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Caffeic acid phenethyl ester (CAPE): scavenger of peroxynitrite in vitro and in sepsis models

Kassim M, Mansor M, Kamalden TA, Shariffuddin II, Hasan MS, Ong G, et al.

Shock, 2014 Aug;42(2):154-60.
PMID: 24667629 DOI: 10.1097/SHK.0000000000000179

Excessive free radical production by immune cells has been linked to cell death and tissue injury during sepsis. Peroxynitrite is a short-lived oxidant and a potent inducer of cell death that has been identified in several pathological conditions. Caffeic acid phenethyl ester (CAPE) is an active component of honeybee products and exhibits antioxidant, anti-inflammatory, and immunomodulatory activities. The present study examined the ability of CAPE to scavenge peroxynitrite in RAW 264.7 murine macrophages stimulated with lipopolysaccharide/interferon-γ that was used as an in vitro model. Conversion of 123-dihydrorhodamine to its oxidation product 123-rhodamine was used to measure peroxynitrite production. Two mouse models of sepsis (endotoxemia and cecal ligation and puncture) were used as in vivo models. The level of serum 3-nitrotyrosine was used as an in vivo marker of peroxynitrite. The results demonstrated that CAPE significantly improved the viability of lipopolysaccharide/interferon-γ-treated RAW 264.7 cells and significantly inhibited nitric oxide production, with effects similar to those observed with an inhibitor of inducible nitric oxide synthase (1400W). In addition, CAPE exclusively inhibited the synthesis of peroxynitrite from the artificial substrate SIN-1 and directly prevented the peroxynitrite-mediated conversion of dihydrorhodamine-123 to its fluorescent oxidation product rhodamine-123. In both sepsis models, CAPE inhibited cellular peroxynitrite synthesis, as evidenced by the absence of serum 3-nitrotyrosine, an in vivo marker of peroxynitrite. Thus, CAPE attenuates the inflammatory responses that lead to cell damage and, potentially, cell death through suppression of the production of cytotoxic molecules such as nitric oxide and peroxynitrite. These observations provide evidence of the therapeutic potential of CAPE treatment for a wide range of inflammatory disorders.
Fulltext Gelam honey scavenges peroxynitrite during the immune response

Kassim M, Mansor M, Suhaimi A, Ong G, Yusoff KM

Int J Mol Sci, 2012;13(9):12113-29.
PMID: 23109904 DOI: 10.3390/ijms130912113

Monocytes and macrophages are part of the first-line defense against bacterial, fungal, and viral infections during host immune responses; they express high levels of proinflammatory cytokines and cytotoxic molecules, including nitric oxide, reactive oxygen species, and their reaction product peroxynitrite. Peroxynitrite is a short-lived oxidant and a potent inducer of cell death. Honey, in addition to its well-known sweetening properties, is a natural antioxidant that has been used since ancient times in traditional medicine. We examined the ability of Gelam honey, derived from the Gelam tree (Melaleuca spp.), to scavenge peroxynitrite during immune responses mounted in the murine macrophage cell line RAW 264.7 when stimulated with lipopolysaccharide/interferon-γ (LPS/IFN-γ) and in LPS-treated rats. Gelam honey significantly improved the viability of LPS/IFN-γ-treated RAW 264.7 cells and inhibited nitric oxide production-similar to the effects observed with an inhibitor of inducible nitric oxide synthase (1400W). Furthermore, honey, but not 1400W, inhibited peroxynitrite production from the synthetic substrate 3-morpholinosydnonimine (SIN-1) and prevented the peroxynitrite-mediated conversion of dihydrorhodamine 123 to its fluorescent oxidation product rhodamine 123. Honey inhibited peroxynitrite synthesis in LPS-treated rats. Thus, honey may attenuate inflammatory responses that lead to cell damage and death, suggesting its therapeutic uses for several inflammatory disorders.
Clinical spectrum of children receiving palliative care in Malaysian Hospitals

Chong LA, Khalid F, Khoo TB, Teh SH, Kuan GL, Aina Mariana AM, et al.

