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Aetiology and classification of acute liver failure

Rosmawati M

Med J Malaysia, 2005 Jul;60 Suppl B:125-6.
PMID: 16108192
Fulltext Cardiovascular risks among shift and non-shift workers in a public medical centre in Kuala Lumpur

Moy, F.M., Hoe, V.C.W., Tan, C.P.L., Rosmawati, M.

JUMMEC, 2010;13(1):45-49.
MyJurnal

Night work and rotating shift work are found to be detrimental to the health of workers. A cross sectional analytical study was conducted among the employees of a public medical centre in Kuala Lumpur. A total of 380 employees participated in the health screening and questionnaire survey. The majority of the respondents were Malays, females, and with mean age of 49 years old. The shift workers persistently had higher but non-significant proportions of being overweight/obesity and unhealthy clinical indicators such as systolic and diastolic blood pressure, fasting blood glucose and lipid profile except waist circumferences and HDL-cholesterol. There were also slightly more shift workers diagnosed with diabetes mellitus, hypertension or coronary heart disease (p>0.05). Although the present study could not provide established evidence for a relationship between shift work and cardiovascular risks, this could serve as a pilot study for future studies in this area.
Fulltext Hepatitis B seroprevalence among University of Malaya Students in the Post-universal Infant Vaccination Era

Ng KP, Ngeow YF, Rozainah K, Rosmawati M

Med J Malaysia, 2013 Apr;68(2):144-7.
PMID: 23629561 MyJurnal

A nationwide HBV vaccination for neonates in the Expanded Programme on Immunization (EPI) was implemented in Malaysia in 1989. The objective of this study was to investigate the prevalence of HBsAg, anti-HBs and anti-HBc among the new student intakes in the Faculties of Medicine and Dentistry, University of Malaya from 2005 to 2011.
Efficacy of a 1-week pantoprazole triple therapy in eradicating Helicobacter pylori in Asian patients

Goh K, Parasakthi N, Cheah P, Ranjeev C, Rosmawati M, Tan Y, et al.

J Gastroenterol Hepatol, 2000 Aug;15(8):910-4.
PMID: 11022833

BACKGROUND: The aim of the present paper was to determine the efficacy and tolerability of a 1-week treatment regimen consisting of pantoprazole and two antibiotics: clarithromycin and amoxycillin, in the eradication of Helicobacter pylori.
METHODS: The patients selected had unequivocal evidence of H. pylori infection based on urease test, culture and histology on antral and corpus biopsies obtained at endoscopy. Patients received pantoprazole 40 mg twice a day, clarithromycin 500 mg twice a day and amoxycillin 1 g twice a day for 1 week and were assessed for successful eradication at least 4 weeks after completion of therapy by repeat gastroscopy and gastric biopsies. Eradication was defined as absence of bacteria in both antral and corpus biopsies tested by culture, histology and urease test.
RESULTS: One hundred and six patients were recruited for the study. The mean age was 48.0 years (range: 23-74 years). Four patients defaulted follow up and five patients were not compliant (taking less than 85%) with medications. Eradication rates on per-protocol analysis were: 88/97 (90.7%; 95% CI: 83.1-95.7); and on intention-to-treat analysis they were: 88/106 (83.0%; 95% CI: 75.9-90.2). Side-effects were in general mild and tolerable: 57 of 106 (53.7%) patients complained of a bitter taste; 15 (14.1%) complained of giddiness; 10 (9.4%) complained of increased abdominal pain; 11 (11.5%) complained of lethargy and 16 (15.1%) complained of loose motions. Pre-treatment metronidazole resistance was encountered in 57/74 strains (77.0%). Clarithromycin resistance was not encountered in any of the strains.
CONCLUSIONS: The pantoprazole 1-week triple therapy with amoxycillin and clarithromycin is effective in H. pylori eradication. The treatment was well tolerated by patients. Metronidazole resistance was reported in a high percentage of strains isolated from patients. Clarithromycin resistance was, however, not detected in any of the strains.
Intrahepatic biloma: an unusual complication of cholangiocarcinoma treated endoscopically

Ranjeev P, Goh KL, Rosmawati M, Tan YM

Gastrointest Endosc, 1999 Nov;50(5):711-3.
PMID: 10536338
The frequency of pre-core gene mutations in chronic hepatitis B infection: a study of Malaysian subjects

Yap SF, Wong PW, Chen YC, Rosmawati M

Southeast Asian J. Trop. Med. Public Health, 2002 Mar;33(1):102-9.
PMID: 12118437

