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Biomedical subjects

S K Lam

Publications and source records attributed to S K Lam.

At least 109 records · Page 6Linked to original sources
PubMed2000

Overexpression of protein kinase C-beta1 isoenzyme suppresses indomethacin-induced apoptosis in gastric epithelial cells.

BACKGROUND & AIMS: We have previously reported that nonsteroidal anti-inflammatory drugs (NSAIDs) could induce apoptosis of gastric epithelial cells both in vivo and in vitro. This study investigated the role of protein kinase C (PKC) isoforms in the regulation of NSAID-induced apoptosis. METHODS: Protein levels of 12 PKC isoforms in AGS cells, in the presence or absence of indomethacin, were determined by Western blot. The effect of PKC-beta1 overexpression by transfection with its complementary DNA (cDNA) on indomethacin-induced apoptosis and apoptosis-related genes, including p53, p21(waf1/cip1), and c-myc, was further investigated. RESULTS: Treatment with indomethacin decreased the abundance of PKC-beta1 and increased that of PKC-beta2, eta, and epsilon, but did not alter the expression of PKC alpha, gamma, zeta, delta, iota, and micro. Overexpression of PKC-beta1 attenuated the apoptotic response of AGS cells to indomethacin, associated with overexpression of p21(waf1/cip1) in both messenger RNA and protein levels. Inhibition of PKC-beta1-mediated overexpression of p21(waf1/cip1) by its antisense cDNA partially reduced the antiapoptotic effect of PKC-beta1. CONCLUSIONS: Indomethacin-induced apoptosis in gastric cancer cells is partly mediated by differential regulation of PKC isoform expression. Enhanced expression of exogenous PKC-beta1 protects against indomethacin-induced apoptosis through up-regulation of p21(waf1/cip1).

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

The predictive value of uvulo-palatoglossal junctional ulcers as an early clinical sign of exanthem subitum due to human herpesvirus 6.

BACKGROUND: The clinical sign of uvulo-palatoglossal junctional (UPJ) ulcers was first noted in 1983 in a 5.5-month-old baby with exanthem subitum (ES). An earlier prospective clinical study showed that there was a strong association of UPJ ulcers and occurrence of ES with a positive predictive value of 95.3% and negative predictive value of 100%. OBJECTIVE: To determine the value of uvulo-palatoglossal junctional (UPJ) ulcers as an early clinical sign of exanthem subitum (ES) due to human herpesvirus 6 (HHV 6) infection. STUDY DESIGN: A case-control study of 20 febrile children with UPJ ulcers versus 26 febrile children without UPJ ulcers. These children were followed up for any development of ES and investigated for human herpesvirus 6 (HHV 6) as the causative agents of the febrile episodes. RESULTS: In this study, 20 out of 46 febrile children aged 3 months to 3 years with UPJ ulcers were virologically and/or serologically confirmed to be due to primary HHV 6 infection. The rest of the 26 children without ulcers did not have HHV 6 infection. Of the 20 children with UPJ ulcers, only 17 of the 19 children with adequate follow-up till subsidence of fever developed ES. None of the 26 children without UPJ ulcers developed ES. CONCLUSION: Statistically, there was a significant association of UPJ ulcers as an early sign of ES with a positive predictive value of 89.5% and negative predictive value of 100%. This finding also suggests that the presence of UPJ ulcers is a useful pathognomic clinical sign of symptomatic primary HHV 6 infection.

Antibodies, Viral↗
PubMed2000

Comparison of lansoprazole-based triple and dual therapy for treatment of Helicobacter pylori-related duodenal ulcer: an Asian multicentre double-blind randomized placebo controlled study.

