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Biomedical subjects

K L Goh

Publications and source records attributed to K L Goh.

At least 19 recordsLinked to original sources

Gastro-oesophageal reflux disease in 'difficult-to-control' asthma: prevalence and response to treatment with acid suppressive therapy.

BACKGROUND: The causal association between gastro-oesophageal reflux disease (GERD) and difficult-to-control asthma is unclear. AIM: To determine the prevalence of GERD and response to proton pump inhibitor therapy in patients with difficult-to-control asthma. METHODS: Consecutive patients with difficult-to-control asthma as defined by persistent and recurrent symptoms despite on optimal asthmatic medications were recruited for the study. GERD was diagnosed by symptoms, gastroscopy and 24-h oesophageal pH monitoring. All patients were prescribed a course of lansoprazole 30 mg daily for 8 weeks. Improvement to treatment was assessed by a change in pulmonary symptom score and also by patient's subjective assessment of improvement. RESULTS: Seventeen of 30 (56.7%) patients with difficult-to-control asthma were diagnosed with GERD. Pulmonary symptom score improved significantly only in patients with GERD (35.0 to 21.0; P = 0.002). Twelve of 16 (75%) patients with GERD reported an improvement in asthma symptoms; 1 of 11 (9.1%) without GERD reported mild symptom improvement. There was no significant change in peak expiratory flow rate and forced expiratory volume. CONCLUSIONS: More than half of patients with difficult-to-control asthma were diagnosed with GERD. In these patients the severity of asthma improved significantly with potent acid suppression therapy. This underlines the critical role of acid reflux in this subset of patients with difficult-to-control asthma.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Crohn's disease in adults: observations in a multiracial Asian population.

AIM: To determine the demography and clinical presentation of CD and secondly to determine any differences in the prevalence between the different ethnic groups in a multiracial Asian population. METHODS: Patients with CD who were seen in 2001-2003 in the University of Malaya Medical Centre (UMMC) were enrolled in this study. Prevalence of disease was calculated for the group as a whole and by race with hospital admissions per ethnic group as the denominator. RESULTS: Thirty-four patients were diagnosed to have CD. Basic demographic data of patients; male:female 17:17; mean age 29.1 years (+/-13.5 years); ethnic group: Malays 5 (14.7%), Chinese 12 (35.3%) and Indians 17 (50%).Twenty-six (76.5%) were diagnosed under the age of 40 and 8 (23.5%) were diagnosed over the age of 40. Location of the disease was as follows:ileocolonic 13 (38.2%), terminal ileum only 9 (26.5%), colon only 8 (23.5%), and upper gastrointestinal 4 (11.8%). Sixteen (47.1%) had penetrating disease, 9 (26.5%) had stricturing disease and 9 (26.5%) had non-penetrating and non-stricturing disease. The hospital admission prevalence of CD was 26.0 overall, Indians 52.6, Chinese 6.9, and Malays 9.3 per 10(5) admissions per ethnic group. The difference between Indians and Malays: [OR 5.67 (1.97, 17.53) P<0.001] was statistically significant but not between the Indians and the Chinese [OR 1.95 (0.89, 4.35) P=0.700]. The difference between the Chinese and the Malays was also not statistically significant. [OR 2.90 (0.95, 9.42) P=0.063]. CONCLUSION: The clinical presentation of CD is similar to the Western experience. Although the overall prevalence is low,there appears to be a clear racial predominance among the Indians.

Adolescent↗

Management consensus of inflammatory bowel disease for the Asia-Pacific region.

At the present there are no large-scale epidemiologic data on inflammatory bowel disease (IBD) in the Asia-Pacific region, but several studies have shown an increased incidence and prevalence of IBD in this region. Compared to the West, there appears to exist a time lag phenomenon. With regard to the two main forms of IBD, ulcerative colitis (UC) is more prevalent than Crohn's disease (CD). In addition to geographic differences, ethnic differences have been observed in the multiracial Asian countries. Moreover, the genetic backgrounds are different in the Asian compared to Western patients. For instance, NOD2/CARD15 variants have not been found in Asian CD patients. In general, the clinical course of IBD seems to be less severe in the Asia-Pacific region than in Western countries. Diagnosis of IBD in this region poses special problems. The lack of a gold standard for the diagnosis of IBD, and the existence of a variety of infectious enterocolitis with similar manifestations to those of IBD make the differential diagnosis particularly difficult. So far, Western diagnostic criteria have been introduced for the diagnosis of IBD. A stepwise approach to exclude non-IBD enterocolitis also must be introduced, and a definite diagnosis must include typical histological features. In some patients, follow up and therapeutic trials might be necessary to obtain a definitive diagnosis. A better understanding of the pathogenesis of IBD will allow the development of better diagnostic markers. The management of IBD also poses some special problems in the Asia-Pacific Region. There is often a delay in using proper medications for IBD, and alternative local remedies are still widely used. With a combination of Western guidelines and regional experiences, similar principles can be used for induction and maintenance of remission. A stepwise selection of medications is advocated depending on the extent, activity and severity of the disease. Comprehensive and individualized approaches are suggested for different IBD patients. Deeper understanding of disease pathogenesis and the unique characteristics of IBD in the Asia-Pacific region, combined with reasonable and practical guidelines for drug management and the future use of biological agents would improve the therapeutic outlook of IBD in this region.

