistant strains and mixed genotypes are common in Hong Kong. This makes it prudent to use bacterial strains from several biopsy sites when testing for traits such as drug resistance or virulence in relation to disease.

Adult↗

Three-day lansoprazole quadruple therapy for Helicobacter pylori-positive duodenal ulcers: a randomized controlled study.

AIM: To compare the efficacy and tolerability of a 3-day quadruple therapy with a standard 7-day triple therapy in eradicating Helicobacter pylori infection and healing duodenal ulcers. METHODS: Patients with H. pylori-positive duodenal ulcers were randomized to receive either lansoprazole 30 mg, clarithromycin 500 mg, and metronidazole 400 mg twice daily for 7 days (LCM-7) or lansoprazole 30 mg, clarithromycin 500 mg, metronidazole 400 mg, and bismuth subcitrate 240 mg twice daily for 3 days (LCMB-3). No pre- or post-treatment acid suppression was used. Follow-up endoscopy was performed at week 6. RESULTS: A total of 118 patients were recruited. Sixty patients in the LCM-7 group and 53 patients in the LCMB-3 group returned for endoscopy. Intention-to-treat eradication rates were 87% and 86% (P=0.94) and per protocol eradication rates were 87% and 94% (P=0.29) in the LCM-7 and LCMB-3 groups, respectively. Per protocol and intention-to-treat ulcer healing rates were 98% and 98% in LCM-7 and 100% and 91% in LCMB-3, respectively. There were no significant differences in efficacy in relation to the initial metronidazole and clarithromycin susceptibility. Significant reduction in the duration of side-effects was found in the LCMB-3 group. CONCLUSION: The 3-day quadruple therapy is highly effective, better tolerated and can be considered as a first-line therapy in duodenal ulcer management.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Epidermal growth factor and its receptor in chronic active gastritis and gastroduodenal ulcer before and after Helicobacter pylori eradication.

BACKGROUND: Helicobacteria pylori infection of gastroduodenal mucosa is strongly associated with gastritis and peptic ulcer disease. The aims of the present study were to compare the gastroduodenal mucosal levels of epidermal growth factor (EGF) and its receptor (EGFR) among H. pylori-negative controls and H. pylori infected patients with chronic active gastritis or gastroduodenal ulcer before and after H. pylori eradication. METHODS: The protein levels of EGF in mucosal tissues and saliva were determined by a solid-phase enzyme-linked immunosorbent assay (ELISA). Repeat transcription-polymerase chain reaction and the following polymerase chain reaction ELISA were employed to examine the mucosal EGFR mRNA expression. RESULTS: Mucosal injury and H. pylori infection increased EGF protein levels and EGFR mRNA expression in the antral mucosa. The concentration of EGF in saliva was not affected by mucosal damage or H. pylori infection. Successful H. pylori eradication normalized the EGFR mRNA back to its basal level 6 weeks after treatment. However, after unsuccessful eradication their high levels in the antrum persisted. All patients experienced ulcer healing after drug treatment, regardless of H. pylori eradication. CONCLUSIONS: Mucosal damage increased the expression of EGF protein and EGFR mRNA in the gastric mucosa. H. pylori could induce the expression of EGFR but not the EGF in the antral mucosa. The expression of EGFR could be a contributing factor for ulcer healing in patients with H. pylori infection.

Adolescent↗

Acute cholangitis--predictive factors for emergency ERCP.

BACKGROUND: Acute cholangitis varies in severity from a mild form to severe cases which require urgent biliary decompression. AIM: This study was undertaken in order to develop a prognostic scoring system that can be used to predict which patients are likely to require emergency endoscopic retrograde cholangiopancreatogram (ERCP) upon admission. METHODS: This is a prospective study of 142 consecutive patients with acute cholangitis. Emergency ERCP was performed in patients who did not respond to medical therapy. RESULTS: Thirty-one patients (21.8%) required emergency ERCP. A maximum heart rate of more than 100/min, albumin of less than 30 g/L, bilirubin of more than 50 micromol/L and prothrombin time of more than 14 s on admission were associated with failure of medical treatment and the need for emergency ERCP (P=0.001, < 0.001, 0.006 and 0.004, respectively). By using these four factors in a scoring system, 50.7% of those with a score of one or more required emergency ERCP compared with 1.5% of those with none of the four risk factors (P < 0.001). This scoring system has a sensitivity of 96.8% and a specificity of 59.6%. CONCLUSIONS: As patients with severe acute cholangitis show a higher mortality, we recommend that emergency ERCP be performed in patients with one or more of the four prognostic factors.

Acute Disease↗

Twenty-minute 50 mg 13C-urea breath test without test meal for the diagnosis of Helicobacter pylori infection in Chinese.