A retrospective study was carried out to determine the frequency of the pre-core stop codon mutant virus in a group of chronic hepatitis B carriers: 81 cases were considered [33 hepatits B e antigen (HBe) positive and 48 HBe negative]. All of the HBe positive cases had detectable viral DNA by hybridization analysis; in the case of the HBe negative cases, one third had detectable viral DNA by hybridization analysis and two thirds had HBV DNA detectable by polymerase chain reaction (PCR) amplification. Pre-core stop codon mutant detection was carried out on all specimens using allele-specific oligonucleotide hybridization following PCR amplification of the target sequence. The pre-core mutant was detected in 13/33 (39.4%) of HBe positive cases and in 32/48 (66.7%) of HBe negative cases. Sequence analysis was carried out on 8 of the 16 HBe negative specimens that did not carry the pre-core mutant virus to determine the molecular basis for the HBe minus phenotype in these cases: the 1762/1764 TA paired mutation in the second AT rich region of the core promoter was detected in five cases; a start codon mutation was detected in one case. The predominant mutation resulting in the HBe minus phenotype in our isolates was the 1896A pre-core ("pre-core stop codon") mutation; other mutations responsible for the phenotype included the core promoter paired mutation and pre-core start codon mutation. In view of the high frequency of the pre-core mutant virus, sequence analysis was performed to determine the virus genotype on the basis of the nucleotide sequence of codon 15. The sequences of 21 wild type virus (14 HBe positive and 7 HBe negative cases) were examined: 15 were found to be codon 15 CCT variants (71.4%); the frequency in the HBe positive group was 12/14 (85.7%), while that in the HBe negative group was 3/7 (42.9%). The high frequency of the codon 15 CCT variant in association with the frequent occurrence of the pre-core mutant in our isolates concurs with the results of other studies.
Predictive factors by multivariate analysis for colorectal cancer in Malaysian patients undergoing colonoscopy

Tan YM, Rosmawati M, Ranjeev P, Goh KL

J Gastroenterol Hepatol, 2002 Mar;17(3):281-4.
PMID: 11982698

BACKGROUND: The majority of colorectal cancers are still diagnosed in patients who present with symptoms especially in countries where colorectal screening programs are not practised. The aim of our study was to determine the predictive factors for colorectal cancer in patients referred for colonoscopy.
METHODS: A prospective study of 485 consecutive patients who underwent colonoscopy during a 22-month period was performed. All patients answered a detailed questionnaire. Indications for colonoscopy and the findings were recorded.
RESULTS: The mean age of the study population was 55.7 +/- 14.7 years. There were 221 (45.6%) males and 264 (54.4%) females. Sixty-five (13.4%) were Malays, 298 (61.4%) were Chinese and 112 (23.1%) were Indians. Multiple backward stepwise regression analysis revealed that independent predictors for colorectal cancer (odds ratio [95% CI]) were the presence of rectal bleeding (4.3 [4.0-8.0]) and iron deficiency anemia (4.0 [3.6-10.2]). In those aged 50 and over, male gender (4.5 [2.2-9.3]) and abdominal pain (3.1 [1.4-6.7]) were also significant positive predictors of cancer.
CONCLUSIONS: With the ever-increasing demand for gastrointestinal endoscopy, the appropriate utilization of colonoscopy is essential to afford prompt patient evaluation. Our study supports the need to prioritize the use of colonoscopy in patients with rectal bleeding and iron deficiency anemia. In the older patient where the background prevalence of colorectal cancer is higher, referral for colonoscopy is also justified.
Histopathological landmarks of hepatocellular carcinoma in Malaysians

Cheah PL, Looi LM, Nazarina AR, Goh KL, Rosmawati M, Vijeyasingam R

Malays J Pathol, 2003 Jun;25(1):37-43.
PMID: 16196376

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.
Decrease of CD69 levels on TCR Vα7.2+CD4+ innate-like lymphocytes is associated with impaired cytotoxic functions in chronic hepatitis B virus-infected patients

Yong YK, Tan HY, Saeidi A, Rosmawati M, Atiya N, Ansari AW, et al.

Innate Immun, 2017 07;23(5):459-467.
PMID: 28606013 DOI: 10.1177/1753425917714854

Hepatitis B virus (HBV) infection is a major cause of chronic liver disease that may progress to liver cirrhosis and hepatocellular carcinoma. Host immune responses represent the key determinants of HBV clearance or persistence. Here, we investigated the role of the early activation marker, CD69 and effector cytokines, granzyme B (GrB) and IFN-γ in the exhaustion of innate-like TCR Vα7.2+CD4+T cells, in 15 individuals with chronic HBV (CHB) infection where six were HBV DNA+ and nine were HBV DNA-. The percentage of cytokine-producing T cells and MAIT cells were significantly perturbed in HBV patients relative to healthy controls (HCs). The intracellular expression of GrB and IFN-γ was significantly reduced in MAIT cells derived from HBV-infected patients as compared to HCs, and the levels correlated with the percentage and levels [mean fluorescence intensity (MFI)] of CD69 expression. The total expression of CD69 (iMFI) was lower in CHB patients as compared to HCs. The frequency of CD69+ cells correlated with the levels of cytokine expression (MFI), particularly in CHB patients as compared to HCs. In summary, the polyfunctionality of peripheral T cells was significantly reduced among CHB patients, especially in the TCR Vα7.2+CD4+T cells, and the levels of cytokine expression correlated with functional cytokine levels.
Multiple systemic embolisms with septicemia after gastric variceal obliteration with cyanoacrylate

Tan YM, Goh KL, Kamarulzaman A, Tan PS, Ranjeev P, Salem O, et al.