BACKGROUND: [corrected] In Asian countries with limited resources, clarithromycin-based triple therapy may not be readily available. There are also few direct comparisons of different regimens in Asia. AIM: To compare two lansoprazole-based non-clarithromycin triple therapies and one dual therapy in a prospective double-blind placebo-controlled study of Helicobacter pylori eradication and duodenal ulcer healing. METHODS: Fourteen centres in Asia participated in this study. Patients with acute duodenal ulcer who were H. pylori-positive were recruited. They were randomized to receive: (a) lansoprazole 30 mg b.d., amoxycillin 1 g b.d. and metronidazole 500 mg b.d. for 2 weeks (LAM-2 W), or (b) LAM for 1 week and placebo (LAM-1 W), or (c) lansoprazole 30 mg b.d., amoxycillin 1 g b.d. and placebo for 2 weeks (LA-2 W). Upper endoscopy was repeated at week 6 to check for duodenal ulcer healing. Symptoms and side-effects were recorded. RESULTS: A total of 228 patients were recruited, and two patients took less than 50% of the drugs. H. pylori eradication rates (intention-to-treat) were 68 out of 82 (83%) with LAM-2 W, 55 out of 71 (78%) with LAM-1 W and 43 out of 75 (57%) with LA-2 W. There were significant differences (P=0. 001) in eradication rates when comparing either LAM-2 W or LAM-1 W with LA-2 W. The eradication rate in patients with metronidazole resistant H. pylori strains were significantly lower than those with metronidazole sensitive strains (P=0.0001). The duodenal ulcer healing rates at week 6 were 85%, 85% and 72% in LAM-2 W, LAM-1 W and LA-2 W, respectively (P=0.065). Side-effects occurred in 13%, 11% and 9% in LAM-2 W, LAM-1 W and LA-2 W, respectively. H. pylori eradication and initial ulcer size were factors affecting duodenal ulcer healing. CONCLUSIONS: This Asian multicentre study showed that 1-week lansoprazole-based triple therapy without clarithromycin has similar efficacy in H. pylori eradication and ulcer healing compared with a 2-week regimen. Both triple therapies were significantly better than dual therapy in H. pylori eradication. Therefore, 1-week lansoprazole-based triple therapy is as safe and effective as 2-week therapy in eradication of H. pylori infection and healing of duodenal ulcer in these Asian centres.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

High prevalence of Helicobacter pylori infection with dual resistance to metronidazole and clarithromycin in Hong Kong.

BACKGROUND: Metronidazole resistance is a common problem in most Asian countries, and clarithromycin has been widely used in Hong Kong. AIM: To determine the prevalence of Helicobacter pylori strains resistant to metronidazole and clarithromycin in Hong Kong and to assess the effect on eradication rates. Also to determine the genetic mutation in relation to phenotypic divergence in clarithromycin-resistant strains. METHODS: H. pylori were cultured from gastric biopsies obtained from 87 patients during upper endoscopy. Minimal inhibitory concentrations of metronidazole and clarithromycin were determined by Etest and agar dilution methods. Mutations in clarithromycin-resistant strains were identified by polymerase chain reaction and restriction analysis. Random amplified polymorphic DNA fingerprinting was performed on clarithromycin-resistant and susceptible isolates. RESULTS: The prevalences of H. pylori strains resistant to metronidazole and clarithromycin were 49.4% and 10.8%, respectively, in Hong Kong. Dual resistance to metronidazole and clarithromycin were found in 7. 2% of patients. The agreement between E-test and agar dilution methods was determined by error-rate bound analysis as 95.4% for metronidazole and 100% for clarithromycin. Dual resistant strains reduced the eradication rate to 66.7%. Among clarithromycin-resistant strains tested, all were due to A2144G point mutation in 23S rRNA gene. Random amplified polymorphic DNA fingerprinting suggested various phenotypically mixed populations. CONCLUSIONS: The prevalence of metronidazole-resistant H. pylori strains remained static whilst the prevalence of clarithromycin-resistant strains was not rare in Hong Kong. An alarming 7.2% of patients were resistant to both the antimicrobials, which had a definite impact on treatment success. All cases of resistance to clarithromycin were due to A2144G mutation in 23S rRNA of H. pylori.

Adolescent↗
PubMed2000

Ulcer-healing drugs are required after eradication of Helicobacter pylori in patients with gastric ulcer but not duodenal ulcer haemorrhage.

