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Ulcerative colitis with concomitant primary sclerosing cholangitis

Mohamed AK, Seow CE

Med J Malaysia, 2020 11;75(6):756-758.
PMID: 33219195

Primary sclerosing cholangitis (PSC) is the most common liver disease and known hepatobiliary complication of ulcerative colitis (UC). Concomitant PSC in UC is associated with increased risk of rapid progression of primary sclerosing cholangitis, and malignancy including colon carcinoma as well as hepatobiliary carcinoma. We report a case of a 26-year-old woman who was diagnosed as ulcerative colitis during her second pregnancy. Her liver function test showed a significant elevation of alkaline phosphatase (ALP) and gamma glutamyl transferase (GGT) with other parameters being within normal range. A clinical suspicion of primary sclerosing cholangitis was then made. Magnetic resonance cholangiopancreticography (MRCP) revealed beaded appearance of the right and left intrahepatic ducts with focal narrowing seen at the ducts, suggestive of primary sclerosing cholangitis. She was subsequently started on oral Ursodeoxycholic acid (UDCA) with improvement in her liver function test within 3 weeks of initiation of treatment.
Fulltext Breast milk immunoprotection and the common mucosal immune system: a review

Prameela KK, Mohamed AK

Malays J Nutr, 2010 Apr;16(1):1-11.
PMID: 22691850 MyJurnal

It is universally known that breastfeeding provides a broad spectrum of nutritional and non-nutritional advantages to the developing infant. Nonnutritive protecting potentials of breast milk towards different infections and non-infectious diseases are still attracting the attention of researchers in different specialties. The neonate, who is suddenly exposed to a wide variety of organisms, is in dire need of protection, enhancement and education of his immature immune system to encounter these organisms. The lactating mammary gland is an integral part of the common mucosal immune system which stands as a sentinel in combating pathogens that enter the body via the mucosal route. The common mucosal immune system also competently controls tolerance mechanisms to innocent proteins and is involved in surveillance of carcinogensis. The diverse roles of general mucosal immunity are nearly well established but the specialised functions of breast tissue and breast milk in boosting the immune responses need more emphasis and highlighting. The detailed understanding and evaluation of breast milk as an immunological tool is reviewed within the domain of the diverse activities of the common mucosal immune system.
Demographics and characteristics of endoscopic findings among COVID-19 patients with upper gastrointestinal bleeding in a single centre

Mohamed AK, Tang YC

Med J Malaysia, 2023 Dec;78(7):893-896.
PMID: 38159924

INTRODUCTION: Novel coronavirus 19 disease (COVID-19) pandemic poses healthcare providers challenges in the endoscopic suite. It is unclear whether it affects the endoscopic manifestations of upper gastrointestinal (GI) bleeding. This retrospective study was done to review demographic data, site of lesions and need of interventions for those lesions.
MATERIALS AND METHODS: Oesophagoduodenoscopy (OGDS) reports of COVID-19 patients with indication of upper GI bleeding from March 2021 to April 2022 were reviewed. Data of 35 patients were then analysed.
RESULTS: Of the 35 patients, 8.6% (n = 3) were female and 91.4% (n = 32) were males. A total of 31.4% (n = 11) were below 50 years and 68.6% (n = 24) were 50 and above. 34.3% (n = 12) with lesions requiring endoscopic intervention, 34.3% (n = 12) with lesions not requiring endoscopic intervention, 31.4% (n = 11) has no significant stigmata of recent haemorrhage. Among subgroup requiring endoscopic intervention, 50% (n = 6) are non-variceal bleeding (NVUIB), and 50% (n = 6) are variceal bleeding (VUGIB). Among NVUGIB, 16.7% (n = 1) is gastric and duodenal angiodysplasia requiring argon plasma coagulation, 50% (n = 3) are duodenal F2A ulcer requiring thermoablation, 16.7% (n = 1) is gastric F2A ulcer requiring hemoclip, and 16.6% (n = 1) is Cameron's ulcer requiring hemoclip. Among VUGIB, 100% (n = 6) are oesophageal varices requiring endoscopic variceal banding (EVL).
CONCLUSIONS: Lower proportion of NVUGIB among COVID-19 patients raises hypothesis on whether prothrombotic state of COVID-19 is a protective factor of NVUGIB. Studies with larger sample size are needed to establish significance.
Cardiotoxicity of cytotoxic chemotherapy and its prevention