Gastrointest Endosc, 2002 Feb;55(2):276-8.
PMID: 11818941
Fulltext Plasma interleukin-7 correlation with human immunodeficiency virus RNA and CD4+ T cell counts, and interleukin-5 with circulating hepatitis B virus DNA may have implications in viral control

Vimali J, Yong YK, Murugesan A, Vishnupriya K, Ashwin R, Daniel EA, et al.

Front Med (Lausanne), 2022;9:1019230.
PMID: 36405584 DOI: 10.3389/fmed.2022.1019230

Chronic viral infections represent a leading cause of global morbidity and mortality. Chronic HBV, HCV, and HIV infections result in cytokine perturbations that may hold key implications in understanding the complex disease mechanisms driving virus persistence and/or resolution. Here, we determined the levels of various plasma cytokines using a commercial Bio-Plex Luminex cytokine array in chronic HBV (n = 30), HCV (n = 15), and HIV (n = 40) infections and correlated with corresponding plasma viral loads (PVLs) and liver parameters. We observed differential perturbations in cytokine profiles among the study groups. The cytokines levels positively correlated with PVL and liver transaminases. The monocyte-derived cytokines viz., MIP-1β, IL-8, and TNF-α, and Th2 cytokines like IL-4, IL-5, and IL-13 showed a better correlation with liver enzymes as compared to their corresponding PVLs. Our investigation also identified two cytokines viz., IL-5 and IL-7 that inversely correlated with HBV DNA and HIV PVLs, respectively. Regression analysis adjusted for age showed that every increase of IL-5 by one unit was associated with a reduction in HBV PVL by log10 0.4, whereas, every elevation by a unit of IL-7 was associated with decreased HIV PVL by log10 2.5. We also found that IL-7 levels correlated positively with absolute CD4+ T cell counts in HIV-infected patients. We concluded that plasma IL-5 and IL-7 may likely have a key role on viral control in HBV and HIV infections, respectively. A noteworthy increase in cytokines appears to bear protective and pathological significance, and indeed is reflective of the host's versatile immune armory against viral persistence.
Fulltext Hyper-Expression of PD-1 Is Associated with the Levels of Exhausted and Dysfunctional Phenotypes of Circulating CD161++TCR iVα7.2+ Mucosal-Associated Invariant T Cells in Chronic Hepatitis B Virus Infection

Yong YK, Saeidi A, Tan HY, Rosmawati M, Enström PF, Batran RA, et al.

Front Immunol, 2018;9:472.
PMID: 29616020 DOI: 10.3389/fimmu.2018.00472

Mucosal-associated invariant T (MAIT) cells, defined as CD161++TCR iVα7.2+ T cells, play an important role in the innate defense against bacterial infections, and their functionality is impaired in chronic viral infections. Here, we investigated the frequency and functional role of MAIT cells in chronic hepatitis B virus (HBV) infection. The peripheral CD3+CD161++TCR iVα7.2+ MAIT cells in chronic HBV-infected patients and healthy controls were phenotypically characterized based on CD57, PD-1, TIM-3, and CTLA-4, as well as HLA-DR and CD38 expression. The frequency of MAIT cells was significantly decreased among chronic HBV-infected individuals as compared to controls. Expression of CD57, PD-1, CTLA-4, as well as HLA-DR and CD38 on MAIT cells was significantly elevated in chronic HBV-infected individuals relative to controls. The percentage of T cell receptor (TCR) iVα7.2+ CD161+ MAIT cells did not correlate with HBV viral load but inversely with HLA-DR on CD4+ T cells and MAIT cells and with CD57 on CD8+ T cells suggesting that decrease of MAIT cells may not be attributed to direct infection by HBV but driven by HBV-induced chronic immune activation. The percentage and expression levels of PD-1 as well as CTLA-4 on MAIT cells inversely correlated with plasma HBV-DNA levels, which may suggest either a role for MAIT cells in the control of HBV infection or the effect of HBV replication in the liver on MAIT cell phenotype. We report that decrease of TCR iVα7.2+ MAIT cells in the peripheral blood and their functions were seemingly impaired in chronic HBV-infected patients likely because of the increased expression of PD-1.