AIM: To study the efficacy of a 2-week anti-Helicobacter therapy in the healing of H. pylori-associated bleeding peptic ulcers. METHODS: Omeprazole 20 mg, clarithromycin 500 mg and amoxycillin 1 g, twice daily, were given for 2 weeks to 180 patients with H. pylori-associated bleeding peptic ulcers. Endoscopy was repeated 4 weeks after the eradication therapy to assess healing of the peptic ulcers. RESULTS: Repeat endoscopies were performed in 168 patients (42 gastric ulcer and 126 duodenal ulcer) who followed the protocol. Thirty-eight patients with bleeding gastric ulcers and 124 patients with bleeding duodenal ulcers healed 4 weeks after treatment (per protocol analysis; gastric ulcer: 91% vs. duodenal ulcer: 98%; P=0. 035). No patients who were compliant to the study medications suffered from re-bleeding. Stepwise discriminant analysis demonstrated that small ulcers (< 15 mm) and the presence of duodenal ulcers best predicted healing of the peptic ulcers. CONCLUSIONS: Ulcer-healing drugs should be continued after a 2-week course of omeprazole-containing anti-Helicobacter therapy for gastric ulcers and large peptic ulcers that have bled, but can be omitted in most patients with a bleeding duodenal ulcer.

Adult↗
PubMed2000

(13)C-urea breath test without a test meal is highly accurate for the detection of Helicobacter pylori infection in Chinese.

BACKGROUND: Conventional (13)C-urea breath testing ((13)C-UBT) includes a test meal to delay gastric emptying, which, theoretically, improves the accuracy of the test. Citric acid has been proposed as the best test meal. However, recent studies have suggested that a test meal may not be necessary. AIM: To investigate a new (13)C-UBT protocol without a test meal in a Chinese population. METHODS: Consecutive dyspeptic patients referred for upper endoscopy were recruited. (13)C-UBT was performed on two separate days with or without a test meal (2.4 Gm citric acid) and compared with the 'gold standard' (CLO test and histology). RESULTS: Two hundred and two patients were tested. Using receiver operating characteristics (ROC) analysis, the optimal delta-value and optimal measurement interval for UBT were 5% and 30 min, respectively, both with or without a test meal. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of (13)C-UBT with citric acid (96.5%, 97.7%, 98.2%, 95.6%, 97.0%) were similar to (13)C-UBT without a test meal (94.7%, 97.7%, 98.2%, 93.5%, 96.0%). CONCLUSION: This simplified (13)C-UBT protocol without a test meal produced highly accurate and reliable results in the Chinese population.

Adolescent↗
PubMed2000

Triple therapy with clarithromycin, omeprazole, and amoxicillin for eradication of Helicobacter pylori in duodenal ulcer patients in Asia and Africa.

BACKGROUND: Studies assessing the efficacy of triple therapy containing clarithromycin and amoxicillin for the eradication of Helicobacter pylori infection and healing of duodenal ulcers in Asian and African countries are limited. AIM: To determine the efficacy and safety of 1-week triple therapy with omeprazole, amoxicillin and clarithromycin for eradicating H. pylori infection in patients with active duodenal ulcer living in Asian and African regions. METHODS: This was an open-label, multicentre study in 11 centres in Asia and Africa. Patients with endoscopy-proven duodenal ulcer and who were H. pylori-positive were treated with clarithromycin 500 mg, omeprazole 20 mg, and amoxicillin 1000 mg, all given twice daily for 7 days. Upper endoscopy was repeated at week 6 to check for ulcer healing and H. pylori status. RESULTS: A total of 117 patients were recruited. H. pylori eradication rates were 85% by per protocol analysis and 80% by intention-to-treat analysis. Ulcer healing was found in 94% of subjects (per protocol analysis). Clinical success, measured by change of pre-treatment ulcer symptoms, was strongly supported by complete resolution or improvement in 100% of the evaluable patients (per protocol analysis). Since treatment-related adverse events, when present, were largely mild or moderate, the triple therapy regimen was considered safe. CONCLUSION: Seven-day triple therapy with omeprazole, amoxicillin, and clarithromycin was efficacious for treating Asian and African patients with duodenal ulcer disease associated with H. pylori infection, and the treatment regimen was well-tolerated.

Amoxicillin↗
PubMed2000

Gastro-oesophageal reflux disease in Asia.