Anti-Inflammatory Agents↗

Chemoprevention of colorectal cancer with nonsteroidal anti-inflammatory drugs.

Colorectal carcinoma is one of the commonest solid organ tumors in the world and its prevalence appears to be increasing in Asia. Recently, there has been much interest in various chemotherapeutic agents for the management of this condition, in particular nonsteroidal anti-inflammatory drugs (NSAIDs). There is a large amount of data that suggest traditional NSAIDs, as well as the new cyclooxygenase (COX)-2 selective inhibitors such as rofecoxib and celecoxib, have a role in the setting of primary and secondary prevention, and adjuvant therapy of both sporadic colorectal carcinoma and familial adenomatous polyposis. This review examines some of this data, as well as the potential problems and limitations of using these agents, particularly in light of the recent withdrawal of rofecoxib.

Anti-Inflammatory Agents, Non-Steroidal↗

Appropriateness of colonoscopy using the ASGE guidelines: experience in a large Asian hospital.

BACKGROUND: The is currently a heavy burden on endoscopy services worldwide and although guidelines for the appropriate use of esophagogastroduodenoscopy (EGD) have been well studied, there are few such studies with respect to colonoscopy and none for the Asia-Pacific region. This study aimed, firstly, to determine the 'appropriateness of colonoscopy' for procedures performed in the endoscopy unit of a large Asian hospital using the American Society of Gastrointestinal Endoscopy (ASGE) 2000 guidelines, and secondly, to determine predictive factors including 'appropriateness of colonoscopy' for positive findings and colorectal cancer (CRC). METHODS: A prospective cross-sectional study was carried out on consecutive colonoscopies performed in the University of Malaya Medical Center. The unit has an open-access endoscopy policy for doctors who work in the hospital. Referrals were from endoscopists (gastroenterologists and surgeon-endoscopists), primary care physicians and other specialists. The indication of a procedure referral was recorded and judged 'appropriate' or 'inappropriate' using the ASGE criteria. The colonoscopic findings were recorded and classified as positive (endoscopies showing any pathology that had direct therapeutic or prognostic consequences) or negative findings (endoscopies showing no pathology or minor pathologies). Predictive factors for positive findings and CRC were determined using multivariate analysis. RESULTS: Of 380 patients referred for colonoscopy, 220 (57.9%) were classified as appropriate according to the ASGE guidelines, and 49 (12.9%) as inappropriate. The remaining 111 patients (29.2%) presented with complaints and conditions that could not be categorized. The rate of appropriate referral was similar for all three categories of physician (endoscopists: 59.8%, primary care physicians: 48.1%, others: 51.1%). When referrals by endoscopists were substratified according to gastroenterologists and surgeon-endoscopists, the rate of appropriate referral among gastroenterologists (78.4%) was significantly higher than that of surgeon-endoscopists (56.1%) (P = 0.049), primary care physicians (P = 0.013) and 'others' (P = 0.009). The most common appropriate indications were unexplained Rectalbleeding (79 cases, 20.8%) followed by CRC surveillance (45 cases, 11.8%). The most common inappropriate indication was inappropriately timed colonic cancer surveillance (32 cases, 8.4%). Chronic constipation in 36 cases (9.5%) was the most common 'unlisted' indication. A positive colonoscopic finding was detected in 131 (34.5%) examinations and CRC was found in 36 patients (9.5%). Appropriateness of indication was not a predictive factor for positive findings or CRC and there was no difference in the proportion of cases with positive findings or CRC in the three 'appropriateness categories'. Multivariate analysis revealed that only Rectalbleeding and smoking were significant independent positive predictive factors for positive findings and CRC. CONCLUSION: The appropriateness of colonoscopy was not high among the different sources of referrals except for the subgroup of 'gastroenterologist'. Furthermore, the rates of positive findings and CRC among the cases with appropriate, inappropriate and unlisted indications did not differ. The ASGE guidelines will need to be modified for Asia to be of practical use.