Selvaratnam G, Philips RH, Mohamed AK

Adverse Drug React Toxicol Rev, 1999 Jun;18(2):61-105.
PMID: 10478286
Adverse effects of cytotoxics-platinum agents

Selvaratnam G, Philips RH, Mohamed AK, Radzi A

Adverse Drug React Toxicol Rev, 1997 Aug;16(3):171-97.
PMID: 9512763
An epidemiological study of syphilis and predictors of treatment failure in University Malaya Medical Centre

Mohamed AK, Raja IA, Rukumani DV

Med J Malaysia, 2020 05;75(3):199-203.
PMID: 32467532

INTRODUCTION: There are limited studies on the epidemiology of syphilis in Malaysia. In this study we describe the clinical features and treatment outcomes of patients with syphilis attending a tertiary referral university hospital.
METHODS: We retrospectively reviewed the case records of patients with positive serology findings for syphilis in University Malaya Medical Center (UMMC) from January 2010 to December 2015. Serological positivity was defined as having a positive rapid plasma reagin (RPR) or Venereal Disease Research Laboratory (VDRL) with a confirmatory positive Treponema pallidum particle agglutination assay (TPPA). Treatment outcomes were divided into two, success or failure. Demographic and clinical characteristics associated with predictors of treatment failure were assessed using statistical package for the social science (SPSS). This study also included a neurosyphilis descriptive sub-study.
RESULTS: There were 637 patients identified with positive syphilis serology, but 258 patients were excluded as they did not meet the inclusion criteria. 379 patients were then taken for the demographic study; 14 patients (3.7%) were treated for neurosyphilis; 170 patients with complete data were included. In all 42/170 (24.7%) failed treatment, 12/170 (7.1%) had reinfection and 116/170 (68.2%) had treatment success. A final number of 158 patients were then taken and analyzed for predictors of treatment failure after excluding the 12 reinfection patients. Only low baseline RPR (<1:16) was found to be significant on multivariate logistic regression analysis (p value: 0.007, 95% CI: 1.42, 9.21).
CONCLUSION: Most of the patients were HIV positive and from the MSM (Men who have sex with Men) population. Low baseline RPR titre is a predictor of treatment failure.
Rapid identification of pork for halal authentication using the electronic nose and gas chromatography mass spectrometer with headspace analyzer

Nurjuliana M, Che Man YB, Mat Hashim D, Mohamed AK

Meat Sci, 2011 Aug;88(4):638-44.
PMID: 21420795 DOI: 10.1016/j.meatsci.2011.02.022

The volatile compounds of pork, other meats and meat products were studied using an electronic nose and gas chromatography mass spectrometer with headspace analyzer (GCMS-HS) for halal verification. The zNose™ was successfully employed for identification and differentiation of pork and pork sausages from beef, mutton and chicken meats and sausages which were achieved using a visual odor pattern called VaporPrint™, derived from the frequency of the surface acoustic wave (SAW) detector of the electronic nose. GCMS-HS was employed to separate and analyze the headspace gasses from samples into peaks corresponding to individual compounds for the purpose of identification. Principal component analysis (PCA) was applied for data interpretation. Analysis by PCA was able to cluster and discriminate pork from other types of meats and sausages. It was shown that PCA could provide a good separation of the samples with 67% of the total variance accounted by PC1.
Fulltext A glutamic acid-producing lactic acid bacteria isolated from Malaysian fermented foods

Zareian M, Ebrahimpour A, Bakar FA, Mohamed AK, Forghani B, Ab-Kadir MS, et al.

