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Fulltext Health seeking behavior among Malaysians with acute diarrheal disease

Tee GH, Kaur G, Ramanathan P, Amal NM, Chinna K

Southeast Asian J. Trop. Med. Public Health, 2011 Mar;42(2):424-35.
PMID: 21710867

About 1.8 million people die annually from acute diarrheal disease globally. A nationwide cross-sectional survey was conducted via face-to-face interview with eligible subjects to determine the incidence and health seeking behavior of Malaysians with acute diarrheal disease (ADD). An acute diarrheal episode was defined as having three or more loose stools in any 24 hour period during the four weeks period prior to the interview. The exclusion criteria included pre-existing chronic diarrhea, such as with cancer of the bowel, ulcerative colitis or Chrohn's disease. Forty three point three percent of those with ADD (95% CI 41.3-45.4) sought treatment for the illness. Younger age groups (0-4 years, 67.7%; 95% CI 61.5-73.4; 5-9 years, 56.5%; 95% CI 48.6-64.1) were more likely to seek care for ADD. Seventy-one point eight percent of those seeking treatment, (95% CI 69.0-74.4) did so within 12 hours of the onset of symptoms. Most people with ADD sought treatment at private clinics. The main reasons given for not seeking treatment were the illness was mild and did not warrant treatment and the practice of self-medication (22.4%; 95% CI 20.0-24.9). These findings show self-medication is a major health seeking behavior among Malaysians with ADD. Self-medication of ADD deserves more in-depth study to ensure it is safe.
Keywords: NHMS-2006
Study name: National Health and Morbidity Survey (NHMS-2006)
Fulltext Prevalence of clinical malaria among an Orang Asli community in Malaysia

Kaur G

Southeast Asian J. Trop. Med. Public Health, 2009 Jul;40(4):665-73.
PMID: 19842399

An epidemiological cross-sectional study was undertaken to determine the prevalence of clinical malaria among the Orang Asli population of Raub, Pahang, Malaysia. The study was conducted on a representative sample of 520 Orang Asli. Malariometric and clinical measurements were taken. The overall parasitemic rate was 24.2% (95% CI 20.7-28.1). Twenty-three point four percent (95% CI 19.5-26.9) of respondents age two years and above were clinically febrile. The prevalence of fever, chills, perspiration and body aches during a one month period prior to the survey among the same group ranged between 4.2% (95% CI 2.7-6.4) and 13.5% (95% CI 10.6-16.7). Children 2-12 years old were more likely to present with fever, and symptoms of malaria than older children. Gender was not significantly associated with fever or any of the other malaria symptoms. Presence of clinical fever and history of malaria symptoms were all strongly associated with current infection. The association was significant even after controlling for age (adjusted OR 2.8-5.1, 95% CI 1.1-8.3). Orang Asli children significantly experienced greater morbidity due to malaria compared to adults. Control and treatment of malaria should focus on children, while further research should explore the effects of malaria morbidity on the quality of life of these children.
Rapid diagnosis of Helicobacter pylori infection in gastric imprint smears

Kaur G, Madhavan M, Basri AH, Sain AH, Hussain MS, Yatiban MK, et al.

Southeast Asian J. Trop. Med. Public Health, 2004 Sep;35(3):676-80.
PMID: 15689086

The objective of this study was to determine the sensitivity, specificity, positive (PPV), and negative predictive values (NPV) of Diff-Quik-stained gastric imprint cytology smears in the detection of H. pylori compared with histology. Air-dried imprint smears of gastric biopsies from 150 patients were stained by the Diff-Quik method in the endoscopy suite and examined for H. pylori, providing results within minutes. The presence of inflammation and intestinal metaplasia were documented. The same biopsy was processed and stained with H&E and Warthin-Starry stains, and reviewed by a different pathologist blind to the imprint cytology results. Ninety-four of the 150 patients were male with a mean age of 50 years. Based on histology, the H. pylori prevalence was very low at 8%. The sensitivity and specificity of imprint cytology in the detection of H. pylori were 83.3% and 100%, respectively. The PPV and NPV were 100% and 98.6%, respectively. There were two false negatives and no false positives. A combination of imprint cytology and histology achieved 100% sensitivity. Imprint smears did not provide added value over histology with regards to inflammation and metaplasia. Gastric imprint smears stained with Diff-Quik method is a rapid, cheap, and reliable method for the detection of H. pylori and have their best results when complemented with histology.
Trichuriasis: localized inflammatory responses in the colon