Adult↗

Influence of fibril taper on the function of collagen to reinforce extracellular matrix.

Collagen fibrils provide tensile reinforcement for extracellular matrix. In at least some tissues, the fibrils have a paraboloidal taper at their ends. The purpose of this paper is to determine the implications of this taper for the function of collagen fibrils. When a tissue is subjected to low mechanical forces, stress will be transferred to the fibrils elastically. This process was modelled using finite element analysis because there is no analytical theory for elastic stress transfer to a non-cylindrical fibril. When the tissue is subjected to higher mechanical forces, stress will be transferred plastically. This process was modelled analytically. For both elastic and plastic stress transfer, a paraboloidal taper leads to a more uniform distribution of axial tensile stress along the fibril than would be generated if it were cylindrical. The tapered fibril requires half the volume of collagen than a cylindrical fibril of the same length and the stress is shared more evenly along its length. It is also less likely to fracture than a cylindrical fibril of the same length in a tissue subjected to the same mechanical force.

Biomechanical Phenomena↗

Human leucocyte antigen determinants of susceptibility to Barrett's oesophagus in Asians--a preliminary study.

BACKGROUND: Characteristic immune profiles have been demonstrated in gastro-oesophageal reflux disease. However, the genetic basis of gastro-oesophageal reflux disease remains unclear. AIM: To investigate whether certain human leucocyte antigen genes are associated with Barrett's oesophagus. METHODS: Asian patients of Malay, Chinese and Indian descent with Barrett's oesophagus (n = 59) and those without reflux symptoms and a normal oesophagus (n =60) were recruited prospectively using endoscopic and histopathological criteria. Human leucocyte antigen class I and II typing was performed using a polymerase chain reaction sequence-specific primers method. RESULTS: The HLA-B7 allele was present in 17% (10 of 59) of patients with Barrett's oesophagus when compared with 0% (zero of 60) of controls [P = 0.0006, corrected P = 0.0171, OR = 25.67]. Subgroup analysis revealed that the HLA-B7 allele was confined almost exclusively to Indians with Barrett's oesophagus, 43% (nine of 21) vs. 0% (zero of 19) Indian controls (P = 0.0014, corrected P = 0.0406, OR = 29.64). No class II associations, protective human leucocyte antigens or extended haplotypes for disease susceptibility were identified. CONCLUSIONS: Barrett's oesophagus in Asians, particularly Indians, is strongly positively associated with HLA-B7; reinforcing a genetic component to gastro-oesophageal reflux disease. A larger sample size and different ethnic populations should be genotyped to further confirm this association and identify possible additional risk factors in the human leucocyte antigen locus.

Asian People↗

Increasing incidence of colorectal cancer in Asia: implications for screening.

Many Asian countries, including China, Japan, South Korea, and Singapore, have experienced an increase of two to four times in the incidence of colorectal cancer during the past few decades. The rising trend in incidence and mortality from colorectal cancer is more striking in affluent than in poorer societies and differs substantially among ethnic groups. Although changes in dietary habits and lifestyle are believed to be the reasons underlying the increase, the interaction between these factors and genetic characteristics of the Asian populations might also have a pivotal role. Non-polypoidal (flat or depressed) lesions and colorectal neoplasms arising without preceding adenoma (de novo cancers) seem to be more common in Asian than in other populations. The absence of polypoid growth preceding malignancy has posed difficulties in screening for early colorectal cancer by radiological imaging or even endoscopic techniques. Although epidemiological data are scanty, most Asian populations are not aware of the growing problem of colorectal cancer. More work is needed to elucidate the magnitude of the problem in Asia.

Asia↗

CYP2C19 genotype and the PPIs--focus on rabeprazole.

Amongst all the proton pump inhibitors (PPI), the hepatic metabolism of rabeprazole is least dependent on the CYP4502C19 system. Rabeprazole is therefore the PPI least affected by CYP4502C19 genetic polymorphism. This unique feature of rabeprazole complements rabeprazole's fast onset of action, and may lead to profound and consistent inhibition of gastric acid secretion in the treatment of acid-related disorders.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Chronic pancreatitis: aetiology, epidemiology and clinical presentation.

Chronic pancreatitis is a difficult disease to treat. Worldwide, alcohol is the most common aetiology but based on recent studies it is clear that genetic susceptibility plays an important role in determining disease. Several important genetic mutations have been identified. The prevalence of chronic pancreatitis appears to be lower in Asia although very high rates have been reported in parts of India. Severe intractable pain is the predominant presenting complaint of patients. The natural history of the disease and the onset of exocrine and endocrine insufficiency depend on the classification of disease as early onset, late-onset or alcohol associated. Complications of chronic pancreatitis are important and include pseudocyst formation, bile duct and duodenal strictures.