Int J Mol Sci, 2012;13(5):5482-97.
PMID: 22754309 DOI: 10.3390/ijms13055482

l-glutamaic acid is the principal excitatory neurotransmitter in the brain and an important intermediate in metabolism. In the present study, lactic acid bacteria (218) were isolated from six different fermented foods as potent sources of glutamic acid producers. The presumptive bacteria were tested for their ability to synthesize glutamic acid. Out of the 35 strains showing this capability, strain MNZ was determined as the highest glutamic-acid producer. Identification tests including 16S rRNA gene sequencing and sugar assimilation ability identified the strain MNZ as Lactobacillus plantarum. The characteristics of this microorganism related to its glutamic acid-producing ability, growth rate, glucose consumption and pH profile were studied. Results revealed that glutamic acid was formed inside the cell and excreted into the extracellular medium. Glutamic acid production was found to be growth-associated and glucose significantly enhanced glutamic acid production (1.032 mmol/L) compared to other carbon sources. A concentration of 0.7% ammonium nitrate as a nitrogen source effectively enhanced glutamic acid production. To the best of our knowledge this is the first report of glutamic acid production by lactic acid bacteria. The results of this study can be further applied for developing functional foods enriched in glutamic acid and subsequently γ-amino butyric acid (GABA) as a bioactive compound.
Enhancement of thermostable lipase production by a genotypically identified extremophilic Bacillus subtilis NS 8 in a continuous bioreactor

Olusesan AT, Azura LK, Abubakar F, Mohamed AK, Radu S, Manap MY, et al.

J. Mol. Microbiol. Biotechnol., 2011 Apr;20(2):105-15.
PMID: 21422764 DOI: 10.1159/000324535

Bacillus strain NS 8, a lipase-producing bacterium isolated from a Malaysian hot spring, is able to tolerate a broad range of temperature and pH, which makes it beneficial for this study. It generated PCR products with molecular weight of 1,532 bp, and the 16S rRNA sequence analysis identified it as Bacillus subtilis with accession number AB110598. It showed a 71% similarity index with B. subtilis using Biolog Microstation System. Its lipase production was optimized using a shake flask system by changing the physical (agitation speed, pH and temperature) and nutritional (nitrogen, carbon and minerals) factors. The most suitable combination of the basal medium for lipase production was 2.5% olive oil (carbon), 1.5% peptone (nitrogen), 0.1% MgSO(4) (mineral) at an optimum temperature of 50°C, pH 7.5 and 150 rpm agitation, giving an enzyme yield of 4.23 U/ml. Statistical optimization using response surface methodology was carried out. An optimum lipase production of 5.67 U/ml was achieved when olive oil concentration of 3%, peptone 2%, MgSO(4)·7H(2)O 0.2% and an agitation rate of 200 rpm were combined. Lipase production was further carried out inside a 2-liter bioreactor, which yielded an enzyme activity of 14.5 U/ml after 15 h of incubation.
Roles of Ki67 in Breast Cancer - Important for Management?

Yip Ch, Bhoo-Pathy N, Daniel J, Foo Y, Mohamed A, Abdullah M, et al.