Med J Malaysia, 2017 02;72(1):32-36.
PMID: 28255137 MyJurnal

INTRODUCTION: Awareness for paediatric palliative care has resulted in the impetus for paediatrician-led palliative care services across Malaysia. However, there is paucity of local data on patients receiving hospital-based paediatric palliative care. We aim to review the clinical spectrum of patients referred to these services.
METHODS: An observational study of children aged between 0-18 years receiving palliative care at 13 hospitals between 1st January and 31st December 2014 was carried out.
RESULTS: There were 315 patients analysed, 90 (28.6%) and 46 (14.6%) were neonates and adolescents respectively. The main ICD-10 diagnostic categories for all patients were identified to be 'Congenital malformations, deformations and chromosomal abnormalities' 117 (37.1%), 'Diseases of nervous system' 76 (24.1%) and 'Neoplasms' 60 (19.0%). At referral 156 (50%) patients had holistic needs assessments. Patients with 'Diseases of nervous system' were assessed to have significantly more physical needs than the other two diagnostic categories. Majority of patients who knew of their diagnosis and prognosis were those with malignancy. Over a fifth of referrals were at their terminal admission. Of 144 who died, 111 (77.1%) had advanced care plans. There was bereavement follow-up in 98 (68.1%) patients.
CONCLUSION: Patients referred for palliative care have varied diagnoses and needs. To ensure all paediatricians are competent to deliver quality care to all children, further education and training initiatives is imperative.
Fulltext Myocardial injury after noncardiac surgery: a large, international, prospective cohort study establishing diagnostic criteria, characteristics, predictors, and 30-day outcomes

Botto F, Alonso-Coello P, Chan MT, Villar JC, Xavier D, Srinathan S, et al.

Anesthesiology, 2014 Mar;120(3):564-78.
PMID: 24534856 DOI: 10.1097/ALN.0000000000000113

BACKGROUND: Myocardial injury after noncardiac surgery (MINS) was defined as prognostically relevant myocardial injury due to ischemia that occurs during or within 30 days after noncardiac surgery. The study's four objectives were to determine the diagnostic criteria, characteristics, predictors, and 30-day outcomes of MINS.
METHODS: In this international, prospective cohort study of 15,065 patients aged 45 yr or older who underwent in-patient noncardiac surgery, troponin T was measured during the first 3 postoperative days. Patients with a troponin T level of 0.04 ng/ml or greater (elevated "abnormal" laboratory threshold) were assessed for ischemic features (i.e., ischemic symptoms and electrocardiography findings). Patients adjudicated as having a nonischemic troponin elevation (e.g., sepsis) were excluded. To establish diagnostic criteria for MINS, the authors used Cox regression analyses in which the dependent variable was 30-day mortality (260 deaths) and independent variables included preoperative variables, perioperative complications, and potential MINS diagnostic criteria.
RESULTS: An elevated troponin after noncardiac surgery, irrespective of the presence of an ischemic feature, independently predicted 30-day mortality. Therefore, the authors' diagnostic criterion for MINS was a peak troponin T level of 0.03 ng/ml or greater judged due to myocardial ischemia. MINS was an independent predictor of 30-day mortality (adjusted hazard ratio, 3.87; 95% CI, 2.96-5.08) and had the highest population-attributable risk (34.0%, 95% CI, 26.6-41.5) of the perioperative complications. Twelve hundred patients (8.0%) suffered MINS, and 58.2% of these patients would not have fulfilled the universal definition of myocardial infarction. Only 15.8% of patients with MINS experienced an ischemic symptom.
CONCLUSION: Among adults undergoing noncardiac surgery, MINS is common and associated with substantial mortality.
An investigation of arsenic contamination in Peninsular Malaysia based on Centella asiatica and soil samples

Ong GH, Yap CK, Maziah M, Suhaimi H, Tan SG

Environ Monit Assess, 2013 Apr;185(4):3243-54.
PMID: 22821327 DOI: 10.1007/s10661-012-2787-6

The first objective of this study was to provide data of arsenic (As) levels in Peninsular Malaysia based on soil samples and accumulation of As in Centella asiatica collected from 12 sampling sites in Peninsular Malaysia. The second objective was to assess the accumulation of As in transplanted C. asiatica between control and semi-polluted or polluted sites. Four sites were selected which were UPM (clean site), Balakong (semi-polluted site), Seri Kembangan (semi-polluted site) and Juru (polluted site). The As concentrations of plant and soil samples were determined by Instrumental Neutron Activation Analysis. The As levels ranged from 9.38 to 57.05 μg/g dw in soils, 0.21 to 4.33 μg/g dw in leaves, 0.18 to 1.83 μg/g dw in stems and 1.32-20.76 μg/g dw in roots. All sampling sites had As levels exceeding the CCME guideline (12 μg/g dw) except for Kelantan, P. Pauh, and Senawang with P. Klang having the highest As in soil (57.05 μg/g dw). In C. asiatica, As accumulation was highest in roots followed by leaves and stems. When the As level in soils were higher, the uptake of As in plants would also be increased. After the transplantation of plants to semi-polluted and polluted sites for 3 weeks, all concentration factors were greater than 50 % of the initial As level. The elimination factor was around 39 % when the plants were transplanted back to the clean sites for 3 weeks. The findings of the present study indicated that the leaves, stems and roots of C. asiatica are ideal biomonitors of As contamination. The present data results the most comprehensive data obtained on As levels in Malaysia.
Fulltext Large volume osteosarcomas of the femur treated with total femoral replacement