Alcoholism↗

Changing epidemiology of gastroesophageal reflux disease in the Asian-Pacific region: an overview.

Gastroesophageal reflux disease (GERD) is a common disease in the West, which now appears to be also increasing in prevalence in the Asian Pacific region. The reasons for this changing epidemiology are two-fold: an increased awareness among doctors and patients, and/or a true increase in the prevalence of the disease. Prevalence rates of reflux esophagitis (RE) of up to 16% and prevalence of GERD symptoms of up to 9% have been reported in the Asian population. However, the frequency of strictures and Barrett's esophagus remain very low. Non-erosive reflux disease (NERD) appears to be the most common form of GERD among Asian patients accounting for 50-70% of cases with GERD. Among Asian patients differences can also be discerned among different ethnic groups. For example, in Malaysia where a multiracial society exists, RE is significantly more common among Indians compared to Chinese and Malays whereas NERD is more frequently seen in the Indian and Malays compared to the Chinese. The reasons for these differences are not known but may indicate both genetic factors and environmental factors peculiar to the particular racial group. GERD has also been increasing in the region demonstrating a time-lag phenomenon compared to the West. Differing predisposition to GERD among different ethnic groups would mean that such an increase would be more prominent among certain racial groups.

Asia↗

Review article: efficacy and safety of rabeprazole in treating gastroesophageal reflux disease.

Proton pump inhibitors (PPI) are the mainstay of gastroesophageal reflux disease (GERD) treatment. They have a good efficacy and short- and long-term safety profile. Rabeprazole is a second generation PPI with rapid onset of action that quickly relieves symptoms of GERD. Rabeprazole consistently and profoundly inhibits gastric acid secretion. Its metabolism is less dependent on CYP4502C19 system and therefore is the least affected among all PPIs by CYP4502C19 genetic polymorphism. Recent studies have also indicated that rabeprazole on-demand is cost effective in preventing non-erosive reflux disease (NERD) symptom relapse.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Cardiovascular effects of treatment of type 2 diabetes with pioglitazone, metformin and gliclazide.

Cardiovascular mortality and morbidity are increased in patients with type 2 diabetes. However, there are few data from clinical trials comparing cardiovascular effects of alternative oral anti-diabetic agents. Major cardiovascular outcomes during four one-year, double-blind trials in over 3700 patients with type 2 diabetes randomised to either a thiazolidinedione, pioglitazone, metformin or a sulphonylurea, gliclazide treatment have been combined. Mean blood pressure was slightly reduced by all treatments, with pioglitazone treatment resulting in the largest falls (approximately 1.5 mmHg). Hospitalisations for cardiac or cerebrovascular events were similar with the different treatments. Overall mortality was seven of 1857 for pioglitazone and 10 of 1856 for non-pioglitazone treatments, of which three and six were cardiac deaths, respectively. The incidence of congestive cardiac failure was similar with pioglitazone (12/1857) and non-pioglitazone (10/1856) treatments. The results show similar cardiovascular outcome for the three different treatments over a one-year period, but demonstrate interesting differences, which will require longer-term formal outcome studies to determine their significance.

Blood Pressure↗

Appropriateness of colonoscopy in a university hospital.

An open access endoscopy system allows for the direct scheduling of endoscopies by non-gastroenterologist physicians without prior gastroenterology consultation. The aim of our study was to examine our practice of open access endoscopy by evaluating the appropriateness of referrals for colonoscopy and to determine whether there were differences depending on the specialty of the referring clinician. The indication for colonoscopy was assessed in 499 consecutive outpatients referred for colonoscopy at University Hospital, Kuala Lumpur over a 12-month period. The American Society of Gastrointestinal Endoscopy (ASGE) guidelines were used to determine the appropriateness of referrals. 80.6% of colonoscopies requested by the gastroenterologist were performed for accepted indications compared to 50.6% of referrals by the primary care physician (p<0.001) and 67.0% of referrals by the surgeon (p=0.006). The rate of colonoscopies generally not indicated was 2.1% for the gastroenterologist, 25.0% for the internist (p=0.002) and 7.5% for the surgeon (p=0.04). The rate of indications not listed in the ASGE guidelines was significantly lower for requests made by gastroenterologists (17.3%) than those requested by primary care physicians (44.2%; p<0.001). Patients who have had prior consultation with the gastroenterologist were significantly more likely to undergo colonoscopy for appropriate indications than among patients who were referred through an open access system. The rate of inappropriate indications for colonoscopy was also significantly lower when the gastroenterologist made the referral. A substantial proportion of colonoscopies (25.4%) was performed for indications not listed in the ASGE guidelines.