Kaur G, Raj SM, Naing NN

Southeast Asian J. Trop. Med. Public Health, 2002 Jun;33(2):224-8.
PMID: 12236416

Most patients with trichuriasis have light worm burdens. Data regarding the inflammatory response to Trichuris worms in the colon of lightly infected persons are scant. Nine patients whose Trichuris infection was found by colonoscopy had biopsies taken from a site adjacent to visible worms and from a second site some 20 cm distally. The biopsies were studied by routine and immunohistochemical methods. None of the biopsies showed mucosal ulceration, significant congestion, fibrosis, gland distortion or goblet cell mucin depletion. There was no difference between worm and worm-free sites in terms of edema, lymphoid follicles or epithelial slough. Worm sites had higher numbers of eosinophils, neutrophils and total inflammatory cells and lower numbers of plasma cells. However there was no difference in lymphocyte, mast cell, and B- and T-cell counts between the two sites. This suggests that the T. trichiura worm incites a local inflammatory response involving eosinophils and neutrophils, even when the colon has only a light burden of worms.
BZD9L1 sirtuin inhibitor as a potential adjuvant for sensitization of colorectal cancer cells to 5-fluorouracil

Tan YJ, Lee YT, Petersen SH, Kaur G, Kono K, Tan SC, et al.

Ther Adv Med Oncol, 2019;11:1758835919878977.
PMID: 31632470 DOI: 10.1177/1758835919878977

Background: This study aims to investigate the combination effect of a novel sirtuin inhibitor (BZD9L1) with 5-fluorouracil (5-FU) and to determine its molecular mechanism of action in colorectal cancer (CRC).
Methods: BZD9L1 and 5-FU either as single treatment or in combination were tested against CRC cells to evaluate synergism in cytotoxicity, senescence and formation of micronucleus, cell cycle and apoptosis, as well as the regulation of related molecular players. The effects of combined treatments at different doses on stress and apoptosis, migration, invasion and cell death mechanism were evaluated through two-dimensional and three-dimensional cultures. In vivo studies include investigation on the combination effects of BZD9L1 and 5-FU on colorectal tumour xenograft growth and an evaluation of tumour proliferation and apoptosis using immunohistochemistry.
Results: Combination treatments exerted synergistic reduction on cell viability on HCT 116 cells but not on HT-29 cells. Combined treatments reduced survival, induced cell cycle arrest, apoptosis, senescence and micronucleation in HCT 116 cells through modulation of multiple responsible molecular players and apoptosis pathways, with no effect in epithelial mesenchymal transition (EMT). Combination treatments regulated SIRT1 and SIRT2 protein expression levels differently and changed SIRT2 protein localization. Combined treatment reduced growth, migration, invasion and viability of HCT 116 spheroids through apoptosis, when compared with the single treatment. In addition, combined treatment was found to reduce tumour growth in vivo through reduction of tumour proliferation and necrosis compared with the vehicle control group. This highlights the potential therapeutic effects of BZD9L1 and 5-FU towards CRC.
Conclusion: This study may pave the way for use of BZD9L1 as an adjuvant to 5-FU in improving the therapeutic efficacy for the treatment of colorectal cancer.
Posttraumatic Stress Disorder Symptoms and Sleep Disturbances Among Asian Indians: A Systematic Review

Contractor AA, Almeida IM, Fentem A, Griffith EL, Kaur G, Slavish DC

Trauma Violence Abuse, 2024 Apr;25(2):1468-1483.
PMID: 37427484 DOI: 10.1177/15248380231184207