Asian Pac J Cancer Prev, 2016;17(3):1077-82.
PMID: 27039727

BACKGROUND: The three standard biomarkers used in breast cancer are the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). The Ki-67 index, a proliferative marker, has been shown to be associated with a poorer outcome, and despite absence of standardization of pathological assessment, is widely used for therapy decision making. We aim to study the role of the Ki-67 index in a group of Asian women with breast cancer.
MATERIALS AND METHODS: A total of 450 women newly diagnosed with Stage 1 to 3 invasive breast cancer in a single centre from July 2013 to Dec 2014 were included in this study. Univariable and multivariable logistic regression was used to determine the association between Ki-67 (positive defined as 14% and above) and age, ethnicity, grade, mitotic index, ER, PR, HER2, lymph node status and size. All analyses were performed using SPSS Version 22.
RESULTS: In univariable analysis, Ki -67 index was associated with younger age, higher grade, ER and PR negativity, HER2 positivity, high mitotic index and positive lymph nodes. However on multivariable analysis only tumour size, grade, PR and HER2 remained significant. Out of 102 stage 1 patients who had ER positive/PR positive/HER2 negative tumours and non-grade 3, only 5 (4.9%) had a positive Ki-67 index and may have been offered chemotherapy. However, it is interesting to note that none of these patients received chemotherapy.
CONCLUSIONS: Information on Ki67 would have potentially changed management in an insignificant proportion of patients with stage 1 breast cancer.
Gefitinib as first line therapy in Malaysian patients with EGFR mutation-positive non-small-cell lung cancer: A single-center retrospective study

Abdullah MM, Bhat A, Mohamed AK, Ching FY, Ahmed N, Gantotti S

Oncol Lett, 2016 Apr;11(4):2757-2762.
PMID: 27073548

The present retrospective, single-center study evaluated the objective response rate (ORR) and progression-free survival (PFS) of epidermal growth factor receptor (EGFR) mutation-positive Malaysian patients with advanced lung adenocarcinoma treated with gefitinib. During May 2008 to July 2013, 33 patients with Stage IV, EGFR mutation-positive non-small-cell lung cancer (NSCLC) were identified and received gefitinib (250 mg) as first line treatment. The primary and secondary end points were ORR, PFS and safety, respectively. A total of 18 (54.5%) and 2 (6.1%) patients achieved partial response (PR) and complete response (CR) to gefitinib therapy, respectively, yielding an ORR of 60.6% (95% CI, 42.1-77.1%). Patients with exon 20 or 21 mutations (n=6, 66.7%) tended to have better ORR compared with exon 19 (n=22, 59.1%). The median PFS was 8.9 months in Malaysian patients with EGFR mutation-positive NSCLC, treated with gefitinib. The majority of treatment-related toxicity was mild in nature. The most frequently reported adverse events included dry skin (39.4%), skin rash (27.2%), and dermatitis acneiform (15.2%). In conclusion, Malaysian patients with locally advanced and metastatic EGFR mutation-positive NSCLC responded favorably to gefitinib therapy in terms of ORR, median PFS, and tolerability, the results of which were consistent with those of the IPASS study conducted in an Asian population. Considering the efficacy and safety profile of gefitinib, it is a favorable option for the first-line treatment of Malaysian patients with EGFR mutation-positive NSCLC. However, future long-term studies in a larger population of Malaysian patients are required to support whether the prolonged PFS conferred by gefitinib will translate into prolonged overall survival.
Purification, characterization and thermal inactivation kinetics of a non-regioselective thermostable lipase from a genotypically identified extremophilic Bacillus subtilis NS 8

Olusesan AT, Azura LK, Forghani B, Bakar FA, Mohamed AK, Radu S, et al.

N Biotechnol, 2011 Oct;28(6):738-45.
PMID: 21238617 DOI: 10.1016/j.nbt.2011.01.002