BACKGROUND: We have previously shown that the 75 mg 13C-urea breath test without citrate test meal is highly accurate for the diagnosis of Helicobacter pylori infection in Chinese subjects. A lower dose 50 mg 13C-urea breath test protocol with a sampling time at 20 min has not been validated previously. AIM: To investigate the accuracy of a 20-min 50 mg 13C-urea breath test protocol in Chinese subjects. METHODS: Consecutive dyspeptic patients referred for upper endoscopy were recruited. 13C-urea breath test was performed using (a) 75 mg and 50 mg of 13C-urea on two separate days without a test meal, and (b) 50 mg of 13C-urea with 2.4 g citrate as test meal, and compared with the gold standard [rapid urease test (CLO test) and histology]. Baseline, 20-min and 30-min breath samples were collected in all cases. RESULTS: Two hundred and six patients were tested. The accuracy of the 50 mg 13C-urea breath test (no citrate) at 20 min and 30 min was 98%, comparable to that of the 50 mg 13C-urea breath test with citrate (99.1%) and the 75 mg 13C-urea breath test without citrate (100%). CONCLUSIONS: A 20-min 50 mg 13C-urea breath test without citrate produced highly accurate results for the diagnosis of Helicobacter pylori infection and is more economical and convenient for the Chinese population.

Adult↗

Clinical and endoscopic characteristics of non-Helicobacter pylori, non-NSAID duodenal ulcers: a long-term prospective study.

BACKGROUND: The proportion of duodenal ulcers not associated with Helicobacter pylori infection or the use of non-steroidal anti-inflammatory drugs (NSAIDs) is increasing. AIM: To identify the clinical and endoscopic characteristics of non-H. pylori, non-NSAID duodenal ulcers. METHODS: Clinical and endoscopic data and H. pylori status were prospectively collected from consecutive patients who underwent upper endoscopy from 1997 to 1999. Patients with duodenal ulcers were identified, and those with non-H. pylori, non-NSAID duodenal ulcers were analysed further. RESULTS: A total of 11 717 upper endoscopies were performed in 8344 patients. Of these, 1153 (14%) had duodenal ulcers. Of 599 patients with active ulcers and known H. pylori status, 104 (17%) had ulcers not associated with H. pylori or the use of NSAIDs, 393 (66%) had ulcers associated with H. pylori alone, 51 (8.5%) had ulcers associated with the use of NSAIDs alone and 51 (8.5%) had ulcers associated with both. Multivariate logistic regression analysis revealed that the presence of concomitant diseases (odds ratio=15.0; 95% confidence interval, 8.64-25.9; P < 0.001) and the absence of epigastric pain/discomfort (odds ratio=0.52; 95% confidence interval, 0.29-0.91; P=0.022) were independent predictors for non-H. pylori, non-NSAID duodenal ulcers. CONCLUSIONS: Non-H. pylori, non-NSAID duodenal ulcers exhibit certain distinct clinical and endoscopic characteristics. The presence of concomitant diseases is an important predictive factor.

Adult↗

Rabeprazole-based 3-day and 7-day triple therapy vs. omeprazole-based 7-day triple therapy for the treatment of Helicobacter pylori infection.

BACKGROUND: Rabeprazole is a new proton pump inhibitor with more potent acid suppressive and anti-Helicobacter effects. AIM: To compare two different regimens of rabeprazole-based triple therapy vs. 7-day omeprazole-based triple therapy for the eradication of Helicobacter pylori infection. METHOD: Patients with proven H. pylori infection were randomized to receive: (i) 7-day rabeprazole, 10 mg, amoxicillin, 1000 mg, and clarithromycin, 500 mg, all twice daily; (ii) 3-day rabeprazole, 20 mg, amoxicillin, 1000 mg, and clarithromycin, 500 mg, all twice daily; or (iii) 7-day omeprazole, 20 mg, amoxicillin, 1000 mg, and clarithromycin, 500 mg, all twice daily. Endoscopy (CLO test, histology) was performed before randomization and 6 weeks after drug treatment. RESULTS: One hundred and seventy-three patients were randomized. H. pylori eradication rates (intention-to-treat, n=173/per protocol, n=167) were 88%/91% for 7-day rabeprazole-based therapy, 72%/72% for 3-day rabeprazole-based therapy and 82%/89% for 7-day omeprazole-based therapy, respectively. The per protocol eradication rate was significantly better in the 7-day rabeprazole-based therapy and 7-day omeprazole-based therapy groups when compared to the 3-day rabeprazole-based therapy group (P=0.01 and P=0.04, respectively). Compliance was excellent and all three regimens were well tolerated. CONCLUSIONS: The efficacy of seven-day rabeprazole-based triple therapy is similar to 7-day omeprazole-based triple therapy for the eradication of H. pylori infection.

