Febrile neutropenia is a common and potentially fatal problem encountered in cancer patients undergoing chemotherapy. We carried out an observational study to evaluate the possible risk factors of developing fever amongst neutropenic children with an underlying malignancy. We also looked at the microbiological profile of causative pathogens in patients with febrile neutropenia. During a study period of 1 year, a total of 90 neutropenic episodes were recorded amongst 57 patients who were on treatment and follow-up during the study period. Multivariate analysis showed that factors such as chemotherapy status, underlying disease, existing central venous catheters, presenting white blood cell counts at chemotherapy, use of steroid therapy or hospitalisation at the onset of neutropenia, were not significant risk factors for developing fever during neutropenic episodes. Although the presence of a central venous catheter was associated with a higher risk of developing fever, it did not reach statistical significance (p=0.11). Of the 90 neutropenic episodes, 59 (65.6%) developed fever and 25 of these had positive blood cultures. The causative organisms include gram-negative bacteria (64%), gram positive bacteria (16%) and fungus (20%). Of the gram-negative organisms, Klebsiella spp. predominated (28%) with the extended spectrum beta-lactamase producing strain forming the majority (16%). Amongst those with fungaemia, Candida spp. and Candida tropicalis formed the majority (8% each) of the isolates.
Fever ; Neutropenia ; Malignant Neoplasms ; Chemotherapy-Oncologic Procedure ; majority

A cross-sectional study was carried out to evaluate the nutritional status of 51 subjects with leukemia aged 4 to 12 years from the Haematology & Oncology Paediatric Ward, Universiti Kebangsaan Malaysia Medical Centre (PPUKM) and the Paediatric Institute of Kuala Lumpur. Nutritional status was assessed using anthropometric measurements, biochemical and haematological parameters. Subjects comprised 32 (62.7%) males and 19 (27.3%) females. Most of the subjects (41.2%) were in the age group of 4 to 6 years. More than half of the children were Malays (70.6%) followed by Indians (15.7%) and Chinese (13.7%). The subjects were diagnosed as acute lymphoblastic leukemia (ALL) (84.3%) followed by acute myelogenous leukemia (AML) (13.7%) and chronic myelogenous leukemia (CML) (2.0%) respectively. Most of the children were in remission status (54.9%). Underweight (<-2 SD for weight-for-age) was observed in 37.3% of the children while 17.6% of them were stunted (<-2 SD for height-for-age), and sign(s) of malnutrition (<-2 SD) for mid upper arm circumference (MUAC)-for-age was observed in 15.7% of the subjects. Approximately 20.0% of the subjects were in the severe malnutrition category with respect to low serum albumin levels (<3.5g/dl). All subjects had hemoglobin levels of less than the normal range. While the results indicated no significant differences in the nutritional status of subjects with leukemia at different stages of treatment, it was observed that the prevalence of malnutrition was higher in children with newly diagnosed leukemia. Thus, the nutritional status of children with leukemia should be monitored closely as there is a likelihood of deterioration owing to the disease.

Child ; Folic Acid ; administration & dosage ; therapeutic use ; Folic Acid Antagonists ; adverse effects ; Hematinics ; administration & dosage ; therapeutic use ; Humans ; Hypesthesia ; chemically induced ; drug therapy ; Injections, Spinal ; Leukoencephalopathies ; chemically induced ; Male ; Methotrexate ; adverse effects ; Quadriplegia ; chemically induced ; drug therapy ; Time Factors ; Vitamin B Complex ; administration & dosage ; therapeutic use