Gastro-oesophageal reflux disease (GORD) occurs more frequently in Europe and North America than in Asia but its prevalence is now increasing in many Asian countries. Many reasons have been given for the lower prevalence of GORD in Asia. Low dietary fat and genetically determined factors, such as body mass index and maximal acid output, may be important. Other dietary factors appear to be less relevant. Increased intake of carbonated drinks or aggravating medicines may influence the increasing rates of GORD in some Asian countries but no strong evidence links other factors, such as the age of the population, smoking or alcohol consumption, to GORD. The management of GORD in Asia is similar to that in Europe and North America but the lower incidence of severe oesophagitis in Asia may alter the approach slightly. Also, because Asians tend to develop stomach cancer at an earlier age, endoscopy is used routinely at an earlier stage of investigation. Gastro-oesophageal reflux disease is essentially a motility disorder, so short-term management of the disease can usually be achieved using prokinetic agents (or histamine (H2)-receptor antagonists). More severe and recurrent GORD may require proton pump inhibitors (PPI) or a combination of prokinetic agents and PPI. The choice of long-term treatment may be influenced by the relative costs of prokinetic agents and PPI.

Asia↗
PubMed2000

Pooled analysis of Helicobacter pylori eradication regimes in Asia.

BACKGROUND AND AIMS: Differences in Helicobacter pylori strains and their resistance to antimicrobials between Asian and Western countries may affect the success in eradicating this bacterium. Our objective was to systematically review the regimens that have been tested in Asia. METHODS: Data on anti-H. pylori therapies reported from Asia in a large number of publications identified up to December 1998 were pooled into a few groups based on the combination of drugs used. A comparison of different groups was made by calculating the pooled eradication rates. RESULTS: Seventy-three studies with 134 treatment arms were reviewed. Pooled eradication rates of dual, triple and quadruple therapies were 61.0, 86.5 and 93.4%, respectively. Proton pump inhibitor (PPI)-based combinations were more widely used and effective, with overall eradication rates of 90.7% in triple therapy and 93.4% in quadruple therapy. Bismuth combined with tetracycline and metronidazole also showed a high eradication rate of 92.0%. CONCLUSIONS: Proton pump inhibitor-based triple therapy with either clarithromycin, amoxycillin or metronidazole was one of the most commonly used and effective anti-H. pylori triple therapy regimens in Asia. The classical triple therapy with a bismuth, tetracycline and metronidazole combination has a similar efficacy. The results of anti-H. pylori treatment in Asia are not different from those in Western countries.

Asia↗
PubMed2000

Differences in peptic ulcer between East and West.

In general, peptic ulcer occurs at equal rates in the East and the West but with marked regional differences in both, even within the same country. In the West, the incidence of peptic ulcer, particularly duodenal ulcer, rose sharply at the turn of the century and has shown a rapid decline in the past three decades. In the East, the rise was equally impressive, but the decline appears to have been delayed, only starting in the past decade. Asians present their ulcer symptoms a decade earlier than Caucasians, and it has been suggested that this early presentation may be attributable to Helicobacter pylori (H. pylori) infection at a younger age. Interestingly, the male-to-female ratio is much higher in the East than in the West, and the duodenal-to-gastric ulcer ratio manifests a much wider variation in Asians than in Caucasians. As in Western countries, peptic ulcer occurrence in the East shows a cyclical trend, with a peak frequency in the winter months. In the West, the placebo healing rate varies widely up to 78%, whereas in the East it is rather consistent at around one-third. These variations in geographical distribution, time trends, sex and ulcer ratios, seasonal rates and behavioral response to placebo treatment indicate that while H. pylori is a major cause of peptic ulceration, other environmental and genetic factors contribute to ulcer formation. The parietal cell mass and acid secretory capacity of Asian patients with duodenal ulcer are only slightly more than half of those of Caucasian patients, which may explain why Asian patients respond equally well to half the standard dose of anti-secretory agents used in Caucasians. H. pylori infection is generally more prevalent in the East than in the West and is more resistant to metronidazole. The response to standard triple therapies for eradication, however, appears to be as effective in the East as in the West.

Asia↗
PubMed2000

Helicobacter pylori sero-prevalence in asthma.