Colonoscopy↗

Clinical usefulness of tumour markers.

Tumour markers are substances related to the presence or progress of a tumour. An ideal tumour marker is (1) detectable only when malignancy is present, (2) specific for the type and site of malignancy, (3) correlates with the amount of malignant tissue present and (4) responds rapidly to a change in tumour size. At present, no tumour marker fulfills all of the above criteria. The first part of the review discusses the clinical usefulness of the commonly requested serum tumour markers, namely, prostate-specific antigen (PSA), CA 19-9, carcinoembryonic antigen (CEA), CA 125, CA 15-3, human chorionic gonadotrophin (hCG) and alpha-foetoprotein (AFP). It is hoped that this review article will decrease the abuse and misuse of these commonly requested serum tumour markers. The second part of the review discusses the clinical usefulness of catecholamines and their metabolites, calcitonin, thyroglobulin, parathyroid hormone, prolactin, adrenocorticotrophic hormone, oestrogen and progesterone receptors, p53, HER-2/c-erbB2, BRCA1 and BRCA2.

Biomarkers, Tumor↗

Histopathological landmarks of hepatocellular carcinoma in Malaysians.

A study was conducted at the Department of Pathology, University of Malaya Medical Centre, Kuala Lumpur into the histological type (WHO classification), grade (modified Edmondson and Steiner's grading system), mitotic rate, bile production, hyaline globule and Mallory hyaline formation of 52 cases of hepatocellular carcinoma (HCC) diagnosed during a 13-year period between 1st January 1990 to 31st December 2002. In addition, associated cirrhosis, dysplasia (large liver cell dysplasia: LLCD and small liver cell dysplasia: SLCD) and microvascular permeation were also looked for whenever the situation permitted. The patients' ages ranged from 21-years to 85-years (mean = 58.7 years) with a predilection for males and Chinese. Histologically, majority (73.1%) of the tumours demonstrated a trabecular pattern of growth. The bulk (73%) of the tumours were either of grade II or III differentiation. Mitotic activity ranged between 0-100/10 high power fields (hpf) with a mean of 22.2/10 hpf. Bile was noted in 25%, hyaline globules 17.3% and Mallory bodies in one case. Concomitant cirrhosis was present in 73.5%. 73.5% of the cases had associated LLCD. 5 with LLCD also showed SLCD. Microvascular permeation was shown in 76.2% of cases. On comparison with findings from other studies, no major difference seems to exist between the histological characteristics of our HCC cases and that of other populations.

Adult↗

Update on the management of Helicobacter pylori infection, including drug-resistant organisms.

Helicobacter pylori infection has many different clinical outcomes. Not all infected persons need to be treated. Therefore, indications for treatment have to be clear, and several consensus guidelines have been formulated to aid the medical practitioner in this decision-making process. Triple therapy with a proton pump inhibitor (PPI), in combination with amoxicillin and clarithromycin is the established treatment of choice. For patients with penicillin hypersensitivity, metronidazole can be substituted for amoxicillin. Bacterial resistance to antibiotics is a major factor adversely affecting treatment success. Resistance to metronidazole has been reported in up to 80%, and resistance to clarithromycin in 2-10% of strains cultured. Resistance to either one of the antibiotics has been reported to result in a drop in efficacy of up to 50%. Emergence of resistance to both metronidazole and clarithromycin following failed therapy is a cause for concern; this underlines the need to use the best available first-line therapy. To avoid the emergence of resistance to both key antibiotics, the combination of metronidazole and clarithromycin should be avoided where possible. For failed treatment, several strategies can be employed. These include ensuring better compliance with repeat therapy, and maximizing the efficacy of repeat treatment by increasing dosage and duration of treatment, as well as altering the choice of drugs. Quadruple therapy incorporating a bismuth compound with a PPI, tetracycline and metronidazole has been a popular choice as a "rescue" therapy. Ranitidine bismuth citrate has been shown to be able to overcome metronidazole and clarithromycin resistance; it may be a useful compound drug to use in place of a PPI in "rescue" therapies. In the case of persistent treatment failures, it is useful to consider repeating gastroscopy and obtaining tissue for culture, and then prescribe antibiotics according to bacterial susceptibility patterns. It is also important in refractory cases to review the original indication for treatment and determine the importance of the indication.

Anti-Bacterial Agents↗