2-Pyridinylmethylsulfinylbenzimidazoles↗

An evaluation of the PyloriTek test for the diagnosis of Helicobacter pylori infection in Chinese patients before and after eradication therapy.

BACKGROUND AND AIM: The PyloriTek Test Kit (a 1-h rapid urease test) was developed for the rapid diagnosis of Helicobacter pylori (H. pylori) during endoscopy. Most studies were performed in Western populations. The aim of this study was to evaluate the PyloriTek test for the diagnosis of H. pylori infection in Chinese population. METHODS: Eligible patients without prior treatment or who had had recent eradication of H. pylori were recruited. During endoscopy, biopsies were taken from the antrum and corpus for an in-house rapid urease test (RUT), histology and for the PyloriTek test (one antral and one corpus biopsy). Results of the PyloriTek test were compared with the gold standard (RUT and histology). RESULTS: Analysis of PyloriTek test results from the antrum alone (101 patients before eradication and 52 patients after eradication) showed a sensitivity, specificity, and accuracy of 96.3, 97.9, and 97.0%, respectively, for cases before eradication, and an accuracy of 100% for cases after eradication. The benefit of an additional body biopsy was marginal and only occurred in the pre-eradication group. CONCLUSION: The PyloriTek test was highly accurate for the diagnosis of H. pylori infection before and after eradication therapy, with a final result available at 1 h, which is unmatched by any invasive test so far. It enhances clinical decision-making by allowing the clinicians or endoscopists to start therapy on the same day of an endoscopy visit. One biopsy from the antrum is highly reliable for this purpose.

Anti-Bacterial Agents↗

Interleukin-1beta induces cyclo-oxygenase-2 expression in gastric cancer cells by the p38 and p44/42 mitogen-activated protein kinase signaling pathways.

BACKGROUND AND AIMS: Cyclo-oxygenase-2 (COX-2) is the inducible enzyme in the gastric mucosa responsible for prostaglandin production during inflammation and ulcer healing. The regulation of COX-2 gene expression in gastric epithelial cells is not well understood. In this study, we investigated the effect of interleukin (IL)-1beta on COX-2 expression in the human gastric cancer cell, and explored the signaling pathways involved. METHODS: Gastric cancer cell line AGS was treated with IL-1beta or the inhibitors of mitogen-activated protein-Erk kinase (MEK) and p38 mitogen-activated protein (MAP) kinase prior to the addition of IL-1beta. The COX-2 mRNA or protein levels were measured by using RT-PCR or western blot analysis, respectively. Prostaglandin E2 (PGE2) production/secretion was determined by using the prostaglandin E2 EIA assay. The phosphorylation/activation of p44/42 and p38 MAP kinases were determined by using western blot analysis and using phospho-specific antibodies. RESULTS: Interleukin-1beta treatment dose- and time-dependently increased COX-2 mRNA and protein expression levels, and enhanced PGE2 production/secretion in AGS cells. In contrast, IL-1beta had no effect on the level of the constitutively expressed COX-1. In parallel to the increase of COX-2, we showed that p44/42 and p38 MAP kinase activities were also upregulated by IL-1beta treatment. To demonstrate the cause-effect relationship, we showed that inhibition of MEK and p38 MAP kinase with specific inhibitors suppressed IL-1beta-mediated increases in COX-2 mRNA and protein levels, and the PGE2 production. CONCLUSIONS: Our results demonstrated that in human gastric cancer cells, IL-1beta upregulates the COX-2 gene expression through the activation of MEK/p44/42 and p38 MAP kinases pathway.

Adenocarcinoma↗

Distribution of distinct vacA, cagA and iceA alleles in Helicobacter pylori in Hong Kong.

BACKGROUND: There is a substantial genetic heterogeneity among Helicobacter pylori strains, and certain genotypes have been suggested to be associated with the virulence of this pathogen. The aim of this study was to investigate the distribution of H. pylori vacA, cagA and iceA genotypes and their association with duodenal ulcer disease in Hong Kong. MATERIALS AND METHODS: Gastric biopsies of 72 H. pylori infected patients were analyzed by specific polymerase chain reactions. RESULTS: Of the 72 cases, 69 (95.8%) had vacA signal sequence s1c strains, and three (4.2%) had s1a strains. vacA middle region sequences, m1b and m2, were detected in 23 (31.9%) and 46 (63.9%), respectively. Six (8.3%) cases contained multiple vacA subtypes. vacA s2 allele was only observed in three (4.3%) cases, which were also infected with s1c subtype. cagA was present in 64 (88.9%) of 72 patients, and iceA1 subtype was detected in 46 (63.9%) cases. Neither cagA nor vacA and iceA were associated with duodenal ulcer disease. CONCLUSION: The distribution of vacA, cagA and iceA alleles in H. pylori strains in Hong Kong is similar to that in east Asia. There is a difference in the distribution of genotypes between strains in Hong Kong and those in mainland China, although strains in the two regions exhibit a very close relation. The association of these virulence genes and duodenal ulcer disease needs reappraisal, particularly under geographic considerations.