Asthma is a very common respiratory disease which is characterized by the presence of cytokine-mediated airway inflammation leading to smooth muscle contraction, oedema and progressive airway damage in some cases. In light of our recent finding of an increased sero-prevalence of Helicobacter pylori in bronchiectasis, we have determined serum levels of H. pylori-specific IgG in asthmatic and control subjects. Altogether 90 consecutive asthmatic [mean age +/- SD 42.6+/-16 years and 52 female (F)] and 97 healthy control subjects (mean age +/- SD 43.2+/-13.3 years and 51 female (F); P = 0.78 and 0.39 respectively) were recruited prospectively. H. pylori sero-prevalence was not significantly different between asthmatic and control subjects (P>0.05). Serum H. pylori IgG levels did not correlate with FEV1 % predicted, FVC % predicted or duration of asthma (P>0.05). Similar to the results of previously published sero-epidemiological studies, there was a weak correlation between serum H. pylori IgG with increasing age (r = 0.43, P = 0.004). Despite the sero-epidemiological association of H. pylori infection with many inflammatory conditions, our data showed no such association for middle age asthmatic patients with mild intermittent asthma in our locality.

Adult↗
PubMed2000

Age, sex, haemoglobin level, and white cell count at diagnosis are important prognostic factors in children with acute lymphoblastic leukemia treated with BFM-type protocol.

The presenting features and treatment outcome for 575 Malaysian children (< or = 12 years of age) with newly diagnosed acute lymphoblastic leukemia (ALL), admitted to the University Hospital, Kuala Lumpur, Malaysia between 1 January 1980 and 30 May 1995 were evaluated to determine their prognostic significance. Two-year overall survival was achieved in 67 per cent of all patients and 55 per cent of patients were relapse-free at 2 years. All except 10 patients, with identified French-American-British L3 morphology were treated with the modified Berlin-Frankfurt-Munster 78 treatment protocol. Univariate analyses of failure rate conferred age, sex, white cell count and hemoglobin level as potentially significant prognostic factors. All four presenting features retained their prognostic strength in a multivariate analysis. Race, platelet count, morphological subtype, liver/spleen size, lymphadenopathy, central nervous system and mediastinal mass involvement did not show any significant effect on treatment outcome. The 2-year survival rate was significantly different with regard to age, white cell count and hemoglobin level. However, sex was not significantly related to overall survival. These prognostic factors may have implications on future stratification of risk-adjusted initial treatment in the management of childhood ALL. Our analysis of Malaysian children is similar to what could be predicted based on previous studies in other populations.

Age Factors↗
PubMed2000

Treatment of Helicobacter pylori in patients with duodenal ulcer hemorrhage--a long-term randomized, controlled study.

OBJECTIVE: Eradication of Helicobacter pylori (H. pylori) in patients with uncomplicated duodenal ulcers prevents long-term recurrence of ulcers. We aimed to study whether treatment of H. pylori prevents the long-term recurrence of duodenal ulcer hemorrhage. METHODS: Patients with duodenal ulcer bleeding and confirmed H. pylori infection were recruited. A total of 120 patients were randomly assigned to triple therapy (DeNoltab 120 mg, amoxycillin 500 mg, and metronidazole 300 mg four times daily) or DeNoltab 120 mg four times daily alone. No maintenance therapy was given during the follow-up period. The endpoints were the cumulative rates of symptomatic and bleeding duodenal ulcer recurrences. RESULTS: Of the patients receiving the triple regimen, 85.1% had H. pylori eradicated as compared to 2.0% of patients receiving DeNoltab (p < 0.05). More patients in the DeNoltab group than those in the Triple group had recurrence of ulcer bleeding, but this did not reach statistical significance (12/60 vs 6/60, p = 0.20). Logistic regression analysis on clinical, personal, and endoscopic characteristics identified persistent H. pylori infection as the only independent predictor of recurrence of duodenal ulcer bleeding. CONCLUSIONS: Treatment of H. pylori alone with the present bismuth-based triple therapy in patients with duodenal ulcer hemorrhage did not result in significant reduction in further bleeding episodes, although a trend was seen for the group that was given triple therapy. On the other hand, posttreatment H. pylori status was found to be an independent predictor of bleeding recurrence.

Adolescent↗
PubMed2000

Differences in genotypes of Helicobacter pylori from different human populations.