Pan K, Chan W, Shanmugam P, Ong G, Kamaruddin F, Tan S

Malays Orthop J, 2014 Mar;8(1):32-6.
PMID: 25347294 MyJurnal DOI: 10.5704/MOJ.1403.015

Patients with extensive malignancies involving the femur often require total femoral replacement when their limbs can be salvaged. Reported series are small and involve heterogeneity of tumours. We present nine patients with osteosarcomas of the femur treated at our institution between 2003 and 2010 with a mean follow-up of 27 (6 to 56) months. Their ages ranged from 9 to 17 (mean 14 years). They had large volume tumours (mean 911 cm3) and presented late with a mean of 5.5 months from the onset of symptoms to definitive treatment. All patients underwent resection and total femur replacement. Six patients have died and two are alive with good function at the time of this report. One was lost to follow-up. These patients require a high level of treatment care and have a guarded prognosis.
Fulltext Stimulation of β-adrenergic receptors plays a protective role via increased expression of RAF-1 and PDX-1 in hyperglycemic rat pancreatic islet (RIN-m5F) cells

Safi SZ, Qvist R, Ong G, Karimian H, Imran M, Shah I

Arch Med Sci, 2017 Mar 01;13(2):470-480.
PMID: 28261303 DOI: 10.5114/aoms.2016.64131

INTRODUCTION: It is a widely held view that a progressive reduction of beta-cell mass occurs in the progression of diabetes. RAF-1 kinase and pancreas duodenal homeobox 1 (PDX-1) are major factors that promote survival of cells and maintain normal insulin functions. In this study we investigated the effect of a β-adrenergic receptor agonist and antagonist on RAF-1 and PDX-1, and their respective effects on apoptosis and insulin release in RIN-m5F cells.
MATERIAL AND METHODS: RIN-m5F cells were cultured in normal (5 mM) and high (25 mM) glucose to mimic diabetic conditions, followed by treatment with 5 µM, 10 µM and 20 µM of isoproterenol and isoproterenol + propranolol for 6, 12 and 24 h. Western blotting and reverse transcription analysis were performed to examine the expression of RAF-1 and PDX-1. Annexin-V-FITC and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assays were used to investigate apoptosis. ELISA was used to measure insulin levels. Reverse transcription polymerase chain reaction was conducted to investigate the expression of genes.
RESULTS: Stimulation of β-adrenergic receptors with isoproterenol significantly induced RAF-1 and PDX-1 genes in a concentration-dependent and time-independent manner. Changes were significant both at protein and mRNA levels. Up-regulation of RAF-1 and PDX-1 was accompanied by improved insulin levels and reduced apoptosis. Concentrations of 10 µM and 20 µM for 12 and 24 h were more effective in achieving significant differences in the experimental and control groups. Propranolol reversed the effect of isoproterenol mostly at maximum concentrations and time periods.
CONCLUSIONS: A positive effect of a β-adrenergic agonist on RAF-1 and PDX-1, reduction in β-cell apoptosis and improved insulin contents can help to understand the pathogenesis of diabetes and to develop novel approaches for the β-cell dysfunction in diabetes.
Fulltext Moulded cement-prosthesis for osteosarcoma of the proximal humerus

Pan KL, Ong GB, Potukuchi AP

Med J Malaysia, 2006 Dec;61 Suppl B:55-7.
PMID: 17600994

We report a case of an 11-year-old boy with osteosarcoma of the proximal humerus treated with wide excision and reconstruction with a cement spacer-prosthesis. After seven years of follow-up, the patient is now almost a young adult. We present his current physical and functional status, which seems to defray the initial doubts regarding long-term problems when we chose this method of reconstruction.
Comparison of propofol consumption and recovery time in Caucasians from Italy, with Chinese, Malays and Indians from Malaysia