Validation of instruments is essential when assessing physical activity (PA). The aim of this study was to validate a Malay language version of the International Physical Activity Questionnaire (IPAQ-M) against Actical accelerometer and to determine its reliability and validity. A total of 90 Malay adults aged 35-65 years old participating in The Malaysian Cohort project were recruited for this study. The IPAQ-M is comprised of 12 items, covering vigorous, moderate, walking, sitting and sleeping activities, and was administered on two occasions (Day 1 and Day 9) by interviewing the participants. Participants wore the Actical accelerometer for seven consecutive days between the two interview sessions. Validity tests showed that time spent in moderate-vigorous physical activity (MVPA) (min wk-1) from IPAQ-M was significantly correlated with MVPA from accelerometer (ρ=0.32, p<0.01). Time spent in vigorous activity (ρ=0.44) and total activity (ρ=0.36) from IPAQ-M were significantly correlated (p<0.01) with that measured by accelerometer, but no correlation was observed for sedentary behaviour. Reliability tests revealed significant correlations between the two interview sessions for all intensities of PA (=ρ0.55 to 0.71, p<0.01). Bland-Altman plots showed that time spent in MVPA for IPAQ-M was significantly different from that measured by accelerometer (mean difference: 98.02 min wk-1; 95% limits of agreement: -785.33 to 1317.83 min wk-1; p<0.01). When classifying people into meeting PA recommendation, the agreement between the two instruments was fair (κ=0.22). The IPAQ-M has acceptable validity for MVPA, vigorous and total physical activity, and was reliable for assessing the physical activity of Malay adults.​

We report a case of bone marrow necrosis preceding infantile acute lymphoblastic leukaemia (ALL). Bone marrow necrosis is a rare antemortem event and has been known to be present in many conditions, notably in haematological malignancies like acute lymphoblastic leukaemia. This case was a 6-month-old Chinese boy who was referred to Hospital Universiti Kebangsaan Malaysia for further investigation of pancytopaenia, high-grade fever, bloody diarrhoea and petechial rashes for one week. His first bone marrow aspirate revealed bone marrow necrosis. His clinical condition improved after ten days. However, his full blood picture then revealed the presence of 5% blast cells. His subsequent marrow 2 weeks later revealed acute lymphoblastic leukaemia (FAB-L1) and immunophenotyping showed precursor B acute lymphoblastic leukaemia-null type. He was started on United Kingdom Acute Lymphoblastic leukaemia (UK ALL) Infantile Leukaemia protocol, however, he defaulted treatment after 3 days. Mode of presentation, mechanism of disease and laboratory investigations and outline of treatment will be discussed.
Acute ; Lymphoblast ; Bone Marrow ; Necrosis ; week

Previous studies have shown that carbamazepine-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) patients is associated with the HLA-B*1502 allele. Screening for HLA-B*1502 before using carbamazepine can prevent SJS/TEN particularly in populations with high frequency of the allele. The objective of this paper was to describe how the UKM Medical Centre, Malaysia was able to set up a cost effective screening of HLA-B*1502 for patients taking carbamazepine. The cost of in-house HLA-B⁄1502 screening was less than those commercially available, and was sensitive and specifi c.

Child ; Codon, Nonsense ; Female ; Hamartoma Syndrome, Multiple ; diagnosis ; genetics ; Humans ; PTEN Phosphohydrolase ; genetics

Childhood obesity is a global epidemic, which leads to the increasing number of studies on genetic locations associated with obesity-related traits. Polymorphisms of insulin (INS) gene have been shown to be associated with obesity-related phenotypes in Europeans; while insulin receptor (INSR) gene has been associated with energy regulation. Therefore, this study was conducted to investigate the association between the INS (rs689) and INSR (rs3745551) gene polymorphisms with childhood obesity risk in a Malay childhood population. Normal weight (538) and overweight or obese (557) children aged 6-12 years old were genotyped using semi-automated Sequenom iPLEX® Gold. Body mass index (BMI) was calculated from measured body weight and height. The rs689 (T/T: 0.006, A/T: 0.159 and A/A: 0.835) and rs3745551 (G/G: 0.054, A/G: 0.378 and A/A: 0.568) genotype distributions were consistent with Hardy Weinberg equilibrium. The T-minor allele frequency for rs689 was 8.6% and G-minor allele frequency for rs3745551 was 24.3%. Minor allele of INS gene polymorphisms significantly increased risk of obesity among Malay children (sex- and age-adjusted OR=1.580; 95%CI: 1.134-2.201). However, INSR gene polymorphisms were not significantly associated with childhood obesity. In conclusion, the polymorphisms of INS gene, rather than INSR gene, were associated with childhood obesity in the Malay population.
Pediatric Obesity ; Receptor, Insulin