Substantial comorbidity exists between posttraumatic stress disorder and sleep disturbances/disorders. Such comorbidities are understudied in minority groups, including Asian Indians residing in countries outside India. Thus, we synthesized the existing literature specific to this group of Asian Indians to determine (a) prevalence estimates of posttraumatic stress disorder (PTSD) and sleep disturbances/disorders; and (b) PTSD-sleep comorbidity estimates. For this systematic review, we searched four databases (PubMed, PsycInfo, PTSDpubs, Web of Science) using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Of 3,796 screened articles, 9 articles (10 studies) met inclusion criteria. Study sample sizes ranged from 11 to 2,112 Asian Indians; studies were conducted in Singapore or Malaysia. No reviewed study examined PTSD. All studies examined sleep disturbances/disorders among Asian Indians; prevalence estimates were: 8.3% to 70.4% for short sleep duration, 2.0% to 22.9% for long sleep duration, 25.9% to 56.3% for poor sleep quality, 3.4% to 67.5% for insomnia diagnosis or probable insomnia, 7.7% for excessive daytime sleepiness, 3.8% to 54.6% for obstructive sleep apnea (OSA) diagnosis or high OSA risk, and 5.1% to 11.1% for sleep-disordered breathing. Specific to Asian Indians residing in countries outside India, this review advances PTSD-sleep literature by (a) suggesting substantial prevalence of sleep disturbances/disorders; (b) highlighting the need for culturally relevant sleep interventions; and (c) highlighting research gaps (e.g., no PTSD-focused research).
Fulltext Germline mutation analysis of MLH1 and MSH2 in Malaysian Lynch syndrome patients

Zahary MN, Kaur G, Abu Hassan MR, Singh H, Naik VR, Ankathil R

World J Gastroenterol, 2012 Feb 28;18(8):814-20.
PMID: 22371642 DOI: 10.3748/wjg.v18.i8.814

To investigate the protein expression profile of mismatch repair (MMR) genes in suspected cases of Lynch syndrome and to characterize the associated germline mutations.
Fulltext Anti-tumour activity and toxicological studies of combination treatment of Orthosiphon stamineus and gemcitabine on pancreatic xenograft model

Yehya AHS, Subramaniam AV, Asif M, Kaur G, Abdul Majid AMS, Oon CE

World J Gastroenterol, 2022 Aug 28;28(32):4620-4634.
PMID: 36157930 DOI: 10.3748/wjg.v28.i32.4620

BACKGROUND: Pancreatic cancer is the most aggressive cancer type. Gemcitabine is the first line chemo-drug used for pancreatic cancer but exerts a broad spectrum of organ toxicities and adverse effects in patients.
AIM: To evaluate the anti-tumour activity and toxicological effects of Orthosiphon stamineus extract formulation (ID: C5EOSEW5050ESA trademarked as Nuva-staticTM), and gemcitabine combination on pancreatic xenograft model.
METHODS: Mice were randomly divided into six groups of 6 mice each (n = 6) and given different treatments for 28 d. The study design consisted of a 2 x 3 factorial treatment structure, with gemcitabine (yes/no) by oral (at 1200 and 400 mg/kg per day). Human pancreatic cancer cells were injected subcutaneously into the flanks of athymic nude mice. C5EOSEW5050ESA (200 or 400 mg/kg per day) was administered orally, while gemcitabine (10 mg/kg per 3 d) was given intraperitoneally either alone or in combination treatment. Histopathological analyses of vital organs, tumour tissues, and incidence of lethality were analysed. Analyses of tumour necrosis and proliferation were determined by haematoxylin-eosin staining and immunohistochemistry for Ki-67, respectively.
RESULTS: No signs of toxicity or damage to vital organs were observed in all treatment groups compared to the untreated group. C5EOSEW5050ESA at 200 mg/kg and gemcitabine combination had no additive antitumor effects compared to a single treatment. Remarkably, a comparably greater response in a reduction in tumour growth, Ki-67 protein expression, and necrosis was demonstrated by 400 mg/kg of C5EOSEW5050ESA and gemcitabine combination than that of the individual agents.
CONCLUSION: These results highlighted the synergistic activity of C5EOSEW5050ESA with gemcitabine to reduce pancreatic tumour growth in mice compared to a single treatment. Thus, this study provides valuable insights into using C5EOSEW5050ESA as a complementary treatment with gemcitabine for pancreatic cancer.
Fulltext BZD9L1 benzimidazole analogue hampers colorectal tumor progression by impeding angiogenesis

Oon CE, Subramaniam AV, Ooi LY, Yehya AHS, Lee YT, Kaur G, et al.