Adolescent↗

Macrophage migration inhibitory factor is an important mediator in the pathogenesis of gastric inflammation in rats.

BACKGROUND & AIMS: Macrophage migration inhibitory factor (MIF) has been shown to play a pivotal role in inflammatory and immune-mediated diseases. This study investigates the role of MIF in gastric inflammation. METHODS: Expression of MIF was examined in a rat gastric ulcer model induced by acetic acid, and the functional role of MIF in acute gastric ulcer was investigated by administration of a neutralizing anti-MIF antibody. RESULTS: MIF messenger RNA and protein were markedly up-regulated in acute gastric ulcer, which correlated with the accumulation of macrophages (P < 0.001) and neutrophils (P < 0.05) at the site of inflammation. Macrophages, like neutrophils, were the major inflammatory cells infiltrating the ulcer base and they strongly expressed inducible nitric oxide synthase. However, macrophages, not neutrophils, were a rich source of MIF production in acute gastric ulcer. In vivo and in vitro blockade of MIF with the neutralizing anti-MIF antibody significantly inhibited the marked up-regulation of MIF, tumor necrosis factor alpha, inducible nitric oxide synthase, and intercellular adhesion molecule-1. This was associated with the marked inhibition of macrophage (70% reduced) and neutrophil (60% reduced) accumulation and activation, thus reducing ulcer sizes and attenuating ulceration. CONCLUSIONS: This study has shown that MIF was markedly up-regulated during acute gastric ulcer. Inhibition of acute gastric ulcer by blockade of MIF indicates that MIF is a key inflammatory mediator and plays a pathogenic role in gastric inflammation.

Acetic Acid↗

The presence of Nipah virus in respiratory secretions and urine of patients during an outbreak of Nipah virus encephalitis in Malaysia.

OBJECTIVES: To study the excretion of Nipah virus in the upper respiratory secretions and urine of infected patients in relation to other clinical features. METHODS: Isolation of Nipah virus from the respiratory secretions and urine was made in Vero cells and identified by indirect immunofluorescence assay using anti-Hendra specific hyperimmune mouse ascitic fluid and FITC-conjugated goat anti-mouse IgG. RESULTS: During the peak outbreak of Nipah virus encephalitis in Malaysia, Nipah virus was isolated from the upper respiratory secretions and urine in eight of 20 patients who were virologically and/or serologically confirmed to be infected with the virus. From these eight patients, Nipah virus was isolated from six throat swab specimens, three urine specimens and only one nasal swab specimen. The positive virus isolation rate was related to the collection of these specimens during the early phase of the illness (P = 0.068). The presence of serum anti-Nipah specific IgM appeared to reduce the chance of isolating the virus (P = 0.049). There was no significant difference in the isolation rate with respect to the age, gender, ethnic group and clinical features associated with grave prognosis and mortality outcome of the patients. CONCLUSION: This study shows that it is possible to be infected from secretions of infected patients, but epidemiological survey on close contacts so far did not suggest that human-to-human transmission is common.

Adolescent↗

12-Lipoxygenase inhibition induced apoptosis in human gastric cancer cells.

Arachidonic acid release from membrane phospholipids is essential for tumour cell proliferation. Lipoxygenases constitute a pathway for arachidonate metabolism. The present study investigated the expression of 12-lipoxygenase and its effect on cell proliferation as well as survival in two human gastric cancer cell lines (AGS and MKN-28). RT-PCR and western blots, respectively, showed 12-LOX mRNA and protein expression in both AGS and MKN-28 cell lines. Treatment with a 12-LOX inhibitor, baicalein, significantly inhibited cancer cell proliferation, but a metabolite of 12-LOX activity, 12 hydroxyeicosatetraenoic acid (12-HETE) reversed baicalein-induced growth inhibition. Furthermore, the blockade of the 12-LOX pathway through a 12-LOX inhibitor and antisense induced apoptosis of gastric cancer cell lines. The biochemical characteristics of apoptosis were p53-independent combined with a decrease in bcl-2 expression. Caspase-7 was proteolytically activated and responsible for the apoptosis execution.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