Aims: VraSR and GraSR were shown to be important in conferring intermediate vancomycin resistance in VISA. Nevertheless, the exact mechanism modulated by these systems leading to the development of VISA remains unclear. We employed a proteomic approach to determine the VraS and GraR regulons and subsequently derive the possible vancomycin resistance regulatory pathway(s) in the Mu50 lineage of Staphylococcus aureus. Methodology and results: Staphylococcus aureus strains Mu50Ω, Mu50Ω-vraSm and Mu50Ω-vraSm-graRm are isogenic strains with ascending levels of vancomycin resistance. Total proteins were extracted from the 3 strains and trypsin digested prior to protein isolation and identification by LC-ESI MS/MS and PLGS 2.4. Expression profiles of resulting proteins were analyzed using Progenesis LC/MS software. Differential expression profiles revealed 3 regulons, each controlled by VraS (Mu50Ω-vraSm vs Mu50Ω), GraR (Mu50Ω-vraSm-graRm vs Mu50Ω-vraSm) and VraS-GraR (Mu50Ω-vraSm-graRm vs Mu50Ω), respectively. The regulon down-regulated by VraS in Mu50Ω-vraSm were proteins associated with virulence (MgrA, Rot, and SarA), while GraR up-regulated resistance-associated proteins (TpiA, ArcB and IsaA) in Mu50Ω-vraSm-graRm. The VraS-GraR regulon mediated both up-regulation of resistance-associated proteins (ArgF, ArcB, VraR and SerS) and down-regulation of virulence-associated protein GapB. Conclusion, significance and impact of study: Down-regulation of virulence- in concert with up-regulation of resistance-associated proteins appears to be integral for development of intermediate-vancomycin resistance in the Mu50 lineage of S. aureus.
Staphylococcus aureus

Background: Mutations in glucocerebrosidase (GBA) have been associated with the risk of developing Parkinson’s disease (PD) in different ethnic populations. The prevalence of GBA mutations among Malay PD patients is unknown. Thus, the aim of this study was to determine the frequency of GBA mutations among Malay PD patients, focusing on early (EOPD) and late-onset (LOPD) patients. Methods:EOPD (n = 50) and LOPD (n = 50) patients along with 50 ethnically and age-matched control wererecruited. The GBA exons of these patients were sequenced using the Ion Torrent PGMTM System. Results: Five heterozygous mutations exclusive to EOPD patients were identified; c.-203A>G,p.S146L, p.R159Q, p.L483P and p.L483R+c.-145G>A. In LOPD patients, c.543C>T(p.(F181=)), c.28-10C>A and p.R202Q were identified in which this p.R202Q was also present in a control subject. In addition, c.259C>A(p.(R87=)) and c.-145G>A were identified in two control subjects. In summary, we observed GBA mutations in 8% and 6% of Malay PD cases and control subject, respectively. The prevalence of GBA mutations was higher in EOPD (10%) than LOPD (6%). However, these differences were not statistically significant; [PD vs. controls: OR = 1.36, 95%CI 0.35-5.38, p = 0.752] and [EOPD vs. LOPD: OR = 1.74, 95%CI 0.39-7.71, p = 0.715]. Conclusion: We identified five exclusive heterozygous GBA mutations in EOPD patients which might predict the increase susceptibility of Malays to develop PD at young age. These findings could add knowledge into the existing evidences linking genetic alterations in GBA and PD.