World J Gastrointest Oncol, 2023 May 15;15(5):810-827.
PMID: 37275453 DOI: 10.4251/wjgo.v15.i5.810

BACKGROUND: The development of new vasculatures (angiogenesis) is indispensable in supplying oxygen and nutrients to fuel tumor growth. Epigenetic dysregulation in the tumor vasculature is critical to colorectal cancer (CRC) progression. Sirtuin (SIRT) enzymes are highly expressed in blood vessels. BZD9L1 benzimidazole analogue is a SIRT 1 and 2 inhibitor with reported anticancer activities in CRC. However, its role has yet to be explored in CRC tumor angiogenesis.
AIM: To investigate the anti-angiogenic potential of BZD9L1 on endothelial cells (EC) in vitro, ex vivo and in HCT116 CRC xenograft in vivo models.
METHODS: EA.hy926 EC were treated with half inhibitory concentration (IC50) (2.5 μM), IC50 (5.0 μM), and double IC50 (10.0 μM) of BZD9L1 and assessed for cell proliferation, adhesion and SIRT 1 and 2 protein expression. Next, 2.5 μM and 5.0 μM of BZD9L1 were employed in downstream in vitro assays, including cell cycle, cell death and sprouting in EC. The effect of BZD9L1 on cell adhesion molecules and SIRT 1 and 2 were assessed via real-time quantitative polymerase chain reaction (qPCR). The growth factors secreted by EC post-treatment were evaluated using the Quantibody Human Angiogenesis Array. Indirect co-culture with HCT116 CRC cells was performed to investigate the impact of growth factors modulated by BZD9L1-treated EC on CRC. The effect of BZD9L1 on sprouting impediment and vessel regression was determined using mouse choroids. HCT116 cells were also injected subcutaneously into nude mice and analyzed for the outcome of BZD9L1 on tumor necrosis, Ki67 protein expression indicative of proliferation, cluster of differentiation 31 (CD31) and CD34 EC markers, and SIRT 1 and 2 genes via hematoxylin and eosin, immunohistochemistry and qPCR, respectively.
RESULTS: BZD9L1 impeded EC proliferation, adhesion, and spheroid sprouting through the downregulation of intercellular adhesion molecule 1, vascular endothelial cadherin, integrin-alpha V, SIRT1 and SIRT2 genes. The compound also arrested the cells at G1 phase and induced apoptosis in the EC. In mouse choroids, BZD9L1 inhibited sprouting and regressed sprouting vessels compared to the negative control. Compared to the negative control, the compound also reduced the protein levels of angiogenin, basic fibroblast growth factor, platelet-derived growth factor and placental growth factor, which then inhibited HCT116 CRC spheroid invasion in co-culture. In addition, a significant reduction in CRC tumor growth was noted alongside the downregulation of human SIRT1 (hSIRT1), hSIRT2, CD31, and CD34 EC markers and murine SIRT2 gene, while the murine SIRT1 gene remained unaffected, compared to vehicle control. Histology analyses revealed that BZD9L1 at low (50 mg/kg) and high (250 mg/kg) doses reduced Ki-67 protein expression, while BZD9L1 at the high dose diminished tumor necrosis compared to vehicle control.
CONCLUSION: These results highlighted the anti-angiogenic potential of BZD9L1 to reduce CRC tumor progression. Furthermore, together with previous anticancer findings, this study provides valuable insights into the potential of BZD9L1 to co-target CRC tumor vasculatures and cancer cells via SIRT1 and/or SIRT2 down-regulation to improve the therapeutic outcome.