DNA motifs at several informative loci in more than 500 strains of Helicobacter pylori from five continents were studied by PCR and sequencing to gain insights into the evolution of this gastric pathogen. Five types of deletion, insertion, and substitution motifs were found at the right end of the H. pylori cag pathogenicity island. Of the three most common motifs, type I predominated in Spaniards, native Peruvians, and Guatemalan Ladinos (mixed Amerindian-European ancestry) and also in native Africans and U.S. residents; type II predominated among Japanese and Chinese; and type III predominated in Indians from Calcutta. Sequences in the cagA gene and in vacAm1 type alleles of the vacuolating cytotoxin gene (vacA) of strains from native Peruvians were also more like those from Spaniards than those from Asians. These indications of relatedness of Latin American and Spanish strains, despite the closer genetic relatedness of Amerindian and Asian people themselves, lead us to suggest that H. pylori may have been brought to the New World by European conquerors and colonists about 500 years ago. This thinking, in turn, suggests that H. pylori infection might have become widespread in people quite recently in human evolution.

Amino Acid Isomerases↗
PubMed2000

Sequential inactivation of rdxA (HP0954) and frxA (HP0642) nitroreductase genes causes moderate and high-level metronidazole resistance in Helicobacter pylori.

Helicobacter pylori is a human-pathogenic bacterial species that is subdivided geographically, with different genotypes predominating in different parts of the world. Here we test and extend an earlier conclusion that metronidazole (Mtz) resistance is due to mutation in rdxA (HP0954), which encodes a nitroreductase that converts Mtz from prodrug to bactericidal agent. We found that (i) rdxA genes PCR amplified from 50 representative Mtz(r) strains from previously unstudied populations in Asia, South Africa, Europe, and the Americas could, in each case, transform Mtz(s) H. pylori to Mtz(r); (ii) Mtz(r) mutant derivatives of a cultured Mtz(s) strain resulted from mutation in rdxA; and (iii) transformation of Mtz(s) strains with rdxA-null alleles usually resulted in moderate level Mtz resistance (16 microg/ml). However, resistance to higher Mtz levels was common among clinical isolates, a result that implicates at least one additional gene. Expression in Escherichia coli of frxA (HP0642; flavin oxidoreductase), an rdxA paralog, made this normally resistant species Mtz(s), and frxA inactivation enhanced Mtz resistance in rdxA-deficient cells but had little effect on the Mtz susceptibility of rdxA(+) cells. Strains carrying frxA-null and rdxA-null alleles could mutate to even higher resistance, a result implicating one or more additional genes in residual Mtz susceptibility and hyperresistance. We conclude that most Mtz resistance in H. pylori depends on rdxA inactivation, that mutations in frxA can enhance resistance, and that genes that confer Mtz resistance without rdxA inactivation are rare or nonexistent in H. pylori populations.

Amino Acid Substitution↗
PubMed2000

The role of polyamines in gastric mucus synthesis inhibited by cigarette smoke or its extract.

BACKGROUND: Cigarette smoking was shown to delay gastric ulcer healing and reduce synthesis of mucus, which is important for gastric ulcer protection and healing. Polyamines are important in these processes. AIMS: To study the effects of cigarette smoking on the synthesis of mucus and to investigate if such an effect is acting by interference with the polyamine pathway. METHODS: Gastric mucosal ornithine decarboxylase activity, mucous secreting layer thickness, and ulcer size were determined after different concentrations of cigarette smoke exposure (0, 2, or 4%) in intact animals and animals with ulcers. Synthesis of mucus and ornithine decarboxylase activity and mRNA expression were also assessed in cigarette smoke extract treated MKN-28 cells. RESULTS: Exposure to cigarette smoke significantly reduced the thickness of the mucous secreting layer and gastric mucosal ornithine decarboxylase activity in animals with or without ulcers. Spermidine not only reversed inhibition of mucus synthesis in both intact and ulcer bearing animals but also reversed the delay in ulcer healing. Cigarette smoke extract significantly reduced mucus synthesis and ornithine decarboxylase activity but not its mRNA expression in MKN-28 cells. The reduction in mucus synthesis was restored by spermidine. CONCLUSIONS: Cigarette smoke and its extract repress mucus synthesis in vivo and in vitro, respectively. Reduction of ornithine decarboxylase activity in gastric mucosa is closely associated with this effect.

Animals↗