Ortolani O, Conti A, Chan YK, Sie MY, Ong GS

Anaesth Intensive Care, 2004 Apr;32(2):250-5.
PMID: 15957725

Differences in sensitivity to anaesthetic drugs may exist among different ethnic groups. Allelic variants for drug metabolizing isoenzymes and pharmacokinetic differences may account for a variable response to some anaesthetic drugs. This study was designed to compare propofol consumption and recovery characteristics in four ethnic groups: Chinese, Malays, and Indians in Malaysia and Caucasians in Italy. Patients undergoing total intravenous anaesthesia with propofol and fentanyl were evaluated for propofol consumption and recovery time. The Bispectral Index (BIS) was used to maintain the same anaesthesia depth in all patients. The BIS value, the response to verbal stimuli and eye-opening time were used to assess recovery. After propofol discontinuation the BIS values returned to baseline in 11+/-4.2 min for Caucasians, in 12.5+/-5.1 min for Chinese, 15.9+/-6.3 min for Malays and 22.1+/-8.1 for Indians. Time to eye-opening was 11.63+/-4.2 min in Caucasians, 13.23+/-4.9 min in Chinese, 16.97+/-5.2 min in Malays and 22.3+/-6.6 min in Indians. The propofol consumption was significantly lower in Indians compared to the other three groups (P<0.01). The recovery of Indians was much slower compared to Chinese, Malays and Caucasians. The recovery time of Malays is significantly slower compared to Chinese and Caucasians. Differences in propofol consumption and recovery time were not significant between Chinese and Caucasians, but the ratio recovery time/propofol consumption was significantly lower in Caucasians compared to all the other groups.
Subcutaneous emphysema and pneumomediastinum after endotracheal anaesthesia

Chiu CL, Ong GS

Ann Acad Med Singap, 2000 Mar;29(2):256-8.
PMID: 10895351

INTRODUCTION: We report a case of subcutaneous emphysema and pneumomediastinum that presented postoperatively after tracheal extubation.
CLINICAL PICTURE: A 51-year-old man had an uneventful anaesthesia lasting about 6.5 hours. Intubation was performed by a very junior medical officer and was considered difficult. He developed sore throat, chest pain, numbness of both hands and palpable crepitus around the neck postoperatively. Chest X-ray revealed diffuse subcutaneous emphysema, pneumomediastinum and possible pneumopericardium.
TREATMENT: He was treated conservatively with bed rest, oxygen, analgesia, antibiotic prophylaxis, reassurance and close monitoring.
OUTCOME: The patient made an uneventful recovery.
CONCLUSIONS: We discussed the possible causes.
Severe bronchospasm during epidural anaesthesia

Wang CY, Ong GS

Anaesthesia, 1993 Jun;48(6):514-5.
PMID: 8322993

A case of severe bronchospasm occurring during epidural anaesthesia in a patient undergoing Caesarean section is described. The aetiology of the bronchospasm may have been related to sympathetic nervous blockade allowing unopposed parasympathetically mediated bronchoconstriction.
Fulltext Bacterial contamination of a closed enteral feeding system: difference between laboratory evaluation and clinical experience

Ngeow YF, Chan L, Yasmin AH, Ong GS

Med J Malaysia, 1994 Dec;49(4):427.
PMID: 7674983
Fulltext Evaluation of the bacteriological contamination of a closed feeding system for enteral nutrition

Chan L, Yasmin AH, Ngeow YF, Ong GS

Med J Malaysia, 1994 Mar;49(1):62-7.
PMID: 8057993

A closed enteral delivery system consisting of a cardboard tetrapack containing the sterile ready-to-use liquid feed and an independent sterile administration set, has been devised. We found bacterial contamination within 24 hours in this system in patients on ventilatory support in intensive care. This emphasises the need for meticulous care in handling enteral feeding systems to prevent environmental contamination.
Fulltext Acute respiratory failure in melioidosis

Puthucheary SD, Vadivelu J, Wong KT, Ong GS

Singapore Med J, 2001 Mar;42(3):117-21.
PMID: 11405563

In melioidosis caused by Burkholderia pseudomallei, although every organ in the body may be involved, the highest mortality of 73% occurs when the respiratory system is affected. These patients invariably die of acute respiratory failure. Most of them also have underlying predisposing factors like diabetes mellitus.
Fulltext Early presentation of right adrenal mass, hepatoblastoma and hepatic cavernous haemangioma in Beckwith-Wiedemann Syndrome

Teh SH, Ong GB

Med J Malaysia, 2007 Oct;62(4):345-6.
PMID: 18551945 MyJurnal

Beckwith-Wiedemann Syndrome (BWS) is associated with early development of embryonal tumours usually in the first four years of life. We describe a patient who presented with a right adrenal cyst in the first month of life and hepatoblastoma in the third month of life. A cavernous haemangioma was subsequently found in the resected tumour.
Radical hysterectomy and pelvic lymphadenectomy for early invasive cancer of the cervix - 14-year experience