Thermostable lipase produced by a genotypically identified extremophilic Bacillus subtilis NS 8 was purified 500-fold to homogeneity with a recovery of 16% by ultrafiltration, DEAE-Toyopearl 650M and Sephadex G-75 column. The purified enzyme showed a prominent single band with a molecular weight of 45 kDa. The optimum pH and temperature for activity of lipase were 7.0 and 60°C, respectively. The enzyme was stable in the pH range between 7.0 and 9.0 and temperature range between 40 and 70°C. It showed high stability with half-lives of 273.38 min at 60°C, 51.04 min at 70°C and 41.58 min at 80°C. The D-values at 60, 70 and 80°C were 788.70, 169.59 and 138.15 min, respectively. The enzyme's enthalpy, entropy and Gibb's free energy were in the range of 70.07-70.40 kJ mol(-1), -83.58 to -77.32 kJ mol(-1)K(-1) and 95.60-98.96 kJ mol(-1), respectively. Lipase activity was slightly enhanced when treated with Mg(2+) but there was no significant enhancement or inhibition of the activity with Ca(2+). However, other metal ions markedly inhibited its activity. Of all the natural vegetable oils tested, it had slightly higher hydrolytic activity on soybean oil compared to other oils. On TLC plate, the enzyme showed non-regioselective activity for triolein hydrolysis.
Breast Cancer Survival at a Leading Cancer Centre in Malaysia

Abdullah MM, Mohamed AK, Foo YC, Lee CM, Chua CT, Wu CH, et al.

Asian Pac J Cancer Prev, 2015;16(18):8513-7.
PMID: 26745110

BACKGROUND: GLOBOCAN12 recently reported high cancer mortality in Malaysia suggesting its cancer health services are under-performing. Cancer survival is a key index of the overall effectiveness of health services in the management of patients. This report focuses on Subang Jaya Medical Centre (SJMC) care performance as measured by patient survival outcome for up to 5 years.
MATERIALS AND METHODS: All women with breast cancer treated at SJMC between 2008 and 2012 were enrolled for this observational cohort study. Mortality outcome was ascertained through record linkage with national death register, linkage with hospital registration system and finally through direct contact by phone or home visits.
RESULTS: A total of 675 patients treated between 2008 and 2012 were included in the present survival analysis, 65% with early breast cancer, 20% with locally advanced breast cancer (LABC) and 4% with metastatic breast cancer (MBC). The overall relative survival (RS) at 5 years was 88%. RS for stage I was 100% and for stage II, III and IV disease was 95%, 69% and 36% respectively.
CONCLUSIONS: SJMC is among the first hospitals in Malaysia to embark on routine measurement of the performance of its cancer care services and its results are comparable to any leading centers in developed countries.
Fulltext Closing the global cancer divide--performance of breast cancer care services in a middle income developing country

Lim GC, Aina EN, Cheah SK, Ismail F, Ho GF, Tho LM, et al.

BMC Cancer, 2014;14:212.
PMID: 24650245 DOI: 10.1186/1471-2407-14-212

BACKGROUND: Cancer is the leading cause of deaths in the world. A widening disparity in cancer burden has emerged between high income and low-middle income countries. Closing this cancer divide is an ethical imperative but there is a dearth of data on cancer services from developing countries.
METHODS: This was a multi-center, retrospective observational cohort study which enrolled women with breast cancer (BC) attending 8 participating cancer centers in Malaysia in 2011. All patients were followed up for 12 months from diagnosis to determine their access to therapies. We assess care performance using measures developed by Quality Oncology Practice Initiative, American Society of Clinical Oncology/National Comprehensive Cancer Network, American College of Surgeons' National Accreditation Program for Breast Centers as well as our local guideline.
RESULTS: Seven hundred and fifty seven patients were included in the study; they represent about 20% of incident BC in Malaysia. Performance results were mixed. Late presentation was 40%. Access to diagnostic and breast surgery services were timely; the interval from presentation to tissue diagnosis was short (median = 9 days), and all who needed surgery could receive it with only a short wait (median = 11 days). Performance of radiation, chemo and hormonal therapy services showed that about 75 to 80% of patients could access these treatments timely, and those who could not were because they sought alternative treatment or they refused treatment. Access to Trastuzumab was limited to only 19% of eligible patients.
CONCLUSIONS: These performance results are probably acceptable for a middle income country though far below the 95% or higher adherence rates routinely reported by centres in developed countries. High cost trastuzumab was inaccessible to this population without public funding support.

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