Sivanesaratnam V, Sen DK, Jayalakshmi P, Ong G

Int. J. Gynecol. Cancer, 1993 Jul;3(4):231-238.
PMID: 11578351

During a 14-year period, 397 radical hysterectomies and pelvic lymphadenectomies were performed for early invasive carcinoma of the cervix. Twenty-one patients were in stage IA2 with lymphatic/vascular channel permeation (5.2%), 340 in stage IB (85.6%) and 34 in early stage 2A disease (8.5%). Eighteen patients (4.5%) were pregnant. Adenocarcinoma comprised 26.9% of cases. The mean operative time was 4.14 h; the intraoperative blood loss was less than 1.51 in 77.3% patients. There was no operative mortality; one patient died 3 weeks after surgery from clostridium difficile enterocilitis. Eleven patients (2.7%) developed venous thrombosis; severe lymphedema occurred in four (1%). The incidence of uretero-vaginal fistula was 0.2% and that of vesico-vaginal fistula 0.5%. Ovarian metastases were noted in 4.3% of cases with adenocarcinoma. Sixty-six patients had positive nodes (16.6%). Five-year survival in patients with more than 2 positive nodes was 68%. The use of adjuvant chemotherapy in patients with 'high risk' factors resulted in survival rates approaching those without risk factors. Neo-adjuvant chemotherapy was used in 10 patients with large bulky tumors; the results were favorable. Recurrences occurred in 47 patients (11.8%); 36 patients have died (9.1%). Age did not appear to influence survival. The overall 5-year survival was 92.2%.
Major gynaecological surgery in patients with severe coronary artery disease--the combined approach

Kannan P, Sivanesaratnam V, Jeyamalar R, Delilkan A, Ong G

Aust N Z J Obstet Gynaecol, 1990 May;30(2):146-9.
PMID: 2400358

The gynaecologist today is likely to encounter elderly patients with severe coronary heart disease requiring major gynaecological surgery. The successful outcome in 2 such patients with compromised coronary circulation and impaired left ventricular function emphasized the importance of combined care with the cardiologist and the anaesthetist. The insertion of a Swan-Ganz catheter for close perioperative monitoring is vital. The intra-and postoperative problems are discussed.
Fulltext Long-term ventilatory support in an infant with broncho-pulmonary dysplasia--a case report

Sivarajah RS, Koh MT, Tan P, Ooi SE, Ong G

Med J Malaysia, 1984 Mar;39(1):88-91.
PMID: 6549042

Long-term ventilatory support of a child with bronchopulmonary dysplasia is described. Dedicated nursing care and emotional support of child and family were two important factors in the management of the child in intensive care, and in the weaning of the child from the ventilator.
Fulltext Organophosphate poisoning: a Malaysian intensive care experience of one hundred cases

Delilkan AE, Namazie M, Ong G

Med J Malaysia, 1984 Sep;39(3):229-33.
PMID: 6544925

From 1970 to 1984, 100 patients suffering from organophosphate poisoning were treated in the Intensive Care Unit at the University Hospital. These patients developed signs and symptoms of cholinergic over-activity and were treated with continuous intravenous atropine. Many of the patients also developed acute respiratory failure, which necessitated ventilatory support in the form of intermittent positive pressure ventilation. Other measures included the use of inotropes and nutritional support. Daily estimation of serum cholinesterase levels were useful in assessing degree of recovery of the patients from the effects of the organophosphates.
Fulltext Effects of immunonutrition on biomarkers in traumatic brain injury patients in Malaysia: a prospective randomized controlled trial

Rai VRH, Phang LF, Sia SF, Amir A, Veerakumaran JS, Kassim MKA, et al.

BMC Anesthesiol, 2017 06 15;17(1):81.
PMID: 28619005 DOI: 10.1186/s12871-017-0369-4

BACKGROUND: Head injury is one of the top three diagnosis leading to intensive care unit (ICU) admission in Malaysia. There has been growing interest in using immunonutrition as a mode of modulating the inflammatory response to injury or infection with the aim of improving clinical outcome. The aim of the present study was to evaluate the effect of an immunonutrition on biomarkers (IL-6, glutathione, CRP, total protein and albumin) in traumatic brain injury patients.
METHODS: Thirty six patients with head injury admitted to neurosurgical ICU in University Malaya Medical Centre were recruited for this study, over a 6-month period from July 2014 to January 2015. Patients were randomized to receive either an immunonutrition (Group A) or a standard (Group B) enteral feed. Levels of biomarkers were measured at day 1, 5 and 7 of enteral feeding.
RESULTS: Patients in Group A showed significant reduction of IL-6 at day 5 (p

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